1. BACKGROUND
Lung cancer is the leading cause of death due to cancer in the world. Lung cancer is categorized into two types, small cell lung cancer (“SCLC”) and non-small cell lung cancer (“NSCLC”). SCLC is an extremely aggressive form of lung cancer with poor prognosis and a median length of survival after diagnosis of about 1 to 3 months. About 80% of lung cancer cases are categorized as NSCLC, which is categorized into three sub-types: adenocarcinoma, squamous cell carcinoma and large cell carcinoma. Greater than 85% of all NSCLCs are either adenocarcinoma or squamous-cell carcinoma.
Lung cancer is difficult to diagnose in the early stages because it may manifest no outward symptoms. When symptoms do occur, they can vary depending on the type, location and spreading pattern of the cancer, and therefore, are not readily associated with cancer. Often, lung cancer is only correctly diagnosed when it has already metastasized.
Current techniques for diagnosing lung cancer include chest x-ray and/or computed tomography (“CT”) scan. Diagnosis by one of these techniques is usually confirmed by a more invasive procedure, such as transthoracic needle biopsy or transbronchial biopsy, which may still result in misdiagnosis of lung cancer. (Butnor (2008) Arch. Pathol. Lab. Med. 132:1118-1132.)
Despite advances in treatment (e.g., by surgery, chemotherapy, radiation or a combination), the prognosis for lung cancer remains poor, with only 15% of patients surviving more than 5 years from the time of diagnosis. Of the most common NSCLCs, adenocarcinoma progresses more rapidly and therefore has a poorer prognosis than squamous-cell carcinoma, which takes several years to develop and is therefore more likely to be diagnosed in an early stage.
One proposal for reducing the mortality and morbidity of lung cancer is to institute regular screening of high-risk individuals, e.g., those who smoke or have smoked heavily for a certain period of time, in order to detect and treat lung cancer in asymptomatic individuals. In this way, early stage lung cancer can be eradicated by surgical resection, which is thought to be the only realistic option for a cure. (Field et al. (2008) Br. J. Cancer 99:557-562).
There remains a need for molecular markers in lung cancer.
2. SUMMARY
In some embodiments, methods of detecting the presence of lung cancer in a subject are provided. In some embodiments, a method comprises detecting a level of at least one target RNA in a sample from the subject. In some embodiments, the at least one target RNA: (i) is capable of specifically hybridizing to a nucleic acid having a sequence selected from SEQ ID NOs: 1 to 397, 1063 to 1210, 2064 to 2183, 2673 to 2680, and 2689; or (ii) comprises a sequence that is complementary to at least 15 contiguous nucleotides of a sequence selected from SEQ ID NOs: 1 to 397, 1063 to 1210, 2064 to 2183, 2673 to 2680, and 2689; or (iii) comprises at least 15 contiguous nucleotides of a sequence selected from SEQ ID NOs: 794 to 1043, 2576 to 2672, and 2692. In some embodiments, a level of at least one target RNA in the sample that is greater than a normal level of the at least one target RNA indicates the presence of lung cancer in the subject. In some embodiments, the method further comprises comparing the level of the at least one target RNA in the sample to a normal level of the at least one target RNA.
In some embodiments, methods for facilitating the detection of lung cancer in a subject are provided. In some embodiments, a method comprises detecting a level of at least one target RNA in a sample from the subject. In some embodiments, the target RNA (i) is capable of specifically hybridizing to a nucleic acid having a sequence selected from SEQ ID NOs: 1 to 397, 1063 to 1210, 2064 to 2183, 2673 to 2680, and 2689; or (ii) comprises a sequence that is complementary to at least 15 contiguous nucleotides of a sequence selected from SEQ ID NOs: 1 to 397, 1063 to 1210, 2064 to 2183, 2673 to 2680, and 2689; or (iii) comprises at least 15 contiguous nucleotides of a sequence selected from SEQ ID NOs: 794 to 1043, 2576 to 2672, and 2692. In some embodiments, a method comprises communicating the results of the detection to a medical practitioner for the purpose of determining whether the subject has lung cancer.
In some embodiments, detecting a level of at least one target RNA in a sample comprises hybridizing nucleic acids of the sample with at least one polynucleotide that is complementary to a target RNA in the sample or to a complement thereof; and detecting at least one complex comprising a polynucleotide hybridized to at least one nucleic acid selected from the target RNA, a DNA amplicon of the target RNA, and a complement of the target RNA.
In some embodiments, a method for detecting the presence of lung cancer in a subject comprises (a) obtaining a sample from the subject; (b) providing the sample to a laboratory for detection of the level of at least one target RNA in the sample; and (c) receiving from the laboratory a communication indicating the level of at least one target RNA in the sample. In some embodiments, the at least one target RNA (i) is capable of specifically hybridizing to a nucleic acid having a sequence selected from SEQ ID NOs: 1 to 397, 1063 to 1210, 2064 to 2183, 2673 to 2680, and 2689; or (ii) comprises a sequence that is complementary to at least 15 contiguous nucleotides of a sequence selected from SEQ ID NOs: 1 to 397, 1063 to 1210, 2064 to 2183, 2673 to 2680, and 2689; or (iii) comprises at least 15 contiguous nucleotides of a sequence selected from SEQ ID NOs: 794 to 1043, 2576 to 2672, and 2692. In some embodiments, a level of at least one target RNA that is greater than a normal level of the at least one target RNA indicates the presence of lung cancer.
In some embodiments, levels of at least two, at least three, or at least five target RNAs are detected. In some embodiments, detection of levels of at least one, at least two, at least three, or at least five target RNAs that are greater than a normal level of the at least one target RNA indicates the presence of lung cancer.
In some embodiments, a method further comprises detecting a level of at least one target RNA that: (i) does not specifically hybridize to a nucleic acid having a sequence selected from SEQ ID NOs: 1 to 397, 1063 to 1210, 2064 to 2183, 2673 to 2680, and 2689; or (ii) does not comprise a sequence that is complementary to at least 15 contiguous nucleotides of a sequence selected from SEQ ID NOs: 1 to 397, 1063 to 1210, 2064 to 2183, 2673 to 2680, and 2689; and (iii) does not comprise at least 15 contiguous nucleotides of a sequence selected from SEQ ID NOs: 794 to 1043, 2576 to 2672, and 2692.
In some embodiments, a method comprises detection of at least one target RNA (a) is capable of specifically hybridizing to a polyncleotide sequence in Table 6; or (b) comprises a sequence that is complementary to at least 15 contiguous nucleotides of a polynucleotide sequence in Table 6. In some such embodiments, detection of a level of the at least one target RNA that is greater than a normal level of the at least one target RNA indicates the presence of non-small cell lung cancer.
In some embodiments, a method comprises detection of at least one target RNA (a) is capable of specifically hybridizing to a polyncleotide sequence in Table 7; or (b) comprises a sequence that is complementary to at least 15 contiguous nucleotides of a polynucleotide sequence in Table 7. In some such embodiments, detection of a level of the at least one target RNA that is greater than a normal level of the at least one target RNA indicates the presence of squamous cell carcinoma.
In some embodiments, a method comprises detection of at least one target RNA (a) is capable of specifically hybridizing to a polyncleotide sequence in Table 8; or (b) comprises a sequence that is complementary to at least 15 contiguous nucleotides of a polynucleotide sequence in Table 8. In some such embodiments, detection of a level of the at least one target RNA that is greater than a normal level of the at least one target RNA indicates the presence of adenocarcinoma.
In some embodiments, a method comprises detection of at least one target RNA (a) is capable of specifically hybridizing to a polyncleotide sequence in Table 9; or (b) comprises a sequence that is complementary to at least 15 contiguous nucleotides of a polynucleotide sequence in Table 9. In some such embodiments, detection of a level of the at least one target RNA that is greater than a normal level of the at least one target RNA indicates the presence of aggressive lung cancer.
In some embodiments, a method comprises detection of at least one target RNA (a) is capable of specifically hybridizing to a polyncleotide sequence in Tables 32 or 33; or (b) comprises a sequence that is complementary to at least 15 contiguous nucleotides of a polynucleotide sequence in Table 32 or Table 33.
In some embodiments, a method of detecting the presence of lung cancer is provided that comprises detecting a level of at least one target RNA in a sample from the subject, wherein the at least one target RNA (i) is capable of specifically hybridizing to a nucleic acid having a sequence selected from SEQ ID NOs: 1 to 397, 1363 to 1707, and 2312 to 2452; or (ii) comprises a sequence that is complementary to at least 15 contiguous nucleotides of a sequence selected from SEQ ID NOs: 1 to 397, 1363 to 1707, and 2312 to 2452. In some embodiments, a level of at least one target RNA in the sample that is reduced relative to a normal level of the at least one target RNA indicates the presence of lung cancer in the subject. In some embodiments, a method comprises comprises comparing the level of the at least one target RNA in the sample to a normal level of the at least one target RNA.
In some embodiments, a method of facilitating the detection of lung cancer in a subject is provided, comprising (a) detecting a level of at least one target RNA in a sample from the subject, wherein the at least one target RNA (i) is capable of specifically hybridizing to a nucleic acid having a sequence selected from SEQ ID NOs: 1 to 397, 1363 to 1707, and 2312 to 2452; or (ii) comprises a sequence that is complementary to at least 15 contiguous nucleotides of a sequence selected from 1 to 397, 1363 to 1707, and 2312 to 2452; and (b) communicating the results of the detection to a medical practitioner for the purpose of determining whether the subject has lung cancer.
In some embodiments, a method of detecting the presence of lung cancer in a subject is provided, wherein the method comprises (a) obtaining a sample from the subject, (b) providing the sample to a laboratory for detection of the level of at least one target RNA in the sample, wherein the at least one target RNA (i) is capable of specifically hybridizing to a nucleic acid having a sequence selected from SEQ ID NOs: 1 to 397, 1363 to 1707, and 2312 to 2452; or (ii) comprises a sequence that is complementary to at least 15 contiguous nucleotides of a sequence selected from SEQ ID NOs: 1 to 397, 1363 to 1707, and 2312 to 2452; and (c) receiving from the laboratory a communication indicating the level of at least one target RNA in the sample. In some embodiments, a level of at least one target RNA that is reduced relative to a normal level of the at least one target RNA indicates the presence of lung cancer.
In some embodiments, a method further comprises detecting a level of at least one second target RNA in a sample from the subject, wherein the at least one second target RNA: (i) is capable of specifically hybridizing to a nucleic acid having a sequence selected from SEQ ID NOs: 1 to 397, 1063 to 1210, 2064 to 2183, 2673 to 2680, and 2689; or (ii) comprises a sequence that is complementary to at least 15 contiguous nucleotides of a sequence selected from SEQ ID NOs: 1 to 397, 1063 to 1210, 2064 to 2183, 2673 to 2680, and 2689; or (iii) comprises at least 15 contiguous nucleotides of a sequence selected from SEQ ID NOs: 794 to 1043, 2576 to 2672, and 2692. In some embodiments, a level of at least one second target RNA in the sample that is greater than a normal level of the at least one second target RNA indicates the presence of lung cancer in the subject.
In some embodiments, a method comprises isolating nucleic acids from a sample. In some embodiments, the nucleic acids comprise RNA that has been separated from DNA. In some embodiments, a target RNA in its mature form comprises fewer than 30 nucleotides. In some embodiments, a target RNA is a microRNA.
In some embodiments, synthetic polynucleotides are provided. In some embodiments, compositions comprising a plurality of synthetic polynucleotides are provided. In some embodiments, a synthetic polynucleotide comprises a first region, wherein the first region comprises a sequence of at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, or at least 15 contiguous nucleotides that is identical or complementary to a sequence of at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, or at least 15 contiguous nucleotides of one of SEQ ID NOs: 1 to 165, 254 to 360, 1063 to 1081, 1090 to 1190, 2064 to 2091, 2107 to 2168, 1363 to 1659, 2312 to 2440, and 2576 to 2680. In some embodiments, a synthetic polynucleotide comprises a detectable label. In some embodiments, the detectable label is a FRET label. In some embodiments, the first region is identical or complementary to a region of a target RNA. In some embodiments, the polynucleotide further comprises a second region that is not identical or complementary to a region of the target RNA.
In some embodiments, kits are provided. In some embodiments, a kit comprises a synthetic polynucleotide. In some embodiments, a kit comprises a composition comprising a plurality of synthetic polynucleotides. In some embodiments, a kit comprises at least one polymerase. In some embodiments, a kit comprises dNTPs.
Further embodiments and details of the inventions are described below.
3. BRIEF DESCRIPTION OF THE FIGURES
FIG. 1 shows an electropherogram obtained on an Agilent Bioanalyser 2100 to assess the quality of total RNA purified as described in Example 1 from A549 human adenocarcinoma cell line.
4. DETAILED DESCRIPTION
4.1. Detecting Lung Cancer
4.1.1. General Methods
Methods of detecting lung cancer by measuring levels of target RNAs are provided. In some embodiments, methods are presented for detecting non-small cell lung cancer in a human. In some embodiments, a method comprises detecting altered levels of at least one target RNA relative to normal levels of the at least one target RNA. In some embodiments, elevated levels of one or more target RNAs are indicative of lung cancer. In some embodiments, reduced levels of one or more target RNAs are indicative of lung cancer. In some embodiments, the method comprises detecting an altered level of at least one target RNA that is capable of specifically hybridizing to a sequence selected from the sequences in Tables 1, 2, 6 to 9, 18, 20, 23, 27, 28, 30, and 32 to 34. In some embodiments, the method comprises detecting an altered level of at least one target RNA that is capable of specifically hybridizing to a sequence selected from SEQ ID NOs: 1 to 397, 1063 to 1210, 1363 to 1707, 2064 to 2183, 2312 to 2452, 2673 to 2680, and 2689. In some embodiments, the method comprises detecting an altered level of at least one target RNA selected from the microRNAs in Tables 4, 5, and 38. In some embodiments, the method comprises detecting an altered level of at least one target RNA that comprises at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23, or at least 24 contiguous nucleotides of a sequence selected from SEQ ID NOs.: 794 to 1043, 2576 to 2672, and 2692. In some embodiments, the method comprises detecting an altered level of at least one target RNA that comprises a sequence that is complementary to at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23, or at least 24 contiguous nucleotides of a sequence selected from SEQ ID NO.: 1 to 397, 1063 to 1210, 1363 to 1707, 2064 to 2183, 2312 to 2452, 2673 to 2680, and 2689. In some embodiments, an altered level is an elevated level. In some embodiments, an altered level is a reduced level. In some embodiments, a method comprises detecting an elevated level of at least one target RNA and a reduced level of at least one other target RNA. In some embodiments, the target RNA, in its mature form, comprises fewer than 30 nucleotides. The target RNA, in some embodiments, is a microRNA.
In the present disclosure, “a sequence selected from” encompasses both “one sequence selected from” and “one or more sequences selected from.” Thus, when “a sequence selected from” is used, it is to be understood that one, or more than one, of the listed sequences may be chosen.
Detection of a level of target RNA that is greater than a normal level of target RNA indicates the presence of lung cancer in the patient from whom the sample is taken. In some embodiments, the detecting is done quantitatively. In other embodiments, the detecting is done qualitatively. In some embodiments, detecting a target RNA comprises forming a complex comprising a polynucleotide and a nucleic acid selected from a target RNA, a DNA amplicon of a target RNA, and a complement of a target RNA. In some embodiments, the level of the complex is then detected and compared to a normal level of the same complex. The level of the complex, in some embodiments, correlates with the level of the target RNA in the sample.
“Non-small cell lung cancer” or “NSCLC” is one of two categories of lung cancer found in humans. About 80% of patients diagnosed with lung cancer have non-small cell lung cancer. NSCLC is further broken down into three sub-categories, depending on the cells in which they originate: (i) adenocarcinoma, which originates in the cells that line the alveoli and make substances such as mucus; (ii) squamous cell or epidermoid carcinoma, which originates in the squamous cells; and (iii) large cell carcinoma, which may originate in several different types of large cells. More than 50% of patients with NSCLC have either adenocarcinoma or squamous cell carcinoma. The histology class nonsquamous cell carcinoma includes both adenocarcinoma and large cell carcinoma.
Cancer can be divided into clinical and pathological stages. The clinical stage is based on all available information about a tumor, such as information gathered through physical examination, radiological examination, endoscopy, etc. The pathological stage is based on the microscopic pathology of a tumor.
The TNM (tumor, node, metastasis) system classifies a cancer by three parameters—the size of the tumor and whether it has invaded nearby tissues, involvement of lymph nodes, and metastases. T (tumor) is assigned a number from 1 to 4, according to the size and extent of the primary tumor. N (node) is assigned a number from 0 to 3, in which 0 means no spreading to the lymph nodes, 1 is spreading to the closest lymph nodes, and 3 is spreading to the most distant and greatest number of lymph nodes, and 2 is intermediate between 1 and 3. M (metastasis) is assigned 0 for no distant metastases, or 1 for distant metastases beyond regional lymph nodes.
For lung cancer, Overall Stage Grouping assigns a cancer a roman numeral of 0, I, II, III, and IV, and a letter, A or B, depending on the stage. Stage 0 is carcinoma in situ, which usually does not form a tumor. Stages IA (T1N0M0) and IB (T2N0M0) is cancer that is localized to one part of the body. Stage IIA (T1N1M0) and IIB (T2N1M0 and T3N0M0) is cancer that is localized, but more advanced. Stage IIIA (T1-3N2M0 or T3N1M0) and IIIB (any T4 or any N3M0) cancer is also locally advanced. Stage IV (any M1) is cancer that has metastasized. As used herein, the term “early stage cancer” refers to Stages IA and IB and Stages IIA and IIB cancers.
As used herein, an “aggressive” form of lung cancer is a lung cancer that advances quickly from one stage to the next and/or metastasizes at an early stage, resulting in a poor prognosis for the patient.
Tables 1 and 2, below, list 397 hybridization probes that have been found to be complementary to, and hybridize with, target RNAs in lung cancer cells. These target RNAs were detected at elevated levels or at reduced levels in certain primary tumors and/or human lung cancer cell lines (respectively Examples 1 and 2). Two hundred seventy-five of the probes are complementary to, and hybridize with, novel target RNA species that are expressed in human cells. The other one hundred and twenty-two probes are complementary to, and hybridize with, publicly known microRNAs that have been accessioned by others into miRBase (http://microrna.sanger.ac.uk/; see Griffiths-Jones S. et al. (2007) Nucl. Acids Res. 36:154-158). These latter probes are designated by either “mir” or “let” in Tables 1 and 2.
Tables 18 to 21, below, list hybridization probes that have been found to be complementary to, and hybridize with, target RNAs that were detected at elevated levels in certain primary tumors (see Example 4). Certain probes listed in Tables 18 and 20 are complementary to, and hybridize with, novel target RNA species that are expressed in human cells. Other probes in Tables 18 and 20 are complementary to, and hybridize with, publicly known microRNAs that have been accessioned by others into miRBase (http://microrna.sanger.ac.uk/; see Griffiths-Jones S. et al. (2007) Nucl. Acids Res. 36:154-158). These latter probes are designated by either “mir” or “let.”
Tables 23 and 24, below, list hybridization probes that have been found to be complementary to, and hybridize with, target RNAs that were detected at reduced levels in certain primary tumors (see Example 4). Certain probes listed in Tables 23 and 24 are complementary to, and hybridize with, novel target RNA species that are expressed in human cells. Other probes in Tables 23 and 24 are complementary to, and hybridize with, publicly known microRNAs that have been accessioned by others into miRBase (http://microrna.sanger.ac.uk/; see Griffiths-Jones S. et al. (2007) Nucl. Acids Res. 36:154-158). These latter probes are designated by either “mir” or “let.”
Tables 27 and 28, below, list hybridization probes that have been found to be complementary to, and hybridize with, target RNAs that were detected at elevated levels in certain lung cancer cell lines (see Example 5). Certain probes listed in Tables 27 and 28 are complementary to, and hybridize with, novel target RNA species that are expressed in human cells. Other probes in Tables 27 and 28 are complementary to, and hybridize with, publicly known microRNAs that have been accessioned by others into miRBase (http://microrna.sanger.ac.uk/; see Griffiths-Jones S. et al. (2007) Nucl. Acids Res. 36:154-158). These latter probes are designated by either “mir” or “let.”
Table 30, below, lists hybridization probes that have been found to be complementary to, and hybridize with, target RNAs that were detected at reduced levels in certain lung cancer cell lines (see Example 5). Certain probes listed in Table 30 are complementary to, and hybridize with, novel target RNA species that are expressed in human cells. Other probes in Table 30 are complementary to, and hybridize with, publicly known microRNAs that have been accessioned by others into miRBase (http://microrna.sanger.ac.uk/; see Griffiths-Jones S. et al. (2007) Nucl. Acids Res. 36:154-158). These latter probes are designated by either “mir” or “let.”
In Tables 1 and 2, respectively, the expression levels of target RNAs measured for each of the identified primary tumors, and for each of the identified cell lines, are expressed as fold-changes in expression relative to expression levels measured in normal human lung total RNA (see Examples 1 and 2). Similarly, in Tables 18 to 21, 23, 24, 27, 28, and 30, the expression levels of target RNAs measured for each of the identified primary tumors, and for each of the identified cell lines, are expressed as fold-changes in expression relative to expression levels measured in normal human lung total RNA (see Examples 4 and 5).
Table 6 lists target RNAs from Table 1 that are present at increased levels in NSCLCs. Table 7 lists target RNAs that are more frequently present at elevated levels in squamous cell carcinoma. In some embodiments, a method comprises detecting an elevated level of at least one target RNA from Table 7. In some such embodiments, detection of an elevated level of at least one target RNA from Table 7 is indicative of squamous cell carcinoma. Table 8 lists target RNAs that are more frequently present at elevated levels in adenocarcinoma. In some embodiments, a method comprises detecting an elevated level of at least one target RNA from Table 8. In some such embodiments, detection of an elevated level of at least one target RNA from Table 8 is indicative of adenocarcinoma. Table 9 lists target RNAs that are present at increased levels in aggressive forms of lung cancer. In some embodiments, a method comprises detecting an elevated level of at least one target RNA from Table 9. In some such embodiments, detection of an elevated level of at least one target RNA from Table 9 is indicative of an aggressive form of lung cancer.
In some embodiments, a method comprises detecting multiple isomirs with a single probe. Detection of an elevated level of one or multiple isomirs is considered to be indicative of lung cancer. When multiple microRNAs having the same sequence but are expressed from different genes, one or more of the genes may be upregulated in a lung cancer patient. Detection of a microRNA expressed from any one of the genes is considered to be indicative of lung cancer.
For convenience of reference herein, and not by way of limitation, some “target RNA” species are denominated “microRNAs” in the tables set forth herein and Example 1. In some embodiments, the target RNA is a single mature microRNA capable of specifically hybridizing to a hybridization probe set forth in any of Tables 1, 2, 6 to 9, 18, 20, 23, 27, 28, 30, and 32 to 34. In some embodiments, a target RNA is a single mature microRNA that comprises a sequence that is complementary to at least 15 contiguous nucleotides of a sequence selected from SEQ ID NO.: 1 to 397, 1063 to 1210, 1363 to 1707, 2064 to 2183, 2312 to 2452, 2673 to 2680, and 2689. In some embodiments, a target RNA is a single mature microRNA that comprises at least 15 contiguous nucleotides of a sequence selected from SEQ ID NOs: 794 to 1043, 2576 to 2672, and 2692. In some embodiments, target RNA may include a plurality of target RNAs, all of which are capable of specifically hybridizing to a single complementary probe sequence (for example, when two or more target microRNAs are isomirs). In some embodiments, the so-denominated “microRNA” is one or more RNA species capable of specifically hybridizing to the respective hybridization probe, such that one or more target RNAs do not meet canonical definitions for mature microRNAs. In some embodiments, a target RNA is an mRNA. In some embodiments, the “target RNA” is a piwi-interacting RNA (piRNA), i.e., a small RNA expressed in animal cells that is distinct in size (26-31 nt) from microRNA and that forms distinct complexes with Piwi proteins that are involved in transcriptional gene silencing.
Mature human microRNAs are typically composed of 17 to 27 contiguous ribonucleotides, and often are from 19 to 25 nucleotides in length, or 21 or 22 nucleotides in length. The sequences of some target microRNAs that can be detected in accordance with the present disclosure can be found within the pre-microRNA sequences shown in Tables 3, 22, 25, 29, 31, and 37 (SEQ ID NOs: 398 to 793, 1211 to 1362, 1708 to 2063, 2184 to 2311, 2453 to 2575, and 2681 to 2688, 2690, and 2691). In some embodiments, more than one mature target RNA is derived from a single pre-microRNA shown in Tables 3, 22, 25, 29, 31, and 37. The sequences of some publicly known mature microRNAs are shown below in Tables 4 and 5 (SEQ ID NOs: 794 to 1043, and 2692). Further, in some embodiments, a microRNA comprises at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23, at least 24, at least 25, or at least 26 contiguous nucleotides of a sequence in Table 38 (SEQ ID NOs: 2576 to 2672).
While not intending to be bound by theory, mammalian microRNAs mature as described herein. A gene coding for a microRNA is transcribed, leading to production of a microRNA precursor known as the “pri-microRNA” or “pri-miRNA.” The pri-miRNA can be part of a polycistronic RNA comprising multiple pri-miRNAs. In some circumstances, the pri-miRNA forms a hairpin with a stem and loop, which may comprise mismatched bases. The hairpin structure of the pri-miRNA is recognized by Drosha, which is an RNase III endonuclease protein. Drosha can recognize terminal loops in the pri-miRNA and cleave approximately two helical turns into the stem to produce a 60-70 nucleotide precursor known as the “pre-microRNA” or “pre-miRNA.” Drosha can cleave the pri-miRNA with a staggered cut typical of RNase III endonucleases yielding a pre-miRNA stem loop with a 5′ phosphate and an approximately 2-nucleotide 3′ overhang. Approximately one helical turn of the stem (about 10 nucleotides) extending beyond the Drosha cleavage site can be essential for efficient processing. The pre-miRNA is subsequently actively transported from the nucleus to the cytoplasm by Ran-GTP and the export receptor Exportin-5.
The pre-miRNA can be recognized by Dicer, another RNase III endonuclease. In some circumstances, Dicer recognizes the double-stranded stem of the pre-miRNA. Dicer may also recognize the 5′ phosphate and 3′ overhang at the base of the stem loop. Dicer may cleave off the terminal loop two helical turns away from the base of the stem loop leaving an additional 5′ phosphate and an approximately 2-nucleotide 3′ overhang. The resulting siRNA-like duplex, which may comprise mismatches, comprises the mature microRNA and a similar-sized fragment known as the microRNA*. The microRNA and microRNA* may be derived from opposing arms of the pri-miRNA and pre-miRNA. The mature microRNA is then loaded into the RNA-induced silencing complex (“RISC”), a ribonucleoprotein complex. In some cases, the microRNA* also has gene silencing or other activity.
It is understood that where a sequence includes thymine (T) bases, a target RNA may contain uracil (U) bases instead.
TABLE 1
|
|
probe
|
Array
SEQ
fold-changes in primary tumors vs. normal Lung
|
probe
Array probe sequence (5′ to 3′, without linker)
ID NO:
Epi4
Epi7
Epi5
Adk1
Adk3
Adk11
Adk8
Adk9
Adk2
Adk10
|
|
266-R4-1
GTCGCCCCCTCCCCCAAGTTGAGACTTGCAGCTAC
1
7.33
1.43
1.97
3.81
−3.74
−2.28
−3.72
−1.19
−11.61
−2.38
|
|
673-L4-1
GCTCCCCTCACTGTGAACTTTTCACCCAGCTAACCTGC
2
3.55
1.45
−1.26
1.44
(nd)
−2.70
−5.73
−1.21
−6.23
−4.03
|
TCCTCAC
<−6.23
|
|
836-R4-1
AAATAATCATTCCAAATGGTTCTCCCTGCTATGATTCAC
3
6.78
1.06
(nd)
2.23
−1.23
−2.34
−3.54
−1.02
−6.03
−1.43
|
<−6.03
|
|
3249-L4-1
GCGGAGCCGCCGCCATCCCCGGAGCCGCCGCCGCCG
4
1.46
1.91
2.34
−1.38
−2.37
−3.34
−3.73
−2.89
−6.52
−2.00
|
CCGCC
|
|
3371-L4-1
TTTCCTTTCCTCCCCTCCACACCCCATGACTCCCCACA
5
7.78
1.44
(nd)
3.28
(nd)
−1.54
−2.45
−1.89
(nd)
−1.75
|
CTTGAG
<−3.63
<−3.63
<−3.63
|
|
3717-L2-1
CCGCCCTCCCCATAGCCTCACCCCAAACCCACTCACA
6
5.45
−1.46
2.40
2.66
−3.24
−3.42
−6.97
−22.96
−22.96
−2.75
|
|
3799-R3-1
CCAGAGGCCCCCCGCCGGCC
7
4.81
1.62
1.19
3.07
−4.42
−2.84
−5.33
−1.46
−18.87
−2.91
|
|
3872-L1-1
TCATTTTCTTGTCTTCTTCCCTTATGCAC
8
>6.17
nd
nd
>2.09
nd
nd
nd
nd
nd
nd
|
|
3875-R3-1
CTCTCTCCCACTTTAATAA
9
>20.25
nd
nd
>2.90
nd
nd
nd
nd
nd
nd
|
|
3897-R3-1
CAGCCGCCTCCCCCTCAGCGTTAA
10
5.07
1.62
1.80
1.97
−3.20
−3.17
−4.86
−1.07
−2.38
−1.89
|
|
3923-R3-1
GCCTCTCACAAAGGATCTCCTTCATCCCTCTCC
11
17.53
1.49
(nd)
4.86
(nd)
2.05
−1.32
(nd)
(nd)
−1.16
|
<−1.39
<−1.39
<−1.39
<−1.39
|
|
3953-R3-2
ACTCCAGCCTCCGCCGCCTCAGCTTCCCGAGC
12
1.50
1.86
2.21
1.28
−2.29
−3.82
−5.17
nd G3
nd G3
−2.73
|
|
3995-L2-2
CTATAAAACTTCGAAAAGTCCCTCCTCCTCACGT
13
6.16
1.93
1.05
3.01
−3.51
−2.18
−4.19
1.21
−5.70
−1.85
|
|
4026-R3-1
GGCGAGAGAGAAAGCCCCCCT
14
6.37
−1.17
2.06
3.81
−3.69
−3.06
−5.40
−1.70
−18.38
−4.41
|
|
4037-R3-2
GCCTGTTCCCTGGCATGTACTGTAATTTATCT
15
6.57
1.44
(nd)
2.17
(nd)
2.17
2.34
2.64
6.81
−1.06
|
<−1.28
<−1.28
|
|
4143-R3-1
TCAGCGTCTTGCTCTCCTCCTGGTA
16
>7.19
nd
nd
>2.08
nd
nd
nd
nd
nd
nd
|
|
4203-R3-2
GCACATTCCCACTTCCCCAGAGGCAGGCTCCATAT
17
>4.30
nd
nd
nd
nd
nd
nd
nd
nd
nd
|
|
4205-R3-2
GCCCTACAACTTCATCCTCACCACTCACACCAC
18
>3.92
nd
nd
>2.47
nd
nd
nd
nd
nd
nd
|
|
4303-R1-1
AGTGCCCGCTCCTCCGACCTCCCTGCGCACC
19
4.55
2.06
1.53
2.49
−3.30
−1.83
−3.64
−2.09
−10.57
−2.26
|
|
4315-R3-2
TCCCCGGCCCTCTCCATTCTCGGCTCCGGAGCA
20
5.42
1.69
1.44
2.31
−2.65
−2.17
−2.74
−1.64
−4.81
−1.87
|
|
4361-R3-1
CGTCTCCCTCCCTCATGTGC
21
13.35
3.46
(nd)
4.34
(nd)
−1.41
−1.74
2.20
(nd)
1.27
|
<−1.73
<−1.73
<−1.73
|
|
4440-L3-2
TTTGACATTCAGAGCACTGGGCAGAAATCACA
22
6.02
−1.51
1.14
1.60
(nd)
−1.05
−1.83
−1.14
1.57
−2.75
|
<−3.39
|
|
4440-R3-2
GTCATAGTTACTCCCGCCGTTTACCCGCATTTC
23
9.42
1.72
1.53
3.52
−3.11
−1.63
−3.21
−1.13
−1.70
−2.72
|
|
4448-R3-1
CCTACCCCCAGCATCTCCTCACGCCATTGCC
24
>2.43
nd
nd
>1.62
nd
nd
nd
nd
nd
nd
|
|
4479-R3-1
AGCCCCCTGCCCGGAAATTCAAAACAACTGC
25
3.07
3.03
−1.01
2.30
−7.11
−3.04
−3.90
−2.34
−5.33
−2.81
|
|
4593-R3-1
AGCAGATGACATAACTCCCCCGGCATCAG
26
8.31
2.80
1.23
1.93
−4.73
−2.65
−5.00
1.79
−9.77
1.20
|
|
4666-R4-1
GCCGACTCCCCCCAACACCTGCGGGTGGCAC
27
24.77
2.27
3.49
7.40
−2.36
−1.70
−2.05
2.37
−3.62
−1.01
|
|
4790-L4-1
AACCTGTCTCCCTCATTACTAGAATTCTGGG
28
>14.59
>1.58
nd
>4.07
nd
nd
nd
nd
nd
nd
|
|
4829-R2-1
TCCCTTTGTGCTGCCCGAGTGCCTTCCCCCTG
29
12.09
1.52
1.69
5.73
−6.10
−1.29
−4.20
−1.12
−9.92
−2.88
|
|
4855-R3-1
GGGCTGCCGGGTCTCCCGCTTCC
30
8.26
1.91
1.44
1.78
−3.56
−1.50
−1.81
1.87
−2.80
1.20
|
|
4875-R2-2
CACAGCCCCTTCCTGTGACTTCACAC
31
4.28
−1.44
1.02
2.82
(nd)
−2.46
−5.03
−1.17
(nd)
−4.78
|
<−5.97
<−5.97
|
|
4988-R4-1
CTCCTCCTCCCCGTCTTTGGATACCAAACACTGGAC
32
9.10
1.72
1.15
2.70
(nd)
−2.04
−2.34
−1.34
(nd)
−1.55
|
<−3.75
<−3.75
|
|
5006-L3-1
ACAGCTCCCTCTGCTGGCTCC
33
6.58
1.11
2.00
5.46
(nd)
(nd)
(nd)
(nd)
(nd)
(nd)
|
<−1.43
<−1.43
<−1.43
<−1.43
<−1.43
<−1.43
|
|
5080-R3-1
CTTGCAAAGGGTCTCCTTCATCCCTCTCCA
34
5.91
−1.01
−1.35
2.60
(nd)
1.28
−1.87
1.18
(nd)
−3.70
|
<−4.53
<−4.53
|
|
5192-L3-2
CATTTTTCCCCTTCCTTCCTCTATATCAGCAA
35
1.54
1.24
(nd)
2.92
(nd)
(nd)
−1.79
1.39
(nd)
(nd)
|
<−1.61
<−1.61
<−1.61
<−1.61
<−1.61
|
|
5342-L3-1
CACCACCAAACCAAATGCCGCTGCTCTCCTTCCA
36
1.95
1.46
2.07
1.19
(nd)
−2.70
−4.03
−1.81
(nd)
−1.99
|
<−4.91
<−4.91
|
|
5521-L2-1
GTCTTGGGTGGGCCCTCCCCAGAGCACACCCTCT
37
4.19
(nd)
2.44
2.24
(nd)
(nd)
(nd)
(nd)
(nd)
(nd)
|
<−1.44
<−1.44
<−1.44
<−1.44
<−1.44
<−1.44
<−1.44
|
|
5554-R2-1
CCCCACCCCCTCATCAGCTGCTCCCAGAT
38
3.45
1.79
1.00
1.73
(nd)
−2.78
−2.03
−1.57
(nd)
−1.91
|
<−6.36
<−6.36
|
|
5638-R2-1
GGCCCTCCCCCTGCCTGTGATAGGCTGCTTG
39
5.54
−1.87
2.47
3.18
−2.79
−3.13
−9.55
1.18
−15.66
−3.29
|
|
5640-L3-1
GCCATGGAACACCGTGCCTGCCCCTCTCGAGA
40
3.56
2.33
1.22
2.16
−4.15
−1.75
−2.54
−1.31
−9.19
−2.51
|
|
5726-L3-1
TAATAAAATATCTTCTCACTGTGCCCTTG
41
>8.13
nd
nd
>1.83
nd
nd
nd
nd
nd
nd
|
|
5782-L3-1
GATTCCAGCCCCTTCCCCC
42
6.87
1.80
1.13
3.16
(nd)
−1.78
−3.13
(nd)
(nd)
−2.66
|
<−3.21
<−3.21
<−3.21
|
|
5795-R1-1
CTGCCCTCCAAGAAATAAATTACCCGCAATTACT
43
3.41
1.05
1.52
2.16
(nd)
(nd)
(nd)
(nd)
(nd)
(nd)
|
<−2.02
<−2.02
<−2.02
<−2.02
<−2.02
<−2.02
|
|
5836-R3-2
CATTAACCCCCATTATCACAGCACGCCCCATTC
44
13.99
1.99
(nd)
2.26
(nd)
(nd)
(nd)
(nd)
(nd)
(nd)
|
<−1.09
<−1.09
<−1.09
<−1.09
<−1.09
<−1.09
<−1.09
|
|
5854-R3-1
CCCTCCCTCTCCGAAAGAATGTGTCAC
45
22.51
−1.01
1.54
4.54
(nd)
−1.03
−2.56
5.86
−1.93
−1.08
|
<−4.11
|
|
5971-R3-1
CTGCTCAGCCTCCCACATCTGT
46
5.67
−1.01
(nd)
2.33
(nd)
−1.08
−1.64
2.13
(nd)
−1.38
|
<−1.78
<−1.78
<−1.78
|
|
6008-R1-1
ACAATACCCCCACCTTTTTCCTGTACCTTAC
47
>3.56
nd
nd
>2.06
nd
nd
nd
nd
nd
nd
|
|
6016-R2-1
AAACTCCAGCAGCCCCGTCAGCCTCCTGCT
48
4.31
1.91
1.65
2.09
(nd)
(nd)
−2.58
−1.41
(nd)
−1.80
|
<−2.53
<−2.53
<−2.53
|
|
6037-R3-2
GCAATTCCCTTTCCTCCATCTCCAATTTTCCTC
49
4.15
−1.55
1.15
1.38
(nd)
(nd)
(nd)
(nd)
(nd)
(nd)
|
<−2.24
<−2.24
<−2.24
<−2.24
<−2.24
<−2.24
|
|
6096-R3-1
TGTTTTAATCCTGCCCCGT
50
8.12
2.89
2.83
1.81
(nd)
(nd)
(nd)
(nd)
(nd)
(nd)
|
<−1.12
<−1.12
<−1.12
<−1.12
<−1.12
<−1.12
|
|
6183-R3-1
GATTCCACTTTTCTTAATGACTTTCCCCTCCT
51
>2.90
nd
nd
>3.58
nd
nd
nd
nd
nd
>1.17
|
|
6192-L3-1
AGATAAAAAACCACCCACCCAGCAC
52
6.12
1.20
(nd)
1.36
(nd)
−1.17
−3.42
(nd)
(nd)
(nd)
|
<−3.75
<−3.75
<−3.75
<−3.75
<−3.75
|
|
6233-L3-1
AAAATTAGATTTCCACTTTATCCTTCTCCC
53
>15.87
nd
nd
>4.27
nd
nd
nd
>2.53
nd
nd
|
|
6235-R3-1
GCTCCAAAAATCCATTTAATATATTGTCCTT
54
7.85
1.15
−2.40
2.29
−6.59
−2.77
−3.73
−1.08
−12.11
−2.01
|
|
6287-L3-2
GCCCCGCCCCACCTTTCGGGGCTCACCTGGC
55
5.41
2.01
1.64
3.04
(nd)
−2.07
−2.75
(nd)
(nd)
−2.87
|
<−3.75
<−3.75
<−3.75
|
|
6409-L3-1
CGTTCCCAACCGCACGCGCCGCCTTCTGGAAC
56
2.22
1.37
2.40
1.28
−2.50
−3.09
−5.39
−2.53
−6.45
−2.76
|
|
6434-R3-1
AGCCCTCCCACCAGCCAGCTGCAGTGC
57
2.54
−1.65
1.71
2.49
−3.08
−2.94
−6.08
−3.25
−44.90
−7.25
|
|
6484-R3-2
CGCTTCGGGATCCTCTCCAACTGCAACCACA
58
>6.42
nd
>2.40
>4.37
nd
nd
nd
nd
nd
nd
|
|
6490-R4-1
CCCATCCCCCATATGACGCTTCCCCCTCCTAACCTCAC
59
3.28
1.04
1.30
2.00
−4.20
−3.75
−5.00
−2.07
−7.58
−2.49
|
CACCCCCAGCA
|
|
6496-R3-1
CCCCTCCCCCACCCACCACTTCCCCTAGAGTCC
60
14.40
1.47
1.69
4.18
−3.34
−2.65
−2.54
−2.65
−5.20
−1.59
|
|
6584-L1-1
TCGGCCCTGCCTCCTCCTCCT
61
8.46
1.93
1.09
2.11
(nd)
(nd)
(nd)
(nd)
(nd)
−1.50
|
<−2.02
<−2.02
<−2.02
<−2.02
<−2.02
|
|
6602-R3-2
AGAGCCCCAGTGGAAATCTCTCCTCCAAATCCAT
62
>4.95
nd
nd
>1.86
nd
nd
nd
nd
nd
nd
|
|
6642-R3-1
CACGTCCTCCCCTCCCCTCGAGGTGTCACACA
63
5.93
1.20
(nd)
2.84
(nd)
−2.73
−3.47
−1.15
(nd)
−2.02
|
<−5.26
<−5.26
<−5.26
|
|
6681-R2-1
CCTGTTTTCTCCCCTCTCTCTCTGCCCCTCC
64
6.76
2.18
1.13
3.85
(nd)
−1.90
−2.74
−1.12
(nd)
−1.77
|
<−6.34
<−6.34
|
|
6683-R3-1
AAAATAAACTCTTCCTGCTCAAG
65
>10.55
>1.57
nd
>4.34
nd
nd
nd
nd
nd
nd
|
|
6752-R1-1
CCCTCCTTTCCCCACCTCAGT
66
14.74
1.34
(nd)
4.34
(nd)
(nd)
(nd)
(nd)
(nd)
(nd)
|
<−1.39
<−1.39
<−1.39
<−1.39
<−1.39
<−1.39
<−1.39
|
|
6795-R4-1
CTTCCCGAGGCCACATGCTTCTTTATATCCCCATA
67
>11.94
nd
nd
>1.62
nd
>1.60
nd
nd
nd
nd
|
|
6803-R3-1
GCTCCCTCTCTGGTTGGACCTCACCCAAAGAT
68
19.16
1.39
1.71
4.21
(nd)
−1.08
−3.03
1.87
(nd)
−1.90
|
<−4.36
<−4.36
|
|
6839-L3-1
GCCCGCTGGGCCCTGCCACCCCCACCCCT
69
1.71
1.71
1.97
1.77
(nd)
−3.04
−3.58
−2.14
(nd)
−2.36
|
<−6.04
<−6.04
|
|
6880-L3-2
ACCTCCCCCGCGAAGACATCCACATTCTGCA
70
7.16
1.64
1.21
3.97
−4.57
−2.33
−3.69
1.35
−12.07
−1.50
|
|
6906-L3-1
GTGTCTTCTCCCCAACCAGCCAGCTCTCCTGG
71
>7.07
nd
nd
>2.10
nd
nd
nd
nd
nd
nd
|
|
6930-R3-1
ATTAATCCTTCTCTCCCCTCTG
72
34.08
2.60
2.04
9.78
(nd)
(nd)
(nd)
2.54
(nd)
1.50
|
<−1.68
<−1.68
<−1.68
<−1.68
|
|
6984-R4-1
CCCCCTGCCCAAGCATTTGCTTGGGCACCAAAGTCCCT
73
17.80
2.11
2.35
4.74
(nd)
(nd)
(nd)
1.69
(nd)
(nd)
|
GCAA
<−1.93
<−1.93
<−1.93
<−1.93
<−1.93
|
|
7026-L3-2
CCTGATCGAAAACCTCACCCACCAGATCCGGG
74
4.22
2.58
(nd)
1.21
(nd)
(nd)
−1.35
(nd)
(nd)
(nd)
|
<−1.59
<−1.59
<−1.59
<−1.59
<−1.59
<−1.59
|
|
7061-R3-1
ATGGAAACCCCACCCTTCCC
75
3.76
2.16
−1.23
−1.09
−4.11
−2.69
−1.66
−1.31
−9.30
−1.73
|
|
7066-R4-1
CAAGGCCCGTAGCCTGAAAAAAGATGCCCCCACCAGC
76
2.80
1.32
1.45
1.90
(nd)
−4.34
−4.43
−3.00
(nd)
−3.99
|
CCTGCC
<−7.42
<−7.42
|
|
7126-L3-1
GCACACCCGCTCTCCGGCCCGCGCCCCTG
77
4.39
2.59
1.54
1.19
−3.23
−2.33
−3.21
−1.99
−3.87
−2.12
|
|
7182-L4-1
TCTGGGTAACTAGCCGTTTCCGTCACCTTCCCCTGCCC
78
8.66
1.60
(nd)
3.08
(nd)
−2.00
−2.46
−1.11
−1.39
−1.82
|
CC
<−7.09
<−7.09
|
|
7192-R4-1
GCAAAGCACTTCCCCCTCTAAGTCTGCCTGGGCTCTTG
79
5.65
1.06
1.60
3.31
(nd)
(nd)
−2.07
1.24
(nd)
−1.76
|
GCAC
<−2.01
<−2.01
<−2.01
|
|
7292-L3-2
TAAATAGCTTCTGAACCTCCCTGCATTCTAATTGC
80
6.77
1.34
1.45
3.96
(nd)
(nd)
(nd)
1.41
(nd)
(nd)
|
<−1.55
<−1.55
<−1.55
<−1.55
<−1.55
|
|
7352-R3-2
GCCCCTGCCAGAATCCTCTAACAGCTCTAATTGG
81
2.28
2.91
(nd)
1.79
(nd)
−2.74
−3.58
−1.97
(nd)
−2.31
|
<−5.74
<−5.74
<−5.74
|
|
7356-L2-1
ACCGCGACATAGCCTCGCCCCC
82
5.16
2.76
1.18
2.46
(nd)
−1.64
−3.10
−1.59
(nd)
−1.82
|
<−3.81
<−3.81
|
|
7356-R2-1
GAAGCTCCGCGGCGACGTCCCGTTACTCC
83
>15.13
nd
nd
>1.62
nd
nd
nd
nd
nd
nd
|
|
7367-L1-1
AGGGTTAGAGCTGCCCCCTCTGGGGACCG
84
2.18
−1.94
−1.30
1.62
(nd)
(nd)
−3.23
(nd)
(nd)
−1.80
|
<−3.55
<−3.55
<−3.55
<−3.55
|
|
7384-R3-1
CTCGCAAAGGATCTCCTTCATCCCTCCCCA
85
6.05
1.05
2.67
3.02
(nd)
−1.86
(nd)
1.20
(nd)
−1.32
|
<−2.34
<−2.34
<−2.34
|
|
7411-R3-2
AGTCCCCTGCCTCATCTGCCACCCCTAATGAC
86
2.46
2.81
−1.22
1.74
(nd)
−2.99
−3.82
−1.84
(nd)
−2.12
|
<−5.03
<−5.03
|
|
7421-R2-1
TAAAGAGACTTCCTCCACTGCCAGAGATCT
87
3.81
(nd)
(nd)
3.90
(nd)
(nd)
(nd)
(nd)
(nd)
(nd)
|
<−1.11
<−1.11
<−1.11
<−1.11
<−1.11
<−1.11
<−1.11
<−1.11
|
|
7426-L3-1
TGGGAGACGAACACCTCCTGCTGTGCTTG
88
>6.19
nd
nd
>3.67
nd
nd
nd
>2.02
nd
nd
|
|
7569-L3-1
TCAGGCCACAAAGCTACCCCCAAGACAGGCC
89
1.43
1.15
−1.03
−1.03
(nd)
(nd)
(nd)
(nd)
(nd)
(nd)
|
<−3.88
<−3.88
<−3.88
<−3.88
<−3.88
<−3.88
|
|
7571-L1-1
AGGGCTCCCCCACCCCTAAG
90
2.27
−1.15
−1.09
1.24
−8.82
−5.67
−5.94
−2.92
−13.36
−3.96
|
|
7572-R2-1
ATCACCCTTCCCCCTCCCAAATAAAG
91
11.01
1.19
1.42
4.86
(nd)
−2.48
−3.89
−1.79
(nd)
−1.63
|
<−4.50
<−4.50
|
|
7578-L3-1
CGCAGTGCACACCCTGAGCTACAGCCCCTC
92
−1.03
−1.06
−2.38
−1.25
−14.04
−6.24
−17.14
−2.93
−6.73
−2.44
|
|
7660-L2-1
CCCGGCCTCCGCCTGGCCCGAGCGATAA
93
3.94
2.11
2.13
1.41
(nd)
(nd)
−3.26
−1.11
(nd)
−1.77
|
<−3.09
<−3.09
<−3.09
|
|
7702-L2-1
CCCAGAGAACCGGAATTCCTCCCCGCCCC
94
6.99
2.64
3.18
3.26
(nd)
−1.95
−2.34
−1.20
(nd)
−1.44
|
<−3.36
<−3.36
|
|
7726-R3-2
CATCCCTCTCCAGAAGAGGAGAAGAGGAAACA
95
4.39
−1.31
(nd)
2.45
(nd)
1.32
−1.96
−1.06
(nd)
(nd)
|
<−3.13
<−3.13
<−3.13
<−3.13
|
|
7764-R3-2
CCCTCTCTGCCTCTCTCATCACCAATAACAGAC
96
9.88
1.35
1.56
3.58
(nd)
−1.06
(nd)
1.15
(nd)
−1.46
|
<−1.65
<−1.65
<−1.65
|
|
8004-R3-2
GGAACTGCTTCTCCTTGCTCCAGTCATTGAAG
97
6.92
1.21
−2.65
3.26
(nd)
−3.19
−4.22
(nd)
(nd)
−2.06
|
<−9.22
<−9.22
<−9.22
|
|
8016-L3-1
TCAGCGCAACAAGCCCCGCAGTCACCCCTCT
98
4.04
2.25
1.06
1.40
(nd)
−2.38
−3.04
−1.84
(nd)
−2.39
|
<−4.39
<−4.39
|
|
8077-R3-1
CCATTCCCCACCCTCAGGTAGTAAAAATA
99
4.61
2.89
(nd)
1.35
(nd)
(nd)
−1.28
1.17
(nd)
−1.04
|
<−1.93
<−1.93
<−1.93
<−1.93
|
|
8169-L3-1
AACAGAAATGATTATTTACCTCCCCACATG
100
8.55
1.42
1.85
5.76
(nd)
(nd)
(nd)
1.97
(nd)
−1.39
|
<−1.59
<−1.59
<−1.59
<−1.59
|
|
8250-R3-1
CAGCCGCCTCTCCCTCAGCGTTAA
101
7.73
1.48
1.79
2.25
−2.24
−3.20
−5.50
1.35
−1.23
−1.26
|
|
8263-R3-1
GATTAAAAACAAGAATCTATCTTCCCCCAGT
102
>4.54
nd
nd
>1.78
nd
nd
nd
nd
nd
nd
|
|
8281-L3-1
AGCCCCTCCCCAGCTGCAGCTGAGGGCTGG
103
2.72
−1.03
1.97
3.10
−3.22
−2.88
−5.10
−2.09
−19.58
−4.66
|
|
8316-R3-1
ATCAGGGTATCCTCTCCCCA
104
>39.96
nd
nd
>7.56
nd
nd
nd
>2.43
nd
nd
|
|
8394-L3-1
CCCCCGCCCTGCCCATCTCCGACT
105
3.70
2.46
1.62
2.36
−4.53
−3.13
−3.91
−2.65
−14.49
−2.52
|
|
8433-L3-1
AAATGGCTCCTTTCCCCTTTCCCTCCACCG
106
11.25
1.11
1.90
4.23
(nd)
−1.64
−2.20
1.18
(nd)
−1.36
|
<−2.16
<−2.16
|
|
8564-L3-1
CCCTTCACCCCAGTTGCCAAACA
107
>12.45
nd
nd
>3.14
nd
nd
nd
nd
nd
nd
|
|
8587-R2-2
CCCGGCGCCCCTCGCCGGCTCCAAACTTTCCCCAA
108
3.02
1.99
1.87
2.01
(nd)
(nd)
−3.33
(nd)
(nd)
−1.53
|
<−3.01
<−3.01
<−3.01
<−3.01
|
|
8724-R3-1
GCCAAGCTTGGAACCTCTCCCTGCCAGCATCAC
109
16.37
1.40
1.47
5.34
(nd)
(nd)
(nd)
1.87
(nd)
−1.00
|
<−1.51
<−1.51
<−1.51
<−1.51
|
|
8731-R3-1
TCATTCATGCCCCATCCTGCCAG
110
3.79
3.51
(nd)
3.09
(nd)
(nd)
(nd)
(nd)
(nd)
(nd)
|
<−1.34
<−1.34
<−1.34
<−1.34
<−1.34
<−1.34
<−1.34
|
|
8808-R3-1
CCAAAGACCCCTTTCTCCCAGCCTGTTTCTGCAA
111
15.38
(nd)
1.74
3.85
(nd)
(nd)
(nd)
1.65
(nd)
−1.15
|
<−1.38
<−1.38
<−1.38
<−1.38
<−1.38
|
|
8898-R3-1
CGGACGCCCGCTCCCGCCA
112
4.61
2.99
2.21
2.39
−3.44
−2.32
−3.50
−1.73
−8.22
−2.57
|
|
9021-L4-1
AAACAAACACCCAAGCTCCCCACACCATC
113
4.79
1.54
−1.06
1.48
(nd)
(nd)
−3.04
−1.15
(nd)
(nd)
|
<−3.02
<−3.02
<−3.02
<−3.02
|
|
9053-R3-1
TTCTTGCCCTCCAATCCCCGGGCTCCACCAGCC
114
2.98
1.64
−1.13
1.16
−3.72
−2.19
−3.05
−1.88
−8.27
−2.12
|
|
9068-R2-1
CTGCCCTCCCTCTTGATCAAGACTGCTCTCCTAA
115
3.42
−1.69
2.79
2.64
−2.57
−3.10
−11.82
−1.57
−40.43
−4.16
|
|
9087-L4-1
GGAAAAGAAACCCTCCCAGTCCATTCCCTTCCT
116
2.03
−2.72
1.81
1.31
−2.99
−3.69
−4.84
−1.39
−9.51
−2.38
|
|
9217-L3-1
ACGATCCCCGCCGTGACTAAAGCCAACAGTGGA
117
3.28
2.48
1.88
1.93
(nd)
−2.32
−3.01
−1.46
(nd)
−1.91
|
<−4.55
<−4.55
|
|
9245-R2-1
AACCTCTCATTAGCCAGCCACTCGCTCCCAAG
118
5.25
4.01
1.82
1.83
(nd)
(nd)
(nd)
(nd)
(nd)
(nd)
|
<−1.69
<−1.69
<−1.69
<−1.69
<−1.69
<−1.69
|
|
9287-L4-1
GATATTCAGAGCCCTCCCCAGCCCACACATGC
119
4.16
−1.56
2.12
2.52
−2.91
−2.86
−6.49
−1.43
−32.89
−4.05
|
|
9347-L2-1
GCCCAATATGCATTTTACATTTTAACAAAGA
120
>3.17
nd
nd
>1.54
nd
nd
nd
nd
nd
nd
|
|
9349-R3-1
GTGATGCAGAGGACTTCCTGCTCCAGGTCTC
121
22.69
1.06
(nd)
7.70
(nd)
(nd)
(nd)
(nd)
(nd)
(nd)
|
<−1.13
<−1.13
<−1.13
<−1.13
<−1.13
<−1.13
<−1.13
|
|
9387-R2-2
TCCATCCTTGCCGTCGCCTTCATCTCAAAGCCATC
122
2.28
1.28
2.25
−1.06
−2.17
−3.48
−4.42
−2.26
−4.76
−1.91
|
|
9391-R3-1
CAGCTGCCAGGGAGACATAGAAATTAAAAACAA
123
−1.34
1.31
1.27
−1.69
−1.57
−1.49
−2.45
nd
nd
−1.82
|
|
9507-L3-2
GTCTCCCTCATCCATCATCC
124
>8.07
nd
nd
>3.35
nd
nd
nd
nd
nd
nd
|
|
9564-R1-1
GCCGCCCGCCGGGCACCGGGCC
125
1.64
1.84
2.11
1.01
−2.74
−3.42
−4.08
−2.21
−7.78
−2.50
|
|
9594-R2-1
CTTAGACTTCCTTCCCACTCCCTGCAT
126
11.20
1.01
(nd)
1.95
(nd)
(nd)
(nd)
2.21
(nd)
−1.03
|
<−2.11
<−2.11
<−2.11
<−2.11
<−2.11
|
|
9656-R3-1
GCCCTTAAAGTACATACTGTGGAGATTAATGCT
127
>5.47
nd
nd
>2.33
nd
nd
nd
nd
nd
nd
|
|
9691-L4-1
AATCATCCATTTCATCCGCATCTCCCTCTTGGCCCCTTGC
128
5.99
1.18
1.32
1.99
(nd)
−1.97
−2.87
−1.57
(nd)
−3.39
|
<−4.24
<−4.24
|
|
9733-L3-1
AAGGCTGTCCCTCACCAGACTTCCCCACCCCT
129
7.61
3.56
(nd)
2.44
(nd)
(nd)
1.07
1.69
(nd)
1.33
|
<−1.48
<−1.48
<−1.48
<−1.48
|
|
9774-R2-2
CCGCCCCCTCACCGCCTCCTGCTCCCATCAGGC
130
3.72
1.83
2.45
2.54
−2.98
−2.83
−4.46
−1.84
−12.28
−2.00
|
|
9816-R2-1
CTGGCCCTTTAAGAGCCTCTCCGCGCGCTGCCG
131
2.42
2.46
2.03
2.04
−2.71
−2.17
−2.86
−1.67
−4.18
−2.08
|
|
9840-L3-2
TTCAGGTTTTTATAAATCAGGATGTCAACAAAT
132
−1.39
1.32
1.13
−2.15
−1.71
−1.66
−2.89
nd
nd
−1.70
|
|
10010-R2-2
CCCGGCGCCCCTCGCCGGCTCCAAACTTTCCCCAA
133
4.99
2.90
2.53
3.23
(nd)
(nd)
−1.85
(nd)
(nd)
−1.31
|
<−1.75
<−1.75
<−1.75
<−1.75
|
|
10030-R3-1
AACTCAGCTGCCTTCCGCC
134
>6.94
>1.63
>3.55
>2.08
nd
nd
nd
nd
nd
nd
|
|
10138-L2-1
AGCCTGCTCCGCTCTCCCCTCCCACCAGAAAAAGT
135
10.06
2.02
1.51
3.69
−3.13
−2.11
−3.65
1.01
−7.30
−1.76
|
|
10145-L2-1
CTTTGCTCTCTCTTCTGTTATCTGGACC
136
>5.20
nd
nd
>1.95
nd
nd
nd
nd
nd
nd
|
|
10175-L1-1
CCTGCTCCTAGCAACCAGGAGCCACAA
137
>7.31
nd
nd
>4.44
nd
nd
nd
nd
nd
nd
|
|
10209-L3-1
AGAAAATAAGTTAGCTATGTAACAAATTGA
138
−1.56
1.29
−1.09
−2.17
−2.06
−1.65
−3.13
nd
nd
−1.86
|
|
10231-L3-1
GTGCAGCAGCCCGCGCCAGCCTCCGCAGCCGCC
139
1.76
1.50
3.56
−1.02
−1.97
−3.47
−5.87
−6.71
−3.38
−2.65
|
|
10231-R3-1
TGAACTTTAGCTGGGCCGCCGCCTGTCAGC
140
1.15
1.48
2.17
−1.45
−2.34
−4.21
−5.32
−3.26
−4.14
−2.20
|
|
10242-R3-1
GGAAGAAGCCCTTCCGCTTCCACCCCGAACAC
141
5.35
2.89
1.21
3.14
−2.60
−1.56
−3.46
−1.09
−6.84
−2.88
|
|
10333-L3-1
TGTGCCCTGCCCACCCCCTCCCCTGCCCCG
142
5.80
1.70
1.74
2.93
−3.43
−2.75
−4.34
−2.25
−9.80
−2.32
|
|
10335-L3-1
CACTCCCCTCCTTTTTAATTAGAAAGCACTAAGA
143
10.97
1.56
2.36
6.06
(nd)
(nd)
(nd)
(nd)
(nd)
−1.22
|
<−2.08
<−2.08
<−2.08
<−2.08
<−2.08
|
|
10342-R2-2
CCCGCCGCCGGAGCATCTCGAAGTTAATTAAA
144
1.75
2.08
2.13
−1.05
−2.55
−2.86
−2.31
−2.36
−10.37
−1.85
|
|
10366-R3-2
AAACACCACCCACGCTCTTGCTACAAGACCCACAT
145
2.46
1.21
−1.12
−1.11
(nd)
−2.45
−2.94
(nd)
(nd)
(nd)
|
<−3.19
<−3.19
<−3.19
<−3.19
|
|
10374-R3-2
GACACCGCCCGCTACTTTGTTAATGAAAAGCCCCC
146
2.59
2.62
2.48
1.28
−2.47
−2.10
−4.29
nd
nd
−1.97
|
|
10533-R3-1
GCCCCTTCTTTATATTGCCAAGA
147
4.36
(nd)
(nd)
2.33
(nd)
(nd)
(nd)
(nd)
(nd)
(nd)
|
<−1.58
<−1.58
<−1.58
<−1.58
<−1.58
<−1.58
<−1.58
<−1.58
|
|
11370-L4-1
CCTCCGCCCCCACACTGCATCCTTGCCCAGTTTGGCTG
148
7.22
1.56
(nd)
2.49
−2.48
−2.20
−6.13
−1.28
−3.12
−1.10
|
CCATCAGTATTGTCCCCTGAGAACTGGAC
<−6.13
|
|
12184-L4-1
GACCTCAGCGTGCCCCCTTTCAACCACAGACGAATATT
149
2.50
1.10
−1.39
1.69
(nd)
−2.20
−3.80
−1.92
(nd)
−1.97
|
GTGTACAA
<−4.07
<−4.07
|
|
12223-L4-1
CCCAGAAGACATCAGACAGAGTTGTTTCTTCTCCCTCTA
150
1.99
1.06
(nd)
1.27
(nd)
1.25
−1.49
1.03
−2.26
−3.14
|
<−4.89
<−4.89
|
|
4315_C-
GCAGCCCCTCCTCCGAGAGGTTGGGGGTCGCGGCCG
151
−2.79
1.91
1.97
2.72
−3.38
−2.74
−3.87
−1.53
−9.33
−7.93
|
L4-1
CCCGGCCCTCCCGGTCCCCTCCCC
|
|
4315_D-
GGAAAGTCAGCCCCCAGCGCCCCCCGGAGTTCTTGG
152
4.01
1.41
1.66
2.02
−4.14
−2.64
−7.06
−2.32
−9.62
−2.60
|
R4-1
|
|
4315_E-
CCCCCACCAAACCTATTCCCGCATCCTCCCCGGCTCTGG
153
7.07
1.72
1.30
2.47
−4.50
−2.77
−5.04
−2.24
−10.19
−2.01
|
R4-1
|
|
4315_F-
AACCCGGGCTCCCCCACCCGCTCCCTGAGC
154
3.58
1.70
1.23
1.44
−5.04
−3.19
−3.15
−2.24
−20.64
−2.42
|
R4-1
|
|
4315_I-L4-1
ACACCTCTGCGCCCCTCAGGCGCCCTGGGCCTCGGCG
155
5.01
2.26
2.05
2.48
−3.25
−2.26
−2.87
−1.61
−6.36
−2.28
|
CCCCGCCCGTCCCAG
|
|
4315_K-
TCCCAGGGGGCCCTGAACTTGTCAAATCCTCGCCATCC
156
4.24
1.87
2.15
1.72
−3.72
−2.41
−4.85
−1.91
−6.99
−1.83
|
L4-1
TCCACCCCCAGCCCCGG
|
|
10010_B-
GCCGAGCCCCCGCCCCCGCCGGGATGCTGCCCTCCG
157
2.68
2.95
1.31
1.80
−4.25
−3.10
−3.43
−2.54
−5.76
−2.39
|
L4-1
GAAGGAGGGGCGCTGCCC
|
|
10010_D-
TGGCGCCCTCCCCCGCCCGGGGCTCAGCCTCTCACCTG
158
4.06
1.62
1.93
2.59
−3.56
−2.99
−4.26
−1.54
−15.24
−2.37
|
L4-1
|
|
7356_A-
CAGAGCCCGCTCTCGCGACCGACCTGCCGCCGACCGC
159
1.71
1.65
3.03
−1.13
−1.99
−3.31
−4.25
−3.28
−3.88
−2.82
|
R4-1
CACAG
|
|
12722-L4-1
AATACGGACAAGCCCCACTCCCTCATTAGCATAAAAAA
160
3.15
2.05
2.31
2.04
−3.42
−2.39
−3.53
−2.00
−5.91
−2.63
|
CAAAGTACTTCCGACCTCCCCGCCCGCCCGC
|
|
999999-
CCCCTTGTCACCCCCAGCCCCTTCCTGGCCAGGACCC
161
10.71
2.08
1.97
3.33
(nd)
−1.64
−2.59
2.58
(nd)
−1.53
|
R4-1
CAGCGAGGCCCAGAGAA
<−2.88
<−2.88
|
|
999997-
TCCTCACTGGGCCCCACCAAAACTGTGCCACCCCCTCA
162
6.84
−1.42
1.59
2.77
−3.46
−2.91
−4.06
−1.00
−5.37
−1.68
|
R4-1
AGCCCCCAGGAGCTTCCTTAAC
|
|
8433_B-
CATATTTTTGTGTTGCTGAGTATTTGGGGTTTGCTCGCC
163
>5.03
>3.56
>2.45
>2.44
nd
nd
nd
nd
nd
nd
|
L4-1
CGT
|
|
8433_C-
AAACCAAAAAAAAAAAATTAAAAAGCGACGAAAATGCAA
164
24.29
1.73
1.87
5.70
(nd)
(nd)
(nd)
1.95
(nd)
1.13
|
R4-1
TTGTGTGCCTTCTCCCTCC
<−1.45
<−1.45
<−1.45
<−1.45
|
|
8433_D-
CCCGAGCCCGGCGCCCTGTGTTGTGCTCCGCTCTCCG
165
8.52
2.31
1.63
2.00
(nd)
−1.76
−3.76
−1.33
(nd)
−2.68
|
R4-1
GGAAATGCCATCACTAAT
<−4.10
<−4.10
|
|
let-7a
AACTATACAACCTACTACCTCA
166
−5.65
−1.33
1.33
−2.81
1.20
−1.63
−1.75
−1.18
1.20
−3.59
|
|
let-7b
AACCACACAACCTACTACCTCA
167
−2.30
−1.30
1.41
−2.86
1.19
−1.79
−2.26
1.05
1.51
−4.67
|
|
let-7c
AACCATACAACCTACTACCTCA
168
−2.52
−1.34
1.39
−2.93
1.22
−1.77
−1.97
1.17
1.38
−3.51
|
|
let-7d
AACTATGCAACCTACTACCTCT
169
−2.41
−1.35
1.23
−2.86
−1.03
−1.69
−2.05
1.31
1.64
−3.27
|
|
let-7e
AACTATACAACCTCCTACCTCA
170
−2.38
−1.32
−1.20
−2.76
−1.49
−1.83
−5.03
1.11
1.34
−8.91
|
|
let-7f
AACTATACAATCTACTACCTCA
171
−3.05
−1.28
1.19
−3.04
1.01
−1.73
−4.92
−1.20
1.06
−3.85
|
|
let-7g
AACTGTACAAACTACTACCTCA
172
−2.34
−1.12
1.13
−2.73
−3.04
−1.16
−1.34
1.28
2.07
−3.06
|
|
let-7i
AACAGCACAAACTACTACCTCA
173
−1.56
1.86
(nd)
−1.68
1.05
2.20
−3.56
1.63
3.60
−1.90
|
<−3.56
|
|
miR-100
CACAAGTTCGGATCTACGGGTT
174
−1.91
−1.56
1.24
−3.21
−1.72
−2.50
−2.63
1.39
2.17
−5.22
|
|
miR-1224-
CCACCTCCCGAGTCCTCAC
175
5.56
1.51
1.89
1.57
(nd)
(nd)
−1.11
(nd)
(nd)
(nd)
|
5p
<−1.14
<−1.14
<−1.14
<−1.14
<−1.14
|
|
miR-1225-
CCCCCCACTGGGCCGTACCCAC
176
8.21
−1.18
2.95
4.25
(nd)
(nd)
−2.35
(nd)
(nd)
(nd)
|
5p
<−2.30
<−2.30
<−2.30
<−2.30
<−2.30
|
|
miR-1228*
CACACACCTGCCCCCGCCCAC
177
3.27
3.43
1.06
1.96
−6.69
−3.06
−3.39
−1.87
−12.52
−2.10
|
|
miR-125a-
TCACAGGTTAAAGGGTCTCAGGGA
178
(nd)
−1.52
1.28
−3.29
−2.87
−1.81
−6.80
−1.99
−1.10
−6.52
|
5p
<−10.19
|
|
miR-125b
TCACAAGTTAGGGTCTCAGGGA
179
−3.83
−1.52
1.33
−3.15
−1.08
−1.77
−2.46
−1.78
1.01
−5.55
|
|
miR-126
CGCATTATTACTCACGGTACGA
180
−2.39
−1.40
5.58
−2.14
1.33
−1.45
−1.81
1.07
1.71
−1.42
|
|
miR-135a*
CGCCACGGCTCCAATCCCTATA
181
>3.61
nd
nd
2.49
nd
nd
nd
nd
nd
nd
|
|
miR-142-
TCCATAAAGTAGGAAACACTACA
182
−2.17
1.15
1.09
−2.54
−4.28
1.14
1.45
−1.22
1.18
−3.10
|
3p
|
|
miR-145
AGGGATTCCTGGGAAAACTGGAC
183
−4.94
−1.08
2.41
−2.67
1.13
1.01
−1.07
−2.03
1.31
−3.13
|
|
miR-146b-
AGCCTATGGAATTCAGTTCTCA
184
(nd)
1.12
2.44
<−1.89
<−1.89
2.71
1.07
1.30
2.48
−1.21
|
5p
<−1.89
|
|
miR-149*
GCACAGCCCCCGTCCCTCCCT
185
3.46
3.38
−1.02
2.16
−8.57
−3.25
−6.43
−2.34
−21.89
−2.17
|
|
miR-150*
CTGTCCCCCAGGCCTGTACCAG
186
>4.16
nd
nd
>1.76
nd
nd
nd
nd
nd
nd
|
|
miR-155
ACCCCTATCACGATTAGCATTAA
187
nd
nd
nd
nd
nd
>1.83
>1.07
nd
nd
nd
|
|
miR-16
CGCCAATATTTACGTGCTGCTA
188
−4.17
−1.04
(nd)
−3.62
−1.53
−1.05
−1.04
1.73
2.03
−3.14
|
<−10.19
|
|
miR-181c
ACTCACCGACAGGTTGAATGTT
189
(nd)
−1.73
1.58
−2.37
−1.79
1.13
−2.25
−1.16
1.07
−3.23
|
<−3.23
|
|
miR-198
GAACCTATCTCCCCTCTGGACC
190
>33.49
>2.21
nd
>8.74
nd
nd
nd
nd
nd
nd
|
|
miR-199a-
TAACCAATGTGCAGACTACTGT
191
−3.52
1.40
1.43
−1.94
1.72
1.56
1.33
1.59
2.97
−4.20
|
3p
|
|
miR-19b
TCAGTTTTGCATGGATTTGCACA
192
−1.07
−1.01
1.41
−1.94
(nd)
−1.10
1.48
1.28
4.82
(nd)
|
<−2.18
<−2.18
|
|
miR-200b
TCATCATTACCAGGCAGTATTA
193
1.18
1.01
(nd)
1.43
−1.58
−1.56
−1.38
1.72
2.60
−1.45
|
<−5.45
|
|
miR-200c
TCCATCATTACCCGGCAGTATTA
194
1.45
1.11
−1.19
1.72
−1.88
−1.84
−1.47
1.92
2.85
−1.10
|
|
miR-205
CAGACTCCGGTGGAATGAAGGA
195
>11.24
>24.11
nd
nd
nd
nd
nd
>3.48
>9.48
nd
|
|
miR-21
TCAACATCAGTCTGATAAGCTA
196
−2.52
1.77
−1.51
1.45
1.41
3.51
2.27
3.43
5.38
1.25
|
|
miR-23a
GGAAATCCCTGGCAATGTGAT
197
1.38
2.90
(nd)
1.37
(nd)
2.28
(nd)
2.38
7.76
−2.09
|
<−4.40
<−4.4
<−4.4
|
|
miR-23a*
AAATCCCATCCCCAGGAACCCC
198
>4.54
nd
nd
>1.79
nd
nd
nd
nd
nd
nd
|
|
miR-23b
GGTAATCCCTGGCAATGTGAT
199
−1.43
1.45
(nd)
−1.34
1.26
1.24
−2.02
1.27
4.35
−1.98
|
<−9.07
|
|
miR-24
CTGTTCCTGCTGAACTGAGCCA
200
−2.08
1.26
2.49
−1.46
1.08
1.22
−1.17
1.09
2.86
−2.76
|
|
miR-25*
CAATTGCCCAAGTCTCCGCCT
201
>4.17
nd
nd
>1.38
nd
nd
nd
nd
nd
nd
|
|
miR-26a
AGCCTATCCTGGATTACTTGAA
202
−2.98
−1.73
2.04
−3.66
1.04
1.00
−1.33
1.07
1.67
−2.29
|
|
miR-26b
ACCTATCCTGAATTACTTGAA
203
−2.84
−1.67
1.20
−3.56
−1.49
−1.16
−1.18
1.13
1.74
−2.23
|
|
miR-27a
GCGGAACTTAGCCACTGTGAA
204
−1.27
1.78
2.19
−1.78
−1.02
1.44
1.07
1.73
4.25
−2.26
|
|
miR-27b
GCAGAACTTAGCCACTGTGAA
205
−1.11
2.20
2.52
−1.91
1.18
1.64
1.24
2.05
6.50
−1.85
|
|
miR-298
TGGGAGAACCTCCCTGCTTCTGCT
206
24.71
2.84
(nd)
10.70
(nd)
(nd)
−1.15
2.09
(nd)
1.13
|
<−1.29
<−1.29
<−1.29
<−1.29
|
|
miR-29a
TAACCGATTTCAGATGGTGCTA
207
−2.68
1.00
3.18
1.50
−1.90
2.13
1.41
1.23
2.18
−2.96
|
|
miR-29b
AACACTGATTTCAAATGGTGCTA
208
−5.79
−1.32
1.33
−1.17
−3.06
1.46
1.26
1.01
1.30
−5.30
|
|
miR-29c*
TAACCGATTTCAAATGGTGCTA
209
−4.12
−1.00
3.14
1.30
−3.52
2.01
1.49
1.66
2.61
−4.26
|
|
miR-30a
CTTCCAGTCGAGGATGTTTACA
210
−4.44
−3.14
3.50
−3.84
−1.50
−2.18
−3.97
−7.98
2.09
1.23
|
|
miR-30b
AGCTGAGTGTAGGATGTTTACA
211
(nd)
−1.98
2.09
−4.38
−2.50
−1.73
−2.27
2.12
2.77
1.03
|
<−6.56
|
|
miR-30b*
GAAGTAAACATCCACCTCCCAG
212
3.38
−1.21
1.05
−1.36
−2.31
−2.53
−2.76
−1.56
−3.51
−3.51
|
|
miR-30c
GCTGAGAGTGTAGGATGTTTACA
213
−4.45
−2.14
(nd)
(nd)
(nd)
−1.95
(nd)
1.86
2.21
−2.40
|
<−6.05
<−6.05
<−6.05
<−6.05
|
|
miR-30c-
GGAGTAAACAACCCTCTCCCAG
214
39.98
(nd)
1.57
7.84
(nd)
(nd)
−1.42
2.67
(nd)
(nd)
|
1*
<−1.58
<−1.58
<−1.58
<−1.58
<−1.58
|
|
miR-30c-2
GCTGAGAGTGTAGGATGTTTACA
215
−4.45
−2.14
(nd)
(nd)
(nd)
−1.95
(nd)
1.86
2.21
−2.40
|
<−6.05
<−6.05
<−6.05
<−6.05
|
|
miR-30d
CTTCCAGTCGGGGATGTTTACA
216
−6.68
−2.87
3.73
−3.55
−1.26
−2.03
−4.02
1.32
3.66
1.39
|
|
miR-30e
CTTCCAGTCAAGGATGTTTACA
217
(nd)
−2.42
2.08
(nd)
(nd)
−2.00
(nd)
1.45
1.71
−1.30
|
<−4.99
<−4.99
<−4.99
<−4.99
|
|
miR-320a
TCGCCCTCTCAACCCAGCTTTT
218
4.68
1.05
2.16
2.43
1.02
1.33
−1.39
nd
nd
−1.20
|
|
miR-331-
TTCTAGGATAGGCCCAGGGGC
219
(nd)
(nd)
2.17
1.42
1.24
1.47
1.27
−1.21
−1.21
1.36
|
3p
<−1.21
<−1.21
|
|
miR-371-
AGTGCCCCCACAGTTTGAGT
220
>2.65
nd
nd
>1.30
nd
nd
nd
nd
nd
nd
|
5p
|
|
miR-373*
GGAAAGCGCCCCCATTTTGAGT
221
10.21
1.72
2.16
3.92
(nd)
−1.66
−3.39
1.66
(nd)
−1.73
|
<−3.77
<−3.77
|
|
miR-375
TCACGCGAGCCGAACGAACAAA
222
nd
nd
nd
nd
nd
nd
nd
nd
nd
>2.88
|
|
miR-423-
AAAGTCTCGCTCTCTGCCCCTCA
223
6.96
1.49
1.63
1.87
(nd)
−1.38
−1.95
1.01
−1.06
−1.83
|
5p
<−6.09
|
|
miR-424
TTCAAAACATGAATTGCTGCTG
224
nd
nd
nd
nd
nd
>2.14
nd
>2.99
>11.35
nd
|
|
miR-483-
CTCCCTTCTTTCCTCCCGTCTT
225
24.38
1.51
1.68
5.17
(nd)
1.11
−1.64
3.19
(nd)
−1.03
|
5p
<−1.54
<−1.54
|
|
miR-486-
ATCCTGTACTGAGCTGCCCCG
226
3.44
2.92
2.61
1.43
(nd)
(nd)
−1.85
1.05
(nd)
(nd)
|
3p
<−1.91
<−1.91
<−1.91
<−1.91
|
|
miR-491-
GTAGAAGGGAATCTTGCATAAG
227
−2.17
1.13
4.21
−2.65
(nd)
−1.40
−3.03
nd
nd
−3.87
|
3p
<−3.87
|
|
miR-491-
CCTCATGGAAGGGTTCCCCACT
228
>2.09
nd
nd
nd
nd
nd
nd
nd
nd
nd
|
5p
|
|
miR-513a-
ATGACACCTCCCTGTGAA
229
>6.38
nd
nd
>3.28
nd
nd
nd
nd
nd
nd
|
5p
|
|
miR-513b
ATAAATGACACCTCCTTGTGAA
230
>1.98
nd
nd
>1.29
nd
nd
nd
nd
nd
nd
|
|
miR-516a-
GAAAGTGCTTCTTTCCTCGAGAA
231
>23.45
nd
nd
>5.80
nd
>1.65
nd
>2.27
nd
nd
|
5p
|
|
miR-550
GGGCTCTTACTCCCTCAGGCACT
232
>2.04
nd
nd
nd
nd
nd
nd
nd
nd
nd
|
|
miR-557
AGACAAGGCCCACCCGTGCAAAC
233
4.19
1.38
2.01
1.78
(nd)
(nd)
−1.15
1.57
(nd)
−1.21
|
<−1.39
<−1.39
<−1.39
|
|
miR-575
GCTCCTGTCCAACTGGCTC
234
>4.55
nd
nd
nd
nd
nd
nd
nd
nd
nd
|
|
miR-612
AAGGAGCTCAGAAGCCCTGCCCAGC
235
5.20
2.50
−1.18
1.81
(nd)
−2.60
−2.93
−1.98
(nd)
−2.85
|
<−5.94
<−5.94
|
|
miR-614
CCACCTGGCAAGAACAGGCGTTC
236
>2.61
nd
nd
nd
nd
nd
nd
nd
nd
nd
|
|
miR-630
ACCTTCCCTGGTACAGAATACT
237
>4.81
nd
nd
>1.88
nd
nd
nd
nd
nd
nd
|
|
miR-637
ACGCAGAGCCCGAAAGCCCCCAGT
238
1.35
5.51
2.82
7.31
(nd)
(nd)
(nd)
1.46
(nd) <−1.81
−1.52
|
<−1.81
<−1.81
<−1.81
|
|
miR-638
AGGCCGCCACCCGCCCGCGATCCCT
239
2.50
2.06
3.13
1.32
−1.55
−3.45
−4.86
−2.17
−2.60
−2.40
|
|
miR-658
ACCAACGGACCTACTTCCCTCCGCC
240
3.65
3.18
1.67
3.41
(nd)
−1.70
−1.93
1.04
(nd)
−1.76
|
<−3.56
<−3.56
|
|
miR-663
GCGGTCCCGCGGCGCCCCGCCT
241
3.51
2.57
2.02
1.44
(nd)
(nd)
(nd)
(nd)
(nd)
(nd)
|
<−3.06
<−3.06
<−3.06
<−3.06
<−3.06
<−3.06
|
|
miR-671-
CTCCAGCCCCTCCAGGGCTTCCT
242
>7.67
nd
nd
>5.82
nd
nd
nd
>1.94
nd
nd
|
5p
|
|
miR-675
CACTGTGGGCCCTCTCCGCACCA
243
7.25
4.60
(nd)
4.46
(nd)
(nd)
−1.07
1.88
(nd)
(nd)
|
<−1.19
<−1.19
<−1.19
<−1.19
<−1.19
|
|
miR-708
CCCAGCTAGATTGTAAGCTCCTT
244
nd
nd
nd
nd
nd
nd
<−1.01
nd
nd
>2.16
|
|
miR-744
TGCTGTTAGCCCTAGCCCCGCA
245
4.02
1.97
1.40
1.40
(nd)
−2.20
−3.66
−1.68
(nd)
(nd)
|
<−3.47
<−3.47
<−3.47
|
|
miR-765
CATCACCTTCCTTCTCCTCCA
246
25.46
3.15
3.08
6.06
(nd)
3.70
1.82
3.00
(nd)
1.02
|
<−1.58
<−1.58
|
|
miR-920
TACTGCTTCCACAGCTCCCC
247
>3.57
nd
nd
nd
nd
nd
nd
nd
nd
nd
|
|
miR-923
AGTTTCTTTTCCTCCGCTGAC
248
6.70
1.19
1.24
1.35
−2.18
1.11
−1.43
1.19
2.00
−2.79
|
|
miR-92a-
GTAATGCAACAAATCCCCACCC
249
3.79
2.45
1.23
1.20
(nd)
(nd)
(nd)
1.18
(nd)
−1.59
|
2*
<−1.93
<−1.93
<−1.93
<−1.93
|
|
miR-92b*
CACTGCACCGCGTCCCGTCCCT
250
5.09
1.52
1.50
1.81
(nd)
(nd)
−3.14
(nd)
(nd)
(nd)
|
<−3.06
<−3.06
<−3.06
<−3.06
<−3.06
|
|
miR-93
CTACCTGCACGAACAGCACTTTG
251
(nd)
1.27
(nd)
(nd)
(nd)
1.17
−1.22
1.14
2.52
1.03
|
<−2.50
<−2.50
<−2.50
<−2.50
|
|
miR-98
AACAATACAACTTACTACCTCA
252
−4.47
−1.37
1.17
−2.84
−4.10
−1.83
−2.38
−1.22
1.21
−4.82
|
|
miR-99b
CGCAAGGTCGGTTCTACGGGTG
253
(nd)
−1.36
1.59
−2.74
(nd)
−2.23
(nd)
1.30
−1.51
(nd)
|
<−3.33
<−3.33
<−3.33
<−3.33
|
|
TABLE 2
|
|
fold-changes in cell lines v. normal Lung
|
BEA2B
|
(Immortalized
|
bronchial
|
epithelial
|
probe
H460
H1703
cells -
A549
|
Array
Array probe sequence
SEQ
(Large cell
(Adeno-
normal
(Adeno-
|
probe
(5′ to 3′, without linker)
ID NO:
carcinoma)
carcinoma)
phenotype)
carcinoma)
|
|
3717-L2-1
CCGCCCTCCCCATAGCCTCACCCCAAACCCACTCACA
6
1.02
1.86
1.77
2.27
|
|
3758-R2-2
TGCAGGCTCCACTGACATTTTCACAATTTAAATCAT
254
−1.85
2.07
1.89
2.26
|
|
3799-R3-1
CCAGAGGCCCCCCGCCGGCC
7
−1.63
1.14
1.33
(nd) <6.30
|
|
3820-R3-1
CCCCCACCCCTCTGTGGGGCCATCCCTG
255
1.60
nd
nd
nd
|
|
3851-R3-4
GAGCTCCCAACCCTCCTTTATGTTTTGTCTAAAGC
256
nd
nd
6.82
nd
|
|
3874-L3-1
TGAATATTATCCCTAATACCTGCCACCCCA
257
2.75
10.71
10.14
10.68
|
|
3897-R3-1
CAGCCGCCTCCCCCTCAGCGTTAA
10
−1.97
1.50
1.79
1.75
|
|
3906-L3-1
AACATATGTAAACCCCTTTATTCCTCATTCTG
258
(nd) <4.59
1.25
1.70
2.14
|
|
3923-R3-1
GCCTCTCACAAAGGATCTCCTTCATCCCTCTCC
11
−1.74
2.11
1.72
2.03
|
|
3952-L3-2
GCGCACAGAGCACTCAATCTGACACCCCTCGC
259
−1.66
1.90
1.73
2.13
|
|
3953-R3-2
ACTCCAGCCTCCGCCGCCTCAGCTTCCCGAGC
12
−1.22
1.78
1.59
1.81
|
|
3976-L2-2
TCATACTCCTGCTTGCTGATCCACATCTGCTGGAA
260
1.58
5.83
7.55
8.31
|
|
3995-L2-2
CTATAAAACTTCGAAAAGTCCCTCCTCCTCACGT
13
−1.17
1.41
1.31
1.36
|
|
4037-R3-2
GCCTGTTCCCTGGCATGTACTGTAATTTATCT
15
−2.05
2.26
1.66
1.88
|
|
4064-R3-1
CATAGCTGAATTCCATCCCAGCCCCAG
261
2.32
nd
nd
nd
|
|
4118-L2-2
TCATACTCCTGCTTGCTGATCCACATCTGCTGGAA
262
1.80
6.34
8.91
9.64
|
|
4130-L3-1
GCCAGCACGCCGTCCATGTCCACCAGCACCC
263
−1.51
1.55
1.91
(nd) <4.64
|
|
4143-R3-1
TCAGCGTCTTGCTCTCCTCCTGGTA
16
2.11
3.64
nd
nd
|
|
4155-R1-1
AGACCGGACTCGCCTCTTCCAACTCGAGTTCA
264
nd
3.56
nd
nd
|
|
4182-R2-2
AGTTCAGCAGCCCAGTGGACATGCTGGGGGTGGT
265
9.76
14.90
nd
nd
|
|
4203-R3-2
GCACATTCCCACTTCCCCAGAGGCAGGCTCCATAT
17
nd
5.60
7.52
nd
|
|
4205-R3-1
ACTTCATCCTCACCACTCACACCACCCTAG
266
−1.94
1.83
2.35
(nd) <3.98
|
|
4216-R3-1
TCCCTCCCTTATACACAGATCAATTCCCCC
267
−1.53
1.78
1.86
2.51
|
|
4303-R1-1
AGTGCCCGCTCCTCCGACCTCCCTGCGCACC
19
−1.09
1.56
1.42
1.57
|
|
4315-R3-2
TCCCCGGCCCTCTCCATTCTCGGCTCCGGAGCA
20
−1.54
1.63
1.53
1.61
|
|
4340-R3-1
ATTTTCCAGCCCCTTGTCCCCAGGCCAAAC
268
−1.75
1.98
1.79
2.09
|
|
4361-R3-1
CGTCTCCCTCCCTCATGTGC
21
−1.60
1.46
1.56
(nd) <4.18
|
|
4391-R2-1
GCCAAATTCTCAACCAATATAACTCTGTGA
269
2.65
7.30
10.84
nd
|
|
4413-L3-1
GGCACCTCCAGCTACAGTAAACAAAT
270
−1.65
1.74
1.74
1.99
|
|
4417-R1-1
GCTCATCAAAAAGTTCCCTGT
271
−1.75
1.40
1.49
1.66
|
|
4440-R3-1
TACTCCCGCCGTTTACCCGCATTTCACTGAA
272
−1.71
1.75
1.76
2.23
|
|
4440-L3-1
TTCAGAGCACTGGGCAGAAATCACATCAC
273
−1.70
1.70
1.81
2.20
|
|
4448-R3-1
CCTACCCCCAGCATCTCCTCACGCCATTGCC
24
−1.76
2.12
1.76
2.36
|
|
4479-R3-1
AGCCCCCTGCCCGGAAATTCAAAACAACTGC
25
−1.47
1.10
1.38
1.60
|
|
4498-L3-2
GAGATCCAGACGGCCGTGCGCCTGCTGCTGCCT
274
−1.95
2.00
1.73
2.11
|
|
4567-L1-1
ATCTGCCCAGTTCCCAGCACACTCCC
275
2.50
6.95
8.90
nd
|
|
4579-L3-2
GGCTTCACTTGCCTCCTGCAAAACACCAATAGC
276
−1.75
1.60
1.64
1.82
|
|
4593-R3-1
AGCAGATGACATAACTCCCCCGGCATCAG
26
−1.83
−1.24
1.68
1.74
|
|
4610-R3-1
GCCCTCTGGCCCCTGCCTAATTGGCTGC
277
1.04
1.55
1.43
1.66
|
|
4724-L3-2
CTTGGCATCTCTAGCACCTTCAGCTTTCTGTGCCT
278
−1.60
1.82
1.71
1.91
|
|
4754-R3-2
CCAAAGCCTTAGACAAGTGCCAAGCCCATCTTT
279
−1.58
1.60
2.35
2.49
|
|
4801-L3-1
AACTCTGCCTCCTGTTTGCTACAAAAACATTAAT
280
−1.47
1.76
1.15
1.36
|
|
4829-R2-1
TCCCTTTGTGCTGCCCGAGTGCCTTCCCCCTG
29
−1.59
1.81
1.62
1.92
|
|
4855-R3-1
GGGCTGCCGGGTCTCCCGCTTCC
30
2.95
3.52
3.97
nd
|
|
4964-L3-2
AGGGCTAACTTCTGAAAACCCACCAAATTCCCCAA
281
−2.00
1.44
1.52
1.79
|
|
5006-L3-1
ACAGCTCCCTCTGCTGGCTCC
33
−2.37
1.57
1.68
1.78
|
|
5071-R2-1
CCCCAGTCCCAGCCCAATTAATAAATGGG
282
−1.48
1.42
2.11
2.49
|
|
5080-R3-1
CTTGCAAAGGGTCTCCTTCATCCCTCTCCA
34
−1.69
2.01
1.67
1.96
|
|
5192-L3-1
CCCCTTCCTTCCTCTATATCAGCAAAGAC
283
−1.45
1.75
1.73
2.15
|
|
5306-L3-2
CCTCTGACCCCAGCTCTGGCCCTTTCTAGGG
284
−1.72
1.66
1.75
2.05
|
|
5327-L3-1
CTCAACCTCTGGGACTATGTCCTGTCTCC
285
nd
6.36
8.44
nd
|
|
5342-L3-1
CACCACCAAACCAAATGCCGCTGCTCTCCTTCCA
36
2.47
nd
nd
nd
|
|
5372-R3-2
CCCTCTGTTTTCAACTTACACAAGATTCTTTTT
286
−2.07
2.01
1.61
2.10
|
|
5380-R2-2
GGCTCCCAGATGTGTCCCACATTGAAGAATTATC
287
−2.19
1.91
1.82
1.88
|
|
5441-L3-2
GCCAAGCTCCAAGTCAGTATAGCTAACAGAGCAG
288
nd
3.14
nd
nd
|
|
5474-L3-2
CTCCTCTCACCTGGCCAGACTCTGACCCACCTAC
289
2.77
4.11
7.78
8.58
|
|
5513-L3-1
CAACTGTTCTCCATGATGCCTCAGAGCCACTT
290
−2.43
2.15
1.58
1.91
|
|
5554-R2-1
CCCCACCCCCTCATCAGCTGCTCCCAGAT
38
−1.67
1.88
1.71
2.23
|
|
5598-R2-2
CTCCCACCTCCGTGAAGCTATTTTTAACTGTGCA
291
−1.27
1.56
1.62
1.72
|
|
5618-R3-1
TCCCAGCCCACCAGTGCCACATTACAGCCCA
292
−1.39
1.41
1.93
1.95
|
|
5619-L3-1
AATGCCAGTTCTGCTCAATCTTCCCTCAATGAG
293
−2.45
1.94
1.69
2.04
|
|
5638-R2-1
GGCCCTCCCCCTGCCTGTGATAGGCTGCTTG
39
−1.06
1.87
1.63
1.59
|
|
5640-L3-1
GCCATGGAACACCGTGCCTGCCCCTCTCGAGA
40
−1.37
1.75
1.80
1.84
|
|
5733-R3-2
CTCACCCAGCTCATCCTGCTTCTCAGTCCCAC
294
−1.58
1.47
1.34
1.76
|
|
5735-L3-1
AGAAAGTTGCTGTTTCCTCTGGCCTCAAGCCT
295
−1.64
1.94
1.78
2.10
|
|
5782-L3-1
GATTCCAGCCCCTTCCCCC
42
3.41
5.68
7.06
9.69
|
|
5795-R1-1
CTGCCCTCCAAGAAATAAATTACCCGCAATTACT
43
−1.04
2.08
1.83
2.32
|
|
5836-R3-2
CATTAACCCCCATTATCACAGCACGCCCCATTC
44
−1.60
1.58
2.26
2.56
|
|
5854-R3-1
CCCTCCCTCTCCGAAAGAATGTGTCAC
45
−1.42
2.05
1.96
2.24
|
|
5863-L3-1
GCCGTTGCTGCTGGCAATTCCTGTCG
296
−2.05
2.24
1.56
2.05
|
|
5919-L3-1
AAGCAACACTGTCACTTTATCTCCCTAGA
297
−1.92
1.46
1.50
2.28
|
|
5971-R3-1
CTGCTCAGCCTCCCACATCTGT
46
−1.53
1.49
2.17
2.31
|
|
6008-R1-1
ACAATACCCCCACCTTTTTCCTGTACCTTAC
47
2.16
4.91
7.51
8.14
|
|
6016-R2-1
AAACTCCAGCAGCCCCGTCAGCCTCCTGCT
48
−1.45
1.75
1.66
1.86
|
|
6026-R3-1
CAGCCACCTTGGTTTTGTGGTTTGGCAAA
298
nd
5.34
7.28
7.92
|
|
6192-L3-1
AGATAAAAAACCACCCACCCAGCAC
52
nd
4.46
nd
nd
|
|
6218-R3-1
AATCACATTACTGCCTCTCATGTCACA
299
4.96
nd
nd
nd
|
|
6235-R3-1
GCTCCAAAAATCCATTTAATATATTGTCCTT
54
−1.96
2.79
−1.84
(nd) <12.83
|
|
6253-L3-1
CCTGACAATATCCTGGCTGCCATAATGCCAGC
300
−2.63
1.74
1.98
(nd) <6.02
|
|
6287-L3-2
GCCCCGCCCCACCTTTCGGGGCTCACCTGGC
55
−2.16
1.72
1.47
1.68
|
|
6355-R3-1
TCCAGATCATCTGTTCCCTGAGGATTTACAGT
301
1.94
5.81
nd
nd
|
|
6409-L3-1
CGTTCCCAACCGCACGCGCCGCCTTCTGGAAC
56
−1.32
2.14
1.60
2.05
|
|
6421-R3-2
CCCTCCTGTGAGAGTCTGAAGGACACTATTG
302
nd
10.40
nd
10.50
|
|
6434-R3-1
AGCCCTCCCACCAGCCAGCTGCAGTGC
57
1.33
1.69
1.63
1.70
|
|
6450-R3-2
CTCCAATGGTGCTCTCCTGGTACTCATGGAAC
303
1.41
nd
nd
nd
|
|
6478-R2-2
GCCAAATTCTGCCCCTGGATATGCATGCACAATT
304
−1.72
1.93
1.69
2.04
|
|
6496-R3-1
CCCCTCCCCCACCCACCACTTCCCCTAGAGTCC
60
−1.36
1.95
2.28
2.20
|
|
6554-L3-2
TCCTTGTCATCTAGAACTACTTTGGTGCCTCCATA
305
nd
3.79
nd
nd
|
|
6584-L1-1
TCGGCCCTGCCTCCTCCTCCT
61
−1.36
1.82
1.33
1.52
|
|
6602-R3-2
AGAGCCCCAGTGGAAATCTCTCCTCCAAATCCAT
62
2.63
13.21
10.59
18.66
|
|
6642-R3-1
CACGTCCTCCCCTCCCCTCGAGGTGTCACACA
63
1.20
1.79
1.25
1.90
|
|
6647-R2-1
CTCAGCCCCAGCTGGAGAATTTTTCCCCTCATTA
306
1.56
nd
nd
nd
|
|
6664-R2-1
GCCACCACCTCTCTTTTTCACAGGACATTACCA
307
nd
nd
5.29
nd
|
|
6681-R2-1
CCTGTTTTCTCCCCTCTCTCTCTGCCCCTCC
64
4.99
7.90
9.03
11.45
|
|
6712-L2-1
GCTGTGGTCTTGTGATATCAGTTGTCAGCCTG
308
1.83
4.86
4.41
nd
|
|
6718-L3-2
GCCTCCACCACCATAGGGGCCAGAGCTTCTGCCT
309
−1.53
2.03
1.89
1.92
|
|
6718-R3-1
ATAGCCACCTTGGTTTTGTGGTTTGGCAAAG
310
1.66
7.03
nd
nd
|
|
6752-R1-1
CCCTCCTTTCCCCACCTCAGT
66
−2.15
1.89
1.60
2.23
|
|
6803-R3-1
GCTCCCTCTCTGGTTGGACCTCACCCAAAGAT
68
−1.53
2.01
1.94
2.16
|
|
6839-L3-1
GCCCGCTGGGCCCTGCCACCCCCACCCCT
69
−1.88
1.57
1.43
1.81
|
|
6880-L3-2
ACCTCCCCCGCGAAGACATCCACATTCTGCA
70
−2.04
1.49
1.48
2.07
|
|
6906-L3-1
GTGTCTTCTCCCCAACCAGCCAGCTCTCCTGG
71
nd
3.61
nd
nd
|
|
6912-L3-1
GCCTTCAGCCTCTGGGTCCAGCAGTTAATTCT
311
−1.45
1.82
1.06
1.68
|
|
6930-R3-1
ATTAATCCTTCTCTCCCCTCTG
72
2.11
nd
nd
nd
|
|
7019-R3-1
AGCATCAAACCTCCGTGCTAAATTTAAA
312
2.73
nd
nd
nd
|
|
7061-R3-1
ATGGAAACCCCACCCTTCCC
75
nd
5.97
nd
nd
|
|
7070-R3-1
AGTCAACCTATACTGTCAGCACCAGGACCCAC
313
(nd) <3.72
1.57
2.14
2.63
|
|
7089-R1-1
CCTGAGCCAGCTCACATCACCCCTGACC
314
−2.12
1.57
1.68
2.43
|
|
7126-L3-1
GCACACCCGCTCTCCGGCCCGCGCCCCTG
77
−1.46
1.95
1.68
2.00
|
|
7158-R3-1
TACATTTATAGATTCCCTCTTCAGCCATA
315
nd
nd
8.25
nd
|
|
7292-L3-4
GTCACCCAGTTAAATAGCTTCTGAACCTCCCTGCA
316
(nd) <4.32
1.40
1.39
(nd) <4.32
|
|
7304-L3-1
TTGATCCAAGCTCCCACATTTG
317
1.98
5.85
8.70
8.84
|
|
7340-R3-1
CTGCCACCAACTCTAATTGATTC
318
(nd) <4.01
1.56
2.37
2.64
|
|
7352-R3-2
GCCCCTGCCAGAATCCTCTAACAGCTCTAATTGG
81
−1.43
1.57
1.61
2.40
|
|
7356-R2-1
GAAGCTCCGCGGCGACGTCCCGTTACTCC
83
−1.80
2.04
2.41
3.11
|
|
7375-L3-1
AGCGCTGCTGTCTCCACAGTTACATACCTG
319
nd
7.15
9.97
12.05
|
|
7384-R3-1
CTCGCAAAGGATCTCCTTCATCCCTCCCCA
85
−1.49
2.00
1.91
2.17
|
|
7411-R3-2
AGTCCCCTGCCTCATCTGCCACCCCTAATGAC
86
−1.61
1.70
1.62
1.87
|
|
7421-R2-1
TAAAGAGACTTCCTCCACTGCCAGAGATCT
87
2.12
4.83
8.07
nd
|
|
7426-L3-1
TGGGAGACGAACACCTCCTGCTGTGCTTG
88
4.29
nd
nd
nd
|
|
7435-L3-2
CTCCCCATCTGTTGCTAAGCCCCATTAGCTGTGT
320
−1.79
2.09
1.86
2.33
|
|
7543-L3-2
TGCCGATGTCGTCCTAATTCACCAGGCCCCGA
321
nd
3.71
6.97
nd
|
|
7571-L1-1
AGGGCTCCCCCACCCCTAAG
90
−1.73
1.43
1.50
1.43
|
|
7572-R2-1
ATCACCCTTCCCCCTCCCAAATAAAG
91
−1.39
1.80
1.94
2.21
|
|
7578-L3-1
CGCAGTGCACACCCTGAGCTACAGCCCCTC
92
1.13
6.99
5.80
1.72
|
|
7597-L3-1
TTAATGGAACCTGGGCTCTGTGTC
322
1.75
4.17
8.05
8.93
|
|
7660-L2-1
CCCGGCCTCCGCCTGGCCCGAGCGATAA
93
−1.11
1.74
1.69
1.78
|
|
7702-L2-1
CCCAGAGAACCGGAATTCCTCCCCGCCCC
94
−2.10
1.41
1.47
1.48
|
|
7726-R3-2
CATCCCTCTCCAGAAGAGGAGAAGAGGAAACA
95
−1.60
1.79
2.31
2.56
|
|
7763-R3-1
GTGCTCCCAATCCAGACGATCCATTA
323
−1.67
1.67
2.28
2.52
|
|
7764-R3-2
CCCTCTCTGCCTCTCTCATCACCAATAACAGAC
96
−1.09
1.93
1.74
2.01
|
|
7824-R3-1
TGGTGCCAGCTTCATCGCCG
324
nd
3.25
nd
nd
|
|
8004-R3-2
GGAACTGCTTCTCCTTGCTCCAGTCATTGAAG
97
nd
3.51
nd
nd
|
|
8016-L3-1
TCAGCGCAACAAGCCCCGCAGTCACCCCTCT
98
−1.99
1.68
1.62
2.30
|
|
8075-L3-1
CCCAGCTACACCTCCACGCA
325
−1.64
1.92
1.68
1.83
|
|
8077-R3-1
CCATTCCCCACCCTCAGGTAGTAAAAATA
99
−1.69
1.48
2.13
2.56
|
|
8169-L3-1
AACAGAAATGATTATTTACCTCCCCACATG
100
−2.46
1.52
1.79
(nd) <5.79
|
|
8250-R3-1
CAGCCGCCTCTCCCTCAGCGTTAA
101
−1.41
1.55
1.60
1.84
|
|
8263-R3-1
GATTAAAAACAAGAATCTATCTTCCCCCAGT
102
nd
nd
5.24
nd
|
|
8281-L3-1
AGCCCCTCCCCAGCTGCAGCTGAGGGCTGG
103
−1.34
1.78
2.04
2.78
|
|
8336-R3-1
CTCAGTCCCCACACCCCCAGCCAGAGTC
326
−1.64
1.95
1.94
2.16
|
|
8394-L3-1
CCCCCGCCCTGCCCATCTCCGACT
105
−1.43
1.63
1.71
1.75
|
|
8433-L3-1
AAATGGCTCCTTTCCCCTTTCCCTCCACCG
106
−1.35
1.78
1.76
2.47
|
|
8434-R3-1
CCTGAGGCTCCACTCCTAGAAGAATTGC
327
−1.61
2.16
1.98
2.42
|
|
8552-R3-1
CTCCCAAGGGTCACCATAAAGAGGACACTATAAA
328
nd
3.14
nd
nd
|
|
8564-L3-1
CCCTTCACCCCAGTTGCCAAACA
107
nd
nd
5.92
nd
|
|
8587-R2-1
CTCGCCGGCTCCAAACTTTCCCCAACTCCAGG
329
−2.38
1.99
1.58
2.15
|
|
8685-L3-1
CTGCTCTTTGCCTCCTATAAGTGGAATGTCTCCC
330
−1.07
2.02
1.43
1.80
|
|
8719-L3-2
CTCACTTGCCTCCTGCAAAGCACCAGTAGCTGC
331
nd
3.12
nd
nd
|
|
8724-R3-1
GCCAAGCTTGGAACCTCTCCCTGCCAGCATCAC
109
nd
3.62
7.40
nd
|
|
8731-R3-1
TCATTCATGCCCCATCCTGCCAG
110
−1.66
1.77
1.84
2.45
|
|
8760-L3-1
CTGGAGCCCCGAGGCAAAACTCACCCCAGGCA
332
−1.85
1.57
2.29
2.59
|
|
8808-R3-1
CCAAAGACCCCTTTCTCCCAGCCTGTTTCTGCAA
111
−1.69
2.22
1.94
2.25
|
|
8898-R3-1
CGGACGCCCGCTCCCGCCA
112
−1.39
1.61
1.58
1.74
|
|
8898-L3-1
GAGTTGCCGGCGGCCGCCCCGGCCGACAGCGCC
333
−1.51
1.99
1.88
2.15
|
|
9053-L3-1
GGCCCTGGGAATCAGAGAGACAGTGCCCTTCC
334
−1.75
2.11
1.90
2.20
|
|
9053-R3-1
TTCTTGCCCTCCAATCCCCGGGCTCCACCAGCC
114
−1.57
1.95
1.65
2.13
|
|
9068-R2-1
CTGCCCTCCCTCTTGATCAAGACTGCTCTCCTAA
115
nd
nd
nd
71.77
|
|
9092-R3-2
TCCTAGAAGCCATCAGTATCCCACAGAGCCAG
335
−1.79
1.53
2.01
2.23
|
|
9217-L3-1
ACGATCCCCGCCGTGACTAAAGCCAACAGTGGA
117
−1.38
2.00
1.87
2.15
|
|
9245-R2-1
AACCTCTCATTAGCCAGCCACTCGCTCCCAAG
118
1.91
4.41
6.66
nd
|
|
9387-R2-2
TCCATCCTTGCCGTCGCCTTCATCTCAAAGCCATC
122
1.93
nd
nd
nd
|
|
9507-L3-2
GTCTCCCTCATCCATCATCC
124
−1.86
2.14
1.82
2.24
|
|
9557-R3-1
ACTGGCCCAGTCCATTCTGCACCTCTTGCCCTA
336
−1.26
1.52
1.53
2.58
|
|
9582-R3-2
TACAAATCCTCAGATGTTTCCACAAAGGCTCCCTT
337
−1.80
1.69
2.19
2.19
|
|
9688-L2-1
GCTAAATGGCCCCAGACTGTTCTGCTGCA
338
nd
3.61
6.62
nd
|
|
9694-R3-1
GCCATCTGCCACCGACACTCATACTCTGT
339
−1.27
1.56
1.76
2.24
|
|
9733-L3-1
AAGGCTGTCCCTCACCAGACTTCCCCACCCCT
129
−1.55
2.36
2.12
2.58
|
|
9747-L3-1
GCACACCGCCTCCGGCAAACTGC
340
−1.27
1.88
1.37
1.56
|
|
9772-L3-1
ATTCTACAGCATTTTTCCCATGACCTTTCCTGA
341
−2.02
2.12
1.72
2.14
|
|
9774-R2-2
CCGCCCCCTCACCGCCTCCTGCTCCCATCAGGC
130
−1.09
1.68
1.54
1.66
|
|
9798-R3-2
GTGCTTTCATTCCCCCAACAGAAGGGCATTA
342
−2.10
1.69
2.24
2.40
|
|
9812-L3-1
AAGCTCTATTTATCTGGGCTCCCCAGCTTGCT
343
−1.54
1.49
2.00
(nd) <4.17
|
|
9813-R3-2
GAAAGTAGAATTTGGCCCTCCAACTGTACAGGATGA
344
−1.08
1.68
1.65
1.87
|
|
9816-R2-1
CTGGCCCTTTAAGAGCCTCTCCGCGCGCTGCCG
131
−1.25
1.26
1.67
1.80
|
|
9987-R2-2
CAGGCTTCACCCCTCAGCCCACTTTGTTAAC
345
−1.73
2.09
1.92
2.17
|
|
10010-R2-1
CTCGCCGGCTCCAAACTTTCCCCAACTCCAGG
346
−1.90
2.06
1.75
2.07
|
|
10030-R3-1
AACTCAGCTGCCTTCCGCC
134
−1.41
1.98
1.48
1.79
|
|
10093-R2-2
ACCAGCCAGACCCCCTGTAGGTCTAACCCAAGGT
347
−2.07
2.17
1.72
2.24
|
|
10120-R3-1
TTCCCCTTGTTAAAATTACAGCTGCACCA
348
−1.97
1.92
1.73
1.98
|
|
10133-R3-1
CTCCTCCCATTTCCTAATTTGATTTCAC
349
−1.45
1.90
1.88
2.28
|
|
10138-L2-1
AGCCTGCTCCGCTCTCCCCTCCCACCAGAAAAAGT
135
1.10
1.72
1.74
1.93
|
|
10154-R1-1
GATCTGTGCCCTTTGCCCTT
350
3.51
7.66
5.06
(nd) <8.10
|
|
10198-R3-1
AATTCTCTTTACCTGGCACCTTTAGGGCAAAGCA
351
1.64
3.88
7.36
8.75
|
|
10231-L3-1
GTGCAGCAGCCCGCGCCAGCCTCCGCAGCCGCC
139
−1.49
1.78
1.67
1.98
|
|
10231-R3-1
TGAACTTTAGCTGGGCCGCCGCCTGTCAGC
140
−2.21
−1.70
−1.39
(nd) <8.10
|
|
10242-R3-1
GGAAGAAGCCCTTCCGCTTCCACCCCGAACAC
141
−1.11
1.49
1.33
1.40
|
|
10260-L3-1
AGGGCCCCCACCCGATGTCTCCCAC
352
−1.85
2.24
1.79
2.27
|
|
10333-L3-1
TGTGCCCTGCCCACCCCCTCCCCTGCCCCG
142
−1.21
1.48
1.74
1.85
|
|
10335-L3-1
CACTCCCCTCCTTTTTAATTAGAAAGCACTAAGA
143
−1.31
1.94
1.97
2.22
|
|
10342-L2-1
CCACTTTCCTGGCGACCCTCCGTGCGTGGG
353
−1.41
1.54
1.44
1.68
|
|
10342-R2-2
CCCGCCGCCGGAGCATCTCGAAGTTAATTAAA
144
−2.74
−2.11
−1.51
(nd) <13.60
|
|
10346-R3-2
AGCCTGTCTGTGCCCTCTGCAGCAGCTCACC
354
2.40
4.47
4.41
nd
|
|
10366-R3-2
AAACACCACCCACGCTCTTGCTACAAGACCCACAT
145
−1.64
1.88
1.91
2.29
|
|
10539-R3-1
TATTTGAGAAAATTTACTATCCCCCAGCCT
355
−1.64
1.82
1.96
2.08
|
|
10543-R3-1
GCCTTCACCCTTCCCATCC
356
−1.44
1.70
1.76
2.27
|
|
10553-R1-1
GCTGGCTCCATGCTCCAGTGGG
357
−2.27
2.01
1.64
2.01
|
|
10562-L1-2
GGGTCCTGACTCCCACAGCCTGTCATATCAAGCGC
358
2.42
6.15
8.86
8.95
|
|
10594-L3-1
ATTGTTACCCACACCAACACCCACTCAACAG
359
−1.91
1.96
1.74
2.18
|
|
10639-R2-1
AGACCGGACTCGCCTCTTCCAACTCGAGTTCA
360
1.44
nd
6.00
nd
|
|
let-7a
AACTATACAACCTACTACCTCA
166
−1.87
−1.06
1.39
−1.34
|
|
let-7b
AACCACACAACCTACTACCTCA
167
−1.85
−1.12
1.72
−1.38
|
|
let-7c
AACCATACAACCTACTACCTCA
168
−2.23
−1.18
1.47
−1.30
|
|
let-7d
AACTATGCAACCTACTACCTCT
169
−2.07
−1.13
1.38
−1.40
|
|
let-7e
AACTATACAACCTCCTACCTCA
170
−2.12
−1.05
1.46
−1.10
|
|
let-7f
AACTATACAATCTACTACCTCA
171
−1.94
1.00
1.29
−1.33
|
|
let-7g
AACTGTACAAACTACTACCTCA
172
2.40
1.81
1.31
1.75
|
|
let-7i
AACAGCACAAACTACTACCTCA
173
3.29
1.99
1.31
2.02
|
|
miR-100
CACAAGTTCGGATCTACGGGTT
174
−3.44
1.01
1.30
(nd) <7.51
|
|
miR-103
TCATAGCCCTGTACAATGCTGCT
361
3.15
4.00
3.73
nd
|
|
miR-106a
CTACCTGCACTGTAAGCACTTTT
362
−1.18
1.46
−1.32
(nd) <8.74
|
|
miR-106b
ATCTGCACTGTCAGCACTTTA
363
3.49
7.29
4.80
nd
|
|
miR-107
TGATAGCCCTGTACAATGCTGCT
364
3.09
4.03
3.57
nd
|
|
miR-125a-5p
AGGGACTCTGGGAAATTGGACACT
365
nd
4.38
4.89
nd
|
|
miR-125b
TCACAAGTTAGGGTCTCAGGGA
179
nd
9.62
7.23
nd
|
|
miR-130a
ATGCCCTTTTAACATTGCACTG
366
2.00
4.87
5.06
nd
|
|
miR-130b
ATGCCCTTTCATCATTGCACTG
367
1.85
4.20
4.06
nd
|
|
miR-134
CCCCTCTGGTCAACCAGTCACA
368
−1.92
1.87
1.64
1.92
|
|
miR-138
CGGCCTGATTCACAACACCAGCT
369
1.56
nd
nd
nd
|
|
miR-155
ACCCCTATCACGATTAGCATTAA
187
nd
nd
3.73
nd
|
|
miR-15a
CACAAACCATTATGTGCTGCTA
370
nd
nd
5.75
nd
|
|
miR-15b
TGTAAACCATGATGTGCTGCTA
371
nd
nd
6.48
nd
|
|
miR-16
CGCCAATATTTACGTGCTGCTA
188
−1.03
2.33
3.10
(nd) <5.85
|
|
miR-17
CAAAGTGCTTACAGTGCAGGTAG
372
−1.18
1.52
−1.35
(nd) <8.91
|
|
miR-181a
ACTCACCGACAGCGTTGAATGTT
373
−1.45
(nd) <3.46
−1.05
(nd) <3.46
|
|
miR-181b
ACCCACCGACAGCAATGAATGTT
374
2.17
nd
nd
nd
|
|
miR-191
CAGCTGCTTTTGGGATTCCGTTG
375
1.89
6.53
3.50
nd
|
|
miR-195
GCCAATATTTCTGTGCTGCTA
376
nd
4.38
5.32
nd
|
|
miR-196b
CCCAACAACAGGAAACTACCTA
377
1.49
nd
nd
nd
|
|
miR-198
GAACCTATCTCCCCTCTGGACC
190
nd
5.34
7.25
nd
|
|
miR-19a
TCAGTTTTGCATAGATTTGCACA
378
−1.38
1.29
−1.40
(nd) <7.33
|
|
miR-19b
TCAGTTTTGCATGGATTTGCACA
192
−1.42
1.30
−1.56
(nd) <10.00
|
|
miR-200b
TCATCATTACCAGGCAGTATTA
193
(nd) <8.612
(nd) <8.61
(nd) <8.61
(nd) <8.61
|
|
miR-200c
TCCATCATTACCCGGCAGTATTA
194
(nd) <18.47
(nd) <18.47
(nd) <18.47
(nd) <18.47
|
|
miR-205
CAGACTCCGGTGGAATGAAGGA
195
(nd) <28.34
(nd) <28.34
(nd) <28.34
(nd) <28.34
|
|
miR-20a
CTACCTGCACTATAAGCACTTTA
379
−1.33
1.22
−1.87
(nd) <8.17
|
|
miR-20b
CTACCTGCACTATGAGCACTTTG
380
−1.53
1.33
−1.76
(nd) <6.30
|
|
miR-21
TCAACATCAGTCTGATAAGCTA
196
−7.45
1.45
1.38
1.98
|
|
miR-22
ACAGTTCTTCAACTGGCAGCTT
381
−1.31
−1.07
1.33
−1.71
|
|
miR-221
GAAACCCAGCAGACAATGTAGCT
382
−4.50
−1.92
−1.27
−2.19
|
|
miR-222
ACCCAGTAGCCAGATGTAGCT
383
−3.60
−2.07
−1.17
(nd) <11.32
|
|
miR-23a
GGAAATCCCTGGCAATGTGAT
197
−2.44
−1.24
1.05
(nd) <14.57
|
|
miR-23b
GGTAATCCCTGGCAATGTGAT
199
−2.14
−1.20
1.22
−1.04
|
|
miR-24
CTGTTCCTGCTGAACTGAGCCA
200
−2.89
1.30
1.02
1.18
|
|
miR-25
TCAGACCGAGACAAGTGCAATG
384
3.98
8.33
5.07
nd
|
|
miR-26a
AGCCTATCCTGGATTACTTGAA
202
−3.08
1.23
1.24
(nd) <7.67
|
|
miR-26b
ACCTATCCTGAATTACTTGAA
203
nd
3.58
nd
nd
|
|
miR-27a
GCGGAACTTAGCCACTGTGAA
204
−2.28
−1.28
−1.04
1.02
|
|
miR-27b
GCAGAACTTAGCCACTGTGAA
205
−1.92
1.27
1.14
1.38
|
|
miR-29a
TAACCGATTTCAGATGGTGCTA
207
−1.77
1.26
−1.01
−1.07
|
|
miR-29b
AACACTGATTTCAAATGGTGCTA
208
1.16
1.16
−1.30
(nd) <5.77
|
|
miR-29c
GAACACCAGGAGAAATCGGTCA
385
−1.29
1.29
−1.29
(nd) <7.48
|
|
miR-30a
ACATTTGTAGGAGCTGACCTTC
386
−1.62
3.78
2.06
(nd) <4.49
|
|
miR-30d
CTTCCAGTCGGGGATGTTTACA
216
2.12
16.27
7.18
nd
|
|
miR-31
AGCTATGCCAGCATCTTGCCT
387
−10.63
−2.12
−2.25
−1.74
|
|
miR-320a
TTTTCGACCCAACTCTCCCGCT
388
−1.22
−1.05
1.49
1.15
|
|
miR-335
ACATTTTTCGTTATTGCTCTTGA
389
nd
nd
3.55
nd
|
|
miR-342-3p
AGAGTGTGTCTTTAGCGTGGGCA
390
−3.37
1.81
1.25
1.76
|
|
miR-370
ACCAGGTTCCACCCCAGCAGGC
391
2.02
5.04
8.94
nd
|
|
miR-424
TTCAAAACATGAATTGCTGCTG
222
nd
nd
5.25
nd
|
|
miR-452
TCAGTTTCCTCTGCAAACAGTT
392
nd
nd
4.54
nd
|
|
miR-494
GAGGTTTCCCGTGTATGTTTCA
393
1.30
2.20
1.01
1.55
|
|
miR-513a-5p
AAGTGTCCCTCCACAGTA
394
3.47
5.11
7.21
nd
|
|
miR-614
CCACCTGGCAAGAACAGGCGTTC
236
−1.85
1.83
1.69
1.99
|
|
miR-638
AGGCCGCCACCCGCCCGCGATCCCT
239
−1.95
−1.02
1.09
−1.05
|
|
miR-658
ACCAACGGACCTACTTCCCTCCGCC
240
−1.35
1.50
1.30
1.60
|
|
miR-663
GCGGTCCCGCGGCGCCCCGCCT
241
−1.86
1.08
1.37
(nd) <6.22
|
|
miR-671-5p
TCCTTCGGGACCTCCCCGACCTC
242
1.85
nd
nd
nd
|
|
miR-7
ACAACAAAATCACTAGTCTTCCA
395
3.27
nd
nd
nd
|
|
miR-765
CATCACCTTCCTTCTCCTCCA
246
nd
4.51
nd
nd
|
|
miR-92-a
ATAACGTGAACAGGGCCGGACA
396
4.00
6.61
3.83
nd
|
|
miR-93
CTACCTGCACGAACAGCACTTTG
251
−1.07
1.75
−1.04
(nd) <5.78
|
|
miR-98
AACAATACAACTTACTACCTCA
252
−1.90
−1.05
1.43
(nd) <5.20
|
|
miR-99a
CACAAGATCGGATCTACGGGTT
397
−2.49
1.13
1.31
(nd) <5.34
|
|
miR-99b
CGCAAGGTCGGTTCTACGGGTG
253
2.05
4.50
3.79
nd
|
|
TABLE 3
|
|
Pre-target RNA
pre-micro
|
Candidate
chrom. Location
Pre-microRNA sequences
RNA SEQ ID NO:
|
|
266-R4-1
12q14.3
GTTGCTATTTCCCTCAGTTGAGGGCGAAGTTAGCAAATCCGTAGCTGCAAGTCTCAACTTGGGGGAGGGGGCGAC
398
|
|
673-L4-1
01p36.21
GTGAGGAGCAGGTTAGCTGGGTGAAAAGTTCACAGTGAGGGGAGCTGTCTGTTCCCTCGCTTAATTTATCCACTATTTGGCTAACCTTGCTC
399
|
TGAAC
|
|
836-R4-1
03q26.2
AAATAAGCCATTCCAAACCATTCTCTGATTTGCTGTGAGTGGCAGAATCATTCACCGTGGTGAATCATAGCAGGGAGAACCATTTGGAATGAT
400
|
TATTT
|
|
3249-L4-1
01q22
GGCGGCGGCGGCGGCGGCTCCGGGGATGGCGGCGGCTCCGCTGCTGCTGCTGCTGCTGCTCGTGCCCGTGCCGCTGCTGCC
401
|
GCTGCT
|
|
3371-L4-1
18q21.33
CTCAAGTGTGGGGAGTCATGGGGTGTGGAGGGGAGGAAAGGAAAGGTATTTTGTTTCTTTGTCTATACATTTCCTAGATTTCTATGCAGTT
402
|
GGG
|
|
3717-L2-1
01q22
TGTGAGTGGGTTTGGGGTGAGGCTATGGGGAGGGCGGGGTGCCGCCTTGCCCAGCCCCTGAGGGCCCCAGCCCAGTACA
403
|
|
3799-R3-1
11q13.1
GAATTTGCCCTACGGTGTGACCCCAGCCTCTCCCTCTGGCCACAGCCAGGGCCGGCGGGGGGCCTCTGGGAGCATCTTCAGCA
404
|
AGTTC
|
|
3872-L1-1
16p13.2
GTGCATAAGGGAAGAAGACAAGAAAATGATATTGTCGTTTAATAGTTCACTTTAGATCTTCATCTCTTATCAC
405
|
|
3875-R3-1
05p15.1
GGCTCGGTTTCAAATCTCTCCTAATCCACTAATGAACCTTTATTAAAGTGGGAGAGAGAGGTTGAATCAGTC
406
|
|
3897-R3-1
09p11.2
CGGAGCCGCCCGCGCCAGCCTCTCCATCTCGCAAGTTTTAATTAACGCTGAGGGGGAGGCGGCTGACGGGCGGGTCGG
407
|
|
3923-R3-1
19p12
GGCTCTGCACCAGGCGTTTCTTCTTGTGTTTCCTCTTCTCTTCTGGAGAGGGATGAAGGAGATCCTTTGTGAGAGGC
408
|
|
3953-R3-2
09q33.3
GCTCCTGCTCCGCCGCGGGAGCTGCTCCGGCGGCCGCAGGGCTCGCTCGGGAAGCTGAGGCGGCGGAGGCTGGAGT
409
|
|
3995-L2-2
07p21.1
TGGCCTGACGTGAGGAGGAGGGACTTTTCGAAGTTTTATAGGAAAGTTTCCGCTTTCCAGTCCCCCTCCCCCGTCCCA
410
|
|
4026-R3-1
10q24.32
GGCTCTGGGAAAGCCTTCCTTTCCCGGCTGGCCTGGCATTCAAAGCCAGACAAAGGGGGGCTTTCTCTCTCGCC
411
|
|
4037-R3-2
03q13.31
GCCCATTTCCCTAATGGCAGCCGATTGCCATTTGCTATTCAAATCAGACTAGATAAATTACAGTACATGCCAGGGAACAGGC
412
|
|
4143-R3-1
22q12.3
TCAGCGTCAGGAACTTCATCCTGGCAGCCGACCTCATGAAGAGCATCTGGCTGCTGTTACCAGGAGGAGAGCAAGACGCTGA
413
|
|
4203-R3-2
11q23.3
AGCAATTCCAACTGCCCCATTTATATTCCTAAGTAGAGGACTTGTTAATATGGAGCCTGCCTCTGGGGAAGTGGGAATGTGCT
414
|
|
4205-R3-2
15q26.2
GTCATAGATGGCCTCATTGTCTACCATGAAGCACAATCAGAGTGCTCTAGGGTGGTGTGAGTGGTGAGGATGAAGTTGTAGGGC
415
|
4205-R3-1
|
|
4303-R1-1
22q11.21
GGCTGGCCAGGCTCCGCCCCCGGCCCTCCCTGCGCCCGGCCGGTGCGCAGGGAGGTCGGAGGAGCGGGCACTGCCCACCC
416
|
|
4315-R3-2
01q22
GCTCCCCGGCTCCCTCACTGCGGCAGCCGCGGCCCCATAAATCGTGAGAGCGACGTGCTCCGGAGCCGAGAATGGAGAGGGC
417
|
CGGGGAGC
|
|
4361-R3-1
Xp11.22
TGCTGGAGGTAAGGGTTTTCTGAAGCCTGGTGCCATGGCCACATGTGCACATGAGGGAGGGAGACGCTGAGGCTAGCA
418
|
|
4440-L3-2
07q11.22
GTGATGTGATTTCTGCCCAGTGCTCTGAATGTCAAACTGAAGAAATTCAGTGAAATGCGGGTAAACGGCGGGAGTAACTATGAC
419
|
4440-L3-1
|
4440-R3-2
|
4440-R3-1
|
|
4448-R3-1
01p36.32
TTTCCTCTCTCCTTTCTCCTCAAGCTGATTAGCGGGTCGGGCAATGGCGTGAGGAGATGCTGGGGGTAGGAAA
420
|
|
4479-R3-1
01p32
CCCAAGCTCCTTCCTGGAGGACTTAACACTGTGTTGAGCAGTTGTTTTGAATTTCCGGGCAGGGGGCTGCAAAAGGG
421
|
|
4593-R3-1
15q23
CAATCAATTAGCACATGAGTAATACCAAGCCCATTAGGACAAACTGATGCCGGGGGAGTTATGTCATCTGCTATAGAAATGATTG
422
|
|
4666-R4-1
01q22
GCCGGCTCCAACCCAGAGGCCCGGAATAGGCGCGGAGTTATAAATAGTGCCACCCGCAGGTGTTGGGGGGAGTCGGC
423
|
|
4790-L4-1
02q14.1
CCCAGAATTCTAGTAATGAGGGAGACAGGTTATGCCAAGCCTGCTTCTCCCAGGATGCACTGGGAGCCTGGG
424
|
|
4829-R2-1
01q21.3
GGTGTGTCTGCCTCTCTTTCTGCCCCCCTATACCCCTTGACCCCAGGGGGAAGGCACTCGGGCAGCACAAAGGGAGCAGATGCCC
425
|
|
4855-R3-1
12q13.2
GGGTCCGGGTCTCTACCGCGCCCTCATGCAGGAGGCCCTTGGAGCAGGAGGGGGAAGCGGGAGACCCGGCAGCCC
426
|
|
4875-R2-2
03p22.1
TGTGAAGCCACAGGAAGGGGCTCTGTGACATCACAGGTAGGGGCAGTGTGAAGTCACAGGAAGGGGCTGTGGGAAGTCACA
427
|
|
4988-R4-1
14q24.3
CTTTTTCTCTCTGCTGGGAAACCTTGCTTGACTTCATGTCCAGTGTTTGGTATCCAAAGACGGGGAGGAGGAG
428
|
|
5006-L3-1
07q32.1
GGAGCCAGCAGAGGGAGCTGTCGTCCCAGAACTTTCTTAGAGCTGCTAAGAAATTCTGATTTTGAAAAAGATCTTCCTAGGCTCC
429
|
|
5080-R3-1
11q23.3
GGCGTTTCTTCTTGTGTTTCCTCTTCTCCTTTTCTGGAGAGGGATGAAGGAGACCCTTTGCAAGAGGCATGTT
430
|
|
5192-L3-2
05q34
GTCTTTGCTGATATAGAGGAAGGAAGGGGAAAAATGAGCGCATTAGTTCTCTTTTATTAAAAGAGTTATTTCAGCATGAC
431
|
5192-L3-1
|
|
5342-L3-1
08p21.2
TGGAAGGAGAGCAGCGGCATTTGGTTTGGTGGTGGGCAGATTTTCTTTTACGACTGCTAAATGCCTGCCTTTCTCCCCA
432
|
|
5521-L2-1
05q31.3
AGAGGGTGTGCTCTGGGGAGGGCCCACCCAAGACAGACCTCATGGCCTTCAGTCCCAGCCTTCCTCAGGGTCCATCCTCT
433
|
|
5554-R2-1
01p34.3
CCCCACCAACCACCAGTGCTCAGGACTTCTGCAAATCCCATTCGGATCTGGGAGCAGCTGATGAGGGGGTGGGG
434
|
|
5638-R2-1
06q23.2
GGCTTTGCCCTTTTCGGTGACACAGGCTGTTGCTATTCCAAGCAGCCTATCACAGGCAGGGGGAGGGCC
435
|
|
5640-L3-1
01p34.1
TCTCGAGAGGGGCAGGCACGGTGTTCCATGGCAAGACGGCGGTTGATGTATAGGCGTGGCATGAAGCTGGGCTTGCTGCTCTCAGA
436
|
|
5726-L3-1
03p14.3
CAAGGGCACAGTGAGAAGATATTTTATTACCCGTGTATTTATTTATGGGTTTTGGGGGTTTTAAAACTGGCAATTAAAACCTTG
437
|
|
5782-L3-1
05q35.1
GGGGGAAGGGGCTGGAATCATCGTGGGTTGGAACAGTTAAAGGAACCTCTGTTCAGCCCCAGCCCCAAGGCTCCC
438
|
|
5795-R1-1
10q26.3
CTCTCTACCACCAAAATAAATTCAATTACTAACTTTGAGTAATTGCGGGTAATTTATTTCTTGGAGGGCAGAGAG
439
|
|
5836-R3-2
11q23.3
GCCATGGGCCTCCATAGTTTCCTGTAGCCCCCTTGGTTCCCAAGAATAGTTTTGGAATGGGGCGTGCTGTGATAATGGGGGTTAATGGT
440
|
|
5854-R3-1
11p14.1
GCCCTCCCTCCCACCGCACTTACACCTGAACTTGTCTCCAGCACTGCGGACACCCGGGTGACACATTCTTTCGGAGAGGGAGGGC
441
|
|
5971-R3-1
01q24.1
TGCCATCTGCTCTGAAGCCTCCCAAGCTGGGCCTCCCCTCCCACTTCTGGAGCCCAGGAACAGATGTGGGAGGCTGAGCAGGCA
442
|
|
6008-R1-1
04p15
CGACTTTATCACCCATCGGTTATCTGTGTCGCCTGAAGGAACTCCGGGTAAGGTACAGGAAAAAGGTGGGGGTATTGTTG
443
|
|
6016-R2-1
01q23.3
TTTCTGTATATGTTTCTGGAGTCCTGAGCCTGAGCTAAACAAAAGCAGGAGGCTGACGGGGCTGCTGGAGTTTGCAGAGA
444
|
|
6037-R3-2
16q22.1
GCAGGATCCCTCTTTTCATCTGAAAATTACCACTAATTTGCAATTAGTTGGAGGAAAATTGGAGATGGAGGAAAGGGAATTGC
445
|
|
6096-R3-1
03q29
GCCATTTGGTACCTGATGTGATCGGGCTTTTTCCTGTCGTGTGAAAAAACGGGGCAGGATTAAAACATAAGGGAAAGGTGGT
446
|
|
6183-R3-1
12q21.33
GATTCATCTATTCTTTTTCTCCTTCTTCAAAGATAACTCTGTAAGCACTTAAGGAGGGGAAAGTCATTAAGAAAAGTGGAATC
447
|
|
6192-L3-1
11q25
GTGCTGGGTGGGTGGTTTTTTATCTTCACGGATTTATGGAGTCCTTAAAACATCTGTTCCGTTCTGATTCCCCCGCTCAGTAC
448
|
|
6233-L3-1
06q16.1
GGAAATGGGAGAAGGATAAAGTGGAAATCTAATTTTGAGAAATAAGGATTAAAGGTTCCATTATTCATGCTGTTTTC
449
|
|
6235-R3-1
15q26.2
TCTGTTTTTATCAGTTTAATATATGATACATCTTCTATCCAAGGACAATATATTAAATGGATTTTTGGAGCAGA
450
|
|
6287-L3-2
01p34.1
AGCAGCCAGGTGAGCCCCGAAAGGTGGGGCGGGGCAGGGGCGCTCCCAGCCCCACCCCGGGATCTGGTGACGCT
451
|
|
6409-L3-1
11q13.1
GTTCCAGAAGGCGGCGCGTGCGGTTGGGAACGCGGAGCGGACGGATTCGATTCAACGGGGTTCCGGACCGCGCTGCGCTATGGAGC
452
|
|
6434-R3-1
15q25.2
GTGGGCTGCATGTTCCCGCATTGCTGGTGAGGGTGCACGATCTGGCACTGCAGCTGGCTGGTGGGAGGGCTGCATCCTAC
453
|
|
6484-R3-2
12q21.32
ACTGCTTAGCACTCCTCCACTTGCGAATGCACTTAAGACAGTAGGTGTGGTTGCAGTTGGAGAGGATCCCGAAGCGGT
454
|
|
6490-R4-1
01q22
TCCTTCCCCCTTCGTGGCTTGCGGTCTCTCTTCCCCGCCTCGGCCCCCAGGAAGTGTGAGTGCTGGGGGTGGTGAGGTTAGGA
455
|
GGGGGAAGCGTCATATGGGGGATGGGG
|
|
6496-R3-1
05q31.1
CTCCCTCAGGCCCCGCCTGCACCTTTCCCAGCCCCCAGGACTCTAGGGGAAGTGGTGGGTGGGGGAGGGGG
456
|
|
6584-L1-1
12q24.23
GCTTGGTGAGAGGAGGAGGAGGCAGGGCCGACCGCCACCCGCCTGTCTGCCATCTGGTCCCCTTCCCCTCCCTCCTCTCATTGC
457
|
|
6602-R3-2
03p13
CAGAGTCTAAATGGAAGAGTCCTCCGTATTTACCCAGCTCATCTCCTGTGTAATGGATTTGGAGGAGAGATTTCCACTGGGGCTC
458
|
TG
|
|
6642-R3-1
14q11.2
ACACTCTCCTCTTGTCTCCTTGTAATCAATTCATTGTCATCAGAAATGTGTGACACCTCGAGGGGAGGGGAGGACGTGT
459
|
|
6681-R2-1
11q12.2
TGTGCTCTCATTGTTATTCCAAAAGTCTCTGTCTAGATCACTGGAGGGGCAGAGAGAGAGGGGAGAAAACAGGGAGATACA
460
|
|
6683-R3-1
12q23.2
GTTCTAGTTCCAGGATGCTGATACTTTAAGCCCGAGGCTCTAACTTGAGCAGGAAGAGTTTATTTTGGGATGAAGAAT
461
|
|
6752-R1-1
Xq13.1
CCCTCCCAGTTCCCATAGCAACTGGGCTGTAGCAGCCAGAACTTGATTGAGCCCAGCAGTGGCCCGACTGAGGTGGGGAAAGG
462
|
AGGG
|
|
6795-R4-1
06p12.2
GGGCCAGCGAGGAGGCACTTGCCGAAACCACACACTTCCTTACATTCCATAGCAAAGTAATCCATATGGGGATATAAAGAAGCAT
463
|
GTGGCCTCGGGAAGCAGTGTC
|
|
6803-R3-1
22q12.3
GCCACCTTTCATGGTGAGGATGCCTGCCACCTTCAGGATCACATCTTTGGGTGAGGTCCAACCAGAGAGGGAGC
464
|
|
6839-L3-1
03p21.31
AGGGGTGGGGGTGGCAGGGCCCAGCGGGCTGGCAGGCAAACCCTGGTTTTGGCCCAGGGACCTATAATCAGCTCCTGCCCCT
465
|
|
6880-L3-2
01q42.13
GGCTTGCAGAATGTGGATGTCTTCGCGGGGGAGGTGGCCACGTTCTCCTGTGAGGTGTCTCACGCGGGTGGGCC
466
|
|
6906-L3-1
06p21.1
CCAGGAGAGCTGGCTGGTTGGGGAGAAGACACTAACCCTGTGAGTCTGACCTCAGCCAGCTAACCTGCCCTGG
467
|
|
6930-R3-1
09p21
TGTCATTTGTCCATTTTCTCTTCTGACCCAGTGGTATTCTGCAAGATCAGAGGGGAGAGAAGGATTAATGTCA
468
|
|
6984-R4-1
01q22
CCCCACTCCCTTGCAGGCTGCAGGCACTAGGGCTCTCAGGAATTGCAGGGACTTTGGTGCCCAAGCAAATGCTTGGGCAGGGGG
469
|
|
7026-L3-2
15q15.3
TCGTTCCCGGATCTGGTGGGTGAGGTTTTCGATCAGGGCAAATACCTGATCACAGACCTTCACAGGATTCTGGATGA
470
|
|
7061-R3-1
01p13
TCATGGCAGCGACCCACCTCCAGTCCCCTGGACAATCGGGTACAAGAGACTTAAGGTTGGGCATGGGAAGGGTGGGGTTTCCAT
471
|
GA
|
|
7066-R4-1
15q23
CAAGGTCTTTGGTCTTGGAGGAAGGTGTGCTACTGGAAGAGGCCACCGAGGCAGGGCTGGTGGGGGCATCTTTTTTCAGGCTAC
472
|
GGGCCTTG
|
|
7126-L3-1
05q31.1
CAGGGGCGCGGGCCGGAGAGCGGGTGTGCAAAGTGGGCGCAGGGCCCTGGGGCCGCGCCCCTTGCTCTGCCGGCTCGACTC
473
|
TTG
|
|
7182-L4-1
12q13.3
GGGGGCAGGGGAAGGTGACGGAAACGGCTAGTTACCCAGAATTCTCTGGGGGAACCAGAAAAATCGGTTATCTAGAATTCTCCC
474
|
|
7192-R4-1
09q33.1
TGTAGCAAATCCCATCCATCTGTTTGGCTGCTCTTGCCTCAGTGACAGTGCCAAGAGCCCAGGCAGACTTAGAGGGGGAAGTGC
475
|
TTTGCA
|
|
7292-L3-2
01p34.1
GCAATTAGAATGCAGGGAGGTTCAGAAGCTATTTAACTGGGTGACCCCTGAGGTCGCTGCATCTGACTCCCATCCCTGGATAAAT
476
|
ATTGT
|
|
7352-R3-2
01q25.2
GCCTCTGTGCGCATGGATATAATCAGCTTTGATAGGCAGAGGCTGAGGCTGTTTTTCCAATTAGAGCTGTTAGAGGATTCTGGCA
477
|
GGGGC
|
|
7356-L2-1
08q24.3
GGGGGCGAGGCTATGTCGCGGTGGCAGCCCGGATGGGCCGGCAGGGCCGGGAGTAACGGGACGTCGCCGCGGAGCTTCTTC
478
|
7356-R2-1
CCCC
|
|
7367-L1-1
06p21.33
CGGTCCCCAGAGGGGGCAGCTCTAACCCTAAACAAGTGCTCAACCCTTGAATGGGCCTGGATGGCTCCCCTGGGGACTG
479
|
|
7384-R3-1
12q12
GGCATTTCTTCTTGTGTTTCCTCTTCTCCTCTTCTGGGGAGGGATGAAGGAGATCCTTTGCGAGAGGCATGTT
480
|
|
7411-R3-2
18q22.3
GAGTGTGAACTGGCTCCAGCTGTGACAATAAAACAGCAGGTGGCTGCTGTCATTAGGGGTGGCAGATGAGGCAGGGGACTAACA
481
|
TTC
|
|
7421-R2-1
12p13.31
TGAAGAATTTCTTCTGGATGACTGACCAAGAGGCTATTCAAGATCTCTGGCAGTGGAGGAAGTCTCTTTA
482
|
|
7426-L3-1
02q22.3
AAATCAAGCACAGCAGGAGGTGTTCGTCTCCCAGGTAATGGGTAAATGATGAGCAGATGAGCCATCCTTCTATTGATTT
483
|
|
7569-L3-1
11q23.3
GGCCTGTCTTGGGGGTAGCTTTGTGGCCTGAAAACAAATCATCCTTCACAGCTTGCTCCCAAGTCCAATAAGCC
484
|
|
7571-L1-1
02p21
CTTAGGGGTGGGGGAGCCCTGTTAGCCCTGTAAATAAAGTTTAACGAGGTGAACAATGGCTGGCTCTGTCCCTGAG
485
|
|
7572-R2-1
11q12.1
ATCACCTTTCCCCCTCCCATGTGCTTTCCTTCATTTGAGATCTTTTGACCTTTGGCTTTATTTGGGAGGGGGAAGGGTGAT
486
|
|
7578-L3-1
02q12.1
GAGGGGCTGTAGCTCAGGGTGTGCACTGCGAGGCTGGACCTGTTGAGTCTGCAGTGGACATCCATTTAGCTTCAGGTTGTC
487
|
|
7660-L2-1
19q13.32
GAGCTTTATCGCTCGGGCCAGGCGGAGGCCGGGCGGCCCCGTGGCTTCCGGAGGCGCCCGGGCGGGATGAGCTC
488
|
|
7702-L2-1
10q21.3
GGGGCGGGGAGGAATTCCGGTTCTCTGGGACTTTCCAAAAAAGGCGAAGATCCGGTGCCGGCGGCTCCGCCTCCCTAGCCCT
489
|
|
7726-R3-2
12p13.32
CATTTCACATCCATGAAGTAGGAATTGGGGCTCTGCACCAGGCGTTTCTTCTTGTGTTTCCTCTTCTCCTCTTCTGGAGAGGGATG
490
|
|
7764-R3-2
05q11.2
TGCTATCTCGCCTCACACATCAACACACGTGCCAGACAGATTCTGACTGCAAAGTCTGTTATTGGTGATGAGAGAGGCAGAGAGG
491
|
GCA
|
|
8004-R3-2
Xq28
GGGGCTGCCATCCTGCTGTCCGTCATCTGTGTGGTGCTGGTCACGGCCTTCAATGACTGGAGCAAGGAGAAGCAGTTCC
492
|
|
8016-L3-1
12q21.1
AGAGGGGTGACTGCGGGGCTTGTTGCGCTGAAGATTTACAATGTACTTCTTGCAGGCGGCTCAGCAACCCCCTCT
493
|
|
8077-R3-1
Xq22.3
CCAATTCTCACTTAGGTGTTAGGGATTTAATGATACTCCTCTGAAGAGTATTTTTACTACCTGAGGGTGGGGAATGG
494
|
|
8169-L3-1
06q16.1
CATGTGGGGAGGTAAATAATCATTTCTGTTATGTCAGTGGAAAATTTTCTGGAGATCATAAAGAAATCAGTTTACCCTGAAGCATG
495
|
|
8250-R3-1
09p11.2
CGGAGCCGCCCGCGCCAGCCTCTCCATCTCGCAAGTTTTAATTAACGCTGAGGGAGAGGCGGCTGACGGGCGGGTCGG
496
|
|
8263-R3-1
Xq25.1
ACAGACATCCAGTCTAATTACAGGTGTCTTTTTAACCAGTGAGAGGAAACTGGGGGAAGATAGATTCTTGTTTTTAATCTGCTATCT
497
|
GT
|
|
8281-L3-1
11q13.4
CCAGCCCTCAGCTGCAGCTGGGGAGGGGCTGAAGGGTAGGGAGCCCTATCCCACCTGCATCAGAGGCCTGG
498
|
|
8316-R3-1
14q24.3
GTCAGGCTGCTGTATTCTCTTACACAGATGCCAGTAAGAACAAAGGCATCACGTGGGGAGAGGATACCCTGAT
499
|
|
8394-L3-1
07p13
GGGGCCAGGGATAGTCGGAGATGGGCAGGGCGGGGGCCCCACTGGCGAGGGGCCCTCGGCTTCTGGGGTCCCTGAGCCCC
500
|
|
8433-L3-1
17q25.3
CGGTGGAGGGAAAGGGGAAAGGAGCCATTTTCTGCTGCACATCAGTCAGTGCCTGCGCCCTCCCTCCCTCCGCCG
501
|
|
8564-L3-1
05q13.2
AGGGGGTGGGAGGTCTGTTTGGCAACTGGGGTGAAGGGATTGCCCTTCCCCTGCTGGGATTCCCCCAGCCCCT
502
|
|
10010-R2-2
17q23.3
CCGGGCGCCCCCGAGAGCCGGCCCTCCCTTCCTCCGTGACAGGTGGGCCTGGAGTTGGGGAAAGTTTGGAGCCGGCGAGGGG
503
|
8587-R2-2
CGCCGGG
|
8587-R2-1
|
|
8724-R3-1
15q23
GGCCCAGAAGATGAAAAGCTGAAGTCCTTTCCCTTCCAGCTGAAGCCAGGTGTGATGCTGGCAGGGAGAGGTTCCAAGCTTGGCC
504
|
|
8731-R3-1
Xq13.1
GTCAAAACTGGTTTTCCCTGCCCTAACCCAGGCGCCTTTGTTAAGGGCCTGGCAGGATGGGGCATGAATGAGGGTGAC
505
|
|
8808-R3-1
03p14.3
CCGATTATGGCTTTCTTCTCCTGCCCTTTCAGTAGTGATTTGCAGAAACAGGCTGGGAGAAAGGGGTCTTTGG
506
|
|
8898-R3-1
17p13.3
GGCGCTGTCGGCCGGGGCGGCCGCCGGCAACTCGTCCGTCTTGATAACCATGGTGGCGGGAGCGGGCGTCCGCCTCGGCTGT
507
|
9989-L3-1
CCGCGCC
|
|
9021-L4-1
10q23.1
GATGGTGTGGGGAGCTTGGGTGTTTGTTTCCCATTTCACAAAACAAAGCAGCCAACCTTACATTCATC
508
|
|
9053-R3-1
Xq27.3
GGAAGGGCACTGTCTCTCTGATTCCCAGGGCCTGTCATTTCCCGAGGGCTGGTGGAGCCCGGGGATTGGAGGGCAAGAAGCCC
509
|
9053-L3-1
AGCC
|
|
9068-R2-1
14q24.3
GTCTGCCTCTTTCTCTGCAGTAATTGCTTCCTGACATTTGTTTATTTTAATTAGGAGAGCAGTCTTGATCAAGAGGGAGGGCAGAC
510
|
|
9087-L4-1
03p13
AGGAAGGGAATGGACTGGGAGGGTTTCTTTTCCTGATGGAAAGCCTATTTTTCTTATTGTGTTCCTTTTCT
511
|
|
9217-L3-1
02q31.2
TCCACTGTTGGCTTTAGTCACGGCGGGGATCGTCAGTTTAGCGCGGCCATCGCTAAAGGAGATCTGCACGCCGGGCAGAGTGGA
512
|
AGTGGA
|
|
9245-R2-1
05q21.1
AGCCTAAATACATTAGCGAGCTGGTAAAGCTTTTAAGGCCTTCTTGGGAGCGAGTGGCTGGCTAATGAGAGGTT
513
|
|
9287-L4-1
17q21.1
TGCATGTGTGGGCTGGGGAGGGCTCTGAATATCTCCTGGAACGGTACCCAGAGCCCTGTGGCTCTGCGCATGCG
514
|
|
9347-L2-1
06q15
TCTTTGTTAAAATGTAAAATGCATATTGGGCAAATGCTCCAGGGCAATTTGCATAAAAAGTGATGACAAAGA
515
|
|
9349-R3-1
21q22.11
GGACACTCTGAACCCCAAGTGGAATTCCAACTGCCAGTTCTTCATCCGAGACCTGGAGCAGGAAGTCCTCTGCATCACTGTGTTC
516
|
|
9387-R2-2
03p21.2
TCTCCATCCTCTGTCTCCCTTGATCCTCTGTTCTCCCTGATGGCTTTGAGATGAAGGCGACGGCAAGGATGGAGG
517
|
|
9391-R3-1
02p14
TAGCTGCCTCAGAGTAGAAAATAAAACTCAACAAGATTTTATCTTGTTTTTAATTTCTATGTCTCCCTGGCAGCTG
518
|
|
9507-L3-2
16q22.3
GGTGTTTGGATGGATGAGGATGGTGGATGATGGATGAGGGAGACGGAGGATTCCCTTATTAAAGCATCAAATTCTTCCCTAAATATC
519
|
|
9564-R1-1
09q33.2
GGCGCCCGCCGGGCTGTCCGGAGCGGCCGATGGGGCCCGTGTGAGCGCGCCCAGGCCCGGCCCGGTGCCCGGCGGGCGGC
520
|
|
9594-R2-1
02q12.1
TTCCAGCTATTTAGTAACTCTTCCAAAACACTGTCAGCACCCATGCTAGGATGCAGGGAGTGGGAAGGAAGTCTAAGTAGGGAA
521
|
|
9656-R3-1
03q25.33
GTCCTTTAAGACAGTGGTTCTAAAAATGTGAGCCGAGGATCTTTTGGCTTGCAGCATTAATCTCCACAGTATGTACTTTAAGGGC
522
|
|
9691-L4-1
14q24.3
GCAAGGGGCCAAGAGGGAGATGCGGATGAAATGGATGATTTAATGGGTCATCTCTCCTGTAGTTAATTTCTCTAGATCTCTTGT
523
|
|
9733-L3-1
15q23
AGGGGTGGGGAAGTCTGGTGAGGGACAGCCTTGAGTCAAAGGATGGTCACCGCTCCATGTGGCTGCCCCACCCCT
524
|
|
9774-R2-2
13q13.3
GCTTGTCCTAAAAGATCTTCCTTCTGTTTCCCTGGGTTTATCCACTTGGTTGGCCTGATGGGAGCAGGAGGCGGTGAGGGGGCGGGC
525
|
|
9816-R2-1
17q12
CTGGCCCATTTTCATTCTGCATAAAATTTTAATGGTCTCTCTGGCTGATCCGGGACGGCAGCGCGCGGAGAGGCTCTTAAAGGGC
526
|
CAG
|
|
9840-L3-2
05q14.1
CTTGTATTTGTTGACATCCTGATTTATAAAAACCTGAACAAGTTCAGTTTCAATAATTCTTTTTGTTCAAGGAACACAAG
527
|
|
10010-R2-2
07q32.1
CCGGGCGCCCCCGAGAGCCGGCCCTCCCTTCCTCCGTGACAGGTGGGCCTGGAGTTGGGGAAAGTTTGGAGCCGGCGAGGGG
528
|
10010-R2-1
CGCCGGG
|
|
10030-R3-1
10q24.1
GGATGCAACCGTGGAAGCCGGTGCCGTTGAGGATCTGCCACAGGCGGAAGGCAGCTGAGTTGACATCCACGGGCATCC
529
|
|
10138-L2-1
17q22
ACTTTTTCTGGTGGGAGGGGAGAGCGGAGCAGGCTCACGTGTAACCGCGCAGGAGCCTCCTCTGGCTTGAGCCCTTTCTTGGTA
530
|
AGT
|
|
10145-L2-1
05p15.33
GGTCCAGATAACAGAAGAGAGAGCAAAGGAAAAAGAATTTTTTGAAGATCAAAAGTGGCTGTTCATTTTGTTATCTGACC
531
|
|
10175-L1-1
Xq13.2
CATCTTTGTGGCTCCTGGTTGCTAGGAGCAGGTGCTTCTGTTACTAAGCAACAGGAGCCTGTTGGATG
532
|
|
10209-L3-1
02q33.1
TCAATTTGTTACATAGCTAACTTATTTTCTAATAGACTATGTTGGTAATAAGAAAATGAATTACATGCTGTTGGCAGAGTGA
533
|
|
10231-L3-1
09p11.2
GGCGGCTGCGGAGGCTGGCGCGGGCTGCTGCACCTTTAACGCTTTCTGGCGCTGACAGGCGGCGGCCCAGCTAAAGTTCACAG
534
|
10231-R3-1
CGCC
|
|
10242-R3-1
22q13.2
GGCAGGAAGGCCTCCGGCTTCACAAAGTGGCCCTGGGCATCCAGGAAGTGTTCGGGGTGGAAGCGGAAGGGCTTCTTCC
535
|
|
10333-L3-1
11q12.2
CGGGGCAGGGGAGGGGGTGGGCAGGGCACAAGCCTCCCACTGTGCCGTGTCCCCACCCTCCCCCGTTCCCCG
536
|
|
10335-L3-1
15q26.1
TCTTAGTGCTTTCTAATTAAAAAGGAGGGGAGTGGTGATCTTTTTGCTCTCTAAGTTCTGTTTCCTCTGAGTGGAAAGCAGAGGG
537
|
|
10342-R2-2
19q12
CCCACGCACGGAGGGTCGCCAGGAAAGTGGACATTACCGCTTTAATTAACTTCGAGATGCTCCGGCGGCGGG
538
|
10342-L2-1
|
|
10366-R3-2
Xq22.3
GAATACCATTAATCTGTTCACTAGGAGATTAATTTGCAATTTGTTGGCAAATCACATGTGGGTCTTGTAGCAAGAGCGTGGGTGGT
539
|
GTTT
|
|
10374-R3-2
16q12.1
CAGGGGATTTGTTACCGCTGATGTGTGGCCCGTCCGAATGAAGGGGGCTTTTCATTAACAAAGTAGCGGGCGGTGTCATCTTCC
540
|
CCTG
|
|
10533-R3-1
20q12
TAATTGCCTGAATCGCCGGGTTACATATCTGTTAGGAAATCTCTTGGCAATATAAAGAAGGGGCTCAGGACAGTTA
541
|
|
11370-L4-1
12q13.3
GTCCAGTTCTCAGGGGACAATACTGATGGCAGCCAAACTGGGCAAGGATGCAGTGTGGGGGCGGAGGGGGCATGACCTCTATT
542
|
CAAGTTCTGTGTCTTGGCCCCTGGCTGAGGTATTGAGTGTGAGGAAGGGAACACTGGGC
|
|
12184-L4-1
03p13
TTGTACACAATATTCGTCTGTGGTTGAAAGGGGGCACGCTGAGGTCAAGTGATGTAGTGTTTTCCATTTTTCCATATGAGTCTCAC
543
|
AGTGTGCGA
|
|
12223-L4-1
04q27
TAGAGGGAGAAGAAACAACTCTGTCTGATGTCTTCTGGGATGGCCTTAATACAGATAGCATTGTCTCTTCCATTTCTG
544
|
|
4315_C-L4-1
01q22
GGGGAGGGGACCGGGAGGGCCGGGCGGCCGCGACCCCCAACCTCTCGGAGGAGGGGCTGCCGCTCGCCGCTCCGCTCTTTG
545
|
TTGTTTGGGGCTCCGCGCCTCCCCCTCTCTCCCTCCTC
|
|
4315_D-R4-1
01q22
GGGGACGTGGCCCCTCCCCCCCGGAGCGGGACTCCAAGAACTCCGGGGGGCGCTGGGGGCTGACTTTCC
546
|
|
4315_E-R4-1
01q22
TCCCCGCCACCCTTGGAGCACCTCAGCGTTCTTAGGGGAAGCCAGAGCCGGGGAGGATGCGGGAATAGGTTTGGTGGGGG
547
|
|
4315_F-R4-1
01q22
GATCAGGTTCCCCTCCCCCGCATACACCTGGGCGCAGGTGAAAGCTCAGGGAGCGGGTGGGGGAGCCCGGGTT
548
|
|
4315_I-L4-1
01q22
CTGGGACGGGCGGGGCGCCGAGGCCCAGGGCGCCTGAGGGGCGCAGAGGTGTCAGCGTGCAACCGCCGCCCCCCAGCGTTC
549
|
CCGCCACCACCGCCACCACCCTCAAAGCCCGG
|
|
4315_K-L4-1
01q22
CCGGGGCTGGGGGTGGAGGATGGCGAGGATTTGACAAGTTCAGGGCCCCCTGGGATCCTTTCCCTACTCCCTGGTCTTGTTGG
550
|
ACACCCTGTTTACCTGCCCTAATTGCCCCGG
|
|
10010_B-L4-1
07q32.1
GGGCAGCGCCCCTCCTTCCGGAGGGCAGCATCCCGGCGGGGGCGGGGGCTCGGCTTTGATGCCAGGGCACCTTTTGTCCCTG
551
|
GAGACGCTCTGCCAGCCAGGTGCGTGGAGGGAGTGCAGCCC
|
|
10010_D-L4-1
07q32.1
CAGGTGAGAGGCTGAGCCCCGGGCGGGGGAGGGCGCCAGGCCTGGGGCATTAACCGTCCCGGGGACCCTTTTGGCCTG
552
|
|
7356_A-R4-1
08q24.3
CGGAGGTCGCTCGCTCGCTCGCTCGGCTCGCTGACTCGCCGGAGCGCTCTGTGGCGGTCGGCGGCAGGTCGGTCGCGAGAGC
553
|
GGGCTCTG
|
|
12722-L4-1
13q31.3
GCGGGCGGGCGGGGAGGTCGGAAGTACTTTGTTTTTTATGCTAATGAGGGAGTGGGGCTTGTCCGTATTTACGTTGAGGCGGGA
554
|
GCCGCCGCCCTTCATTCACCCACATGGTCCTTCGAGGTGCCGCCGCCGCCGCCCGACCTGC
|
|
999999-R4-1
17q25.3
CCCTTTGCACCTCCCGGGATTGGGCGGTCAGGGCCAGGGCCCCTTGAGAGTCTGGGAATCCCTTCTCTGGGCCTCGCTGGGGT
555
|
CCTGGCCAGGAAGGGGCTGGGGGTGACAAGGGG
|
|
999997-R4-1
17q25.3
TCTTCCTCCACCCTGCCCCACCCCTAGGTCTCTTTATTGATTCAAAGGTTAAGGAAGCTCCTGGGGGCTTGAGGGGGTGGCACAG
556
|
TTTTGGTGGGGCCCAGTGAGGA
|
|
8433_B-L4-1
17q25.3
ACGGGCGAGCAAACCCCAAATACTCAGCAACACAAAAATATGCCTCCGTGTGTGTGTGTGAGTGTGCGTGTGCCTGCGCGT
557
|
|
8433_C-R4-1
17q25.3
AAATTAAAGAAAAAAAATTCTCCACCAAAAGCGCCGCAGTGACAGTTCCCAACATTTTCTGCCTTTCTTCTTCCCCTCCCTGCACCA
558
|
CTAGGAGGGAGAAGGCACACAATTGCATTTTCGTCGCTTTTTAATTTTTTTTTTTTGGTTT
|
|
8433_D-R4-1
17q25.3
CCCGGCTCGGCCCCGCGTCTCTCCAGCTCCTCCGGCTCCTTTTAGTGCATAAATTAGTGATGGCATTTCCCGGAGAGCGGAGCACAA
559
|
CACAGGGCGCCGGGCTCGGG
|
|
3758-R2-2
18q21.31
TGCAGGAAAATCAGTAACATTAGTCATCTTAAAAGGGTTATTACTCAAGATGATTTAAATTGTGAAAATGTCAGTGGAGCCTGCA
560
|
|
3820-R3-1
16p11.2
GGCCTTCACCCGGGCAGCCACCTTGTCTCCAGGTCTGGCCACGTAGTCTCCTGAGGCAGGGATGGCCCCACAGAGGGGTGGGG
561
|
GCC
|
|
3851-R3-4
16q21
ATGGAGATTTCTAGCCCTTCTAAAGTCTATTAAAAACCTTTAAATTCTGCTTTAGACAAAACATAAAGGAGGGTTGGGAGCTCTGT
562
|
|
3874-L3-1
07q35
TGGGGTGGCAGGTATTAGGGATAATATTCATTTAGCTTTCTGAGCTTTCTGGGGAGACTTGGTGACCATGCCAGCTCCA
563
|
|
3906-L3-1
03p24.3
AGCTACACCAGAATGAGGAATAAAGGGGTTTACATATGTTCCAATTCTAAACCTATCAATCAAACCCATGTTATTCCTTTGGGAGCT
564
|
|
3952-L3-2
01p36.32
CCCCGGCGAGGGGTGTCAGATTGAGTGCTCTGTGCGCATGTGCGAAGGTGTCCAAACTGACAATGCTGGGG
565
|
|
3976-L2-2
14q11.1
GTCCACCTTCCAGCAGATGTGGATCAGCAAGCAGGAGTATGATGAGTCAGGCCCCTCCATTGTCCACCGCAAATGCTTCTAGGTG
566
|
GAC
|
|
4064-R3-1
11q23.3
ACATGGCTGAACAAGATAAGGGTTTTATTCTTGTGTTAGGGACGTGCTGGGGCTGGGATGGAATTCAGCTATGT
567
|
|
4118-L2-2
02q21.1
GTCCACCTTCCAGCAGATGTGGATCAGCAAGCAGGAGTATGATGAGTCAGGCCCCTCCATTGTCCACCGCAAATGCTTCTAGGTG
568
|
GAC
|
|
4130-L3-1
17p11.2
GGGTGCTGGTGGACATGGACGGCGTGCTGGCTGACTTCGAGGGCGGATTCCTCAGGAAGTTCCGCGCGCGCTTTCCCGACCAG
569
|
CCCT
|
|
4155-R1-1
03p12.3
TGACGACTGGCCCCGCCTCTTCCTCTCGGTCCCATATTGAACTCGAGTTGGAAGAGGCGAGTCCGGTCTCA
570
|
|
4182-R2-2
02q23.3
AGTTCTTGTAGTCCACATCGCTGACTAAGGTCTGGCACTTCTTGGCCAGCACCACCCCCAGCATGTCCACTGGGCTGCTGAACT
571
|
|
4216-R3-1
04q24
TCCTTCCAACCCAAATGATTATATGATTAAGATACCAGTACCCAGGGGGAATTGATCTGTGTATAAGGGAGGGAAGAGA
572
|
|
4340-R3-1
10q22.1
GCTCTGCTTCCAGGCTGTATTTTTAGGCTGGCATTTAGGTTTGGCCTGGGGACAAGGGGCTGGAAAATGCAAGGC
573
|
|
4391-R2-1
Xp11.3
TAAGCCAGATTCTCAACTTACGTAATTCTATGGGAATTCACAGAGTTATATTGGTTGAGAATTTGGCTTA
574
|
|
4413-L3-1
11q23.2
ATTTGTTTACTGTAGCTGGAGGTGCCGAGTAATGAAATGCACTTGTGTCTGCAGCTCACTGCTAAACAAAT
575
|
|
4417-R1-1
14q13.2
GCTGGGGTTCATCGGAGAAACTCCCTGCGATGAGCCACTAGGGTCACGGACAGGGAACTTTTTGATGAGCGCCGAGT
576
|
|
4498-L3-2
06p22.2
TTCCCCAGGCAGCAGCAGGCGCACGGCCGTCTGGATCTCCCTGGAGGTGATGGTCGAGCGCTTGTCATAATGCGCCAGGCGGGA
577
|
|
4567-L1-1
Xq26.2
GGGAGTGTGCTGGGAACTGGGCAGATAAAAAGGGCTGGAACTTATTATTTGGCTAGACTCTCAATTCCC
578
|
|
4579-L3-2
06q14.1
AGCACAGCTATTGGTGTTTTGCAGGAGGCAAGTGAAGCCCATCTGGTTGGCCTTTTTGAAGACACCAAATTGTGTGCT
579
|
|
4610-R3-1
08p12
GCCCAGTTAATTGGTCTCTCAACCTACATTAGCTGTTGCATTGCAGCCAATTAGGCAGGGGCCAGAGGGC
580
|
|
4724-L3-2
15q24.2
ACAGACCAGGCACAGAAAGCTGAAGGTGCTAGAGATGCCAAGTGAAACATGTGCATTTTTGGTAACTGTGTACTTCTGGTGACTGT
581
|
|
4754-R3-2
04q25
CCACCAACTTGACATACACAGGCTCATCACAGTTGGATGCAAGCACACAAAGATGGGCTTGGCACTTGTCTAAGGCTTTGG
582
|
|
4801-L3-1
01q32.2
ATTAATGTTTTTGTAGCAAACAGGAGGCAGAGTTCTCCAAAGGCTCTCATCTCTGTGCTTCCAGAAAATATTGAT
583
|
|
4964-L3-2
02p14
TTGGGGAATTTGGTGGGTTTTCAGAAGTTAGCCCTTCTGGTGTAGGGTTTGTTGATTTCGATACACCAGATTATACTCGTCCCAA
584
|
|
5071-R2-1
17q12
GATTCCTGCTCCCAGAGCCATAAAGTGGGAGCCCCCATTTATTAATTGGGCTGGGACTGGGGCGGGGGTC
585
|
|
5306-L3-2
12q13.13
GGACCCCTAGAAAGGGCCAGAGCTGGGGTCAGAGGCCACCTCCTCCATTCTCTGCCCTGCTCTGCTGGGTCC
586
|
|
5327-L3-1
09q31.3
GGAGACAGGACATAGTCCCAGAGGTTGAGCTGGCTTATGGAGCCCACAAAAGACTCAGCTGGGCTGAATCCCTCTCC
587
|
|
5372-R3-2
10q22.2
TGTTTCCCTGTGGAAAAGATTACTCTAGGCAAATTTTAGAAAATGCTTTTAAAAAGAATCTTGTGTAAGTTGAAAACAGAGGGAAAGA
588
|
|
5380-R2-2
1p36.22
GGCCCTGAGAGCAATACTCATATTGATTGCATTTATTTCACTCTAGGGAGGAGAGATAATTCTTCAATGTGGGACACATCTGGGAG
589
|
CC
|
|
5441-L3-2
1q24.1
GTAGCTGCTGCTCTGTTAGCTATACTGACTTGGAGCTTGGCTGTAGGATCAAGTTTGGGGTGGGTAACTAGTGGGAGGCAGCTGC
590
|
|
5474-L3-2
9p13.3
GCTGAGGTAGGTGGGTCAGAGTCTGGCCAGGTGAGAGGAGGCACCCCAGTGCTTGGCCCTGACTCTGCCCCCTGGACACCTTC
591
|
TTCAGT
|
|
5513-L3-1
8p12
AAGTGGCTCTGAGGCATCATGGAGAACAGTTGAAAATCACATTGTCAGCTCGAAATGCATCAAAGCTATTT
592
|
|
5598-R2-2
11q13.2
CTCCCACGGCCTGAAGCTGCTGCCAAGCTATTTTTGGTTCTGCACAGTTAAAAATAGCTTCACGGAGGTGGGAG
593
|
|
5618-R3-1
8q21.11
TCCCCCAACCCATCCATTAGGCCAGCAACGCTTGTAGAGCTCACTGTGGGCTGTAATGTGGCACTGGTGGGCTGGGACACCAGG
594
|
GA
|
|
5619-L3-1
15q25.3
CTCATTGAGGGAAGATTGAGCAGAACTGGCATTGCTTGCTTTCGTCAAATTGATTGTGCCCGTCTGTTTGATCCAATTCAGTGAG
595
|
|
5733-R3-2
16q22.1
CTCTCCCAGCCCAGCCTGAGTCCTTGTGTATCGTGGAAATGGGTGGGACTGAGAAGCAGGATGAGCTGGGTGAG
596
|
|
5735-L3-1
5q31.1
CCCCCACAGGCTTGAGGCCAGAGGAAACAGCAACTTTCTTCGCTGGGAAAGTGTTGTGGGGCTCAAGCATTTGGGGG
597
|
|
5863-L3-1
9p13.3
GACATCTTCCTGGCGACAGGAATTGCCAGCAGCAACGGCCTTGGCGGTTGCCATGGTGATACCCTTGGTCATTCGGATGAAGTC
598
|
|
5919-L3-1
7p21.3
TCTAGGGAGATAAAGTGACAGTGTTGCTTGTTCAGGCTATTGTTCAAAGAAGCACGTCTTTTATTTATAGA
599
|
|
6026-R3-1
18q22.3
TTGGAGGCAGAAGCTCTGGCCCCTATGGTGGTGGAAGCCAGTACTTTGCCAAACCACAAAACCAAGGTGGCTGGGGTGGTTCCAG
600
|
|
6218-R3-1
2p16.1
TTCTATTAATATGTATCATATTGGTATCCATTTTCACTAATGTGACATGAGAGGCAGTAATGTGATTACTTTTTTAGTGGAA
601
|
|
6253-L3-1
4q31.23
GCTGGCATTATGGCAGCCAGGATATTGTCAGGAGGAACTTGGCAGTGCTCGTAGGTGTTATGATGCTGGC
602
|
|
6355-R3-1
2p14
AGCCTCCTTGTCTGGAGATTCTAACAAATGGGTTTGCAGTGTTGGAAACTGTAAATCCTCAGGGAACAGATGATCTGGACAATGTA
603
|
GCT
|
|
6421-R3-2
11q13.1
CCCTCCTTGATCTGGGGAACTATTTCTTCATTCCAGAAGGTCAGAGCTCTGGCAATAGTGTCCTTCAGACTCTCACAGGAGGG
604
|
|
6450-R3-2
12q13.2
CTGCAGTGGGAAAGTCAAGCCTGGTATTACGTTTTGTCAAAGGGCAGTTCCATGAGTACCAGGAGAGCACCATTGGAG
605
|
|
6478-R2-2
2q22.3
GCTGGATTCTGCCCTTGGATACACACAACAAAACCCCCATTGAAGTCAATGGAAATTGTGCATGCATATCCAGGGGCAGAATTTG
606
|
GC
|
|
6554-L3-2
15q26.1
TCCCAGAATATGGAGGCACCAAAGTAGTTCTAGATGACAAGGATTATTTCCTATTTAGAGATGGTGACATTCTTGGA
607
|
|
6647-R2-1
1q23.3
CTCAGTATCTTCAGCTTGGGAAACTGACCTCGTTAATTTTAATGAGGGGAAAAATTCTCCAGCTGGGGCTGAG
608
|
|
6664-R2-1
14q31.1
GCACATTATAAACTCTAATTCATTAACGTCATCATAAATGGTAATGTCCTGTGAAAAAGAGAGGTGGTGGC
609
|
|
6712-L2-1
9q21.13
CAGGCTGACAACTGATATCACAAGACCACAGCTAAGAGTGGTTTATTACTTTTAGTGGGATTTATTTAATTCAGTCTCACAGCCTG
610
|
|
6718-L3-2
3p22.1
CTTTGGAGGCAGAAGCTCTGGCCCCTATGGTGGTGGAGGCCAATACTTTGCCAAACCACAAAACCAAGGTGGCTATGGCGGTTC
611
|
6718-R3-1
CAGTAG
|
|
6912-L3-1
13q22.3
AGAATTAACTGCTGGACCCAGAGGCTGAAGGCACGTTGAAGGAATCCTTCATTTCTTGAGCCCTTGGTTTGAAAAGCTAGTGATTTT
612
|
|
7019-R3-1
18q22.3
TTCAAAGAAATTACTTAGCAATTAAACCTTCAGCAAAATTGTAATTCATTTTAAATTTAGCACGGAGGTTTGATGCTGTTTCTGAGGAA
613
|
|
7070-R3-1
14q12
TCTCCTTCTTTCAAACATGTCAGTGACCAATTTCCTACAGTAAGTTTAGTGGGTCCTGGTGCTGACAGTATAGGTTGACTTGAAGTA
614
|
GA
|
|
7089-R1-1
6q16.2
ATGCACTCTGCTGTCATTTGCAGCCTGACCTGCAGGTCAGGGGTGATGTGAGCTGGCTCAGGGATGCAT
615
|
|
7158-R3-1
3q13.31
ATTCAACACAGATTCAGGTGCTCTCAACAGCCATGAAAATATATGGCTGAAGAGGGAATCTATAAATGTAATGAAT
616
|
|
7292-L3-4
1p34.1
GCAATTAGAATGCAGGGAGGTTCAGAAGCTATTTAACTGGGTGACCCCTGAGGTCGCTGCATCTGACTCCCATCCCTGGATAAAT
617
|
ATTGT
|
|
7304-L3-1
1q24.2
CAAATGTGGGAGCTTGGATCAATGTTGAAGAATAATTTTCATCATAGTGAAAATGTTGGTTCAAATAAATTTCTACACTTG
618
|
|
7340-R3-1
6q16.1
GCTCACATGGGAATCCAAAACCTTCTAATTTTCTATACAGATTCATTTCAGAATCAATTAGAGTTGGTGGCAGCCTTCTCCCTGTGT
619
|
GC
|
|
7375-L3-1
6q23.3
CAGGTATGTAACTGTGGAGACAGCAGCGCTGCAGAAGAGGCCTCCTGATCAGAAAGAATGTCTGTCCCACAGTTGACTCTCTG
620
|
|
7435-L3-2
6q16.1
GTAGGAAACACAGCTAATGGGGCTTAGCAACAGATGGGGAGCCAGCACAAAGCTGTAGGTTCTTCCTCTGCCTCGGCTGTGACT
621
|
TCCTGC
|
|
7543-L3-2
1p36.22
TCATCTCGGGGCCTGGTGAATTAGGACGACATCGGCATTTTTTATTGCTAAAGACGTCCAGATTGATCCAGCCCTTGGCTGA
622
|
|
7597-L3-1
11p14.1
GGGATTGATCTGAGGGACACAGAGCCCAGGTTCCATTAAAGTGTATTAATGCCAAGGTCTGTGCAATTAGTGAAAAGTCAATTCC
623
|
|
7763-R3-1
8q11.21
GGCTTGGGCTTTGTTGGTCTTCCACTGCTCTGCTACATCATTTGCTAATGGATCGTCTGGATTGGGAGCACATAACAAGGCCTGG
624
|
GTT
|
|
7824-R3-1
6q16.2
CCTGGATGCTGTTTCATTATGTAGAGTCAGGCAAAAGACAGACGGATGTGTGTGTGAGGCGGCGATGAAGCTGGCACCAGG
625
|
|
8075-L3-1
10q22.1
CAGCTGGCCTGGTGCCCTGGTGCGTGGAGGTGTAGCTGGGCTCTGACCCAGCTCCTCAAACAGGTTCCATATGGCCCTCCCGG
626
|
CTG
|
|
8336-R3-1
Xq13.1
CCTCCCCAAGCAATCTGCTCACCCACTTGTTGTCATGGTGACTCTGGCTGGGGGTGTGGGGACTGAGTGGGGAGG
627
|
|
8434-R3-1
9q34.11
AGGAGGCCCTGAGTGCTAGTAGCCACTTATAGAAAGTCGCTTCCAGCAATTCTTCTAGGAGTGGAGCCTCAGGGCTGCCT
628
|
|
8552-R3-1
13q21.33
CTCCTAGTGGTATCTGTCATAAAGATACTGTTCAAGGCATATTTCATTATATTTTATAGTGTCCTCTTTATGGTGACCCTTGGGAG
629
|
|
8685-L3-1
17p13.3
GGGAGACATTCCACTTATAGGAGGCAAAGAGCAGGATATCTGCACAGGAAGAGTTCATCTTATATGACTTTCGGGGATGGATTGT
630
|
CTCCT
|
|
8719-L3-2
5q22.3
AGAGCGCAGCTACTGGTGCTTTGCAGGAGGCAAGTGAGGCCTATCTGGTTGGCCTTTTTGAAGACACCAACCTGTGCGCT
631
|
|
8760-L3-1
3q27.3
GGTCATGCTATGCCTGGGGTGAGTTTTGCCTCGGGGCTCCAGGCGGCACTGGAGCAGAGCTGAGCTAATTTTACCCACAGGAGC
632
|
TGACT
|
|
9092-R3-2
18q22.3
CTTCTTATAAGTCTGTGGTCACAGTATGTTTTTTGCAGTTCAGCATCTGGCTCTGTGGGATACTGATGGCTTCTAGGAAG
633
|
|
9557-R3-1
22q12.1
TGCCTGCTCTGGCCAGAACCAAAGCACGTGTCAGCTTTTTTATTTAGGGCAAGAGGTGCAGAATGGACTGGGCCAGTCCAGGCA
634
|
|
9582-R3-2
5q31.1
TTTTACACATTGTCAGCTGCATCTATTAATTTTCTTACTGTCAGAGACAGTTAAGGGAGCCTTTGTGGAAACATCTGAGGATTTGTA
635
|
AAA
|
|
9688-L2-1
Xq26.2
TGCAGCAGAACAGTCTGGGGCCATTTAGCTTAGGGGCAAATAGTTCCTCATACTTCAAAGAGCCCTAAGGACATTGCTGCA
636
|
|
9694-R3-1
7q21.2
TTATTATGCAACATCTGCTCTGAATTTCAAATGTGATAAACAGAGTATGAGTGTCGGTGGCAGATGGCTAATGA
637
|
|
9747-L3-1
18q11.2
GAGCTGCTTTGAATTGCTCGCAGTTTGCCGGAGGCGGTGTGCTGGGTTGGACGCTCCGGGAAACAAAGCAACCCAAAACAGCTC
638
|
|
9772-L3-1
10p15.2
TCAGGAAAGGTCATGGGAAAAATGCTGTAGAATTTTCTAATGGTTCATCCATCAAAAATGCAGCTCTCCATTGATTCTTCCCGA
639
|
|
9798-R3-2
5q12.3
GTGCTTTTCTTTCCCCCCAAAGAAGTCATACCAGGTATATATAGAGAGATCTATAATGCCCTTCTGTTGGGGGAATGAAAGCAC
640
|
|
9812-L3-1
5p13.3
AGCAAGCTGGGGAGCCCAGATAAATAGAGCTTTCTGTTTCCTTTCCTGGAGTCTAAAATATCTGATCTGGAGGTTCCCTCCCTGCT
641
|
|
9813-R3-2
12p13.32
GAAAGTGTCGGGCCTTTTGAAATTGTCAGAGAAACTGATTTTCTTGTCAAGTCTCATCCTGTACAGTTGGAGGGCCAAATTCTACT
642
|
TTC
|
|
9987-R2-2
13q13.3
CAGGCATTGCCTGGCTCAGAGACCTTTGCTGCTGAGCAAACTGAGTTAACAAAGTGGGCTGAGGGGTGAAGCCTG
643
|
|
10093-R2-2
2p11.2
TGTTTCCAGCATTCCCAGGTAGGCCAAGGTGTCCTACAGAAAAACCTTGGGTTAGACCTACAGGGGGTCTGGCTGGTGTTAACA
644
|
|
10120-R3-1
7p14.1
CAAGTTTCCTGAGCCCTGGGTTGATATACTGTACCATCTTTGGTGCAGCTGTAATTTTAACAAGGGGAACCGACTTG
645
|
|
10133-R3-1
Xp11.4
CTCTTCCCATATTTAATGTGGCTCTAATTCTGACTTCATTGCAGAGCGGTGAAATCAAATTAGGAAATGGGAGGAG
646
|
|
10154-R1-1
6p12.2
ATTCCAAGGGTCTGACACTTGTCTAAATCCTGTAGAAATGAGATCAAGGGCAAAGGGCACAGATCCTGGGAAT
647
|
|
10198-R3-1
2p16.1
GAGCAGTTCTTGTTGCCCATCACATTTTAGTGCAGGGAAGTGCTTTGCCCTAAAGGTGCCAGGTAAAGAGAATTGCC
648
|
|
10260-L3-1
22q13.1
GTGGGAGACATCGGGTGGGGGCCCTGGCGAACAATAGGTGGGCCCAGCTGGGGCCCCCTCCTGCCTGCCTCACCGC
649
|
|
10346-R3-2
10q25.3
TGGGCAGAGCCAGGTCTGCACCCTCGGGAGCCCTGGAGGCCAGGTGAGCTGCTGCAGAGGGCACAGACAGGCTCATACTCA
650
|
|
10539-R3-1
2p22.3
TAGATGGGAATTTGAGTGGCATTGTTTCTCAGGCCTGCTGGAGGCTGGGGGATAGTAAATTTTCTCAAATACCATTTA
651
|
|
10543-R3-1
1p31.1
GCCTTAACCTTTTTATCATTTATCTTCTTGTATTAATGTCACTGAATTATTAATTCATGAGCCAGGATGGGAAGGGTGAAGGC
652
|
|
10553-R1-1
1q24.2
GCTGGCTCCTGCTCAGAGTGACAGCACCCTGTGGAGTCTGCTGGTACTGACCTAACCACCACAGAGCCCCACTGGAGCATGGAG
653
|
CCAGC
|
|
10562-L1-2
8p12
TGATCAGGCGCTTGATATGACAGGCTGTGGGAGTCAGGACCCCTTGAACAGAGTGGGCCTTGTCTGTCACAGTCCGCCTGACA
654
|
|
10594-L3-1
3p14.2
CTGTTGAGTGGGTGTTGGTGTGGGTAACAATAATGTTGTTTTCATAATATGTGCTGGCAGATTAGCACACTTCTCTACAG
655
|
|
10639-R2-1
2q31.2
TGACGACTGGCCCCGCCTCTTCCTCTCGGTCCCATATTGAACTCGAGTTGGAAGAGGCGAGTCCGGTCTCA
656
|
|
let-7a
09q22.32
TGGGATGAGGTAGTAGGTTGTATAGTTTTAGGGTCACACCCACCACTGGGAGATAACTATACAATCTACTGTCTTTCCTA
657
|
|
let-7a
11q24.1
AGGTTGAGGTAGTAGGTTGTATAGTTTAGAATTACATCAAGGGAGATAACTGTACAGCCTCCTAGCTTTCCT
658
|
|
let-7a
22q13.31
GGGTGAGGTAGTAGGTTGTATAGTTTGGGGCTCTGCCCTGCTATGGGATAACTATACAATCTACTGTCTTTCCT
659
|
|
let-7b
22q13.31
CGGGGTGAGGTAGTAGGTTGTGTGGTTTCAGGGCAGTGATGTTGCCCCTCGGAAGATAACTATACAACCTACTGCCTTCCCTG
660
|
|
let-7c
21q21.1
GCATCCGGGTTGAGGTAGTAGGTTGTATGGTTTAGAGTTACACCCTGGGAGTTAACTGTACAACCTTCTAGCTTTCCTTGGAGC
661
|
|
let-7d
09q22.32
CCTAGGAAGAGGTAGTAGGTTGCATAGTTTTAGGGCAGGGATTTTGCCCACAAGGAGGTAACTATACGACCTGCTGCCTTTCTTA
662
|
GG
|
|
let-7e
19q13.41
CCCGGGCTGAGGTAGGAGGTTGTATAGTTGAGGAGGACACCCAAGGAGATCACTATACGGCCTCCTAGCTTTCCCCAGG
663
|
|
let-7f
09q22.32
TCAGAGTGAGGTAGTAGATTGTATAGTTGTGGGGTAGTGATTTTACCCTGTTCAGGAGATAACTATACAATCTATTGCCTTCCCTGA
664
|
|
let-7f
xp11.22
TGTGGGATGAGGTAGTAGATTGTATAGTTTTAGGGTCATACCCCATCTTGGAGATAACTATACAGTCTACTGTCTTTCCCACG
665
|
|
let-7g
03p21.2
AGGCTGAGGTAGTAGTTTGTACAGTTTGAGGGTCTATGATACCACCCGGTACAGGAGATAACTGTACAGGCCACTGCCTTGCCA
666
|
|
let-7i
12q14.1
CTGGCTGAGGTAGTAGTTTGTGCTGTTGGTCGGGTTGTGACATTGCCCGCTGTGGAGATAACTGCGCAAGCTACTGCCTTGCTA
667
|
|
miR-100
11q24.1
CCTGTTGCCACAAACCCGTAGATCCGAACTTGTGGTATTAGTCCGCACAAGCTTGTATCTATAGGTATGTGTCTGTTAGG
668
|
|
miR-1224-5p
03q27.1
GTGAGGACTCGGGAGGTGGAGGGTGGTGCCGCCGGGGCCGGGCGCTGTTTCAGCTCGCTTCTCCCCCCACCTCCTCTCTCCTC
669
|
AG
|
|
miR-1225-5p
16p13.3
GTGGGTACGGCCCAGTGGGGGGGAGAGGGACACGCCCTGGGCTCTGCCCAGGGTGCAGCCGGACTGACTGAGCCCCTGTGCC
670
|
GCCCCCAG
|
|
miR-1228*
12q13.3
GTGGGCGGGGGCAGGTGTGTGGTGGGTGGTGGCCTGCGGTGAGCAGGGCCCTCACACCTGCCTCGCCCCCCAG
671
|
|
miR-125a-5p
19q13.41
TGCCAGTCTCTAGGTCCCTGAGACCCTTTAACCTGTGAGGACATCCAGGGTCACAGGTGAGGTTCTTGGGAGCCTGGCGTCTGG
672
|
CC
|
|
miR-125b
11q24.1
TGCGCTCCTCTCAGTCCCTGAGACCCTAACTTGTGATGTTTACCGTTTAAATCCACGGGTTAGGCTCTTGGGAGCTGCGAGTCGT
673
|
GCT
|
|
miR-125b
21q21.1
ACCAGACTTTTCCTAGTCCCTGAGACCCTAACTTGTGAGGTATTTTAGTAACATCACAAGTCAGGCTCTTGGGACCTAGGCGGAG
674
|
GGGA
|
|
miR-126
09q34.3
CGCTGGCGACGGGACATTATTACTTTTGGTACGCGCTGTGACACTTCAAACTCGTACCGTGAGTAATAATGCGCCGTCCACGGCA
675
|
miR-126*
|
|
miR-135
03p21.1
AGGCCTCGCTGTTCTCTATGGCTTTTTATTCCTATGTGATTCTACTGCTCACTCATATAGGGATTGGAGCCGTGGCGCACGGCGG
676
|
miR-135a*
GGACA
|
|
miR-142-3p
17q23.2
GACAGTGCAGTCACCCATAAAGTAGAAAGCACTACTAACAGCACTGGAGGGTGTAGTGTTTCCTACTTTATGGATGAGTGTACTGTG
677
|
|
miR-145
05q32.1
CACCTTGTCCTCACGGTCCAGTTTTCCCAGGAATCCCTTAGATGCTAAGATGGGGATTCCTGGAAATACTGTTCTTGAGGTCATGG
678
|
TT
|
|
miR-146b-5p
10q24.32
CCTGGCACTGAGAACTGAATTCCATAGGCTGTGAGCTCTAGCAATGCCCTGTGGACTCAGTTCTGGTGCCCGG
679
|
|
miR-149
02q37.3
GCCGGCGCCCGAGCTCTGGCTCCGTGTCTTCACTCCCGTGCTTGTCCGAGGAGGGAGGGAGGGACGGGGGCTGTGCTGGGGC
680
|
miR-149*
AGCTGGA
|
|
miR-150
19q13.33
CTCCCCATGGCCCTGTCTCCCAACCCTTGTACCAGTGCTGGGCTCAGACCCTGGTACAGGCCTGGGGGACAGGGACCTGGGGAC
681
|
miR-150*
|
|
miR-155
21q21.3
CTGTTAATGCTAATCGTGATAGGGGTTTTTGCCTCCAACTGACTCCTACATATTAGCATTAACAG
682
|
|
miR-16
13q14.2
GTCAGCAGTGCCTTAGCAGCACGTAAATATTGGCGTTAAGATTCTAAAATTATCTCCAGTATTAACTGTGCTGCTGAAGTAAGGTT
683
|
GAC
|
|
miR-16
03q25.33
GTTCCACTCTAGCAGCACGTAAATATTGGCGTAGTGAAATATATATTAAACACCAATATTACTGTGCTGCTTTAGTGTGAC
684
|
|
miR-181c
19p13.12
CGGAAAATTTGCCAAGGGTTTGGGGGAACATTCAACCTGTCGGTGAGTTTGGGCAGCTCAGGCAAACCATCGACCGTTGAGTGG
685
|
ACCCTGAGGCCTGGAATTGCCATCCT
|
|
miR-198
03q13.33
TCATTGGTCCAGAGGGGAGATAGGTTCCTGTGATTTTTCCTTCTTCTCTATAGAATAAATGA
686
|
|
miR-199a-3p
19p13.2
GCCAACCCAGTGTTCAGACTACCTGTTCAGGAGGCTCTCAATGTGTACAGTAGTCTGCACATTGGTTAGGC
687
|
|
miR-199a-3p
01q24.3
AGGAAGCTTCTGGAGATCCTGCTCCGTCGCCCCAGTGTTCAGACTACCTGTTCAGGACAATGCCGTTGTACAGTAGTCTGCACAT
688
|
TGGTTAGACTGGGCAAGGGAGAGCA
|
|
miR-199b-3p
09q34.11
CCAGAGGACACCTCCACTCCGTCTACCCAGTGTTTAGACTATCTGTTCAGGACTCCCAAATTGTACAGTAGTCTGCACATTGGTTA
689
|
GGCTGGGCTGGGTTAGACCCTCGG
|
|
miR-19b
13q31.3
CACTGTTCTATGGTTAGTTTTGCAGGTTTGCATCCAGCTGTGTGATATTCTGCTGTGCAAATCCATGCAAAACTGACTGTGGTAGTG
690
|
|
miR-19b
Xq26.2
ACATTGCTACTTACAATTAGTTTTGCAGGTTTGCATTTCAGCGTATATATGTATATGTGGCTGTGCAAATCCATGCAAAACTGATTG
691
|
TGATAATGT
|
|
miR-200b
01p36.33
CCAGCTCGGGCAGCCGTGGCCATCTTACTGGGCAGCATTGGATGGAGTCAGGTCTCTAATACTGCCTGGTAATGATGACGGCGG
692
|
AGCCCTGCACG
|
|
miR-200c
12p13.31
CCCTCGTCTTACCCAGCAGTGTTTGGGTGCGGTTGGGAGTCTCTAATACTGCCGGGTAATGATGGAGG
693
|
|
miR-205
01q32.2
AAAGATCCTCAGACAATCCATGTGCTTCTCTTGTCCTTCATTCCACCGGAGTCTGTCTCATACCCAACCAGATTTCAGTGGAGTGA
694
|
AGTTCAGGAGGCATGGAGCTGACA
|
|
miR-21
17q23.2
TGTCGGGTAGCTTATCAGACTGATGTTGACTGTTGAATCTCATGGCAACACCAGTCGATGGGCTGTCTGACA
695
|
|
miR-23a
19p13.12
GGCCGGCTGGGGTTCCTGGGGATGGGATTTGCTTCCTGTCACAAATCACATTGCCAGGGATTTCCAACCGACC
696
|
miR-23a*
|
|
miR-23b
09q22.32
CTCAGGTGCTCTGGCTGCTTGGGTTCCTGGCATGCTGATTTGTGACTTAAGATTAAAATCACATTGCCAGGGATTACCACGCAAC
697
|
CACGACCTTGGC
|
|
miR-24-1
09q22.32
CTCCGGTGCCTACTGAGCTGATATCAGTTCTCATTTTACACACTGGCTCAGTTCAGCAGGAACAGGAG
698
|
|
miR-24-2
19p13.12
CTCTGCCTCCCGTGCCTACTGAGCTGAAACACAGTTGGTTTGTGTACACTGGCTCAGTTCAGCAGGAACAGGG
699
|
|
miR-25*
07q22.1
GGCCAGTGTTGAGAGGCGGAGACTTGGGCAATTGCTGGACGCTGCCCTGGGCATTGCACTTGTCTCGGTCTGACAGTGCCGGCC
700
|
|
miR-26a-1
03p22.3
GTGGCCTCGTTCAAGTAATCCAGGATAGGCTGTGCAGGTCCCAATGGGCCTATTCTTGGTTACTTGCACGGGGACGC
701
|
|
miR-26a-2
12q14.1
GGCTGTGGCTGGATTCAAGTAATCCAGGATAGGCTGTTTCCATCTGTGAGGCCTATTCTTGATTACTTGTTTCTGGAGGCAGCT
702
|
|
miR-26b
02q35
CCGGGACCCAGTTCAAGTAATTCAGGATAGGTTGTGTGCTGTCCAGCCTGTTCTCCATTACTTGGCTCGGGGACCGG
703
|
|
miR-27a
19p13.12
CTGAGGAGCAGGGCTTAGCTGCTTGTGAGCAGGGTCCACACCAAGTCGTGTTCACAGTGGCTAAGTTCCGCCCCCCAG
704
|
|
miR-27b
09q22.32
ACCTCTCTAACAAGGTGCAGAGCTTAGCTGATTGGTGAACAGTGATTGGTTTCCGCTTTGTTCACAGTGGCTAAGTTCTGCACCTG
705
|
AAGAGAAGGTG
|
|
miR-298
20q13.32
TCAGGTCTTCAGCAGAAGCAGGGAGGTTCTCCCAGTGGTTTTCCTTGACTGTGAGGAACTAGCCTGCTGCTTTGCTCAGGAGTGA
706
|
GCT
|
|
miR-29a
07q32.3
ATGACTGATTTCTTTTGGTGTTCAGAGTCAATATAATTTTCTAGCACCATCTGAAATCGGTTAT
707
|
|
miR-29b-2
07q32.3
CTTCAGGAAGCTGGTTTCATATGGTGGTTTAGATTTAAATAGTGATTGTCTAGCACCATTTGAAATCAGTGTTCTTGGGGG
708
|
|
miR-29b-1
01q32.2
CTTCTGGAAGCTGGTTTCACATGGTGGCTTAGATTTTTCCATCTTTGTATCTAGCACCATTTGAAATCAGTGTTTTAGGAG
709
|
|
miR-29c*
01q32.2
ATCTCTTACACAGGCTGACCGATTTCTCCTGGTGTTCAGAGTCTGTTTTTGTCTAGCACCATTTGAAATCGGTTATGATGTAGGGG
710
|
GA
|
|
miR-30a
06q13
GCGACTGTAAACATCCTCGACTGGAAGCTGTGAAGCCACAGATGGGCTTTCAGTCGGATGTTTGCAGCTGC
711
|
miR-30a-3p
|
|
miR-30b
08q24.22
ACCAAGTTTCAGTTCATGTAAACATCCTACACTCAGCTGTAATACATGGATTGGCTGGGAGGTGGATGTTTACTTCAGCTGACTTG
712
|
miR-30c*
GA
|
|
miR-30c
01p34.2
ACCATGCTGTAGTGTGTGTAAACATCCTACACTCTCAGCTGTGAGCTCAAGGTGGCTGGGAGAGGGTTGTTTACTCCTTCTGCCA
713
|
miR-30c-1*
06q13
TGGA
|
|
miR-30c-2
06q13
AGATACTGTAAACATCCTACACTCTCAGCTGTGGAAAGTAAGAAAGCTGGGAGAAGGCTGTTTACTCTTTCT
714
|
|
miR-30d
08q24.22
GTTGTTGTAAACATCCCCGACTGGAAGCTGTAAGACACAGCTAAGCTTTCAGTCAGATGTTTGCTGCTAC
715
|
|
miR-30e
01p34.2
GGGCAGTCTTTGCTACTGTAAACATCCTTGACTGGAAGCTGTAAGGTGTTCAGAGGAGCTTTCAGTCGGATGTTTACAGCGGCAG
716
|
GCTGCCA
|
|
miR-320a
08p21.3
GCTTCGCTCCCCTCCGCCTTCTCTTCCCGGTTCTTCCCGGAGTCGGGAAAAGCTGGGTTGAGAGGGCGAAAAAGGATGAGGT
717
|
miR-320
|
|
miR-331-3p
12q22
GAGTTTGGTTTTGTTTGGGTTTGTTCTAGGTATGGTCCCAGGGATCCCAGATCAAACCAGGCCCCTGGGCCTATCCTAGAACCAA
718
|
miR-331
CCTAAGCTC
|
|
miR-371-5p
19q13.42
GTGGCACTCAAACTGTGGGGGCACTTTCTGCTCTCTGGTGAAAGTGCCGCCATCTTTTGAGTGTTAC
719
|
miR-371
|
|
miR-373*
19q13.42
GGGATACTCAAAATGGGGGCGCTTTCCTTTTTGTCTGTACTGGGAAGTGCTTCGATTTTGGGGTGTCCC
720
|
|
miR-375
02q35
CCCCGCGACGAGCCCCTCGCACAAACCGGACCTGAGCGTTTTGTTCGTTCGGCTCGCGTGAGGC
721
|
|
miR-423-5p
17q11.2
ATAAAGGAAGTTAGGCTGAGGGGCAGAGAGCGAGACTTTTCTATTTTCCAAAAGCTCGGTCTGAGGCCCCTCAGTCTTGCTTCCT
722
|
AACCCGCGC
|
|
miR-424
Xq26.3
CGAGGGGATACAGCAGCAATTCATGTTTTGAAGTGTTCTAAATGGTTCAAAACGTGAGGCGCTGCTATACCCCCTCGTGGGGAAG
723
|
GTAGAAGGTGGGG
|
|
miR-483-5p
11p15.5
GAGGGGGAAGACGGGAGGAAAGAAGGGAGTGGTTCCATCACGCCTCCTCACTCCTCTCCTCCCGTCTTCTCCTCTC
724
|
|
miR-486-3p
08p11.21
GCATCCTGTACTGAGCTGCCCCGAGGCCCTTCATGCTGCCCAGCTCGGGGCAGCTCAGTACAGGATAC
725
|
|
miR-491-3p
09p21.3
TTGACTTAGCTGGGTAGTGGGGAACCCTTCCATGAGGAGTAGAACACTCCTTATGCAAGATTCCCTTCTACCTGGCTGGGTTGG
726
|
miR-491-5p
|
|
miR-513a-5p
Xq27.3
GGGATGCCACATTCAGCCATTCAGCGTACAGTGCCTTTCACAGGGAGGTGTCATTTATGTGAACTAAAATATAAATTTCACCTTTC
727
|
TGAGAAGGGTAATGTACAGCATGCACTGCATATGTGGTGTCCC
|
|
miR-513a-5p
Xq27.3
GGATGCCACATTCAGCCATTCAGTGTGCAGTGCCTTTCACAGGGAGGTGTCATTTATGTGAACTAAAATATAAATTTCACCTTTCT
728
|
GAGAAGGGTAATGTACAGCATGCACTGCATATGTGGTGTCC
|
|
miR-513b
Xq27.3
GTGTACAGTGCCTTTCACAAGGAGGTGTCATTTATGTGAACTAAAATATAAATGTCACCTTTTTGAGAGGAGTAATGTACAGCA
729
|
|
miR-516a-5p
19q13.42
TCTCAGGCTGTGACCTTCTCGAGGAAAGAAGCACTTTCTGTTGTCTGAAAGAAAAGAAAGTGCTTCCTTTCAGAGGGTTACGGTTT
730
|
GAGA
|
|
miR-550
07p15.1
TGATGCTTTGCTGGCTGGTGCAGTGCCTGAGGGAGTAAGAGCCCTGTTGTTGTAAGATAGTGTCTTACTCCCTCAGGCACATCTC
731
|
CAACAAGTCTCT
|
|
miR-550
07p14.3
TGATGCTTTGCTGGCTGGTGCAGTGCCTGAGGGAGTAAGAGCCCTGTTGTTGTCAGATAGTGTCTTACTCCCTCAGGCACATCTC
732
|
CAGCGAGTCTCT
|
|
miR-557
01q24.2
AGAATGGGCAAATGAACAGTAAATTTGGAGGCCTGGGGCCCTCCCTGCTGCTGGAGAAGTGTTTGCACGGGTGGGCCTTGTCTT
733
|
TGAAAGGAGGTGGA
|
|
miR-575
04q21.22
AATTCAGCCCTGCCACTGGCTTATGTCATGACCTTGGGCTACTCAGGCTGTCTGCACAATGAGCCAGTTGGACAGGAGCAGTGC
734
|
CACTCAACTC
|
|
miR-612
11q13.1
TCCCATCTGGACCCTGCTGGGCAGGGCTTCTGAGCTCCTTAGCACTAGCAGGAGGGGCTCCAGGGGCCCTCCCTCCATGGCAG
735
|
CCAGGACAGGACTCTCA
|
|
miR-614
12p13.1
TCTAAGAAACGCAGTGGTCTCTGAAGCCTGCAGGGGCAGGCCAGCCCTGCACTGAACGCCTGTTCTTGCCAGGTGGCAGAAGGT
736
|
TGCTGC
|
|
miR-630
15q24.1
AACTTAACATCATGCTACCTCTTTGTATCATATTTTGTTATTCTGGTCACAGAATGACCTAGTATTCTGTACCAGGGAAGGTAGTTC
737
|
TTAACTATAT
|
|
miR-637
19p13.3
TGGCTAAGGTGTTGGCTCGGGCTCCCCACTGCAGTTACCCTCCCCTCGGCGTTACTGAGCACTGGGGGCTTTCGGGCTCTGCGT
738
|
CTGCACAGATACTTC
|
|
miR-638
19p13.2
GTGAGCGGGCGCGGCAGGGATCGCGGGCGGGTGGCGGCCTAGGGCGCGGAGGGCGGACCGGGAATGGCGCGCCGTGCGCC
739
|
GCCGGCGTAACTGCGGCGCT
|
|
miR-658
22q13.1
GCTCGGTTGCCGTGGTTGCGGGCCCTGCCCGCCCGCCAGCTCGCTGACAGCACGACTCAGGGCGGAGGGAAGTAGGTCCGTT
740
|
GGTCGGTCGGGAACGAGG
|
|
miR-663
20p11.1
CCTTCCGGCGTCCCAGGCGGGGCGCCGCGGGACCGCCCTCGTGTCTGTGGCGGTGGGATCCCGCGGCCGTGTTTTCCTGGTG
741
|
GCCCGGCCATG
|
|
miR-671-5p
07q36.1
GCAGGTGAACTGGCAGGCCAGGAAGAGGAGGAAGCCCTGGAGGGGCTGGAGGTGATGGATGTTTTCCTCCGGTTCTCAGGGCT
742
|
CCACCTCTTTCGGGCCGTAGAGCCAGGGCTGGTGC
|
|
miR-675
11p15.5
CCCAGGGTCTGGTGCGGAGAGGGCCCACAGTGGACTTGGTGACGCTGTATGCCCTCACCGCTCAGCCCCTGGG
743
|
|
miR-708
11q14.1
AACTGCCCTCAAGGAGCTTACAATCTAGCTGGGGGTAAATGACTTGCACATGAACACAACTAGACTGTGAGCTTCTAGAGGGCAG
744
|
GGA
|
|
miR-744
17p12
TTGGGCAAGGTGCGGGGCTAGGGCTAACAGCAGTCTTACTGAAGGTTTCCTGGAAACCACGCACATGCTGTTGCCACTAACCTC
745
|
AACCTTACTCGGTC
|
|
miR-765
01q23.1
TTTAGGCGCTGATGAAAGTGGAGTTCAGTAGACAGCCCTTTTCAAGCCCTACGAGAAACTGGGGTTTCTGGAGGAGAAGGAAGG
746
|
TGATGAAGGATCTGTTCTCGTGAGCCTGAA
|
|
miR-920
12p12.1
GTAGTTGTTCTACAGAAGACCTGGATGTGTAGGAGCTAAGACACACTCCAGGGGAGCTGTGGAAGCAGTAACACG
747
|
|
miR-923
17q12
TATTTGTCAGCGGAGGAAAAGAAACTAACCAGGATTCCCTCAGTAATGGCGAGTG
748
|
|
miR-92a-2*
Xq26.2
TCATCCCTGGGTGGGGATTTGTTGCATTACTTGTGTTCTATATAAAGTATTGCACTTGTCCCGGCCTGTGGAAGA
749
|
|
miR-92b*
01q22
CGGGCCCCGGGCGGGCGGGAGGGACGGGACGCGGTGCAGTGTTGTTTTTTCCCCCGCCAATATTGCACTCGTCCCGGCCTCC
750
|
GGCCCCCCCGGCCC
|
|
miR-93
07q22.1
CTGGGGGCTCCAAAGTGCTGTTCGTGCAGGTAGTGTGATTACCCAACCTACTGCTGAGCTAGCACTTCCCGAGCCCCCGG
751
|
|
miR-98
xp11.22
AGGATTCTGCTCATGCCAGGGTGAGGTAGTAAGTTGTATTGTTGTGGGGTAGGGATATTAGGCCCCAATTAGAAGATAACTATAC
752
|
AACTTACTACTTTCCCTGGTGTGTGGCATATTCA
|
|
miR-99b
19q13.41
GGCACCCACCCGTAGAACCGACCTTGCGGGGCCTTCGCCGCACACAAGCTCGTGTCTGTGGGTCCGTGTC
753
|
|
miR-103
5q34
TACTGCCCTCGGCTTCTTTACAGTGCTGCCTTGTTGCATATGGATCAAGCAGCATTGTACAGGGCTATGAAGGCATTG
754
|
|
miR-103
20p13
TTGTGCTTTCAGCTTCTTTACAGTGCTGCCTTGTAGCATTCAGGTCAAGCAGCATTGTACAGGGCTATGAAAGAACCA
755
|
|
miR-106a
Xq26.2
CCTTGGCCATGTAAAAGTGCTTACAGTGCAGGTAGCTTTTTGAGATCTACTGCAATGTAAGCACTTCTTACATTACCATGG
756
|
|
miR-106b
7q22.1
CCTGCCGGGGCTAAAGTGCTGACAGTGCAGATAGTGGTCCTCTCCGTGCTACCGCACTGTGGGTACTTGCTGCTCCAGCAGG
757
|
|
miR-107
10q23.31
CTCTCTGCTTTCAGCTTCTTTACAGTGTTGCCTTGTGGCATGGAGTTCAAGCAGCATTGTACAGGGCTATCAAAGCACAGA
758
|
|
miR-130a
11q12.1
TGCTGCTGGCCAGAGCTCTTTTCACATTGTGCTACTGTCTGCACCTGTCACTAGCAGTGCAATGTTAAAAGGGCATTGGCCGTGT
759
|
AGTG
|
|
miR-130b
22q11.21
GGCCTGCCCGACACTCTTTCCCTGTTGCACTACTATAGGCCGCTGGGAAGCAGTGCAATGATGAAAGGGCATCGGTCAGGTC
760
|
|
miR-134
14q32.31
CAGGGTGTGTGACTGGTTGACCAGAGGGGCATGCACTGTGTTCACCCTGTGGGCCACCTAGTCACCAACCCTC
761
|
|
miR-138
3p21.33
CGTTGCTGCAGCTGGTGTTGTGAATCAGGCCGACGAGCAGCGCATCCTCTTACCCGGCTATTTCACGACACCAGGGTTGCATCA
762
|
|
miR-138
16q13
CCCTGGCATGGTGTGGTGGGGCAGCTGGTGTTGTGAATCAGGCCGTTGCCAATCAGAGAACGGCTACTTCACAACACCAGGGCC
763
|
ACACCACACTACAGG
|
|
miR-15a
13q14.2
CCTTGGAGTAAAGTAGCAGCACATAATGGTTTGTGGATTTTGAAAAGGTGCAGGCCATATTGTGCTGCCTCAAAAATACAAGG
764
|
|
miR-15b
03q25.33
TTGAGGCCTTAAAGTACTGTAGCAGCACATCATGGTTTACATGCTACAGTCAAGATGCGAATCATTATTTGCTGCTCTAGAAATTTA
765
|
AGGAAATTCAT
|
|
miR-17
13q31.3
GTCAGAATAATGTCAAAGTGCTTACAGTGCAGGTAGTGATATGTGCATCTACTGCAGTGAAGGCACTTGTAGCATTATGGTGAC
766
|
|
miR-181a-1
1q31.3
AGAAGGGCTATCAGGCCAGCCTTCAGAGGACTCCAAGGAACATTCAACGCTGTCGGTGAGTTTGGGATTTGAAAAAACCACTGAC
767
|
CGTTGACTGTACCTTGGGGTCCTTA
|
|
miR-181a-2
9q33.3
TGAGTTTTGAGGTTGCTTCAGTGAACATTCAACGCTGTCGGTGAGTTTGGAATTAAAATCAAAACCATCGACCGTTGATTGTACCC
768
|
TATGGCTAACCATCATCTACTCCA
|
|
miR-181b-1
1q31.3
CTGATGGCTGCACTCAACATTCATTGCTGTCGGTGGGTTTGAGTCTGAATCAACTCACTGATCAATGAATGCAAACTGCGGACCAA
769
|
ACA
|
|
miR-181b-2
9q33.3
CCTGTGCAGAGATTATTTTTTAAAAGGTCACAATCAACATTCATTGCTGTCGGTGGGTTGAACTGTGTGGACAAGCTCACTGAACA
770
|
ATGAATGCAACTGTGGCCCCGCTT
|
|
miR-191
03p21.31
CGGCTGGACAGCGGGCAACGGAATCCCAAAAGCAGCTGTTGTCTCCAGAGCATTCCAGCTGCGCTTGGATTTCGTCCCCTGCTC
771
|
TCCTGCCT
|
|
miR-195
17p13.1
AGCTTCCCTGGCTCTAGCAGCACAGAAATATTGGCACAGGGAAGCGAGTCTGCCAATATTGGCTGTGCTGCTCCAGGCAGGGTG
772
|
GTG
|
|
miR-196b
07p15.2
ACTGGTCGGTGATTTAGGTAGTTTCCTGTTGTTGGGATCCACCTTTCTCTCGACAGCACGACACTGCCTTCATTACTTCAGTTG
773
|
|
miR-19a
13q31.3
GCAGTCCTCTGTTAGTTTTGCATAGTTGCACTACAAGAAGAATGTAGTTGTGCAAATCTATGCAAAACTGATGGTGGCCTGC
774
|
|
miR-20a
13q31.3
GTAGCACTAAAGTGCTTATAGTGCAGGTAGTGTTTAGTTATCTACTGCATTATGAGCACTTAAAGTACTGC
775
|
|
miR-20b
Xq26.2
AGTACCAAAGTGCTCATAGTGCAGGTAGTTTTGGCATGACTCTACTGTAGTATGGGCACTTCCAGTACT
776
|
|
miR-22
17p13.3
GGCTGAGCCGCAGTAGTTCTTCAGTGGCAAGCTTTATGTCCTGACCCAGCTAAAGCTGCCAGTTGAAGAACTGTTGCCCTCTGCC
777
|
|
miR-221
Xp11.3
TGAACATCCAGGTCTGGGGCATGAACCTGGCATACAATGTAGATTTCTGTGTTCGTTAGGCAACAGCTACATTGTCTGCTGGGTTT
778
|
CAGGCTACCTGGAAACATGTTCTC
|
|
miR-222
Xp11.3
GCTGCTGGAAGGTGTAGGTACCCTCAATGGCTCAGTAGCCAGTGTAGATCCTGTCTTTCGTAATCAGCAGCTACATCTGGCTACT
779
|
GGGTCTCTGATGGCATCTTCTAGCT
|
|
miR-25
07q22.1
GGCCAGTGTTGAGAGGCGGAGACTTGGGCAATTGCTGGACGCTGCCCTGGGCATTGCACTTGTCTCGGTCTGACAGTGCCGGCC
780
|
|
miR-29c
01q32.2
ATCTCTTACACAGGCTGACCGATTTCTCCTGGTGTTCAGAGTCTGTTTTTGTCTAGCACCATTTGAAATCGGTTATGATGTAGGGG
781
|
GA
|
|
miR-31
09p21.3
GGAGAGGAGGCAAGATGCTGGCATAGCTGTTGAACTGGGAACCTGCTATGCCAACATATTGCCATCTTTCC
782
|
|
miR-335
07q32.2
TGTTTTGAGCGGGGGTCAAGAGCAATAACGAAAAATGTTTGTCATAAACCGTTTTTCATTATTGCTCCTGACCTCCTCTCATTTGCT
783
|
ATATTCA
|
|
miR-342-3p
14q32.2
GAAACTGGGCTCAAGGTGAGGGGTGCTATCTGTGATTGAGGGACATGGTTAATGGAATTGTCTCACACAGAAATCGCACCCGTCA
784
|
CCTTGGCCTACTTA
|
|
miR-370
14q32.31
AGACAGAGAAGCCAGGTCACGTCTCTGCAGTTACACAGCTCACGAGTGCCTGCTGGGGTGGAACCTGGTCTGTCT
785
|
|
miR-452
Xq28
GCTAAGCACTTACAACTGTTTGCAGAGGAAACTGAGACTTTGTAACTATGTCTCAGTCTCATCTGCAAAGAAGTAAGTGCTTTGC
786
|
|
miR-494
14q32.31
GATACTCGAAGGAGAGGTTGTCCGTGTTGTCTTCTCTTTATTTATGATGAAACATACACGGGAAACCTCTTTTTTAGTATC
787
|
|
miR-7-1
9q21.32
TTGGATGTTGGCCTAGTTCTGTGTGGAAGACTAGTGATTTTGTTGTTTTTAGATAACTAAATCGACAACAAATCACAGTCTGCCATA
788
|
TGGCACAGGCCATGCCTCTACAG
|
|
miR-7-3
19p13.3
AGATTAGAGTGGCTGTGGTCTAGTGCTGTGTGGAAGACTAGTGATTTTGTTGTTCTGATGTACTACGACAACAAGTCACAGCCGG
789
|
CCTCATAGCGCAGACTCCCTTCGAC
|
|
miR-7-2
15q26.1
CTGGATACAGAGTGGACCGGCTGGCCCCATCTGGAAGACTAGTGATTTTGTTGTTGTCTTACTGCGCTCAACAACAAATCCCAGT
790
|
CTACCTAATGGTGCCAGCCATCGCA
|
|
miR-92-a1
13q31.3
CTTTCTACACAGGTTGGGATCGGTTGCAATGCTGTGTTTCTGTATGGTATTGCACTTGTCCCGGCCTGTTGAGTTTGG
791
|
|
miR-92-a2
Xq26.2
TCATCCCTGGGTGGGGATTTGTTGCATTACTTGTGTTCTATATAAAGTATTGCACTTGTCCCGGCCTGTGGAAGA
792
|
|
miR-99a
21q21.1
CCCATTGGCATAAACCCGTAGATCCGATCTTGTGGTGAAGTGGACCGCACAAGCTCGCTTCTATGGGTCTGTGTCAGTGTG
793
|
|
TABLE 4
|
|
Mature microRNA Sequences (5′to 3′)
|
microRNA
sequence
SEQ ID NO
|
|
let-7a
UGAGGUAGUAGGUUGUAUAGUU
794
|
|
let-7b
UGAGGUAGUAGGUUGUGUGGUU
795
|
|
let-7c
UGAGGUAGUAGGUUGUAUGGUU
796
|
|
let-7d
AGAGGUAGUAGGUUGCAUAGUU
797
|
|
let-7e
UGAGGUAGGAGGUUGUAUAGUU
798
|
|
let-7f
UGAGGUAGUAGAUUGUAUAGUU
799
|
|
let-7g
UGAGGUAGUAGUUUGUACAGUU
800
|
|
let-7i
UGAGGUAGUAGUUUGUGCUGUU
801
|
|
miR-100
AACCCGUAGAUCCGAACUUGUG
802
|
|
miR-103
AGCAGCAUUGUACAGGGCUAUGA
803
|
|
miR-106a
AAAAGUGCUUACAGUGCAGGUAG
804
|
|
miR-106b
UAAAGUGCUGACAGUGCAGAU
805
|
|
miR-107
AGCAGCAUUGUACAGGGCUAUCA
806
|
|
miR-1224-5p
GUGAGGACUCGGGAGGUGG
807
|
|
miR-1225-5p
GUGGGUACGGCCCAGUGGGGGG
808
|
|
miR-1228*
GUGGGCGGGGGCAGGUGUGUG
809
|
|
miR-125a-5p
UCCCUGAGACCCUUUAACCUGUGA
810
|
|
miR-125b
UCCCUGAGACCCUAACUUGUGA
811
|
|
miR-126
UCGUACCGUGAGUAAUAAUGCG
812
|
|
miR-130a
CAGUGCAAUGUUAAAAGGGCAU
813
|
|
miR-130b
CAGUGCAAUGAUGAAAGGGCAU
814
|
|
miR-134
UGUGACUGGUUGACCAGAGGGG
815
|
|
miR-138
AGCUGGUGUUGUGAAUCAGGCCG
816
|
|
miR-135a*
UAUAGGGAUUGGAGCCGUGGCG
817
|
|
miR-142-3p
UGUAGUGUUUCCUACUUUAUGGA
818
|
|
miR-145
GUCCAGUUUUCCCAGGAAUCCCU
819
|
|
miR-146b-5p
UGAGAACUGAAUUCCAUAGGCU
820
|
|
miR-149*
AGGGAGGGACGGGGGCUGUGC
821
|
|
miR-150*
CUGGUACAGGCCUGGGGGACAG
822
|
|
miR-155
UUAAUGCUAAUCGUGAUAGGGGU
823
|
|
miR-15a
UAGCAGCACAUAAUGGUUUGUG
824
|
|
miR-15b
UAGCAGCACAUCAUGGUUUACA
825
|
|
miR-16
UAGCAGCACGUAAAUAUUGGCG
826
|
|
miR-17
CAAAGUGCUUACAGUGCAGGUAG
827
|
|
miR-181a
AACAUUCAACGCUGUCGGUGAGU
828
|
|
miR-181b
AACAUUCAUUGCUGUCGGUGGGU
829
|
|
miR-181c
AACAUUCAACCUGUCGGUGAGU
830
|
|
miR-191
CAACGGAAUCCCAAAAGCAGCUG
831
|
|
miR-195
UAGCAGCACAGAAAUAUUGGC
832
|
|
miR-196b
UAGGUAGUUUCCUGUUGUUGGG
833
|
|
miR-198
GGUCCAGAGGGGAGAUAGGUUC
834
|
|
miR-199a-3p
ACAGUAGUCUGCACAUUGGUUA
835
|
|
miR-199b-3p
ACAGUAGUCUGCACAUUGGUUA
836
|
|
miR-19a
UGUGCAAAUCUAUGCAAAACUGA
837
|
|
miR-19b
UGUGCAAAUCCAUGCAAAACUGA
838
|
|
miR-200b
UAAUACUGCCUGGUAAUGAUGA
839
|
|
miR-200c
UAAUACUGCCGGGUAAUGAUGGA
840
|
|
miR-205
UCCUUCAUUCCACCGGAGUCUG
841
|
|
miR-20a
UAAAGUGCUUAUAGUGCAGGUAG
842
|
|
miR-20b
CAAAGUGCUCAUAGUGCAGGUAG
843
|
|
miR-21
UAGCUUAUCAGACUGAUGUUGA
844
|
|
miR-22
AAGCUGCCAGUUGAAGAACUGU
845
|
|
miR-221
AGCUACAUUGUCUGCUGGGUUUC
846
|
|
miR-222
AGCUACAUCUGGCUACUGGGU
847
|
|
miR-23a
AUCACAUUGCCAGGGAUUUCC
848
|
|
miR-23a*
GGGGUUCCUGGGGAUGGGAUUU
849
|
|
miR-23b
AUCACAUUGCCAGGGAUUACC
850
|
|
miR-24
UGGCUCAGUUCAGCAGGAACAG
851
|
|
miR-25
CAUUGCACUUGUCUCGGUCUGA
852
|
|
miR-25*
AGGCGGAGACUUGGGCAAUUG
853
|
|
miR-26a
UUCAAGUAAUCCAGGAUAGGCU
854
|
|
miR-26b
UUCAAGUAAUUCAGGAUAGGU
855
|
|
miR-27a
UUCACAGUGGCUAAGUUCCGC
856
|
|
miR-27b
UUCACAGUGGCUAAGUUCUGC
857
|
|
miR-298
AGCAGAAGCAGGGAGGUUCUCCCA
858
|
|
miR-29a
UAGCACCAUCUGAAAUCGGUUA
859
|
|
miR-29b
UAGCACCAUUUGAAAUCAGUGUU
860
|
|
miR-29c
UAGCACCAUUUGAAAUCGGUUA
861
|
|
miR-29c*
UGACCGAUUUCUCCUGGUGUUC
862
|
|
miR-30a
UGUAAACAUCCUCGACUGGAAG
863
|
|
miR-30b
UGUAAACAUCCUACACUCAGCU
864
|
|
miR-30b*
CUGGGAGGUGGAUGUUUACUUC
865
|
|
miR-30c
UGUAAACAUCCUACACUCUCAGC
866
|
|
miR-30c-1*
CUGGGAGAGGGUUGUUUACUCC
867
|
|
miR-30c-2
UGUAAACAUCCUACACUCUCAGC
868
|
|
miR-30d
UGUAAACAUCCCCGACUGGAAG
869
|
|
miR-30e
UGUAAACAUCCUUGACUGGAAG
870
|
|
miR-31
AGGCAAGAUGCUGGCAUAGCU
871
|
|
miR-320a
AAAAGCUGGGUUGAGAGGGCGA
872
|
|
miR-331-3p
GCCCCUGGGCCUAUCCUAGAA
873
|
|
miR-335
UCAAGAGCAAUAACGAAAAAUGU
874
|
|
miR-342-3p
UCUCACACAGAAAUCGCACCCGU
875
|
|
miR-370
GCCUGCUGGGGUGGAACCUGGU
876
|
|
miR-371-5p
ACUCAAACUGUGGGGGCACU
877
|
|
miR-373*
ACUCAAAAUGGGGGCGCUUUCC
878
|
|
miR-375
UUUGUUCGUUCGGCUCGCGUGA
879
|
|
miR-423-5p
UGAGGGGCAGAGAGCGAGACUUU
880
|
|
miR-424
CAGCAGCAAUUCAUGUUUUGAA
881
|
|
miR-452
AACUGUUUGCAGAGGAAACUGA
882
|
|
miR-483-5p
AAGACGGGAGGAAAGAAGGGAG
883
|
|
miR-486-3p
CGGGGCAGCUCAGUACAGGAU
884
|
|
miR-491-3p
CUUAUGCAAGAUUCCCUUCUAC
885
|
|
miR-491-5p
AGUGGGGAACCCUUCCAUGAGG
886
|
|
miR-494
UGAAACAUACACGGGAAACCUC
887
|
|
miR-513a-5p
UUCACAGGGAGGUGUCAU
888
|
|
miR-513b
UUCACAAGGAGGUGUCAUUUAU
889
|
|
miR-516a-5p
UUCUCGAGGAAAGAAGCACUUUC
890
|
|
miR-550
AGUGCCUGAGGGAGUAAGAGCCC
891
|
|
miR-557
GUUUGCACGGGUGGGCCUUGUCU
892
|
|
miR-575
GAGCCAGUUGGACAGGAGC
893
|
|
miR-612
GCUGGGCAGGGCUUCUGAGCUCCUU
894
|
|
miR-614
GAACGCCUGUUCUUGCCAGGUGG
895
|
|
miR-630
AGUAUUCUGUACCAGGGAAGGU
896
|
|
miR-637
ACUGGGGGCUUUCGGGCUCUGCGU
897
|
|
miR-638
AGGGAUCGCGGGCGGGUGGCGGCCU
898
|
|
miR-658
GGCGGAGGGAAGUAGGUCCGUUGGU
899
|
|
miR-663
AGGCGGGGCGCCGCGGGACCGC
900
|
|
miR-671-5p
AGGAAGCCCUGGAGGGGCUGGAG
901
|
|
miR-675
UGGUGCGGAGAGGGCCCACAGUG
902
|
|
miR-7
UGGAAGACUAGUGAUUUUGUUGU
903
|
|
miR-708
AAGGAGCUUACAAUCUAGCUGGG
904
|
|
miR-744
UGCGGGGCUAGGGCUAACAGCA
905
|
|
miR-765
UGGAGGAGAAGGAAGGUGAUG
906
|
|
miR-920
GGGGAGCUGUGGAAGCAGUA
907
|
|
miR-923
GUCAGCGGAGGAAAAGAAACU
908
|
|
miR-92a
UAUUGCACUUGUCCCGGCCUGU
909
|
|
miR-92a-2*
GGGUGGGGAUUUGUUGCAUUAC
910
|
|
miR-92b*
AGGGACGGGACGCGGUGCAGUG
911
|
|
miR-93
CAAAGUGCUGUUCGUGCAGGUAG
912
|
|
miR-98
UGAGGUAGUAAGUUGUAUUGUU
913
|
|
miR-99a
AACCCGUAGAUCCGAUCUUGUG
914
|
|
miR-99b
CACCCGUAGAACCGACCUUGCG
915
|
|
miR-200a
ACAUCGUUACCAGACAGUGUUA
916
|
|
miR-720
UGGAGGCCCCAGCGAGA
917
|
|
miR-1202
CUCCCCCACUGCAGCUGGCAC
918
|
|
miR-1249
UGAAGAAGGGGGGGAAGGGCGU
919
|
|
miR-1275
GACAGCCUCUCCCCCAC
920
|
|
miR-129-3p
AUGCUUUUUGGGGUAAGGGCUU
921
|
|
miR-1321
AUCACAUUCACCUCCCUG
922
|
|
miR-1323
AGAAAAUGCCCCUCAGUUUUGA
923
|
|
miR-376c
ACGUGGAAUUUCCUCUAUGUU
924
|
|
miR-429
ACGGUUUUACCAGACAGUAUUA
925
|
|
TABLE 5
|
|
Mature microRNA Sequences (5′-3′)
|
microRNA
sequence
SEQ ID NO
|
|
miR-1
UGGAAUGUAAAGAAGUAUGUA
926
|
|
miR-9
UCUUUGGUUAUCUAGCUGUAUGA
927
|
|
miR-9*
UAAAGCUAGAUAACCGAAAGU
928
|
|
miR-10a
UACCCUGUAGAUCCGAAUUUGUG
929
|
|
miR-10b
UACCCUGUAGAACCGAAUUUGU
930
|
|
miR-17-3p
ACUGCAGUGAAGGCACUUGU
931
|
|
miR-18
UAAGGUGCAUCUAGUGCAGAUA
932
|
|
miR-20
UAAAGUGCUUAUAGUGCAGGUA
933
|
|
miR-28
AAGGAGCUCACAGUCUAUUGAG
934
|
|
miR-30a-3p
CUUUCAGUCGGAUGUUUGCAGC
935
|
|
miR-32
UAUUGCACAUUACUAAGUUGC
936
|
|
miR-33
GUGCAUUGUAGUUGCAUUG
937
|
|
miR-34a
UGGCAGUGUCUUAGCUGGUUGU
938
|
|
miR-34b
AGGCAGUGUCAUUAGCUGAUUG
939
|
|
miR-34c
AGGCAGUGUAGUUAGCUGAUUG
940
|
|
miR-92
UAUUGCACUUGUCCCGGCCUGU
941
|
|
miR-95
UUCAACGGGUAUUUAUUGAGCA
942
|
|
miR-96
UUUGGCACUAGCACAUUUUUGC
943
|
|
miR-101
UACAGUACUGUGAUAACUGAAG
944
|
|
miR-105
UCAAAUGCUCAGACUCCUGU
945
|
|
miR-122a
UGGAGUGUGACAAUGGUGUUUGU
946
|
|
miR-124a
UUAAGGCACGCGGUGAAUGCCA
947
|
|
miR-126*
CAUUAUUACUUUUGGUACGCG
948
|
|
miR-127
UCGGAUCCGUCUGAGCUUGGCU
949
|
|
miR-128a
UCACAGUGAACCGGUCUCUUUU
950
|
|
miR-128b
UCACAGUGAACCGGUCUCUUUC
951
|
|
miR-129
CUUUUUGCGGUCUGGGCUUGC
952
|
|
miR-132
UAACAGUCUACAGCCAUGGUCG
953
|
|
miR-133a
UUGGUCCCCUUCAACCAGCUGU
954
|
|
miR-133b
UUGGUCCCCUUCAACCAGCUA
955
|
|
miR-135a
UAUGGCUUUUUAUUCCUAUGUGA
956
|
|
miR-135b
UAUGGCUUUUCAUUCCUAUGUG
957
|
|
miR-136
ACUCCAUUUGUUUUGAUGAUGGA
958
|
|
miR-137
UAUUGCUUAAGAAUACGCGUAG
959
|
|
miR-139
UCUACAGUGCACGUGUCU
960
|
|
miR-140
AGUGGUUUUACCCUAUGGUAG
961
|
|
miR-141
AACACUGUCUGGUAAAGAUGG
962
|
|
miR-142-5p
CAUAAAGUAGAAAGCACUAC
963
|
|
miR-143
UGAGAUGAAGCACUGUAGCUCA
964
|
|
miR-144
UACAGUAUAGAUGAUGUACUAG
965
|
|
miR-146
UGAGAACUGAAUUCCAUGGGUU
966
|
|
miR-147
GUGUGUGGAAAUGCUUCUGC
967
|
|
miR-148a
UCAGUGCACUACAGAACUUUGU
968
|
|
miR-148b
UCAGUGCAUCACAGAACUUUGU
969
|
|
miR-149
UCUGGCUCCGUGUCUUCACUCC
970
|
|
miR-150
UCUCCCAACCCUUGUACCAGUG
971
|
|
miR-151
ACUAGACUGAAGCUCCUUGAGG
972
|
|
miR-152
UCAGUGCAUGACAGAACUUGG
973
|
|
miR-153
UUGCAUAGUCACAAAAGUGA
974
|
|
miR-154
UAGGUUAUCCGUGUUGCCUUCG
975
|
|
miR-154*
AAUCAUACACGGUUGACCUAUU
976
|
|
miR-182
UUUGGCAAUGGUAGAACUCACA
977
|
|
miR-182*
UGGUUCUAGACUUGCCAACUA
978
|
|
miR-183
UAUGGCACUGGUAGAAUUCACUG
979
|
|
miR-184
UGGACGGAGAACUGAUAAGGGU
980
|
|
miR-185
UGGAGAGAAAGGCAGUUC
981
|
|
miR-186
CAAAGAAUUCUCCUUUUGGGCUU
982
|
|
miR-187
UCGUGUCUUGUGUUGCAGCCG
983
|
|
miR-188
CAUCCCUUGCAUGGUGGAGGGU
984
|
|
miR-189
GUGCCUACUGAGCUGAUAUCAGU
985
|
|
miR-190
UGAUAUGUUUGAUAUAUUAGGU
986
|
|
miR-192
CUGACCUAUGAAUUGACAGCC
987
|
|
miR-193
AACUGGCCUACAAAGUCCCAG
988
|
|
miR-194
UGUAACAGCAACUCCAUGUGGA
989
|
|
miR-196a
UAGGUAGUUUCAUGUUGUUGG
990
|
|
miR-197
UUCACCACCUUCUCCACCCAGC
991
|
|
miR-200a
UAACACUGUCUGGUAACGAUGU
992
|
|
miR-202
AGAGGUAUAGGGCAUGGGAAGA
993
|
|
miR-203
GUGAAAUGUUUAGGACCACUAG
994
|
|
miR-204
UUCCCUUUGUCAUCCUAUGCCU
995
|
|
miR-206
UGGAAUGUAAGGAAGUGUGUGG
996
|
|
miR-208
AUAAGACGAGCAAAAAGCUUGU
997
|
|
miR-210
CUGUGCGUGUGACAGCGGCUG
998
|
|
miR-211
UUCCCUUUGUCAUCCUUCGCCU
999
|
|
miR-212
UAACAGUCUCCAGUCACGGCC
1000
|
|
miR-213
ACCAUCGACCGUUGAUUGUACC
1001
|
|
miR-214
ACAGCAGGCACAGACAGGCAG
1002
|
|
miR-215
AUGACCUAUGAAUUGACAGAC
1003
|
|
miR-216
UAAUCUCAGCUGGCAACUGUG
1004
|
|
miR-217
UACUGCAUCAGGAACUGAUUGGAU
1005
|
|
miR-218
UUGUGCUUGAUCUAACCAUGU
1006
|
|
miR-219
UGAUUGUCCAAACGCAAUUCU
1007
|
|
miR-220
CCACACCGUAUCUGACACUUU
1008
|
|
miR-223
UGUCAGUUUGUCAAAUACCCC
1009
|
|
miR-224
CAAGUCACUAGUGGUUCCGUUUA
1010
|
|
miR-296
AGGGCCCCCCCUCAAUCCUGU
1011
|
|
miR-299
UGGUUUACCGUCCCACAUACAU
1012
|
|
miR-301
CAGUGCAAUAGUAUUGUCAAAGC
1013
|
|
miR-302a
UAAGUGCUUCCAUGUUUUGGUGA
1014
|
|
miR-302b*
ACUUUAACAUGGAAGUGCUUUCU
1015
|
|
miR-302b
UAAGUGCUUCCAUGUUUUAGUAG
1016
|
|
miR-302c*
UUUAACAUGGGGGUACCUGCUG
1017
|
|
miR-302c
UAAGUGCUUCCAUGUUUCAGUGG
1018
|
|
miR-302d
UAAGUGCUUCCAUGUUUGAGUGU
1019
|
|
miR-320
AAAAGCUGGGUUGAGAGGGCGAA
1020
|
|
miR-321
UAAGCCAGGGAUUGUGGGUUC
1021
|
|
miR-323
GCACAUUACACGGUCGACCUCU
1022
|
|
miR-324-5p
CGCAUCCCCUAGGGCAUUGGUGU
1023
|
|
miR-324-3p
CCACUGCCCCAGGUGCUGCUGG
1024
|
|
miR-325
CCUAGUAGGUGUCCAGUAAGU
1025
|
|
miR-326
CCUCUGGGCCCUUCCUCCAG
1026
|
|
miR-328
CUGGCCCUCUCUGCCCUUCCGU
1027
|
|
miR-330
GCAAAGCACACGGCCUGCAGAGA
1028
|
|
miR-331
GCCCCUGGGCCUAUCCUAGAA
1029
|
|
miR-337
UCCAGCUCCUAUAUGAUGCCUUU
1030
|
|
miR-338
UCCAGCAUCAGUGAUUUUGUUGA
1031
|
|
miR-339
UCCCUGUCCUCCAGGAGCUCA
1032
|
|
miR-340
UCCGUCUCAGUUACUUUAUAGCC
1033
|
|
miR-342
UCUCACACAGAAAUCGCACCCGUC
1034
|
|
miR-345
UGCUGACUCCUAGUCCAGGGC
1035
|
|
miR-346
UGUCUGCCCGCAUGCCUGCCUCU
1036
|
|
miR-367
AAUUGCACUUUAGCAAUGGUGA
1037
|
|
miR-368
ACAUAGAGGAAAUUCCACGUUU
1038
|
|
miR-369
AAUAAUACAUGGUUGAUCUUU
1039
|
|
miR-371
GUGCCGCCAUCUUUUGAGUGU
1040
|
|
miR-372
AAAGUGCUGCGACAUUUGAGCGU
1041
|
|
miR-373
GAAGUGCUUCGAUUUUGGGGUGU
1042
|
|
miR-374
UUAUAAUACAACCUGAUAAGUG
1043
|
|
miR-320c
AAAAGCUGGGUUGAGAGGGU
2692
|
|
TABLE 6
|
|
Up-regulated target RNAs for detection of non-small cell lung cancer
|
Probe SEQ
Fold changes v. normal Lung
|
Array Probe
ID NO.
Epi4
Epi7
Epi5
Adk1
Adk3
Adk11
Adk8
Adk9
Adk2
Adk10
|
|
miR-21
196
−2.52
1.77
−1.51
1.45
1.41
3.51
2.27
3.43
5.38
1.25
|
miR-765
246
25.46
3.15
3.08
6.06
−1.58
3.70
1.82
3.00
−1.58
1.02
|
4037-R3-2
15
6.57
1.44
−1.28
2.17
−1.28
2.17
2.34
2.64
6.81
−1.06
|
miR-27b
205
−1.11
2.20
2.52
−1.91
1.18
1.64
1.24
2.05
6.50
−1.85
|
miR-29a
207
−2.68
1.00
3.18
1.50
−1.90
2.13
1.41
1.23
2.18
−2.96
|
miR-923
248
6.70
1.19
1.24
1.35
−2.18
1.11
−1.43
1.19
2.00
−2.79
|
miR-199a-3p
191
−3.52
1.40
1.43
−1.94
1.72
1.56
1.33
1.59
2.97
−4.20
|
miR-331-3p
219
−1.21
−1.21
2.17
1.42
1.24
1.47
1.27
−1.21
−1.21
1.36
|
miR-23a
197
1.38
2.90
−4.40
1.37
−4.40
2.28
−4.40
2.38
7.76
−2.09
|
miR-146b-5p
184
−1.89
1.12
2.44
−1.89
−1.89
2.71
1.07
1.30
2.48
−1.21
|
miR-483-5p
225
24.38
1.51
1.68
5.17
−1.54
1.11
−1.64
3.19
−1.54
−1.03
|
9733-L3-1
129
7.61
3.56
−1.48
2.44
−1.48
−1.48
1.07
1.69
−1.48
1.33
|
miR-30c-1*
214
39.98
−1.58
1.57
7.84
−1.58
−1.58
−1.42
2.67
−1.58
−1.58
|
4593-R3-1
26
8.31
2.80
1.23
1.93
−4.73
−2.65
−5.00
1.79
−9.77
1.20
|
8433_C-R4-1
164
24.29
1.73
1.87
5.70
−1.45
−1.45
−1.45
1.95
−1.45
1.13
|
4855-R3-1
30
8.26
1.91
1.44
1.78
−3.56
−1.50
−1.81
1.87
−2.80
1.20
|
4666-R4-1
27
24.77*
2.27
3.49*
7.40*
−2.36
−1.70
−2.05
2.37
−3.62
−1.01
|
|
TABLE 7
|
|
Target RNAs more frequently present at elevated levels
|
in squamous cell carcinoma (SCC)
|
Number of
|
Fold
adenocarcinomas
Number of
Pre-
|
change
with
SCC with
Probe
microRNA
|
average in
increased
increased
SEQ ID
SEQ ID
microRNA
|
Gene
SCC
levels
levels
NO
NO
SEQ ID NO
|
|
10366-R3-2
4.1
1
6
145
539
|
12223-L5-1
3.2
2
5
2110
2234
2584
|
12907-L5-1
6.4
0
5
1106
1228
|
12911-L5-1
3.2
2
5
2115
2239
2590
|
12917-R5-2
6.0
1
6
1108
1230
|
13108-L5-2
3.3
1
5
2673
2681
2595
|
13122-L5-1
11.5
2
7
1066
1242
2597
|
13272-R5-2
4.0
1
5
2674
2682
2611
|
13316-R5-2
2.8
0
5
2675
2683
2616
|
13331-L5-2
4.1
1
5
2676
2684
2617
|
13499-R5-1
3.3
2
5
2677
2685
2634
|
3923-R5-1
5.3
3
7
1070
1273
2647
|
4261-R5-1
6.4
0
5
1148
1277
|
4479-R3-1
4.3
1
6
25
421
|
5232-L5-2
5.2
0
5
1154
1287
2653
|
5392-R5-1
7.0
2
5
1155
1288
2654
|
5971-R5-2
2.6
1
5
2678
2686
2657
|
6183-R5-1
2.8
0
5
2149
2274
|
7026-L3-1
2.8
1
5
2679
2687
|
7292-L3-2
3.5
2
6
80
476
|
7471-L5-1
4.5
1
5
2680
2688
|
8004-R3-2
11.0
2
6
97
492
|
8316-R5-1
20.3
1
5
1177
1315
|
9349-R5-2
24.4
3
6
1080
1325
2672
|
9594-R5-1
9.7
2
6
1081
1328
|
miR-1323
4.9
2
6
1197
1338
923
|
miR-205
21.2
3
7
195
694
841
|
miR-675
2.9
2
5
243
743
902
|
miR-923
3.5
3
6
248
748
908
|
|
TABLE 8
|
|
Target RNAs more frequently present at elevated levels in adenocarcinoma
|
Number of
Number of
Pre-
|
Fold change
adenocarcinomas
SCC with
Probe
microRNA
microRNA
|
average in
with increased
increased
SEQ ID
SEQ ID
SEQ ID
|
Gene
adenocarcinoma
levels
levels
NO
NO
NO
|
|
13252-L5-3
4.9
5
1
1123
1249
2609
|
13373-R5-2
5.1
5
3
1130
1257
2624
|
9798-L5-1
9.9
5
3
1188
1329
|
miR-106b
4.5
5
2
363
757
805
|
miR-20b
4.8
6
2
1086
1349
843
|
miR-92a
4.0
4
0
2180
2307
909
|
miR-93
3.8
5
1
251
751
912
|
|
TABLE 9
|
|
Target RNAs present at increased levels in
|
aggressive forms of lung cancer
|
Probe
|
SEQ
Pre-microRNA
microRNA
|
Gene
ID NO
SEQ ID NO(s)
SEQ ID NO
|
|
10083-L5-1
1090
1211
|
10233-R5-1
1091
1212
2576
|
10455-L5-1
1063
1215
2578
|
11444-L5-3
1097
1219
|
12729-R5-1
1103
1225
|
12888-L5-2
1105
1227
|
12907-L5-1
1106
1228
|
12917-R5-2
1108
1230
|
12947-L5-4
1064
1231
|
12974-R5-2
1110
1233
2592
|
12979-R5-2
1111
1234
|
13001-L5-1
1113
1236
|
13070-R5-3
1115
1238
|
13122-L5-1
1066
1242
2597
|
13185-L5-3
1118
1243
2603
|
13219-L5-1
1067
1245
|
13245-L5-4
1122
1248
2607
|
13274-L5-3
1124
1251
2612
|
13357-L5-4
1128
1255
2621
|
13398-R5-4
1132
1259
2627
|
13467-L5-1
1069
1262
2630
|
13468-L5-1
1135
1263
2631
|
13470-R5-1
1136
1264
|
13473-L5-3
1137
1265
2633
|
13500-L5-3
1138
1266
2635, 2636
|
3744-R5-1
1143
1271
2645, 2646
|
3875-R5-2
1144
1272
|
3992-R5-1
1146
1275
|
4790-L5-2
1150
1282
|
5060-R3-1
1073
1285
2650
|
5108-R5-2
1153
1286
|
5392-R5-1
1155
1288
2654
|
6037-R3-2
1159
1292
2658
|
6181-L5-1
1160
1293
|
6233-L5-2
1161
1295
|
6235-R5-2
1075
1296
2661
|
6474-L5-1
1164
1299
|
6602-R3-1
1165
1300
|
6683-R5-1
1167
1302
|
6906-L5-1
1172
1307
2666
|
6930-R5-1
1173
1308
2667
|
7764-R3-2
1175
1312
|
8004-R3-2
97
492
|
8316-R5-1
1177
1315
|
836-R5-2
1079
1316
|
8433_C-R4-1
1177
1317
|
8808-R5-1
1183
1322
|
9349-R5-2
1080
1325
2672
|
9594-R5-1
1081
1328
|
miR-198
1202
1343
834
|
miR-298
1088
1351
858
|
miR-30c-1*
1204
1352
867
|
miR-320c
2689
2690, 2691
2692
|
miR-516a-5p
1209
1357
890
|
miR-765
246
746
906
|
|
In some embodiments, target RNAs can be measured in samples collected at one or more times from a patient to monitor the status or progress of lung cancer in the patient.
In some embodiments, a sample to be tested is obtained using one or more techniques commonly used for collecting lung tissue, e.g., bronchoscopy, bronchial washing, brushing, or transbronchial needle aspiration. In some embodiments, the sample is obtained from a patient without lesions by bronchoalveolar lavage, i.e., washing the airways with saline, to obtain cells. In some embodiments, the sample is obtained by biopsy, such as computed tomography (CT)-aided needle biopsy.
In some embodiments, the sample to be tested is a bodily fluid, such as blood, sputum, mucus, saliva, urine, semen, etc. In some embodiments, a sample to be tested is a blood sample. In some embodiments, the blood sample is whole blood. In some embodiments, the blood sample is a sample of blood cells. In some embodiments, the blood sample is plasma. In some embodiments, the blood sample is serum.
The clinical sample to be tested is, in some embodiments, freshly obtained. In other embodiments, the sample is a fresh frozen specimen. In some embodiments, the sample is a tissue sample, such as a formalin-fixed paraffin embedded sample. In some embodiments, the sample is a liquid cytology sample.
In some embodiments, the methods described herein are used for early detection of lung cancer in a sample of lung cells, such as those obtained by routine bronchoscopy. In some embodiments, the methods described herein are used for early detection of lung cancer in a sample of blood or serum.
In some embodiments, the clinical sample to be tested is obtained from individuals who have one or more of the following risk factors: history of smoking, over 45 years of age, exposure to radon gas, secondhand smoke or occupational carcinogens (e.g., asbestos, radiation, arsenic, chromates, nickel, chloromethyl ethers, mustard gas, or coke-oven emissions), or lungs scarred by prior disease such as tuberculosis. In some embodiments, the clinical sample is obtained from individuals who have diagnostic signs or clinical symptoms that may be associated with lung cancer, such as abnormal chest x-ray and/or computed tomography (“CT”) scan, cough, localized chest pain, or hoarseness.
Thus, in some embodiments, methods described herein can be used for routine screening of healthy individuals with no risk factors. In some embodiments, methods described herein are used to screen asymptomatic individuals having one or more of the above-described risk factors.
In some embodiments, the methods described herein can be used to assess the effectiveness of a treatment for lung cancer in a patient. In some embodiments, the target RNA expression levels are determined at various times during the treatment, and are compared to target RNA expression levels from an archival sample taken from the patient, e.g., by bronchoscopy, before the manifestation of any signs of lung cancer or before beginning treatment. In some embodiments, the target RNA expression levels are compared to target RNA expression levels from an archival sample of normal tissue taken from the patient, i.e., a sample of tissue taken from a tumor-free part of the patient's lung by biopsy. Ideally, target RNA expression levels in the normal sample evidence no aberrant changes in target RNA expression levels. Thus, in such embodiments, the progress of treatment of an individual with lung cancer can be assessed by comparison to a sample of lung cells from the same individual when he was healthy or prior to beginning treatment, or by comparison to a sample of healthy lung cells from the same individual.
In embodiments in which the method comprises detecting expression of more than one target RNA, the expression levels of the plurality of target RNAs may be detected concurrently or simultaneously in the same assay reaction. In some embodiments, expression levels are detected concurrently or simultaneously in separate assay reactions. In some embodiments, expression levels are detected at different times, e.g., in serial assay reactions.
In some embodiments, a method comprises detecting the level of at least one target RNA in a sample from a subject, wherein detection of a level of at least one target RNA that is greater than a normal level of the at least one target RNA indicates the presence of lung cancer in the subject. In some embodiments, a method comprises detecting the level of at least one target RNA in a sample from a subject and comparing the level of the at least one target RNA in the sample to a normal level of the at least one target RNA, wherein a level of at least one target RNA in the sample that is greater than a normal level of the at least one target RNA indicates the presence of lung cancer in the subject.
In some embodiments, a method of facilitating diagnosis of lung cancer in a subject is provided. Such methods comprise detecting the level of at least one target RNA in a sample from the subject. In some embodiments, information concerning the level of at least one target RNA in the sample from the subject is communicated to a medical practitioner. A “medical practitioner,” as used herein, refers to an individual or entity that diagnoses and/or treats patients, such as a hospital, a clinic, a physician's office, a physician, a nurse, or an agent of any of the aforementioned entities and individuals. In some embodiments, detecting the level of at least one target RNA is carried out at a laboratory that has received the subject's sample from the medical practitioner or agent of the medical practitioner. The laboratory carries out the detection by any method, including those described herein, and then communicates the results to the medical practitioner. A result is “communicated,” as used herein, when it is provided by any means to the medical practitioner. In some embodiments, such communication may be oral or written, may be by telephone, in person, by e-mail, by mail or other courier, or may be made by directly depositing the information into, e.g., a database accessible by the medical practitioner, including databases not controlled by the medical practitioner. In some embodiments, the information is maintained in electronic form. In some embodiments, the information can be stored in a memory or other computer readable medium, such as RAM, ROM, EEPROM, flash memory, computer chips, digital video discs (DVD), compact discs (CDs), hard disk drives (HDD), magnetic tape, etc.
In some embodiments, methods of detecting the presence lung cancer are provided. In some embodiments, methods of diagnosing lung cancer are provided. In some embodiments, the method comprises obtaining a sample from a subject and providing the sample to a laboratory for detection of at least one target RNA level in the sample. In some embodiments, the method further comprises receiving a communication from the laboratory that indicates the at least one target RNA level in the sample. In some embodiments, lung cancer is present if the level of at least one target RNA in the sample is greater than a normal level of the at least one target RNA. A “laboratory,” as used herein, is any facility that detects the level of at least one target RNA in a sample by any method, including the methods described herein, and communicates the level to a medical practitioner. In some embodiments, a laboratory is under the control of a medical practitioner. In some embodiments, a laboratory is not under the control of the medical practitioner.
When a laboratory communicates the level of at least one target RNA to a medical practitioner, in some embodiments, the laboratory communicates a numerical value representing the level of at least one target RNA in the sample, with or without providing a numerical value for a normal level. In some embodiments, the laboratory communicates the level of at least one target RNA by providing a qualitative value, such as “high,” “elevated,” etc.
As used herein, when a method relates to detecting lung cancer, determining the presence of lung cancer, and/or diagnosing lung cancer, the method includes activities in which the steps of the method are carried out, but the result is negative for the presence of lung cancer. That is, detecting, determining, and diagnosing lung cancer include instances of carrying out the methods that result in either positive or negative results (e.g., whether target RNA levels are normal or greater than normal).
As used herein, the term “subject” means a human. In some embodiments, the methods described herein may be used on samples from non-human animals.
The common, or coordinate, expression of target RNAs that are physically proximal to one another in the genome permits the informative use of such chromosome-proximal target RNAs in methods herein.
Table 3 identifies the chromosomal location of each of the 397 target RNAs capable of specifically hybridizing to a nucleic acid comprising a sequence that is identically present in one of SEQ ID NOs: 1 to 397 in Tables 1 and 2. Table 22 identifies the chromosomal location of the target RNAs capable of specifically hybridizing to a nucleic acid comprising a sequence that is identically present in one of SEQ ID NOs: 1063 to 1210 in Tables 18 and 20. Table 25 identifies the chromosomal location of the target RNAs capable of specifically hybridizing to a nucleic acid comprising a sequence that is identically present in one of SEQ ID NOs: 1363 to 1707 in Table 23. Table 29 identifies the chromosomal location of the target RNAs capable of specifically hybridizing to a nucleic acid comprising a sequence that is identically present in one of SEQ ID NOs: 2064 to 2183 in Tables 27 and 28. Table 31 identifies the chromosomal location of the target RNAs capable of specifically hybridizing to a nucleic acid comprising a sequence that is identically present in one of SEQ ID NOs: 2312 to 2452 in Table 30. Thus, in some embodiments, the level of expression of one or more target RNAs located within about 1 kilobase (kb), within about 2 kb, within about 5 kb, within about 10 kb, within about 20 kb, within about 30 kb, within about 40 kb, and even within about 50 kb of the chromosomal locations in Tables 3, 22, 25, 29, and 31 is detected in lieu of, or in addition to, measurement of expression of the respective tabulated target RNAs in the methods described herein. See Baskerville, S, and Bartel D. P. (2005) RNA 11:241-247.
In some embodiments, in combination with detecting one or more target RNAs capable of specifically hybridizing to a nucleic acid comprising a sequence selected from SEQ ID NOs: 1 to 397, 1063 to 1210, 1363 to 1707, 2064 to 2183, 2312 to 2452, 2673 to 2680, and 2689 and/or detecting one or more target RNAs comprising at least 15 contiguous nucleotides of a sequence selected from SEQ ID NOs: 794 to 1043, 2576 to 2672, and 2692 and/or detecting one or more target RNAs that comprise a sequence that is complementary to at least 15 contiguous nucleotides of a sequence selected from SEQ ID NOs: 1 to 397, 1063 to 1210, 1363 to 1707, 2064 to 2183, 2312 to 2452, 2673 to 2680, and 2689, methods herein further comprise detecting the level(s) of expression of at least one microRNA from the human miRNome.
In some embodiments, at least one target RNA is capable of specifically hybridizing to a nucleic acid comprising a sequence selected from SEQ ID NOs: 1 to 397, 1063 to 1210, 1363 to 1707, 2064 to 2183, 2312 to 2452, 2673 to 2680, and 2689. In some embodiments, at least one target RNA comprises at least 15 contiguous nucleotides that are complementary to at least a portion of a sequence selected from SEQ ID NOs: 1 to 397, 1063 to 1210, 1363 to 1707, 2064 to 2183, 2312 to 2452, 2673 to 2680, and 2689. In some embodiments, at least one target RNA comprises at least 15 contiguous nucleotides of a sequence selected from SEQ ID NOs: 794 to 1043, 2576 to 2672, and 2692. In some embodiments, a target RNA, in its mature form, comprises fewer than 30 nucleotides. In some embodiments, a target RNA is a microRNA.
In some embodiments, more than one target RNA is detected simultaneously in a single reaction. In some embodiments, at least 2, at least 3, at least 5, or at least 10 target RNAs are detected simultaneously in a single reaction. In some embodiments, all target RNAs are detected simultaneously in a single reaction.
In some embodiments, an increased level of one or more target RNAs capable of specifically hybridizing to a nucleic acid comprising a sequence selected from SEQ ID NOs: 1 to 397, 1063 to 1210, 2064 to 2183, 2673 to 2680, and 2689 in a sample is indicative of the presence of lung cancer in an individual from whom the sample has been taken. In some embodiments, an increased level of one or more target RNAs that comprise at least 15 contiguous nucleotides that are complementary to at least a portion of a sequence selected from SEQ ID NO: 1 to 397, 1063 to 1210, 2064 to 2183, 2673 to 2680, and 2689 in a sample is indicative of the presence of lung cancer in an individual from whom the sample has been taken. In some embodiments, an increased level of one or more target RNAs that comprise at least 15 contiguous nucleotides of a sequence selected from SEQ ID NOs: 794 to 1043, 2576 to 2672, and 2692 in a sample is indicative of the presence of lung cancer in an individual from whom the sample has been taken. In some embodiments, a decreased level of one or more target RNAs capable of specifically hybridizing to a nucleic acid comprising a sequence selected from SEQ ID NOs: 1 to 397, 1363 to 1707, and 2312 to 2452 in a sample is indicative of the presence of lung cancer in an individual from whom the sample has been taken. In some embodiments, a decreased level of one or more target RNAs that comprise at least 15 contiguous nucleotides that are complementary to at least a portion of a sequence selected from SEQ ID NO: 1 to 397, 1363 to 1707, and 2312 to 2452 in a sample is indicative of the presence of lung cancer in an individual from whom the sample has been taken. In some embodiments, a decreased level of one or more target RNAs that comprise at least 15 contiguous nucleotides of a sequence selected from SEQ ID NOs: 794 to 1043, 2576 to 2672, and 2692 in a sample is indicative of the presence of lung cancer in an individual from whom the sample has been taken.
In some embodiments, an increased level of one or more target RNAs capable of specifically hybridizing to a polynucleotide sequence in Table 6 is indicative of the presence of non-small cell lung cancer.
In some embodiments, an increased level of one or more target RNAs capable of specifically hybridizing to a polynucleotide sequence in Table 7 is indicative of squamous cell carcinoma.
In some embodiments, an increased level of one or more target RNAs capable of specifically hybridizing to a polynucleotide sequence in Table 8 is indicative of adenocarcinoma.
In some embodiments, an increased level of one or more target RNAs capable of specifically hybridizing to a polynucleotide sequence in Table 9 is indicative of aggressive lung cancer.
In some embodiments, an increased level of one or more target RNAs capable of specifically hybridizing to a polynucleotide sequence in Table 32 or 33 is indicative of lung cancer.
In some embodiments, a decreased level of one or more target RNAs capable of specifically hybridizing to a polynucleotide sequence in Table 34 is indicative of lung cancer.
In some embodiments, an increased level of one or more target RNAs capable of specifically hybridizing to a sequence selected from SEQ ID NOs: 15, 26, 27, 30, 129, 164, 184, 191, 196, 197, 205, 207, 214, 219, 225, 246, and 248 is indicative of non-small cell lung cancer.
In some embodiments, an increased level of one or more target RNAs capable of specifically hybridizing to a sequence selected from SEQ ID NOs: 15, 26, 27 and 191 and decreased level of one or more target RNAs capable of specifically hybridizing to a sequence selected from SEQ ID NOs: 92 and 171 is indicative of squamous cell carcinoma or adenocarcinoma.
In some embodiments, an increased level of one or more target RNAs capable of specifically hybridizing to a sequence selected from SEQ ID NOs: 4, 36, 50, 93, 122, 125, 139, 140, 144, 146, 159, 226, 239 and 241 is indicative of squamous cell carcinoma or adenocarcinoma.
In some embodiments, an increased level of one or more target RNAs capable of specifically hybridizing to a sequence selected from SEQ ID NOs: 19, 27, 33, 48, 55, 72, 73, 94, 101, 105, 112, 117, 130, 131, 133, 134, 135, 143, 155, 158, 160, 161, 163, 165, 221, 238, 240 and 246 is indicative of squamous cell carcinoma.
In some embodiments, a decreased level of one or more target RNAs capable of specifically hybridizing to a sequence selected from SEQ ID NOs: 19, 27, 33, 48, 55, 72, 73, 94, 101, 105, 112, 117, 130, 131, 133, 134, 135, 143, 155, 158, 160, 161, 163, 165, 221, 238, 240 and 246 is indicative of adenocarcinoma.
In some embodiments, an increased level of one or more target RNAs capable of specifically hybridizing to a sequence selected from SEQ ID NOs: 27, 72, 73, 161 or 246 is indicative of an aggressive form of adenocarcinoma.
4.1.2. Exemplary Controls
In some embodiments, a normal level (a “control”) for each target RNA can be determined as an average level or range that is characteristic of normal human lung cells or other reference material, against which the level measured in the sample can be compared. The determined average or range of target RNA in normal subjects can be used as a benchmark for detecting above-normal or below-normal levels of target RNA indicative of lung cancer. In some embodiments, normal levels of target RNA can be determined using individual or pooled RNA-containing samples from one or more individuals, such as from normal lung tissue from patients undergoing surgical resection for stage I, II or IIIA non-small cell lung cancer.
In some embodiments, determining a normal level of expression of a target RNA comprises detecting a complex comprising a probe hybridized to a nucleic acid selected from a target RNA, a DNA amplicon of the target RNA, and a complement of the target RNA. That is, in some embodiments, a normal level of expression can be determined by detecting a DNA amplicon of the target RNA, or a complement of the target RNA rather than the target RNA itself. In some embodiments, a normal level of such a complex is determined and used as a control. The normal level of the complex, in some embodiments, correlates to the normal level of the target RNA. Thus, when a normal level of a target is discussed herein, that level can, in some embodiments, be determined by detecting such a complex.
In some embodiments, a control comprises RNA from cells of a single individual, e.g., from normal tissue from a patient undergoing surgical resection for stage I, II or IIIA non-small cell lung cancer. In some embodiments, the control is drawn from anatomically and/or cytologically normal areas of the lung of the individual from whom the test sample was obtained. In some embodiments, a control comprises RNA from a pool of cells from multiple individuals. In some embodiments, a control comprises RNA from a pool of blood, such as whole blood or serum, from multiple individuals. In some embodiments, a control comprises commercially-available human RNA, such as, for example, human lung total RNA (Ambion; AM7968). In some embodiments, a normal level or normal range has already been predetermined prior to testing a sample for an elevated level.
In some embodiments, the normal level of target RNA can be determined from one or more continuous cell lines, typically cell lines previously shown to have expression levels of the at least one target RNA that approximate the level of expression in normal human lung cells.
In some embodiments, a method comprises detecting the level of expression of at least one target RNA. In some embodiments, a method further comprises comparing the level of expression of at least one target RNA to a normal level of expression of the at least one target RNA. In some embodiments, a method further comprises comparing the level of expression of at least one target RNA to a control level of expression of the at least one target RNA. A control level of expression of the at least one target RNA is, in some embodiments, the level of expression of the at least one target RNA in a normal cell. In some such embodiments, a control level may be referred to as a normal level. In some embodiments, a greater level of expression of the at least one target RNA relative to the level of expression of the at least one target RNA in a normal cell indicates lung cancer. In some embodiments, a reduced level of expression of the at least one target RNA relative to the level of expression of the at least one target RNA in a normal cell indicates lung cancer.
In some embodiments, the level of expression of the at least one target RNA is compared to a reference level of expression, e.g., from a patient with a confirmed lung cancer. In some such embodiments, a similar level of expression of the at least one target RNA relative to the reference sample indicates lung cancer.
In some embodiments, a level of expression of at least one target RNA that is at least about two-fold greater than a normal level of expression of the respective at least one target RNA indicates the presence of lung cancer. In some embodiments, a level of expression of at least one target RNA that is at least about two-fold greater than the level of the respective at least one target RNA in a control sample comprised of normal cells indicates the presence of a lung cancer. In various embodiments, a level of expression of at least one target RNA that is at least about 3-fold, at least about 4-fold, at least about 5-fold, at least about 6-fold, at least about 7-fold, at least about 8-fold, at least about 9-fold, or at least about 10-fold greater than the level of expression of the respective at least one target RNA in a control sample comprised of normal cells indicates the presence of lung cancer. In various embodiments, a level of expression of at least one target RNA that is at least about 3-fold, at least about 4-fold, at least about 5-fold, at least about 6-fold, at least about 7-fold, at least about 8-fold, at least about 9-fold, or at least about 10-fold greater than a normal level of expression of the at least one target RNA indicates the presence of lung cancer.
In some embodiments, a level of expression of at least one target RNA that is reduced by at least about two-fold relative to a normal level of expression of the respective at least one target RNA indicates the presence of lung cancer. In some embodiments, a level of expression of at least one target RNA that is reduced by at least about two-fold as compared to the level of the respective at least one target RNA in a control sample comprised of normal cells indicates the presence of a lung cancer. In various embodiments, a level of expression of at least one target RNA that is reduced by at least about 3-fold, at least about 4-fold, at least about 5-fold, at least about 6-fold, at least about 7-fold, at least about 8-fold, at least about 9-fold, or at least about 10-fold as compared to the level of expression of the respective at least one target RNA in a control sample comprised of normal cells indicates the presence of lung cancer. In various embodiments, a level of expression of at least one target RNA that is reduced by at least about 3-fold, at least about 4-fold, at least about 5-fold, at least about 6-fold, at least about 7-fold, at least about 8-fold, at least about 9-fold, or at least about 10-fold as compared to a normal level of expression of the at least one target RNA indicates the presence of lung cancer.
In some embodiments, a control level of expression of a target RNA is determined contemporaneously, such as in the same assay or batch of assays, as the level of expression of the target RNA in a sample. In some embodiments, a control level of expression of a target RNA is not determined contemporaneously as the level of expression of the target RNA in a sample. In some such embodiments, the control level of expression has been determined previously.
In some embodiments, the level of expression of a target RNA is not compared to a control level of expression, for example, when it is known that the target RNA is expressed at very low levels, or not at all, in normal cells. In some such embodiments, detection of a high level of the target RNA in a sample is indicative of lung cancer. Alternatively, if the target RNA is known to be expressed at high levels in normal cells, then detection of a very low level of the target RNA in a sample is indicative of lung cancer.
4.1.3. Exemplary Methods of Preparing RNAs
Target RNA can be prepared by any appropriate method. Total RNA can be isolated by any method, including, but not limited to, the protocols set forth in Wilkinson, M. (1988) Nucl. Acids Res. 16(22):10,933; and Wilkinson, M. (1988) Nucl. Acids Res. 16(22): 10934, or by using commercially-available kits or reagents, such as the TRIzol® reagent (Invitrogen™), Total RNA Extraction Kit (iNtRON Biotechnology), Total RNA Purification Kit (Norgen Biotek Corp.), RNAqueous™ (Ambion), MagMAX™ (Ambion), RecoverAll™ (Ambion), RNeasy (Qiagen), etc.
In some embodiments, small RNAs are isolated or enriched. In some embodiments “small RNA” refers to RNA molecules smaller than about 200 nucleotides (nt) in length. In some embodiments, “small RNA” refers to RNA molecules smaller than about 100 nt, smaller than about 90 nt, smaller than about 80 nt, smaller than about 70 nt, smaller than about 60 nt, smaller than about 50 nt, or smaller than about 40 nt.
Enrichment of small RNAs can be accomplished by method. Such methods include, but are not limited to, methods involving organic extraction followed by adsorption of nucleic acid molecules on a glass fiber filter using specialized binding and wash solutions, and methods using spin column purification. Enrichment of small RNAs may be accomplished using commercially-available kits, such as mirVana™ Isolation Kit (Applied Biosystems), mirPremier™ microRNA Isolation Kit (Sigma-Aldrich), PureLink™ miRNA Isolation Kit (Invitrogen), miRCURY™ RNA isolation kit (Exiqon), microRNA Purification Kit (Norgen Biotek Corp.), miRNeasy kit (Qiagen), etc. In some embodiments, purification can be accomplished by the TRIzol® (Invitrogen) method, which employs a phenol/isothiocyanate solution to which chloroform is added to separate the RNA-containing aqueous phase. Small RNAs are subsequently recovered from the aqueous by precipitation with isopropyl alcohol. In some embodiments, small RNAs can be purified using chromatographic methods, such as gel electrophoresis using the flashPAGE™ Fractionator available from Applied Biosystems.
In some embodiments, small RNA is isolated from other RNA molecules to enrich for target RNAs, such that the small RNA fraction (e.g., containing RNA molecules that are 200 nucleotides or less in length, such as less than 100 nucleotides in length, such as less than 50 nucleotides in length, such as from about 10 to about 40 nucleotides in length) is substantially pure, meaning it is at least about 80%, 85%, 90%, 95% pure or more, but less than 100% pure, with respect to larger RNA molecules. Alternatively, enrichment of small RNA can be expressed in terms of fold-enrichment. In some embodiments, small RNA is enriched by about, at least about, or at most about 5×, 10×, 20×, 30×, 40×, 50×, 60×, 70×, 80×, 90×, 100×, 110×, 120×, 130×, 140×, 150×, 160×, 170×, 180×, 190×, 200×, 210×, 220×, 230×, 240×, 250×, 260×, 270×, 280×, 290×, 300×, 310×, 320×, 330×, 340×, 350×, 360×, 370×, 380×, 390×, 400×, 410×, 420×, 430×, 440×, 450×, 460×, 470×, 480×, 490×, 500×, 600×, 700×, 800×, 900×, 1000×, 1100×, 1200×, 1300×, 1400×, 1500×, 1600×, 1700×, 1800×, 1900×, 2000×, 3000×, 4000×, 5000×, 6000×, 7000×, 8000×, 9000×, 10,000× or more, or any range derivable therein, with respect to the concentration of larger RNAs in an RNA isolate or total RNA in a sample.
In yet other embodiments, expression is measured in a sample in which RNA has not first been purified from the cells.
In some embodiments, RNA is modified before target RNAs are detected. In some embodiments, the modified RNA is total RNA. In other embodiments, the modified RNA is small RNA that has been purified from total RNA or from cell lysates, such as RNA less than 200 nucleotides in length, such as less than 100 nucleotides in length, such as less than 50 nucleotides in length, such as from about 10 to about 40 nucleotides in length. RNA modifications that can be utilized in the methods described herein include, but are not limited to, the addition of a poly-dA or a poly-dT tail, which can be accomplished chemically or enzymatically, and/or the addition of a small molecule, such as biotin.
In some embodiments, one or more target RNAs are reverse transcribed. In some embodiments, where present, RNA is modified when it is reverse transcribed, such as when a poly-dA or a poly-dT tail is added to the cDNA during reverse transcription. In other embodiments, RNA is modified before it is reverse transcribed. In some embodiments, total RNA is reverse transcribed. In other embodiments, small RNAs are isolated or enriched before the RNA is reverse transcribed.
When a target RNA is reverse transcribed, a complement of the target RNA is formed. In some embodiments, the complement of the target RNA is detected rather than the target RNA itself (or a DNA copy thereof). Thus, when the methods discussed herein indicate that a target RNA is detected, or the level of a target RNA is determined, such detection or determination may be carried out on a complement of the target RNA instead of, or in addition to, the target RNA itself. In some embodiments, when the complement of the target RNA is detected rather than the target RNA, a probe is used that is complementary to the complement of the target RNA. In such embodiments, the probe comprises at least a portion that is identical in sequence to the target RNA, although it may contain thymidine in place of uridine, and/or comprise other modified nucleotides.
In some embodiments, the method of detecting one or more target RNAs comprises amplifying cDNA complementary to said target RNA. Such amplification can be accomplished by any method. Exemplary methods include, but are not limited to, real time PCR, endpoint PCR, and amplification using T7 polymerase from a T7 promoter annealed to a cDNA, such as provided by the SenseAmp Plus™ Kit available at Implen, Germany.
When a target RNA or a cDNA complementary to a target RNA is amplified, in some embodiments, a DNA amplicon of a target RNA is formed. A DNA amplicon may be single stranded or double-stranded. In some embodiments, when a DNA amplicon is single-stranded, the sequence of the DNA amplicon is related to the target RNA in either the sense or antisense orientation. In some embodiments, the DNA amplicon of the target RNA is detected rather than the target RNA itself. Thus, when the methods discussed herein indicate that a target RNA is detected, or the level of a target RNA is determined, such detection or determination may be carried out on a DNA amplicon of the target RNA instead of, or in addition to, the target RNA itself. In some embodiments, when the DNA amplicon of the target RNA is detected rather than the target RNA, a probe is used that is complementary to the complement of the target RNA. In some embodiments, when the DNA amplicon of the target RNA is detected rather than the target RNA, a probe is used that is complementary to the target RNA. Further, in some embodiments, multiple probes may be used, and some probes may be complementary to the target RNA and some probes may be complementary to the complement of the target RNA.
In some embodiments, the method of detecting one or more target RNAs comprises RT-PCR, as described below. In some embodiments, detecting one or more target RNAs comprises real-time monitoring of an RT-PCR reaction, which can be accomplished by any method. Such methods include, but are not limited to, the use of TaqMan®, Molecular beacon, or Scorpion probes (i.e., FRET probes) and the use of intercalating dyes, such as SYBR green, EvaGreen, thiazole orange, YO-PRO, TO-PRO, etc.
4.1.4. Exemplary Analytical Methods
As described above, methods are presented for detecting lung cancer in a sample from a patient. In some embodiments, the method comprises detecting a level of expression of at least one target RNA capable of specifically hybridizing to a nucleic acid comprising a sequence selected from SEQ ID NOs: 1 to 397, 1063 to 1210, 2064 to 2183, 2673 to 2680, and 2689 that is greater in the sample than a normal level of expression of the at least one target RNA in a control sample, such as a sample derived from normal lung cells. In some embodiments, a method comprises detecting a level of one or more target RNAs that comprise a sequence that is complementary to at least 15 contiguous nucleotides of a sequence selected from SEQ ID NOs: 1 to 397, 1063 to 1210, 2064 to 2183, 2673 to 2680, and 2689 that is greater in the sample than a normal level of expression of the at least one target RNA in a control sample. In some embodiments, a method comprises detecting a level of one or more target RNAs that comprise at least 15 contiguous nucleotides of a sequence selected from SEQ ID NOs: 794 to 1043, 2576 to 2672, and 2692 that is greater in the sample than a normal level of expression of the at least one target RNA in a control sample.
In some embodiments, the method comprises detecting a level of expression of at least one target RNA capable of specifically hybridizing to a nucleic acid comprising a sequence selected from SEQ ID NOs: 1 to 397, 1363 to 1707, and 2312 to 2452 that is reduced in the sample relative to a normal level of expression of the at least one target RNA in a control sample, such as a sample derived from normal lung cells. In some embodiments, a method comprises detecting a level of one or more target RNAs that comprise a sequence that is complementary to at least 15 contiguous nucleotides of a sequence selected from SEQ ID NOs: 1 to 397, 1363 to 1707, and 2312 to 2452 that is reduced in the sample relative to a normal level of expression of the at least one target RNA in a control sample. In some embodiments, a method comprises detecting a level of one or more target RNAs that comprise at least 15 contiguous nucleotides of a sequence selected from SEQ ID NOs: 794 to 1043, 2576 to 2672, and 2692 that is reduced in the sample relative a normal level of expression of the at least one target RNA in a control sample.
In some embodiments, a target RNA, in its mature form, comprises fewer than 30 nucleotides. In some embodiments, a target RNA is a microRNA.
In some embodiments, such as those described above, the method further comprises detecting a level of expression of at least one target RNA of the human miRNome that does not specifically hybridize to a nucleic acid comprising a sequence selected from SEQ ID NOs: 1 to 397, 1063 to 1210, 1363 to 1707, 2064 to 2183, 2312 to 2452, 2673 to 2680, and 2689 and does not comprise at least 15 contiguous nucleotides of a sequence selected from SEQ ID NOs: 794 to 1043, 2576 to 2672, and 2692, that is altered in the sample relative to a normal level of expression of the at least one target RNA in a control sample. As used herein, the term “human miRNome” refers to all microRNA genes in a human cell and the mature microRNAs produced therefrom.
Any analytical procedure capable of permitting specific and quantifiable (or semi-quantifiable) detection of the desired at least one target RNA may be used in the methods herein presented. Such analytical procedures include, but are not limited to, the microarray methods set forth in Examples 1, 2, 4, and 5, the microbead methods set forth in Example 3, and methods known to those skilled in the art.
In some embodiments, detection of a target RNA comprises forming a complex comprising a polynucleotide that is complementary to a target RNA or to a complement thereof, and a nucleic acid selected from the target RNA, a DNA amplicon of the target RNA, and a complement of the target RNA. Thus, in some embodiments, the polynucleotide forms a complex with a target RNA. In some embodiments, the polynucleotide forms a complex with a complement of the target RNA, such as a cDNA that has been reverse transcribed from the target RNA. In some embodiments, the polynucleotide forms a complex with a DNA amplicon of the target RNA. When a double-stranded DNA amplicon is part of a complex, as used herein, the complex may comprise one or both strands of the DNA amplicon. Thus, in some embodiments, a complex comprises only one strand of the DNA amplicon. In some embodiments, a complex is a triplex and comprises the polynucleotide and both strands of the DNA amplicon. In some embodiments, the complex is formed by hybridization between the polynucleotide and the target RNA, complement of the target RNA, or DNA amplicon of the target RNA. The polynucleotide, in some embodiments, is a primer or probe.
In some embodiments, a method comprises detecting the complex. In some embodiments, the complex does not have to be associated at the time of detection. That is, in some embodiments, a complex is formed, the complex is then dissociated or destroyed in some manner, and components from the complex are detected. An example of such a system is a TaqMan® assay. In some embodiments, when the polynucleotide is a primer, detection of the complex may comprise amplification of the target RNA, a complement of the target RNA, or a DNA amplicon of a target RNA.
In some embodiments the analytical method used for detecting at least one target RNA in the methods set forth herein includes real-time quantitative RT-PCR. See Chen, C. et al. (2005) Nucl. Acids Res. 33:e179 and PCT Publication No. WO 2007/117256, which are incorporated herein by reference in its entirety. In some embodiments, the analytical method used for detecting at least one target RNA includes the method described in U.S. Publication No. US2009/0123912 A1, which is incorporated herein by reference in its entirety. In an exemplary method described in that publication, an extension primer comprising a first portion and second portion, wherein the first portion selectively hybridizes to the 3′ end of a particular microRNA and the second portion comprises a sequence for universal primer, is used to reverse transcribe the microRNA to make a cDNA. A reverse primer that selectively hybridizes to the 5′ end of the microRNA and a universal primer are then used to amplify the cDNA in a quantitative PCR reaction.
In some embodiments, the analytical method used for detecting at least one target RNA includes the use of a TaqMan® probe. In some embodiments, the analytical method used for detecting at least one target RNA includes a TaqMan® assay, such as the TaqMan® MicroRNA Assays sold by Applied Biosystems, Inc. In an exemplary TaqMan® assay, total RNA is isolated from the sample. In some embodiments, the assay can be used to analyze about 10 ng of total RNA input sample, such as about 9 ng of input sample, such as about 8 ng of input sample, such as about 7 ng of input sample, such as about 6 ng of input sample, such as about 5 ng of input sample, such as about 4 ng of input sample, such as about 3 ng of input sample, such as about 2 ng of input sample, and even as little as about 1 ng of input sample containing microRNAs.
The TaqMan® assay utilizes a stem-loop primer that is specifically complementary to the 3′-end of a target RNA. In an exemplary TaqMan® assay, hybridizing the stem-loop primer to the target RNA is followed by reverse transcription of the target RNA template, resulting in extension of the 3′ end of the primer. The result of the reverse transcription is a chimeric (DNA) amplicon with the step-loop primer sequence at the 5′ end of the amplicon and the cDNA of the target RNA at the 3′ end. Quantitation of the target RNA is achieved by real time RT-PCR using a universal reverse primer having a sequence that is complementary to a sequence at the 5′ end of all stem-loop target RNA primers, a target RNA-specific forward primer, and a target RNA sequence-specific TaqMan® probe.
The assay uses fluorescence resonance energy transfer (“FRET”) to detect and quantitate the synthesized PCR product. Typically, the TaqMan® probe comprises a fluorescent dye molecule coupled to the 5′-end and a quencher molecule coupled to the 3′-end, such that the dye and the quencher are in close proximity, allowing the quencher to suppress the fluorescence signal of the dye via FRET. When the polymerase replicates the chimeric amplicon template to which the TaqMan® probe is bound, the 5′-nuclease of the polymerase cleaves the probe, decoupling the dye and the quencher so that FRET is abolished and a fluorescence signal is generated. Fluorescence increases with each RT-PCR cycle proportionally to the amount of probe that is cleaved.
Additional exemplary methods for RNA detection and/or quantification are described, e.g., in U.S. Publication No. US 2007/0077570 (Lao et al.), PCT Publication No. WO 2007/025281 (Tan et al.), U.S. Publication No. US2007/0054287 (Bloch), PCT Publication No. WO2006/0130761 (Bloch), and PCT Publication No. WO 2007/011903 (Lao et al.), which are incorporated by reference herein in their entireties for any purpose.
In some embodiments, quantitation of the results of real-time RT-PCR assays is done by constructing a standard curve from a nucleic acid of known concentration and then extrapolating quantitative information for target RNAs of unknown concentration. In some embodiments, the nucleic acid used for generating a standard curve is an RNA (e.g., microRNA) of known concentration. In some embodiments, the nucleic acid used for generating a standard curve is a purified double-stranded plasmid DNA or a single-stranded DNA generated in vitro.
In some embodiments, where the amplification efficiencies of the target nucleic acids and the endogenous reference are approximately equal, quantitation is accomplished by the comparative Ct (cycle threshold, e.g., the number of PCR cycles required for the fluorescence signal to rise above background) method. Ct values are inversely proportional to the amount of nucleic acid target in a sample. In some embodiments, Ct values of the target RNA of interest can be compared with a control or calibrator, such as RNA (e.g., microRNA) from normal tissue. In some embodiments, the Ct values of the calibrator and the target RNA samples of interest are normalized to an appropriate endogenous housekeeping gene.
In addition to the TaqMan® assays, other real-time RT-PCR chemistries useful for detecting and quantitating PCR products in the methods presented herein include, but are not limited to, Molecular Beacons, Scorpion probes and intercalating dyes, such as SYBR Green, EvaGreen, thiazole orange, YO-PRO, TO-PRO, etc., which are discussed below.
In some embodiments, real-time RT-PCR detection is performed specifically to detect and quantify the expression of a single target RNA. The target RNA, in some embodiments, is selected from a target RNA capable of specifically hybridizing to a nucleic acid comprising a sequence selected from SEQ ID NOs: 1 to 397, 1063 to 1210, 1363 to 1707, 2064 to 2183, 2312 to 2452, 2673 to 2680, and 2689. In some embodiments, the target RNA comprises a sequence that is complementary to at least 15 contiguous nucleotides of a sequence selected from SEQ ID NOs: 1 to 397, 1063 to 1210, 1363 to 1707, 2064 to 2183, 2312 to 2452, 2673 to 2680, and 2689. The target RNA, in some embodiments, comprises at least 15 contiguous nucleotides of a sequence selected from SEQ ID NOs.: 794 to 1043, 2576 to 2672, and 2692. In some embodiments, the target RNA specifically hybridizes to a nucleic acid comprising a sequence selected from the probe sequences in Table 6. In some embodiments, the target RNA specifically hybridizes to a nucleic acid comprising a sequence selected from the probe sequences in Table 7. In some embodiments, the target RNA specifically hybridizes to a nucleic acid comprising a sequence selected from the probe sequences in Table 8. In some embodiments, the target RNA specifically hybridizes to a nucleic acid comprising a sequence selected from the probe sequences in Table 9. In some embodiments, the target RNA specifically hybridizes to a nucleic acid comprising a sequence selected from the probe sequences in Tables 32 and 33. In some embodiments, the target RNA specifically hybridizes to a nucleic acid comprising a sequence selected from the probe sequences in Table 34.
In some embodiments, a target RNA, in its mature form, comprises fewer than 30 nucleotides. In some embodiments, a target RNA is a microRNA.
In various embodiments, real-time RT-PCR detection is utilized to detect, in a single multiplex reaction, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, or at least 8 target RNAs. At least one target RNA, in some embodiments, is capable of specifically hybridizing to a nucleic acid comprising a sequence selected from SEQ ID NOs: 1 to 397, 1063 to 1210, 1363 to 1707, 2064 to 2183, 2312 to 2452, 2673 to 2680, and 2689. In some embodiments, at least one target RNA comprises at least 15 contiguous nucleotides of a sequence selected from SEQ ID NOs: 794 to 1043, 2576 to 2672, and 2692. In some embodiments, at least one target RNA comprises a sequence that is complementary to at least 15 contiguous nucleotides of a sequence selected from SEQ ID NOs: 1 to 397, 1063 to 1210, 1363 to 1707, 2064 to 2183, 2312 to 2452, 2673 to 2680, and 2689. In some embodiments, a target RNA, in its mature form, comprises fewer than 30 nucleotides. In some embodiments, a target RNA is a microRNA.
In some embodiments, the method comprises detecting expression in a multiplex RT-PCR reaction of at least 2, at least 3, at least 5, at least 10, or at least 15 target RNAs, wherein each target RNA is capable of specifically hybridizing to a probe sequence in Table 6. In some embodiments, the method comprises detecting expression, using a single multiplex RT-PCR reaction, of at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 12, at least 15, at least 20, or at least 25 target RNAs, wherein each target RNA is capable of specifically hybridizing to a probe sequence in Table 7. In some embodiments, the method comprises detecting expression, using a single multiplex RT-PCR reaction, of at least 2, at least 3, at least 4, at least 5, at least 6, or at least 7 target RNAs, wherein each target RNA is capable of specifically hybridizing to a probe sequence in Table 8. In some embodiments, the method comprises detecting expression in a multiplex RT-PCR reaction of at least 2, at least 3, at least 5, at least 10, at least 15, at least 20, at least 25, at least 30, at least 40, or at least 50 target RNAs, wherein each target RNA is capable of specifically hybridizing to a probe sequence in Table 9. In some embodiments, the method comprises detecting expression in a multiplex RT-PCR reaction of at least two, at least five, at least 10, at least 15, at least 20, at least 25, at least 30, or at least target RNAs, wherein each target RNA is capable of specifically hybridizing to a probe sequence in one of Tables 32 or 33. In some embodiments, the method comprises detecting expression in a multiplex RT-PCR reaction of at least two, at least five, at least 10, at least 15, at least 20, at least 30, at least 40, at least 50, or at least 60 target RNAs, wherein each target RNA is capable of specifically hybridizing to a probe sequence in Table 34.
In some multiplex embodiments, a plurality of probes, such as TaqMan® probes, each specific for a different RNA target, is used. In some embodiments, each target RNA-specific probe is spectrally distinguishable from the other probes used in the same multiplex reaction.
In some embodiments, quantitation of real-time RT PCR products is accomplished using a dye that binds to double-stranded DNA products, such as SYBR Green, EvaGreen, thiazole orange, YO-PRO, TO-PRO, etc. In some embodiments, the assay is the QuantiTect SYBR Green PCR assay from Qiagen. In this assay, total RNA is first isolated from a sample. Total RNA is subsequently poly-adenylated at the 3′-end and reverse transcribed using a universal primer with poly-dT at the 5′-end. In some embodiments, a single reverse transcription reaction is sufficient to assay multiple target RNAs. Real-time RT-PCR is then accomplished using target RNA-specific primers and an miScript Universal Primer, which comprises a poly-dT sequence at the 5′-end. SYBR Green dye binds non-specifically to double-stranded DNA and upon excitation, emits light. In some embodiments, buffer conditions that promote highly-specific annealing of primers to the PCR template (e.g., available in the QuantiTect SYBR Green PCR Kit from Qiagen) can be used to avoid the formation of non-specific DNA duplexes and primer dimers that will bind SYBR Green and negatively affect quantitation. Thus, as PCR product accumulates, the signal from SYBR Green increases, allowing quantitation of specific products.
Real-time RT-PCR is performed using any RT-PCR instrumentation available in the art. Typically, instrumentation used in real-time RT-PCR data collection and analysis comprises a thermal cycler, optics for fluorescence excitation and emission collection, and optionally a computer and data acquisition and analysis software.
In some embodiments, the analytical method used in the methods described herein is a DASL® (cDNA-mediated Annealing, Selection, Extension, and Ligation) Assay, such as the MicroRNA Expression Profiling Assay available from Illumina, Inc. (See http://www.illumina.com/downloads/MicroRNAAssayWorkflow.pdf). In some embodiments, total RNA is isolated from a sample to be analyzed by any method. Additionally, in some embodiments, small RNAs are isolated from a sample to be analyzed by any method. Total RNA or isolated small RNAs may then be polyadenylated (>18 A residues are added to the 3′-ends of the RNAs in the reaction mixture). The RNA is reverse transcribed using a biotin-labeled DNA primer that comprises from the 5′ to the 3′ end, a sequence that includes a PCR primer site and a poly-dT region that binds to the poly-dA tail of the sample RNA. The resulting biotinylated cDNA transcripts are then hybridized to a solid support via a biotin-streptavidin interaction and contacted with one or more target RNA-specific polynucleotides. The target RNA-specific polynucleotides comprise, from the 5′-end to the 3′-end, a region comprising a PCR primer site, region comprising an address sequence, and a target RNA-specific sequence.
In some DASL® embodiments, the target RNA-specific sequence comprises at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23, or at least 24 contiguous nucleotides having a sequence identically present in, or complementary to a region of, one of SEQ ID NOs: 1 to 397, 1063 to 1210, 1363 to 1707, 2064 to 2183, 2312 to 2452, 2673 to 2680, and 2689. In some embodiments, the target RNA-specific sequence comprises a probe sequence that is complementary to at least a portion of a microRNA of the human miRNome.
After hybridization, the target RNA-specific polynucleotide is extended, and the extended products are then eluted from the immobilized cDNA array. A second PCR reaction using a fluorescently-labeled universal primer generates a fluorescently-labeled DNA comprising the target RNA-specific sequence. The labeled PCR products are then hybridized to a microbead array for detection and quantitation.
In some embodiments, the analytical method used for detecting and quantifying the expression of the at least one target RNA in the methods described herein is a bead-based flow cytometric assay. See Lu J. et al. (2005) Nature 435:834-838, which is incorporated herein by reference in its entirety. An example of a bead-based flow cytometric assay is the xMAP® technology of Luminex, Inc. (See http://www.luminexcorp.com/technology/index.html). In some embodiments, total RNA is isolated from a sample and is then labeled with biotin. The labeled RNA is then hybridized to target RNA-specific capture probes (e.g., FlexmiR™ products sold by Luminex, Inc. at http://www.luminexcorp.com/products/assays/index.html) that are covalently bound to microbeads, each of which is labeled with 2 dyes having different fluorescence intensities. A streptavidin-bound reporter molecule (e.g., streptavidin-phycoerythrin, also known as “SAPE”) is attached to the captured target RNA and the unique signal of each bead is read using flow cytometry. In some embodiments, the RNA sample (total RNA or enriched small RNAs) is first polyadenylated, and is subsequently labeled with a biotinylated 3DNA™ dendrimer (i.e., a multiple-arm DNA with numerous biotin molecules bound thereto), such as those sold by Marligen Biosciences as the Vantage™ microRNA Labeling Kit, using a bridging polynucleotide that is complementary to the 3′-end of the poly-dA tail of the sample RNA and to the 5′-end of the polynucleotide attached to the biotinylated dendrimer. The streptavidin-bound reporter molecule is then attached to the biotinylated dendrimer before analysis by flow cytometry. See http://www.marligen.com/vantage-microrna-labeling-kit.html. In some embodiments, biotin-labeled RNA is first exposed to SAPE, and the RNA/SAPE complex is subsequently exposed to an anti-phycoerythrin antibody attached to a DNA dendrimer, which can be bound to as many as 900 biotin molecules. This allows multiple SAPE molecules to bind to the biotinylated dendrimer through the biotin-streptavidin interaction, thus increasing the signal from the assay.
In some embodiments, the analytical method used for detecting and quantifying the expression of the at least one target RNA in the methods described herein is by gel electrophoresis and detection with labeled probes (e.g., probes labeled with a radioactive or chemiluminescent label), such as by Northern blotting. In some embodiments, total RNA is isolated from the sample, and then is size-separated by SDS polyacrylamide gel electrophoresis. The separated RNA is then blotted onto a membrane and hybridized to radiolabeled complementary probes. In some embodiments, exemplary probes contain one or more affinity-enhancing nucleotide analogs as discussed below, such as locked nucleic acid (“LNA”) analogs, which contain a bicyclic sugar moiety instead of deoxyribose or ribose sugars. See, e.g., Várallyay, E. et al. (2008) Nature Protocols 3(2):190-196, which is incorporated herein by reference in its entirety. In some embodiments, the total RNA sample can be further purified to enrich for small RNAs. In some embodiments, target RNAs can be amplified by, e.g., rolling circle amplification using a long probe that is complementary to both ends of a target RNA (“padlocked probes”), ligation to circularize the probe followed by rolling circle replication using the target RNA hybridized to the circularized probe as a primer. See, e.g., Jonstrup, S. P. et al. (2006) RNA 12:1-6, which is incorporated herein by reference in its entirety. The amplified product can then be detected and quantified using, e.g., gel electrophoresis and Northern blotting.
In alternative embodiments, labeled probes are hybridized to isolated total RNA in solution, after which the RNA is subjected to rapid ribonuclease digestion of single-stranded RNA, e.g., unhybridized portions of the probes or unhybridized target RNAs. In these embodiments, the ribonuclease treated sample is then analyzed by SDS-PAGE and detection of the radiolabeled probes by, e.g., Northern blotting. See mirVana™ miRNA Detection Kit sold by Applied Biosystems, Inc. product literature at http://www.ambion.com/catalog/CatNum.php?1552.
In some embodiments, the analytical method used for detecting and quantifying the at least one target RNA in the methods described herein is by hybridization to a microarray. See, e.g., Liu, C. G. et al. (2004) Proc. Nat'l Acad. Sci. USA 101:9740-9744; Lim, L. P. et al. (2005) Nature 433:769-773, each of which is incorporated herein by reference in its entirety, and Examples 1, 2, 4, and 5.
In some embodiments, detection and quantification of a target RNA using a microarray is accomplished by surface plasmon resonance. See, e.g., Nanotech News (2006), available at http://nano.cancer.gov/news_center/nanotech_news—2006-10-30b.asp. In these embodiments, total RNA is isolated from a sample being tested. Optionally, the RNA sample is further purified to enrich the population of small RNAs. After purification, the RNA sample is bound to an addressable microarray containing probes at defined locations on the microarray. Nonlimiting exemplary probes include probes comprising sequences set forth in SEQ ID NOs: 1 to 397, 1063 to 1210, 1363 to 1707, 2064 to 2183, 2312 to 2452, 2673 to 2680, and 2689. Exemplary probes also include, but are not limited to, probes comprising a region that is complementary to at least 15 contiguous nucleotides of a sequence selected from SEQ ID NOs: 794 to 1043, 2576 to 2672, and 2692. Exemplary probes also include, but are not limited to, probes comprising at least 15 contiguous nucleotides of a sequence selected from SEQ ID NOs: 1 to 397, 1063 to 1210, 1363 to 1707, 2064 to 2183, 2312 to 2452, 2673 to 2680, and 2689. In some embodiments, the probes contain one or more affinity-enhancing nucleotide analogs as discussed below, such as locked nucleic acid (“LNA”) nucleotide analogs. After hybridization to the microarray, the RNA that is hybridized to the array is first polyadenylated, and the array is then exposed to gold particles having poly-dT bound to them. The amount of bound target RNA is quantitated using surface plasmon resonance.
In some embodiments, microarrays are utilized in a RNA-primed, Array-based Klenow Enzyme (“RAKE”) assay. See Nelson, P. T. et al. (2004) Nature Methods 1(2):1-7; Nelson, P. T. et al. (2006) RNA 12(2):1-5, each of which is incorporated herein by reference in its entirety. In some embodiments, total RNA is isolated from a sample. In some embodiments, small RNAs are isolated from a sample. The RNA sample is then hybridized to DNA probes immobilized at the 5′-end on an addressable array. The DNA probes comprise, in some embodiments, from the 5′-end to the 3′-end, a first region comprising a “spacer” sequence which is the same for all probes, a second region comprising three thymidine-containing nucleosides, and a third region comprising a sequence that is complementary to a target RNA of interest.
Exemplary target RNAs of interest include, but are not limited to, target RNAs capable of specifically hybridizing to a nucleic acid comprising a sequence selected from SEQ ID NOs: 1 to 397, 1063 to 1210, 1363 to 1707, 2064 to 2183, 2312 to 2452, 2673 to 2680, and 2689; target RNAs comprising a region that is identical to at least 15 contiguous nucleotides of a sequence selected from SEQ ID NOs: 794 to 1043, 2576 to 2672, and 2692; and target RNAs comprising a region that is complementary to at least 15 contiguous nucleotides of a sequence selected from SEQ ID NOs: 1 to 397, 1063 to 1210, 1363 to 1707, 2064 to 2183, 2312 to 2452, 2673 to 2680, and 2689. Target RNAs also include target RNAs in the miRNome that do not specifically hybridize to a nucleic acid comprising a sequence selected from SEQ ID NOs: 1 to 397, 1063 to 1210, 1363 to 1707, 2064 to 2183, 2312 to 2452, 2673 to 2680, and 2689. In some embodiments, a target RNA, in its mature form, comprises fewer than 30 nucleotides. In some embodiments, a target RNA is a microRNA.
After the sample is hybridized to the array, it is exposed to exonuclease Ito digest any unhybridized probes. The Klenow fragment of DNA polymerase I is then applied along with biotinylated dATP, allowing the hybridized target RNAs to act as primers for the enzyme with the DNA probe as template. The slide is then washed and a streptavidin-conjugated fluorophore is applied to detect and quantitate the spots on the array containing hybridized and Klenow-extended target RNAs from the sample.
In some embodiments, the RNA sample is reverse transcribed. In some embodiments, the RNA sample is reverse transcribed using a biotin/poly-dA random octamer primer. When than primer is used, the RNA template is digested and the biotin-containing cDNA is hybridized to an addressable microarray with bound probes that permit specific detection of target RNAs. In some embodiments, the microarray includes at least one probe comprising at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23, or at least 24 contiguous nucleotides identically present in, or complementary to a region of, a sequence selected from SEQ ID NOs: 1 to 397, 1063 to 1210, 1363 to 1707, 2064 to 2183, 2312 to 2452, 2673 to 2680, and 2689. After hybridization of the cDNA to the microarray, the microarray is exposed to a streptavidin-bound detectable marker, such as a fluorescent dye, and the bound cDNA is detected. See Liu C. G. et al. (2008) Methods 44:22-30, which is incorporated herein by reference in its entirety.
In some embodiments, target RNAs are detected and quantified in an ELISA-like assay using probes bound in the wells of microtiter plates. See Mora J. R. and Getts R. C. (2006) BioTechniques 41:420-424 and supplementary material in BioTechniques 41(4):1-5; U.S. Patent Publication No. 2006/0094025 to Getts et al., each of which is incorporated by reference herein in its entirety. In these embodiments, a sample of RNA that is enriched in small RNAs is either polyadenylated, or is reverse transcribed and the cDNA is polyadenylated. The RNA or cDNA is hybridized to probes immobilized in the wells of a microtiter plates, wherein each of the probes comprises a sequence that is identically present in, or complementary to a region of, one of SEQ ID NOs: 1 to 397, 1063 to 1210, 1363 to 1707, 2064 to 2183, 2312 to 2452, 2673 to 2680, and 2689, or a sequence such as one or more sequences of target RNAs (or the reverse complement thereof) of the human miRNome, depending on whether RNA or cDNA is hybridized to the array. In some embodiments, the hybridized RNAs are labeled using a capture sequence, such as a DNA dendrimer (such as those available from Genisphere, Inc., http://www.genisphere.com/about 3dna.html) that is labeled with a plurality of biotin molecules or with a plurality of horseradish peroxidase molecules, and a bridging polynucleotide that contains a poly-dT sequence at the 5′-end that binds to the poly-dA tail of the captured nucleic acid, and a sequence at the 3′-end that is complementary to a region of the capture sequence. If the capture sequence is biotinylated, the microarray is then exposed to streptavidin-bound horseradish peroxidase. Hybridization of target RNAs is detected by the addition of a horseradish peroxidase substrate such as tetramethylbenzidine (TMB) and measurement of the absorbance of the solution at 450 nM.
In still other embodiments, an addressable microarray is used to detect a target RNA using quantum dots. See Liang, R. Q. et al. (2005) Nucl. Acids Res. 33 (2): e17, available at http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=548377, which is incorporated herein by reference in its entirety. In some embodiments, total RNA is isolated from a sample. In some embodiments, small RNAs are isolated from the sample. The 3′-ends of the target RNAs are biotinylated using biotin-X-hydrazide. The biotinylated target RNAs are captured on a microarray comprising immobilized probes comprising sequences that are identically present in, or complementary to a region of, one or more of SEQ ID NOs: 1 to 397, 1063 to 1210, 1363 to 1707, 2064 to 2183, 2312 to 2452, 2673 to 2680, and 2689 and/or probes comprising sequences other than those that are complementary to one or more microRNAs of the human miRNome. The hybridized target RNAs are then labeled with quantum dots via a biotin-streptavidin binding. A confocal laser causes the quantum dots to fluoresce and the signal can be quantified. In alternative embodiments, small RNAs can be detected using a colorimetric assay. In these embodiments, small RNAs are labeled with streptavidin-conjugated gold followed by silver enhancement. The gold nanoparticles bound to the hybridized target RNAs catalyze the reduction of silver ions to metallic silver, which can then be detected colorimetrically with a CCD camera.
In some embodiments, detection and quantification of one or more target RNAs is accomplished using microfluidic devices and single-molecule detection. In some embodiments, target RNAs in a sample of isolated total RNA are hybridized to two probes, one which is complementary to nucleic acids at the 5′-end of the target RNA and the second which is complementary to the 3′-end of the target RNA. Each probe comprises, in some embodiments, one or more affinity-enhancing nucleotide analogs, such as LNA nucleotide analogs and each is labeled with a different fluorescent dye having different fluorescence emission spectra. The sample is then flowed through a microfluidic capillary in which multiple lasers excite the fluorescent probes, such that a unique coincident burst of photons identifies a particular target RNA, and the number of particular unique coincident bursts of photons can be counted to quantify the amount of the target RNA in the sample. See U.S. Patent Publication No. 2006/0292616 to Neely et al., which is hereby incorporated by reference in its entirety. In some alternative embodiments, a target RNA-specific probe can be labeled with 3 or more distinct labels selected from, e.g., fluorophores, electron spin labels, etc., and then hybridized to an RNA sample, such as total RNA, or a sample that is enriched in small RNAs. The target RNA/probe duplex is then passed through channels in a microfluidic device and that comprise detectors that record the unique signal of the 3 labels. In this way, individual molecules are detected by their unique signal and counted. See U.S. Pat. Nos. 7,402,422 and 7,351,538 to Fuchs et al., U.S. Genomics, Inc., each of which is incorporated herein by reference in its entirety.
Nonlimiting exemplary target RNA-specific probes include probes comprising sequences selected from of SEQ ID NOs: 1 to 397. Nonlimiting exemplary target RNA-specific probes include probes comprising sequences that are complementary to sequences selected from of SEQ ID NOs: 1 to 397. Nonlimiting exemplary target RNA-specific probes also include probes comprising at least 15 contiguous nucleotides of, or the complement of at least 15 contiguous nucleotides of, a sequence selected from SEQ ID NOs: 1 to 397, 1063 to 1210, 1363 to 1707, 2064 to 2183, 2312 to 2452, 2673 to 2680, and 2689.
Optionally, the sample RNA is modified before hybridization. The target RNA/probe duplex is then passed through channels in a microfluidic device and that comprise detectors that record the unique signal of the 3 labels. In this way, individual molecules are detected by their unique signal and counted. See U.S. Pat. Nos. 7,402,422 and 7,351,538 to Fuchs et al., U.S. Genomics, Inc., each of which is incorporated herein by reference in its entirety.
In some embodiments, the detection and quantification of one or more target RNAs is accomplished by a solution-based assay, such as a modified Invader assay. See Allawi H. T. et al. (2004) RNA 10:1153-1161, which is incorporated herein by reference in its entirety. In some embodiments, the modified invader assay can be performed on unfractionated detergent lysates of cells. In other embodiments, the modified invader assay can be performed on total RNA isolated from cells or on a sample enriched in small RNAs. The target RNAs in a sample are annealed to two probes which form hairpin structures. A first probe has a hairpin structure at the 5′ end and a region at the 3′-end that has a sequence that is complementary to the sequence of a region at the 5′-end of a target RNA. The 3′-end of the first probe is the “invasive polynucleotide”. A second probe has, from the 5′ end to the 3′-end a first “flap” region that is not complementary to the target RNA, a second region that has a sequence that is complementary to the 3′-end of the target RNA, and a third region that forms a hairpin structure. When the two probes are bound to a target RNA target, they create an overlapping configuration of the probes on the target RNA template, which is recognized by the Cleavase enzyme, which releases the flap of the second probe into solution. The flap region then binds to a complementary region at the 3′-end of a secondary reaction template (“SRT”). A FRET polynucleotide (having a fluorescent dye bound to the 5′-end and a quencher that quenches the dye bound closer to the 3′ end) binds to a complementary region at the 5′-end of the SRT, with the result that an overlapping configuration of the 3′-end of the flap and the 5′-end of the FRET polynucleotide is created. Cleavase recognizes the overlapping configuration and cleaves the 5′-end of the FRET polynucleotide, generates a fluorescent signal when the dye is released into solution.
4.1.5. Exemplary Polynucleotides
In some embodiments, polynucleotides are provided. In some embodiments, synthetic polynucleotides are provided. Synthetic polynucleotides, as used herein, refer to polynucleotides that have been synthesized in vitro either chemically or enzymatically. Chemical synthesis of polynucleotides includes, but is not limited to, synthesis using polynucleotide synthesizers, such as OligoPilot (GE Healthcare), ABI 3900 DNA Synthesizer (Applied Biosystems), and the like. Enzymatic synthesis includes, but is not limited, to producing polynucleotides by enzymatic amplification, e.g., PCR.
In some embodiments, a polynucleotide is provided that comprises at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, or at least 15 contiguous nucleotides of a sequence selected from SEQ ID NOs: 1 to 397, 1063 to 1210, 1363 to 1707, 2064 to 2183, 2312 to 2452, 2673 to 2680, and 2689 and sequences complementary to SEQ ID NOs: 1 to 397, 1063 to 1210, 1363 to 1707, 2064 to 2183, 2312 to 2452, 2673 to 2680, and 2689. In some embodiments, the polynucleotide further comprises a region having a sequence that is not found in, or complementary to, any of SEQ ID NOs: 1 to 397, 1063 to 1210, 1363 to 1707, 2064 to 2183, 2312 to 2452, 2673 to 2680, and 2689. In some embodiments, a polynucleotide is provided that comprises at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, or at least 15 contiguous nucleotides of a sequence selected from SEQ ID NOs: 794 to 1043, 2576 to 2672, and 2692, and sequences complementary to SEQ ID NOs: 794 to 1043, 2576 to 2672, and 2692. In some embodiments, the polynucleotide further comprises a region having a sequence that is not found in, or complementary to, any of SEQ ID NOs: 794 to 1043, 2576 to 2672, and 2692.
A “region” can comprise the full-length sequence, or the complement of the full-length sequence, of a particular sequence, such as any of SEQ ID NOs: 1 to 397, 1063 to 1210, 1363 to 1707, 2064 to 2183, 2312 to 2452, 794 to 1043, and 2576 to 2672 or it can comprise a subsequence, or the complement of a subsequence, of a particular sequence, such as any of SEQ ID NOs: 1 to 397, 1063 to 1210, 1363 to 1707, 2064 to 2183, 2312 to 2452, 794 to 1043, and 2576 to 2672. Such subsequences may comprise, in some embodiments, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or more contiguous nucleotides from a particular SEQ ID NO or its complement.
In various embodiments, a polynucleotide comprises fewer than 500, fewer than 300, fewer than 200, fewer than 150, fewer than 100, fewer than 75, fewer than 50, fewer than 40, or fewer than 30 nucleotides. In various embodiments, a polynucleotide is between 8 and 200, between 8 and 150, between 8 and 100, between 8 and 75, between 8 and 50, between 8 and 40, or between 8 and 30 nucleotides long.
In some embodiments, the polynucleotide is a primer. In some embodiments, the primer is labeled with a detectable moiety. In some embodiments, a primer is not labeled. A primer, as used herein, is a polynucleotide that is capable of specifically hybridizing to a target RNA or to a cDNA reverse transcribed from the target RNA or to an amplicon that has been amplified from a target RNA or a cDNA (collectively referred to as “template”), and, in the presence of the template, a polymerase and suitable buffers and reagents, can be extended to form a primer extension product.
In some embodiments, the polynucleotide is a probe. In some embodiments, the probe is labeled with a detectable moiety. A detectable moiety, as used herein, includes both directly detectable moieties, such as fluorescent dyes, and indirectly detectable moieties, such as members of binding pairs. When the detectable moiety is a member of a binding pair, in some embodiments, the probe can be detectable by incubating the probe with a detectable label bound to the second member of the binding pair. In some embodiments, a probe is not labeled, such as when a probe is a capture probe, e.g., on a microarray or bead. In some embodiments, a probe is not extendable, e.g., by a polymerase. In other embodiments, a probe is extendable.
In some embodiments, the polynucleotide is a FRET probe that in some embodiments is labeled at the 5′-end with a fluorescent dye (donor) and at the 3′-end with a quencher (acceptor), a chemical group that absorbs (i.e., suppresses) fluorescence emission from the dye when the groups are in close proximity (i.e., attached to the same probe). In other embodiments, the donor and acceptor are not at the ends of the FRET probe. Thus, in some embodiments, the emission spectrum of the donor moiety should overlap considerably with the absorption spectrum of the acceptor moiety.
4.1.5.1. Exemplary Polynucleotide Modifications
In some embodiments, the methods of detecting at least one target RNA described herein employ one or more polynucleotides that have been modified, such as polynucleotides comprising one or more affinity-enhancing nucleotide analogs. Modified polynucleotides useful in the methods described herein include primers for reverse transcription, PCR amplification primers, and probes. In some embodiments, the incorporation of affinity-enhancing nucleotides increases the binding affinity and specificity of a polynucleotide for its target nucleic acid as compared to polynucleotides that contain only deoxyribonucleotides, and allows for the use of shorter polynucleotides or for shorter regions of complementarity between the polynucleotide and the target nucleic acid.
In some embodiments, affinity-enhancing nucleotide analogs include nucleotides comprising one or more base modifications, sugar modifications and/or backbone modifications.
In some embodiments, modified bases for use in affinity-enhancing nucleotide analogs include 5-methylcytosine, isocytosine, pseudoisocytosine, 5-bromouracil, 5-propynyluracil, 6-aminopurine, 2-aminopurine, inosine, diaminopurine, 2-chloro-6-aminopurine, xanthine and hypoxanthine.
In some embodiments, affinity-enhancing nucleotide analogs include nucleotides having modified sugars such as 2′-substituted sugars, such as 2′-O-alkyl-ribose sugars, 2′-amino-deoxyribose sugars, 2′-fluoro-deoxyribose sugars, 2′-fluoro-arabinose sugars, and 2′-O-methoxyethyl-ribose (2′MOE) sugars. In some embodiments, modified sugars are arabinose sugars, or d-arabino-hexitol sugars.
In some embodiments, affinity-enhancing nucleotide analogs include backbone modifications such as the use of peptide nucleic acids (PNA; e.g., an oligomer including nucleobases linked together by an amino acid backbone). Other backbone modifications include phosphorothioate linkages, phosphodiester modified nucleic acids, combinations of phosphodiester and phosphorothioate nucleic acid, methylphosphonate, alkylphosphonates, phosphate esters, alkylphosphonothioates, phosphoramidates, carbamates, carbonates, phosphate triesters, acetamidates, carboxymethyl esters, methylphosphorothioate, phosphorodithioate, p-ethoxy, and combinations thereof.
In some embodiments, a polynucleotide includes at least one affinity-enhancing nucleotide analog that has a modified base, at least nucleotide (which may be the same nucleotide) that has a modified sugar, and/or at least one internucleotide linkage that is non-naturally occurring.
In some embodiments, an affinity-enhancing nucleotide analog contains a locked nucleic acid (“LNA”) sugar, which is a bicyclic sugar. In some embodiments, a polynucleotide for use in the methods described herein comprises one or more nucleotides having an LNA sugar. In some embodiments, a polynucleotide contains one or more regions consisting of nucleotides with LNA sugars. In other embodiments, a polynucleotide contains nucleotides with LNA sugars interspersed with deoxyribonucleotides. See, e.g., Frieden, M. et al. (2008) Curr. Pharm. Des. 14(11):1138-1142.
4.1.5.2. Exemplary Primers
In some embodiments, a primer is provided. In some embodiments, a primer is identical or complementary to at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23, or at least 24 contiguous nucleotides of a target RNA. In some embodiments, a primer may also comprise portions or regions that are not identical or complementary to the target RNA. In some embodiments, a region of a primer that is identical or complementary to a target RNA is contiguous, such that any region of a primer that is not identical or complementary to the target RNA does not disrupt the identical or complementary region.
In some embodiments, a primer comprises a portion that is identically present in a target RNA. In some such embodiments, a primer that comprises a region that is identically present in the target RNA is capable of selectively hybridizing to a cDNA that has been reverse transcribed from the RNA, or to an amplicon that has been produced by amplification of the target RNA or cDNA. In some embodiments, the primer is complementary to a sufficient portion of the cDNA or amplicon such that it selectively hybridizes to the cDNA or amplicon under the conditions of the particular assay being used.
As used herein, “selectively hybridize” means that a polynucleotide, such as a primer or probe, will hybridize to a particular nucleic acid in a sample with at least 5-fold greater affinity than it will hybridize to another nucleic acid present in the same sample that has a different nucleotide sequence in the hybridizing region. Exemplary hybridization conditions are discussed in Example 1. In some embodiments, a polynucleotide will hybridize to a particular nucleic acid in a sample with at least 10-fold greater affinity than it will hybridize to another nucleic acid present in the same sample that has a different nucleotide sequence in the hybridizing region.
Nonlimiting exemplary primers include primers comprising sequences that are identically present in, or complementary to a region of, sequences selected from SEQ ID NOs: 1 to 397, 1063 to 1210, 1363 to 1707, 2064 to 2183, 2312 to 2452, 2673 to 2680, and 2689. Exemplary primers also include, but are not limited to, primers comprising regions that are identical or complementary to at least 15 contiguous nucleotides of sequences selected from SEQ ID NOs: 1 to 397, 1063 to 1210, 1363 to 1707, 2064 to 2183, 2312 to 2452, 2673 to 2680, and 2689. Exemplary primers also include, but are not limited to, primers comprising regions that are identical or complementary to at least 15 contiguous nucleotides of sequences selected from SEQ ID NOs: 794 to 1043, 2576 to 2672, and 2692.
In some embodiments, a primer is used to reverse transcribe a target RNA, for example, as discussed herein. In some embodiments, a primer is used to amplify a target RNA or a cDNA reverse transcribed therefrom. Such amplification, in some embodiments, is quantitative PCR, for example, as discussed herein. In some embodiments, a primer comprises a detectable moiety.
4.1.5.3. Exemplary Probes
In various embodiments, methods of detecting the presence of a lung cancer comprise hybridizing nucleic acids of a human sample with a probe. In some embodiments, the probe comprises a portion that is complementary to a target RNA. In some embodiments, the probe comprises a portion that is identically present in the target RNA. In some such embodiments, a probe that is complementary to a target RNA is complementary to a sufficient portion of the target RNA such that it selectively hybridizes to the target RNA under the conditions of the particular assay being used. In some embodiments, a probe that is complementary to a target RNA is complementary to at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23, or at least 24 contiguous nucleotides of the target RNA. In some embodiments, a probe that is complementary to a target RNA comprises a region that is complementary to at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23, or at least 24 contiguous nucleotides of the target RNA. That is, a probe that is complementary to a target RNA may also comprise portions or regions that are not complementary to the target RNA. In some embodiments, a region of a probe that is complementary to a target RNA is contiguous, such that any region of a probe that is not complementary to the target RNA does not disrupt the complementary region.
In some embodiments, the probe comprises a portion that is identically present in the target RNA. In some such embodiments, a probe that comprises a region that is identically present in the target RNA is capable of selectively hybridizing to a cDNA that has been reverse transcribed from the RNA, or to an amplicon that has been produced by amplification of the target RNA or cDNA. In some embodiments, the probe is complementary to a sufficient portion of the cDNA or amplicon such that it selectively hybridizes to the cDNA or amplicon under the conditions of the particular assay being used. In some embodiments, a probe that is complementary to a cDNA or amplicon is complementary to at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23, or at least 24 contiguous nucleotides of the cDNA or amplicon. In some embodiments, a probe that is complementary to a target RNA comprises a region that is complementary to at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23, or at least 24 contiguous nucleotides of the cDNA or amplicon. That is, a probe that is complementary to a cDNA or amplicon may also comprise portions or regions that are not complementary to the cDNA or amplicon. In some embodiments, a region of a probe that is complementary to a cDNA or amplicon is contiguous, such that any region of a probe that is not complementary to the cDNA or amplicon does not disrupt the complementary region.
Nonlimiting exemplary probes include probes comprising sequences set forth in SEQ ID NOs: 1 to 397. Nonlimiting exemplary probes include probes comprising sequences that are identically present in, or complementary to a region of, sequences selected from SEQ ID NOs: 1 to 397, 1063 to 1210, 1363 to 1707, 2064 to 2183, 2312 to 2452, 2673 to 2680, and 2689. Exemplary probes also include, but are not limited to, probes comprising regions that are identical or complementary to at least 15 contiguous nucleotides of sequences selected from SEQ ID NOs: 1 to 397, 1063 to 1210, 1363 to 1707, 2064 to 2183, 2312 to 2452, 2673 to 2680, and 2689.
In some embodiments, the method of detectably quantifying one or more target RNAs comprises: (a) isolating total RNA; (b) reverse transcribing a target RNA to produce a cDNA that is complementary to the target RNA; (c) amplifying the cDNA from (b); and (d) detecting the amount of a target RNA using real time RT-PCR.
As described above, in some embodiments, the real time RT-PCR detection is performed using a FRET probe, which includes, but is not limited to, a TaqMan® probe, a Molecular beacon probe and a Scorpion probe. In some embodiments, the real time RT-PCR detection and quantification is performed with a TaqMan® probe, i.e., a linear probe that typically has a fluorescent dye covalently bound at one end of the DNA and a quencher molecule covalently bound at the other end of the DNA. The FRET probe comprises a sequence that is complementary to a region of the cDNA such that, when the FRET probe is hybridized to the cDNA, the dye fluorescence is quenched, and when the probe is digested during amplification of the cDNA, the dye is released from the probe and produces a fluorescence signal. In such embodiments, the amount of target RNA in the sample is proportional to the amount of fluorescence measured during cDNA amplification.
The TaqMan® probe typically comprises a region of contiguous nucleotides having a sequence that is complementary to a region of a target RNA or its complementary cDNA that is reverse transcribed from the target RNA template (i.e., the sequence of the probe region is complementary to or identically present in the target RNA to be detected) such that the probe is specifically hybridizable to the resulting PCR amplicon. In some embodiments, the probe comprises a region of at least 6 contiguous nucleotides having a sequence that is fully complementary to or identically present in a region of a cDNA that has been reverse transcribed from a target RNA template, such as comprising a region of at least 8 contiguous nucleotides, at least 10 contiguous nucleotides, at least 12 contiguous nucleotides, at least 14 contiguous nucleotides, or at least 16 contiguous nucleotides having a sequence that is complementary to or identically present in a region of a cDNA reverse transcribed from a target RNA to be detected.
In some embodiments, the region of the cDNA that has a sequence that is complementary to the TaqMan® probe sequence is at or near the center of the cDNA molecule. In some embodiments, there are independently at least 2 nucleotides, at least 3 nucleotides, at least 4 nucleotides, at least 5 nucleotides of the cDNA at the 5′-end and at the 3′-end of the region of complementarity.
In some embodiments, Molecular Beacons can be used to detect and quantitate PCR products. Like TaqMan® probes, Molecular Beacons use FRET to detect and quantitate a PCR product via a probe having a fluorescent dye and a quencher attached at the ends of the probe. Unlike TaqMan® probes, Molecular Beacons remain intact during the PCR cycles. Molecular Beacon probes form a stem-loop structure when free in solution, thereby allowing the dye and quencher to be in close enough proximity to cause fluorescence quenching. When the Molecular Beacon hybridizes to a target, the stem-loop structure is abolished so that the dye and the quencher become separated in space and the dye fluoresces. Molecular Beacons are available, e.g., from Gene Link™ (see http://www.genelink.com/newsite/products/mbintro.asp).
In some embodiments, Scorpion probes can be used as both sequence-specific primers and for PCR product detection and quantitation. Like Molecular Beacons, Scorpion probes form a stem-loop structure when not hybridized to a target nucleic acid. However, unlike Molecular Beacons, a Scorpion probe achieves both sequence-specific priming and PCR product detection. A fluorescent dye molecule is attached to the 5′-end of the Scorpion probe, and a quencher is attached to the 3′-end. The 3′ portion of the probe is complementary to the extension product of the PCR primer, and this complementary portion is linked to the 5′-end of the probe by a non-amplifiable moiety. After the Scorpion primer is extended, the target-specific sequence of the probe binds to its complement within the extended amplicon, thus opening up the stem-loop structure and allowing the dye on the 5′-end to fluoresce and generate a signal. Scorpion probes are available from, e.g, Premier Biosoft International (see http://www.premierbiosoft.com/tech_notes/Scorpion.html).
In some embodiments, labels that can be used on the FRET probes include colorimetric and fluorescent labels such as Alexa Fluor dyes, BODIPY dyes, such as BODIPY FL; Cascade Blue; Cascade Yellow; coumarin and its derivatives, such as 7-amino-4-methylcoumarin, aminocoumarin and hydroxycoumarin; cyanine dyes, such as Cy3 and Cy5; eosins and erythrosins; fluorescein and its derivatives, such as fluorescein isothiocyanate; macrocyclic chelates of lanthanide ions, such as Quantum Dye™; Marina Blue; Oregon Green; rhodamine dyes, such as rhodamine red, tetramethylrhodamine and rhodamine 6G; Texas Red; fluorescent energy transfer dyes, such as thiazole orange-ethidium heterodimer; and, TOTAB.
Specific examples of dyes include, but are not limited to, those identified above and the following: Alexa Fluor 350, Alexa Fluor 405, Alexa Fluor 430, Alexa Fluor 488, Alexa Fluor 500. Alexa Fluor 514, Alexa Fluor 532, Alexa Fluor 546, Alexa Fluor 555, Alexa Fluor 568, Alexa Fluor 594, Alexa Fluor 610, Alexa Fluor 633, Alexa Fluor 647, Alexa Fluor 660, Alexa Fluor 680, Alexa Fluor 700, and, Alexa Fluor 750; amine-reactive BODIPY dyes, such as BODIPY 493/503, BODIPY 530/550, BODIPY 558/568, BODIPY 564/570, BODIPY 576/589, BODIPY 581/591, BODIPY 630/650, BODIPY 650/655, BODIPY FL, BODIPY R6G, BODIPY TMR, and, BODIPY-TR; Cy3, Cy5, 6-FAM, Fluorescein Isothiocyanate, HEX, 6-JOE, Oregon Green 488, Oregon Green 500, Oregon Green 514, Pacific Blue, REG, Rhodamine Green, Rhodamine Red, Renographin, ROX, SYPRO, TAMRA, 2′, 4′,5′,7′-Tetrabromosulfonefluorescein, and TET.
Specific examples of fluorescently labeled ribonucleotides useful in the preparation of RT-PCR probes for use in some embodiments of the methods described herein are available from Molecular Probes (Invitrogen), and these include, Alexa Fluor 488-5-UTP, Fluorescein-12-UTP, BODIPY FL-14-UTP, BODIPY TMR-14-UTP, Tetramethylrhodamine-6-UTP, Alexa Fluor 546-14-UTP, Texas Red-5-UTP, and BODIPY TR-14-UTP. Other fluorescent ribonucleotides are available from Amersham Biosciences (GE Healthcare), such as Cy3-UTP and Cy5-UTP.
Examples of fluorescently labeled deoxyribonucleotides useful in the preparation of RT-PCR probes for use in the methods described herein include Dinitrophenyl (DNP)-1′-dUTP, Cascade Blue-7-dUTP, Alexa Fluor 488-5-dUTP, Fluorescein-12-dUTP, Oregon Green 488-5-dUTP, BODIPY FL-14-dUTP, Rhodamine Green-5-dUTP, Alexa Fluor 532-5-dUTP, BODIPY TMR-14-dUTP, Tetramethylrhodamine-6-dUTP, Alexa Fluor 546-14-dUTP, Alexa Fluor 568-5-dUTP, Texas Red-12-dUTP, Texas Red-5-dUTP, BODIPY TR-14-dUTP, Alexa Fluor 594-5-dUTP, BODIPY 630/650-14-dUTP, BODIPY 650/665-14-dUTP; Alexa Fluor 488-7-OBEA-dCTP, Alexa Fluor 546-16-OBEA-dCTP, Alexa Fluor 594-7-OBEA-dCTP, Alexa Fluor 647-12-OBEA-dCTP. Fluorescently labeled nucleotides are commercially available and can be purchased from, e.g., Invitrogen.
In some embodiments, dyes and other moieties, such as quenchers, are introduced into polynucleotide used in the methods described herein, such as FRET probes, via modified nucleotides. A “modified nucleotide” refers to a nucleotide that has been chemically modified, but still functions as a nucleotide. In some embodiments, the modified nucleotide has a chemical moiety, such as a dye or quencher, covalently attached, and can be introduced into a polynucleotide, for example, by way of solid phase synthesis of the polynucleotide. In other embodiments, the modified nucleotide includes one or more reactive groups that can react with a dye or quencher before, during, or after incorporation of the modified nucleotide into the nucleic acid. In specific embodiments, the modified nucleotide is an amine-modified nucleotide, i.e., a nucleotide that has been modified to have a reactive amine group. In some embodiments, the modified nucleotide comprises a modified base moiety, such as uridine, adenosine, guanosine, and/or cytosine. In specific embodiments, the amine-modified nucleotide is selected from 5-(3-aminoallyl)-UTP; 8-[(4-amino)butyl]-amino-ATP and 8-[(6-amino)butyl]-amino-ATP; N6-(4-amino)butyl-ATP, N6-(6-amino)butyl-ATP, N4-[2,2-oxy-bis-(ethylamine)]-CTP; N6-(6-Amino)hexyl-ATP; 8-[(6-Amino)hexyl]-amino-ATP; 5-propargylamino-CTP, 5-propargylamino-UTP. In some embodiments, nucleotides with different nucleobase moieties are similarly modified, for example, 5-(3-aminoallyl)-GTP instead of 5-(3-aminoallyl)-UTP. Many amine modified nucleotides are commercially available from, e.g., Applied Biosystems, Sigma, Jena Bioscience and TriLink.
Exemplary detectable moieties also include, but are not limited to, members of binding pairs. In some such embodiments, a first member of a binding pair is linked to a polynucleotide. The second member of the binding pair is linked to a detectable label, such as a fluorescent label. When the polynucleotide linked to the first member of the binding pair is incubated with the second member of the binding pair linked to the detectable label, the first and second members of the binding pair associate and the polynucleotide can be detected. Exemplary binding pairs include, but are not limited to, biotin and streptavidin, antibodies and antigens, etc.
In some embodiments, multiple target RNAs are detected in a single multiplex reaction. In some such embodiments, each probe that is targeted to a unique cDNA is spectrally distinguishable when released from the probe. Thus, each target RNA is detected by a unique fluorescence signal.
One skilled in the art can select a suitable detection method for a selected assay, e.g., a real-time RT-PCR assay. The selected detection method need not be a method described above, and may be any method.
4.2. Exemplary Compositions and Kits
In another aspect, compositions are provided. In some embodiments, compositions are provided for use in the methods described herein.
In some embodiments, a composition comprises at least one polynucleotide. In some embodiments, a composition comprises at least one primer. In some embodiments, a composition comprises at least one probe. In some embodiments, a composition comprises at least one primer and at least one probe.
In some embodiments, compositions are provided that comprise at least one target RNA-specific primer. The term “target RNA-specific primer” encompasses primers that have a region of contiguous nucleotides having a sequence that is (i) identically present in one of SEQ ID NOs: 1 to 397, 1063 to 1210, 1363 to 1707, 2064 to 2183, 2312 to 2452, 2673 to 2680, and 2689, or (ii) complementary to the sequence of a region of contiguous nucleotides found in one of SEQ ID NOs: 1 to 397, 1063 to 1210, 1363 to 1707, 2064 to 2183, 2312 to 2452, 2673 to 2680, and 2689.
In some embodiments, compositions are provided that comprise at least one target RNA-specific probe. The term “target RNA-specific probe” encompasses probes that have a region of contiguous nucleotides having a sequence that is (i) identically present in one of SEQ ID NOs: 1 to 397, 1063 to 1210, 1363 to 1707, 2064 to 2183, 2312 to 2452, 2673 to 2680, and 2689, or (ii) complementary to the sequence of a region of contiguous nucleotides found in one of SEQ ID NOs: 1 to 397, 1063 to 1210, 1363 to 1707, 2064 to 2183, 2312 to 2452, 2673 to 2680, and 2689.
In some embodiments, target RNA-specific primers and probes comprise deoxyribonucleotides. In other embodiments, target RNA-specific primers and probes comprise at least one nucleotide analog. Nonlimiting exemplary nucleotide analogs include, but are not limited to, analogs described herein, including LNA analogs and peptide nucleic acid (PNA) analogs. In some embodiments, target RNA-specific primers and probes comprise at least one nucleotide analog which increases the hybridization binding energy (e.g., an affinity-enhancing nucleotide analog, discussed above). In some embodiments, a target RNA-specific primer or probe in the compositions described herein binds to one target RNA in the sample. In some embodiments, a single primer or probe binds to multiple target RNAs, such as multiple isomirs.
In some embodiments, more than one primer or probe specific for a single target RNA is present in the compositions, the primers or probes capable of binding to overlapping or spatially separated regions of the target RNA.
It will be understood, even if not explicitly stated hereinafter, that in some embodiments in which the compositions described herein are designed to hybridize to cDNAs reverse transcribed from target RNAs, the composition comprises at least one target RNA-specific primer or probe (or region thereof) having a sequence that is identically present in a target RNA (or region thereof).
In some embodiments, a target RNA is capable of specifically hybridizing to at least one probe sequence in one of Tables 6, 7, 8, 9, 32, 33, or 34. In some embodiments, a target RNA comprises at least 15 contiguous nucleotides of a sequence selected from SEQ ID NOs: 794 to 1043, 2576 to 2672, and 2692. In some embodiments, a target RNA comprises a sequence that is complementary to at least 15 contiguous nucleotides of a sequence selected from SEQ ID NOs: 1 to 397, 1063 to 1210, 1363 to 1707, 2064 to 2183, 2312 to 2452, 2673 to 2680, and 2689. In some embodiments, a target RNA, in its mature form, comprises fewer than 30 nucleotides. In some embodiments, a target RNA is a microRNA.
In some embodiments, the composition comprises a plurality of target RNA-specific primers and/or probes for each of at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, or at least 8 target RNAs, the target RNAs comprising a region of contiguous nucleotides having a sequence that is identically present in one of SEQ ID NOs: 794 to 1043, 2576 to 2672, and 2692. In some embodiments, the plurality includes a target RNA-specific primer and/or probe specific for each of at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, or at least 12 target RNAs, the target RNAs comprising a region of contiguous nucleotides having a sequence that is identically present in one of SEQ ID NOs: 794 to 1043, 2576 to 2672, and 2692. In some embodiments, the plurality includes a target RNA-specific primer and/or probe specific for each of at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 15, at least 20, at least 25, at least 30, at least 40, at least 50, at least 75, or at least 100 target RNAs comprising a region of contiguous nucleotides having a sequence that is identically present in one of SEQ ID NOs: 794 to 1043, 2576 to 2672, and 2692. It will be understood that, in some embodiments, target RNAs described herein comprise a sequence identically present in a sequence set forth in at least one of Tables 4, 5, and 38. It is understood that where a sequence includes thymine (T) bases, a target RNA may contain uracil (U) bases instead.
In some embodiments, a composition is an aqueous composition. In some embodiments, the aqueous composition comprises a buffering component, such as phosphate, tris, HEPES, etc., and/or additional components, as discussed below. In some embodiments, a composition is dry, for example, lyophilized, and suitable for reconstitution by addition of fluid. A dry composition may include a buffering component and/or additional components.
In some embodiments, a composition comprises one or more additional components. Additional components include, but are not limited to, salts, such as NaCl, KCl, and MgCl2; polymerases, including thermostable polymerases; dNTPs; RNase inhibitors; bovine serum albumin (BSA) and the like; reducing agents, such as β-mercaptoethanol; EDTA and the like; etc. One skilled in the art can select suitable composition components depending on the intended use of the composition.
In some embodiments, an addressable microarray component is provided that comprises target RNA-specific probes attached to a substrate.
Microarrays for use in the methods described herein comprise a solid substrate onto which the probes are covalently or non-covalently attached. In some embodiments, probes capable of hybridizing to one or more target RNAs or cDNAs are attached to the substrate at a defined location (“addressable array”). Probes can be attached to the substrate in a wide variety of ways, as will be appreciated by those in the art. In some embodiments, the probes are synthesized first and subsequently attached to the substrate. In other embodiments, the probes are synthesized on the substrate. In some embodiments, probes are synthesized on the substrate surface using techniques such as photopolymerization and photolithography.
In some embodiments, the solid substrate is a material that is modified to contain discrete individual sites appropriate for the attachment or association of the probes and is amenable to at least one detection method. Representative examples of substrates include glass and modified or functionalized glass, plastics (including acrylics, polystyrene and copolymers of styrene and other materials, polypropylene, polyethylene, polybutylene, polyurethanes, TeflonJ, etc.), polysaccharides, nylon or nitrocellulose, resins, silica or silica-based materials including silicon and modified silicon, carbon, metals, inorganic glasses and plastics. In some embodiments, the substrates allow optical detection without appreciably fluorescing.
In some embodiments, the substrate is planar. In other embodiments, probes are placed on the inside surface of a tube, such as for flow-through sample analysis to minimize sample volume. In other embodiments, probes can be in the wells of multi-well plates. In still other embodiments, probes can be attached to an addressable microbead array. In yet other embodiments, the probes can be attached to a flexible substrate, such as a flexible foam, including closed cell foams made of particular plastics.
The substrate and the probe can each be derivatized with functional groups for subsequent attachment of the two. For example, in some embodiments, the substrate is derivatized with one or more chemical functional groups including, but not limited to, amino groups, carboxyl groups, oxo groups and thiol groups. In some embodiments, probes are attached directly to the substrate through one or more functional groups. In some embodiments, probes are attached to the substrate indirectly through a linker (i.e., a region of contiguous nucleotides that space the probe regions involved in hybridization and detection away from the substrate surface). In some embodiments, probes are attached to the solid support through the 5′ terminus. In other embodiments, probes are attached through the 3′ terminus. In still other embodiments, probes are attached to the substrate through an internal nucleotide. In some embodiments the probe is attached to the solid support non-covalently, e.g., via a biotin-streptavidin interaction, wherein the probe biotinylated and the substrate surface is covalently coated with streptavidin.
In some embodiments, the compositions comprise a microarray having probes attached to a substrate, wherein at least one of the probes (or a region thereof) comprises a sequence that is identically present in, or complementary to a region of, one of SEQ ID NOs: 1 to 397, 1063 to 1210, 1363 to 1707, 2064 to 2183, 2312 to 2452, 2673 to 2680, and 2689. In some embodiments, at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 30, at least 40, at least 50, or at least 100 of the probes comprise a sequence that is identically present in, or complementary to a region of, one of SEQ ID NOs: 1 to 397, 1063 to 1210, 1363 to 1707, 2064 to 2183, 2312 to 2452, 2673 to 2680, and 2689. In some embodiments, the microarray comprises at least one target RNA-specific probe comprising a sequence that is identically present in, or complementary to a region of, one of SEQ ID NOs: 1 to 397, 1063 to 1210, 1363 to 1707, 2064 to 2183, 2312 to 2452, 2673 to 2680, and 2689 and at least one target RNA-specific probe comprising a sequence that is identically present in, or complementary to a region of, a target RNA of the human miRNome. In some embodiments, the microarray comprises each target RNA-specific probe at only one location on the microarray. In some embodiments, the microarray comprises at least one target RNA-specific probe at multiple locations on the microarray.
As used herein, the terms “complementary” or “partially complementary” to a target RNA (or target region thereof), and the percentage of “complementarity” of the probe sequence to that of the target RNA sequence is the percentage “identity” to the reverse complement of the sequence of the target RNA. In determining the degree of “complementarity” between probes used in the compositions described herein (or regions thereof) and a target RNA, such as those disclosed herein, the degree of “complementarity” is expressed as the percentage identity between the sequence of the probe (or region thereof) and the reverse complement of the sequence of the target RNA that best aligns therewith. The percentage is calculated by counting the number of aligned bases that are identical as between the 2 sequences, dividing by the total number of contiguous nucleotides in the probe, and multiplying by 100.
In some embodiments, the microarray comprises at least one probe having a region with a sequence that is fully complementary to a target region of a target RNA. In other embodiments, the microarray comprises at least one probe having a region with a sequence that comprises one or more base mismatches when compared to the sequence of the best-aligned target region of a target RNA.
As noted above, a “region” of a probe or target RNA, as used herein, may comprise or consist of 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or more contiguous nucleotides from a particular SEQ ID NO or the complement thereof. In some embodiments, the region is of the same length as the probe or the target RNA. In other embodiments, the region is shorter than the length of the probe or the target RNA.
In some embodiments, the microarray comprises at least one probe having a region of at least 10, at least 11, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23, at least 24, or at least 25 contiguous nucleotides with a sequence that is identically present in, or complementary to a region of, one of SEQ ID NOs: 1 to 397, 1063 to 1210, 1363 to 1707, 2064 to 2183, 2312 to 2452, 2673 to 2680, and 2689.
In some embodiments, the microarray comprises at least one probe having a region with a sequence that is identically present in, or complementary to a region of, a probe sequence in one of Tables 6, 7, 8, 9, 32, 33, and 34. In some embodiments, a microarray further comprises at least one probe that does not have a region that is identically present in, or complementary to a region of, a probe sequence in one of Tables 6, 7, 8, 9, 32, 33, and 34.
In some embodiments, the microarray comprises at least one, at least two, at least three, at least five, at least 10, or at least 15 probes that each comprise a region with a sequence that is identically present in, or complementary to a region of, a probe sequence in Table 6. In some embodiments, the microarray comprises at least one, at least two, at least three, at least five, at least eight, at least 10, at least 12, at least 15, at least 20, or at least 25 probes that each comprise a region with a sequence that is identically present in, or complementary to a region of, a probe sequence in Table 7. In some embodiments, the microarray comprises at least one, at least two, at least three, at least five, at least six, or at least seven probes that each comprise a region with a sequence that is identically present in, or complementary to a region of, a probe sequence in Table 8. In some embodiments, the microarray comprises at least one, at least two, at least three, at least four, at least five, at least ten, at least 15, at least 20, at least 25, at least 30, at least 40, or at least 50 probes that each comprise a region with a sequence that is identically present in, or complementary to a region of, a probe sequence in Table 9. In some embodiments, the microarray comprises at least one, at least two, at least five, at least 10, at least 15, at least 20, at least 25, at least 30, or at least 40 probes that each comprise a region with a sequence that is identically present in, or complementary to a region of, a probe sequence in one of Tables 32 or 33. In some embodiments, the microarray comprises at least one, at least two, at least five, at least 10, at least 15, at least 20, at least 30, at least 40, at least 50, at least 60, or at least 70 probes that each comprise a region with a sequence that is identically present in, or complementary to a region of, a probe sequence in Table 34.
In some embodiments, the microarrays comprise probes having a region with a sequence that is complementary to target RNAs that comprise a substantial portion of the human miRNome (i.e., the publicly known microRNAs that have been accessioned by others into miRBase (http://microrna.sanger.ac.uk/ at the time the microarray is fabricated), such as at least about 60%, at least about 70%, at least about 80%, at least about 90%, or at least about 95% of the human miRNome. In some embodiments, the microarrays comprise probes that have a region with a sequence that is identically present in target RNAs that comprise a substantial portion of the human miRNome, such as at least about 60%, at least about 70%, at least about 80%, at least about 90%, or at least about 95% of the human miRNome.
In some embodiments, components are provided that comprise probes attached to microbeads, such as those sold by Luminex, each of which is internally dyed with red and infrared fluorophores at different intensities to create a unique signal for each bead. In some embodiments, the compositions useful for carrying out the methods described herein include a plurality of microbeads, each with a unique spectral signature. Each uniquely labeled microbead is attached to a unique target RNA-specific probe such that the unique spectral signature from the dyes in the bead is associated with a particular probe sequence. Nonlimiting exemplary probe sequences include SEQ ID NOs: 1 to 397, 1063 to 1210, 1363 to 1707, 2064 to 2183, 2312 to 2452, 2673 to 2680, and 2689. Nonlimiting exemplary probe sequences also include probes comprising a region that is identically present in, or complementary to, a sequence selected from SEQ ID NOs: 1 to 397, 1063 to 1210, 1363 to 1707, 2064 to 2183, 2312 to 2452, 2673 to 2680, and 2689. In some embodiments, a probe sequence comprises at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23, or at least 24 contiguous nucleotides that are identically present in, or complementary to a region of, one of SEQ ID NOs: 1 to 397, 1063 to 1210, 1363 to 1707, 2064 to 2183, 2312 to 2452, 2673 to 2680, and 2689.
In some embodiments, a uniquely labeled microbead has attached thereto a probe having a region with a sequence that is identically present in, or complementary to a region of, one of SEQ ID NOs: 1 to 397, 1063 to 1210, 1363 to 1707, 2064 to 2183, 2312 to 2452, 2673 to 2680, and 2689. In other embodiments, the uniquely labeled microbead has attached thereto a probe having a region with a sequence that comprises one or more base mismatches when compared to the most similar sequence selected from SEQ ID NOs: 1 to 397, 1063 to 1210, 1363 to 1707, 2064 to 2183, 2312 to 2452, 2673 to 2680, and 2689, and sequences complementary to SEQ ID NOs: 1 to 397, 1063 to 1210, 1363 to 1707, 2064 to 2183, 2312 to 2452, 2673 to 2680, and 2689.
In some embodiments, a composition is provided that comprises a plurality of uniquely labeled microbeads, wherein at least one microbead has attached thereto a probe having a region of at least 10, at least 11, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23, at least 24, or at least 25 contiguous nucleotides with a sequence that is identically present in, or complementary to a region of, one of SEQ ID NOs: 1 to 397, 1063 to 1210, 1363 to 1707, 2064 to 2183, 2312 to 2452, 2673 to 2680, and 2689.
In some embodiments, a composition is provided that comprises a plurality of uniquely labeled microbeads, wherein at least one microbead has attached thereto a probe having a region of at least 10, at least 11, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23, at least 24, or at least 25 contiguous nucleotides with a sequence that is identically present in, or complementary to a region of, a probe sequence in one of Tables 6, 7, 8, 9, 32, 33, and 34. In some embodiments, the composition further comprises at least one uniquely labeled microbead having attached thereto a probe that does not have a region that is identically present in, or complementary to a region of, a probe sequence in one of Tables 6, 7, 8, 9, 32, 33, and 34.
In some embodiments, the compositions comprise at least one, at least two, at least three, at least five, at least 10, or at least 15 uniquely labeled microbeads that each have attached thereto a unique target RNA-specific probe having a region with a sequence that is identically present in, or complementary to a region of, a probe sequence in Table 6. In some embodiments, the compositions comprise at least one, at least two, at least three, at least five, at least eight, at least 10, at least 12, at least 15, at least 20, or at least 25 uniquely labeled microbeads that each have attached thereto a unique target RNA-specific probe having a region with a sequence that is identically present in, or complementary to a region of, a probe sequence in Table 7. In some embodiments, the compositions comprise at least one, at least two, at least three, at least five, at least six, or at least seven uniquely labeled microbeads that each have attached thereto a unique target RNA-specific probe having a region with a sequence that is identically present in, or complementary to a region of, a probe sequence in Table 8. In some embodiments, the compositions comprise at least one, at least two, at least three, at least four, at least five, at least ten, at least 15, at least 20, at least 25, at least 30, at least 40, or at least 50 uniquely labeled microbeads that each have attached thereto a unique target RNA-specific probe having a region with a sequence that is identically present in, or complementary to a region of, a probe sequence in Table 9. In some embodiments, the compositions comprise at least one, at least two, at least five, at least 10, at least 15, at least 20, at least 25, at least 30, or at least 40 uniquely labeled microbeads that each have attached thereto a unique target RNA-specific probe having a region with a sequence that is identically present in, or complementary to a region of, a probe sequence in one of Tables 32 or 33. In some embodiments, the compositions comprise at least one, at least two, at least five, at least 10, at least 15, at least 20, at least 30, at least 40, at least 50, at least 60, or at least 70 uniquely labeled microbeads that each have attached thereto a unique target RNA-specific probe having a region with a sequence that is identically present in, or complementary to a region of, a probe sequence in Table 34.
In some embodiments, the compositions comprise a plurality of uniquely labeled microbeads, wherein the plurality comprises at least one microbead having attached thereto a probe having a region with a sequence that is identically present in, or complementary to a region of, one of SEQ ID NOs: 1 to 397, 1063 to 1210, 1363 to 1707, 2064 to 2183, 2312 to 2452, 2673 to 2680, and 2689. In some embodiments, the plurality comprises at least two, at least five, at least 10, at least 15, at least 20, at least 25, at least 30, at least 40, at least 50, at least 60, at least 75, or at least 100 microbeads each of which having attached thereto a probe having a region with a sequence that is identically present in, or complementary to a region of, one of SEQ ID NOs: 1 to 397, 1063 to 1210, 1363 to 1707, 2064 to 2183, 2312 to 2452, 2673 to 2680, and 2689. In some embodiments, a composition comprises at least one uniquely labeled microbead having attached thereto a target RNA-specific probe having a region with a sequence that is not present in, or complementary to a region of, any of SEQ ID NOs: 1 to 397, 1063 to 1210, 1363 to 1707, 2064 to 2183, 2312 to 2452, 2673 to 2680, and 2689.
In some embodiments, the compositions comprise a plurality of uniquely labeled microbeads, at least one of which has attached thereto a probe having a region with a sequence that identically present in, or complementary to a region of, one of SEQ ID NOs: 1 to 397, 1063 to 1210, 1363 to 1707, 2064 to 2183, 2312 to 2452, 2673 to 2680, and 2689 and at least a second bead that has attached thereto a probe having a region with a sequence that is identically present in, or complementary to a region of, a target RNA from the human miRNome.
In some embodiments, the compositions comprise a plurality of uniquely labeled microbeads, each of which has attached thereto a unique probe having a region that is complementary to target RNAs that comprise a substantial portion of the human miRNome, such as at least about 60%, at least about 70%, at least about 80%, at least about 90%, or at least about 95% of the human miRNome. In some embodiments, the compositions comprise a plurality of uniquely labeled microbeads having attached thereto a unique probe having a region with a sequence that is identically present in target RNAs that comprise a substantial portion of the human miRNome, such as at least about 60%, at least about 70%, at least about 80%, at least about 90%, or at least about 95% of the human miRNome.
In some embodiments, compositions are provided that comprise at least one polynucleotide for detecting at least one target RNA. In some embodiments, the polynucleotide is used as a primer for a reverse transcriptase reaction. In some embodiments, the polynucleotide is used as a primer for amplification. In some embodiments, the polynucleotide is used as a primer for RT-PCR. In some embodiments, the polynucleotide is used as a probe for detecting at least one target RNA. In some embodiments, the polynucleotide is detectably labeled. In some embodiments, the polynucleotide is a FRET probe. In some embodiments, the polynucleotide is a TaqMan° probe, a Molecular Beacon, or a Scorpion probe.
In some embodiments, a composition comprises at least one FRET probe having a sequence that is identically present in, or complementary to a region of, one of SEQ ID NOs: 1 to 397, 1063 to 1210, 1363 to 1707, 2064 to 2183, 2312 to 2452, 2673 to 2680, and 2689. In some embodiments, a composition comprises at least two, at least five, at least 10, at least 15, at least 20, at least 25, at least 30, at least 40, at least 50, at least 60, at least 75, or at least 100 FRET probes, each of which has a sequence that is identically present in, or complementary to a region of, a different one of SEQ ID NOs: 1 to 397, 1063 to 1210, 1363 to 1707, 2064 to 2183, 2312 to 2452, 2673 to 2680, and 2689.
In some embodiments, a FRET probe is labeled with a donor/acceptor pair such that when the probe is digested during the PCR reaction, it produces a unique fluorescence emission that is associated with a specific target RNA. In some embodiments, when a composition comprises multiple FRET probes, each probe is labeled with a different donor/acceptor pair such that when the probe is digested during the PCR reaction, each one produces a unique fluorescence emission that is associated with a specific probe sequence and/or target RNA. In some embodiments, the sequence of the FRET probe is complementary to a target region of a target RNA. In other embodiments, the FRET probe has a sequence that comprises one or more base mismatches when compared to the sequence of the best-aligned target region of a target RNA.
In some embodiments, a composition comprises a FRET probe consisting of at least 8, at least 9, at least 10, at least 11, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23, at least 24, or at least 25 nucleotides, wherein at least a portion of the sequence is identically present in, or complementary to a region of, one of SEQ ID NOs: 1 to 397, 1063 to 1210, 1363 to 1707, 2064 to 2183, 2312 to 2452, 2673 to 2680, and 2689. In some embodiments, at least 8, at least 9, at least 10, at least 11, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23, at least 24, or at least 25 nucleotides of the FRET probe are identically present in, or complementary to a region of, one of SEQ ID NOs: 1 to 397, 1063 to 1210, 1363 to 1707, 2064 to 2183, 2312 to 2452, 2673 to 2680, and 2689. In some embodiments, the FRET probe has a sequence with one, two or three base mismatches when compared to the sequence or complement of one of SEQ ID NOs: 1 to 397, 1063 to 1210, 1363 to 1707, 2064 to 2183, 2312 to 2452, 2673 to 2680, and 2689.
In some embodiments, a composition comprises a FRET probe consisting of at least 8, at least 9, at least 10, at least 11, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23, at least 24, or at least 25 nucleotides, wherein at least a portion of the sequence is identically present in, or complementary to a region of, a probe sequence in one of Tables 6, 7, 8, 9, 32, 33, and 34. In some embodiments, a composition comprises at least one FRET probe that does not comprise a portion that is identically present in, or complementary to a region of, a probe sequence in one of Tables 6, 7, 8, 9, 32, 33, and 34.
In some embodiments, the compositions comprise at least one, at least two, at least three, at least five, at least 10, or at least 15 uniquely labeled target RNA-specific FRET probes, each comprising a sequence that is identically present in, or complementary to a region of, a probe sequence in Table 6. In some embodiments, the compositions comprise at least one, at least two, at least three, at least five, at least eight, at least 10, at least 12, at least 15, at least 20, or at least 25 uniquely labeled target RNA-specific FRET probes, each of which comprises a sequence that is identically present in, or complementary to a region of, a probe sequence in Table 7. In some embodiments, the compositions comprise at least one, at least two, at least three, at least five, at least six, or at least seven uniquely labeled target RNA-specific FRET probes, each of which comprises a sequence that is identically present in, or complementary to a region of, a probe sequence in Table 8. In some embodiments, the compositions comprise at least one, at least two, at least three, at least four, at least five, at least ten, at least 15, at least 20, at least 25, at least 30, at least 40, or at least 50 uniquely labeled target RNA-specific FRET probes, each of which comprises a sequence that is identically present in, or complementary to a region of, a probe sequence in Table 9. In some embodiments, the compositions comprise at least one, at least two, at least five, at least 10, at least 15, at least 20, at least 25, at least 30, or at least 40 uniquely labeled target RNA-specific FRET probes, each of which comprises a sequence that is identically present in, or complementary to a region of, a probe sequence in one of Tables 32 or 33. In some embodiments, the compositions comprise at least one, at least two, at least five, at least 10, at least 15, at least 20, at least 30, at least 40, at least 50, at least 60, or at least 70 uniquely labeled target RNA-specific FRET probes, each of which comprises a sequence that is identically present in, or complementary to a region of, a probe sequence in Table 34.
In some embodiments, a kit comprises a polynucleotide discussed above. In some embodiments, a kit comprises at least one primer and/or probe discussed above. In some embodiments, a kit comprises at least one polymerase, such as a thermostable polymerase. In some embodiments, a kit comprises dNTPs. In some embodiments, kits for use in the real time RT-PCR methods described herein comprise one or more target RNA-specific FRET probes and/or one or more primers for reverse transcription of target RNAs and/or one or more primers for amplification of target RNAs or cDNAs reverse transcribed therefrom.
In some embodiments, one or more of the primers and/or probes is “linear”. A “linear” primer refers to a polynucleotide that is a single stranded molecule, and typically does not comprise a short region of, for example, at least 3, 4 or 5 contiguous nucleotides, which are complementary to another region within the same polynucleotide such that the primer forms an internal duplex. In some embodiments, the primers for use in reverse transcription comprise a region of at least 4, at least 5, at least 6, at least 7 or more contiguous nucleotides at the 3′-end that has a sequence that is complementary to region of at least 4, at least 5, at least 6, at least 7 or more contiguous nucleotides at the 5′-end of a target RNA.
In some embodiments, a kit comprises one or more pairs of linear primers (a “forward primer” and a “reverse primer”) for amplification of a cDNA reverse transcribed from a target RNA. Accordingly, in some embodiments, a first primer comprises a region of at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, or at least 10 contiguous nucleotides having a sequence that is identical to the sequence of a region of at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, or at least 10 contiguous nucleotides at the 5′-end of a target RNA. Furthermore, in some embodiments, a second primer comprises a region of at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, or at least 10 contiguous nucleotides having a sequence that is complementary to the sequence of a region of at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, or at least 10 contiguous nucleotides at the 3′-end of a target RNA. In some embodiments, the kit comprises at least a first set of primers for amplification of a cDNA that is reverse transcribed from a target RNA capable of specifically hybridizing to a nucleic acid comprising a sequence identically present in one of SEQ ID NOs: 1 to 397, 1063 to 1210, 1363 to 1707, 2064 to 2183, 2312 to 2452, 2673 to 2680, and 2689 and/or a cDNA that is reverse transcribed from a target RNA that comprises at least 15 contiguous nucleotides of a sequence selected from SEQ ID NOs: 794 to 1043, 2576 to 2672, and 2692.
In some embodiments, the kit comprises at least two, at least five, at least 10, at least 15, at least 20, at least 25, at least 30, at least 40, at least 50, at least 60, at least 75, or at least 100 sets of primers, each of which is for amplification of a cDNA that is reverse transcribed from a different target RNA capable of specifically hybridizing to a sequence selected from SEQ ID NOs: 1 to 397, 1063 to 1210, 1363 to 1707, 2064 to 2183, 2312 to 2452, 2673 to 2680, and 2689 and/or a cDNA that is reverse transcribed from a target RNA that comprises at least 15 contiguous nucleotides of a sequence selected from SEQ ID NOs: 794 to 1043, 2576 to 2672, and 2692. In some embodiments, the kit comprises at least one set of primers that is capable of amplifying more than one cDNA reverse transcribed from a target RNA in a sample.
In some embodiments, probes and/or primers for use in the compositions described herein comprise deoxyribonucleotides. In some embodiments, probes and/or primers for use in the compositions described herein comprise deoxyribonucleotides and one or more nucleotide analogs, such as LNA analogs or other duplex-stabilizing nucleotide analogs described above. In some embodiments, probes and/or primers for use in the compositions described herein comprise all nucleotide analogs. In some embodiments, the probes and/or primers comprise one or more duplex-stabilizing nucleotide analogs, such as LNA analogs, in the region of complementarity.
In some embodiments, the compositions described herein also comprise probes, and in the case of RT-PCR, primers, that are specific to one or more housekeeping genes for use in normalizing the quantities of target RNAs. Such probes (and primers) include those that are specific for one or more products of housekeeping genes selected from U6 snRNA, RNU44, RNU48, U47, 7SL scRNA, U1 snRNA, 5.8S rRNA, and U87 scaRNA.
In some embodiments, the kits for use in real time RT-PCR methods described herein further comprise reagents for use in the reverse transcription and amplification reactions. In some embodiments, the kits comprise enzymes such as reverse transcriptase, and a heat stable DNA polymerase, such as Taq polymerase. In some embodiments, the kits further comprise deoxyribonucleotide triphosphates (dNTPs) for use in reverse transcription and amplification. In further embodiments, the kits comprise buffers optimized for specific hybridization of the probes and primers.
4.2.1. Exemplary Normalization of RNA Levels
In some embodiments, quantitation of target RNA expression levels requires assumptions to be made about the total RNA per cell and the extent of sample loss during sample preparation. In order to correct for differences between different samples or between samples that are prepared under different conditions, the quantities of target RNAs in some embodiments are normalized to the expression of at least one endogenous housekeeping gene.
Appropriate genes for use as reference genes in the methods described herein include those as to which the quantity of the product does not vary between normal samples and samples from lung cancer patients, or between different cell lines or under different growth and sample preparation conditions. In some embodiments, endogenous housekeeping genes useful as normalization controls in the methods described herein include, but are not limited to, U6 snRNA, RNU44, RNU48, U47, 7SL scRNA, U1 snRNA, 5.8S rRNA, and U87 scaRNA. In typical embodiments, the at least one endogenous housekeeping gene for use in normalizing the measured quantity of microRNAs is selected from U6 snRNA, RNU44, RNU48, U47, 7SL scRNA, U1 snRNA, 5.8S rRNA, and U87 scaRNA. In some embodiments, one housekeeping gene is used for normalization. In some embodiments, more than one housekeeping gene is used for normalization.
4.2.2. Exemplary Qualitative Methods
In some embodiments, methods comprise detecting a qualitative change in a target RNA profile generated from a human sample as compared to a normal target RNA profile (in some exemplary embodiments, a target RNA profile of a control sample). Some qualitative changes in the expression profile are indicative of the presence of lung cancer in a sample from a subject. The term “target RNA profile” refers to a set of data regarding the concurrent expression of a plurality of target RNAs in the same sample.
In some embodiments, at least one, at least two, at least three, at least five, at least 10, or at least 15 of the target RNAs of the plurality of target RNAs are capable of specifically hybridizing to a probe sequence in Table 6. In some embodiments, at least one, at least two, at least three, at least five, at least eight, at least 10, at least 12, at least 15, at least 20, or at least 25 of the target RNAs of the plurality of target RNAs are capable of specifically hybridizing to a probe sequence in Table 7. In some embodiments, at least one, at least two, at least three, at least five, at least six, or at least seven of the target RNAs of the plurality of target RNAs are capable of specifically hybridizing to a probe sequence in Table 8. In some embodiments, at least one, at least two, at least three, at least four, at least five, at least ten, at least 15, at least 20, at least 25, at least 30, at least 40, or at least 50 of the target RNAs of the plurality of target RNAs are capable of specifically hybridizing to a probe sequence in Table 9. In some embodiments, at least one, at least two, at least five, at least 10, at least 15, at least 20, at least 25, at least 30, or at least 40 of the target RNAs of the plurality of target RNAs are capable of specifically hybridizing to a probe sequence in one of Table 32 or 33. In some embodiments, at least one, at least two, at least five, at least 10, at least 15, at least 20, at least 30, at least 40, at least 50, at least 60, or at least 70 of the target RNAs of the plurality of target RNAs is capable of specifically hybridizing to a probe sequence in Table 34.
In some embodiments, at least one, at least two, at least five, at least 10, at least 15, at least 20, at least 25, at least 30, at least 40, at least 50, at least 60, or at least 75 of the plurality of target RNAs comprises a sequence that is complementary to at least 15 contiguous nucleotides of a sequence selected from SEQ ID NOs: 1 to 397, 1063 to 1210, 1363 to 1707, 2064 to 2183, 2312 to 2452, 2673 to 2680, and 2689. In some embodiments, at least one, at least two, at least five, at least 10, at least 15, at least 20, at least 25, at least 30, at least 40, at least 50, at least 60, or at least 70 of the plurality of target RNAs comprises at least 15 contiguous nucleotides of a sequence selected from SEQ ID NOs: 794 to 1043, 2576 to 2672, and 2692. In some embodiments, a target RNA, in its mature form, comprises fewer than 30 nucleotides. In some embodiments, a target RNA is a microRNA.
Qualitative expression data for use in preparing target RNA expression profiles is obtained using any suitable analytical method, including the analytical methods presented herein.
In some embodiments, for example, concurrent expression data are obtained using, e.g., a microarray, as described above. Thus, in addition to use for quantitative expression level assays of specific target RNAs as described above, a microarray comprising probes having sequences that are complementary to a substantial portion of the miRNome may be employed to carry out target RNA gene expression profiling, for analysis of target RNA expression patterns.
In some embodiments, distinct target RNA signatures are associated with established markers for lung cancer. In some embodiments, distinct target RNA signatures are associated with established markers for lung cancer caused by bacterial infection, such as for lung cancer caused by gram-positive bacterial infection, lung cancer caused by gram-negative bacterial infection or lung cancer caused by mycobacterial infection. In some embodiments, distinct target RNA signatures are associated with established markers for lung cancer caused by viral infection. In some embodiments, distinct target RNA signatures are associated with established markers for lung cancer caused by multiple infection, such as by co-infection with bacteria and viruses, or by co-infection with more than one viral or more than one bacterial strain. In some embodiments, distinct target RNA signatures are associated directly with the level of severity of the lung cancer.
According to the expression profiling method, in some embodiments, total RNA from a sample from a subject suspected of having lung cancer is quantitatively reverse transcribed to provide a set of labeled oligonucleotides complementary to the RNA in the sample. The oligonucleotides are then hybridized to a microarray comprising target RNA-specific probes to provide a hybridization profile for the sample. The result is a hybridization profile for the sample representing the expression pattern of target RNAs in the sample. The hybridization profile comprises the signal from the binding of the oligonucleotides reverse transcribed from the sample to the target RNA-specific probes in the microarray. In some embodiments, the profile is recorded as the presence or absence of binding (signal vs. zero signal). In some embodiments, the profile recorded includes the intensity of the signal from each hybridization. The profile is compared to the hybridization profile generated from a normal, i.e., nonseptic sample, or in some embodiments, a control sample. An alteration in the signal is indicative of the presence of lung cancer in the subject.
4.3. Exemplary Additional Target RNAs
In some embodiments, in combination with detecting one or more target RNAs that are capable of specifically hybridizing to a nucleic acid comprising a sequence selected from SEQ ID NOs: 1 to 397, 1063 to 1210, 1363 to 1707, 2064 to 2183, 2312 to 2452, 2673 to 2680, and 2689 and/or detecting one or more target RNAs comprising at least 15 contiguous nucleotides of a sequence selected from SEQ ID NOs: 794 to 1043, 2576 to 2672, and 2692 and/or detecting one or more target RNAs that comprise a sequence that is complementary to at least 15 contiguous nucleotides of a sequence selected from SEQ ID NOs: 1 to 397, 1063 to 1210, 1363 to 1707, 2064 to 2183, 2312 to 2452, 2673 to 2680, and 2689, methods herein further comprise detecting the level(s) of expression of at least one other marker associated with lung cancer.
In some embodiments, the methods described herein further comprise detecting altered expression of lung cancer-associated small RNAs with non-canonical hairpins.
In alternative embodiments, the methods described herein further comprise detecting chromosomal codependents, i.e., target RNAs clustered near each other in the human genome which tend to be regulated together. Accordingly, in further embodiments, the methods comprise detecting the expression of one or more target microRNAs, each situated within the chromosome no more than 50,000 bp from the chromosomal location of the pre-microRNA sequences in Tables 3, 22, 25, 29, and 31.
In some embodiments, the methods comprise detecting the expression of one or more target RNAs clustered on chromosome 8 at 8p21.3-21.2, at 8p12, at 8p11.21, at 8q11.21, at 8q21.11, or at 8q24.22-24.3; on chromosome 9 at 9p21.3, at 9p13.3, at 9p11.2, at 9q22.32, at 9q31.3-34.11, or at 9q34.3; on chromosome 10 at 10q21.3-23.31, at 10q24.1, at 10q24.32, at 10q25.3, or at 10q26.3; on chromosome 11 at 11p15.5, at 11p14.1, at 11q12.1-23.2, at 11q13.4-14.1, at 11q23.2-24.1, or at 11q25; on chromosome 12 at 12p13.32-13.31, at 12p13.1, at 12p12.1, at 12q12-14.1, at 12q14.3-21.1, at 12q21.32-23.2, or at 12q24.23; on chromosome 13 at 13q13.3, at 13q14.2, at 13q21.33, at 13q22.3, or at 13q31.3; at chromosome 14 at 14q11.1-13.2, at 14q24.3-31.1, or at 14q32.2-32.31; on chromosome 15 at 15q3, at 15q23-24.32, or at 15q25.3-26.2; on chromosome 16 at 16p13.3-13.2, at 16p11.2, or at 16q12.1-22.3; on chromosome 17 at 17p13.3, at 17p13.1-11.2, at 17q12-21.1, at 17q22-23.3, or at 17q25.31; on chromosome 18 at 18q11.2, at 18q21.31-33, or at 18q22.3; on chromosome 19 at 19p13.3-13.2, at 19p13.12-12, at 19q12, or at 19q13.32-13.42; on chromosome 20 at 20p13, at 20p11.1, at 20q12, or at 20q13.32; on chromosome 21 at 21q21.1-22.11; on chromosome 22 at 22q11.21, or at 22q12.1-13.31; or on the X chromosome at Xp11.4-11.22, at Xq 13.1-13.3, at Xq22.3, at Xq25-27.1, or at Xq27.3-28.
4.4. Pharmaceutical Compositions and Methods of Treatment
In some embodiments, the disclosure relates to methods of treating lung cancer in which expression of a target RNA is deregulated, e.g., either down-regulated or up-regulated in the lung cancer cells of an individual. When at least one target RNA is up-regulated in the cancer cells, the method comprises administering to the individual an effective amount of at least one compound that inhibits the expression of the at least one target RNA, such that proliferation of lung cancer cells is inhibited. Alternatively, in some embodiments, when at least one target RNA is up-regulated in the cancer cells, the method comprises administering to the individual an effective amount of at least one compound that inhibits the activity of the at least one target RNA, such that proliferation of lung cancer cells is inhibited. Such a compound may be, in some embodiments, a polynucleotide, including a polynucleotide comprising modified nucleotides.
When at least one target RNA is down-regulated in the lung cancer cells, the method comprises administering an effective amount of an isolated target RNA (i.e., in some embodiments, a target RNA that is chemically synthesized, recombinantly expressed or purified from its natural environment), or an isolated variant or biologically-active fragment thereof, such that proliferation of cancer cells in the individual is inhibited.
The disclosure further provides pharmaceutical compositions for treating lung cancer. In some embodiments, the pharmaceutical compositions comprise at least one isolated target RNA, or an isolated variant or biologically-active fragment thereof, and a pharmaceutically-acceptable carrier. In some embodiments, the at least one isolated target RNA corresponds to a target RNA that exhibits a decreased level of expression in lung cancer cells relative to normal levels (in some exemplary embodiments, relative to the level of the target RNA in a control sample). In some embodiments, the isolated target RNA is a target RNA that is capable of selectively hybridizing to at least one nucleic acid probe comprising a sequence that is identically present in one of SEQ ID NOs: 1 to 397, 1363 to 1707, and 2312 to 2452. In some embodiments, the isolated target RNA that has a decreased level of expression in lung cancer relative to normal levels is capable of selectively hybridizing to at least one nucleic acid probe comprising a sequence that is identically present in one of SEQ ID NOs: 92 or 171, or a sequence that is identically present in the probe sequences of Table 34.
In some embodiments, the pharmaceutical compositions are useful for treating adenocarcinoma and comprise an isolated target RNA that is capable of selectively hybridizing to at least one nucleic acid probe comprising a sequence that is identically present in one of SEQ ID NOs: 4, 36, 50, 93, 122, 125, 139, 140, 144, 146, 159, 226, 239 or 241. In some embodiments, the pharmaceutical compositions are useful for treating adenocarcinoma and comprise an isolated target RNA that is capable of selectively hybridizing to at least one nucleic acid probe comprising a sequence that is identically present in one of SEQ ID NOs: 19, 27, 33, 48, 55, 72, 73, 94, 101, 105, 112, 117, 130, 131, 133, 134, 135, 143, 155, 158, 160, 161, 163, 165, 221, 238, 240 or 246.
In some embodiments the isolated target RNA is identical to an endogenous wild-type target RNA gene product (such as a product of a gene set forth in Table 3) that is down-regulated in the cancer cell. In some embodiments, the isolated target RNA is a variant target RNA or biologically active fragment thereof. As used herein, a “variant” refers to a target RNA gene product that has less than 100% sequence identity to the corresponding wild-type target RNA, but still possesses one or more biological activities of the wild-type target RNA (e.g., ability to inhibit expression of a target RNA molecule and cellular processes associated with lung cancer). A “biologically active fragment” of a target RNA is a fragment of the target RNA gene product that possesses one or more biological activities of the wild-type target RNA. In some embodiments, the isolated target RNA can be administered with one or more additional anti-cancer treatments including, but not limited to, chemotherapy, radiation therapy and combinations thereof. In some embodiments, the isolated target RNA is administered concurrently with additional anti-cancer treatments. In some embodiments, the isolated target RNA is administered sequentially to additional anti-cancer treatments.
In some embodiments, the pharmaceutical compositions comprise at least one compound that inhibits expression of the target RNA. In some embodiments, the compound is specific for one or more target RNAs, the expression of which is increased in lung cancer cells relative to normal levels (in some exemplary embodiments, relative to the level of the target RNA in a control sample). In some embodiments, the target RNA expression inhibitor is specific for at least one target RNA that is capable of selectively hybridizing to at least one nucleic acid probe comprising a sequence that is identically present in one of SEQ ID NOs: 1 to 397, 1063 to 1210, 2064 to 2183, 2673 to 2680, and 2689. In some embodiments, the target RNA expression inhibitor is specific for at least one target RNA that is capable of selectively hybridizing to at least one nucleic acid probe comprising a sequence that is identically present in one of SEQ ID NOs: 15, 26, 27 or 191. In some embodiments, the target RNA expression inhibitor is specific for at least one target RNA that is capable of selectively hybridizing to at least one nucleic acid probe comprising a sequence that is identically present in one of SEQ ID NOs: 15, 26, 27, 30, 129, 164, 184, 191, 196, 205, 207, 214, 219, 225, 246 or 248. In some embodiments, the target RNA expression inhibitor is specific for at least one target RNA that is capable of selectively hybridizing to at least one nucleic acid probe in one of Tables 6, 7, 8, 9, 32, and 33. In some embodiments, a target RNA expression inhibitor that is specific for at least one target RNA that is capable of selectively hybridizing to at least one nucleic acid probe in Table 6 is useful for treating non-small cell lung cancer. In some embodiments, a target RNA expression inhibitor that is specific for at least one target RNA that is capable of selectively hybridizing to at least one nucleic acid probe in Table 7 is useful for treating squamous cell carcinoma. In some embodiments, a target RNA expression inhibitor that is specific for at least one target RNA that is capable of selectively hybridizing to at least one nucleic acid probe in Table 8 is useful for treating adenocarcinoma. In some embodiments, a target RNA expression inhibitor that is specific for at least one target RNA that is capable of selectively hybridizing to at least one nucleic acid probe in Table 9 is useful for treating aggressive forms of lung cancer.
In some embodiments, the pharmaceutical compositions are useful for treating squamous cell carcinoma and comprise a target RNA expression inhibitor that is specific to a target RNA capable of selectively hybridizing to at least one nucleic acid probe comprising a sequence that is identically present in one of SEQ ID NOs: 4, 36, 50, 93, 122, 125, 139, 140, 144, 146, 159, 226, 239 and 241. In some embodiments, the pharmaceutical compositions are useful for treating squamous cell carcinoma and comprise a target RNA expression inhibitor that is specific to a target RNA capable of selectively hybridizing to at least one nucleic acid probe comprising a sequence that is identically present in one of SEQ ID NOs: 19, 27, 19, 27, 33, 48, 55, 72, 73, 94, 101, 105, 112, 117, 130, 131, 133, 134, 135, 143, 155, 158, 160, 161, 163, 165, 221, 238, 240 or 246. In some embodiments, the pharmaceutical compositions are useful for treating squamous cell carcinoma and comprise a target RNA expression inhibitor that is specific to a target RNA capable of selectively hybridizing to at least one nucleic acid probe in Table 7. In some embodiments, the pharmaceutical compositions are useful for treating adenocarcinoma and comprise a target RNA expression inhibitor that is specific to a target RNA capable of selectively hybridizing to at least one nucleic acid probe in Table 8. In some embodiments, the pharmaceutical compositions are useful for treating aggressive forms of lung cancer and comprise a target RNA expression inhibitor that is specific to a target RNA capable of selectively hybridizing to at least one nucleic acid probe in Table 9.
In some embodiments, the target RNA inhibitor is selected from double-stranded RNA, antisense nucleic acids and enzymatic RNA molecules. In some embodiments, the target RNA inhibitor is a small molecule inhibitor. In some embodiments, the target RNA inhibitor can be administered in combination with other anti-cancer treatments, including but not limited to, chemotherapy, radiation therapy and combinations thereof. In some embodiments, the target RNA inhibitor is administered concurrently with other anti-cancer treatments. In some embodiments, the target RNA inhibitor is administered sequentially to other anti-cancer treatments.
In some embodiments, a pharmaceutical composition is formulated and administered according to Semple et al., Nature Biotechnology advance online publication, 17 Jan. 2010 (doi:10.1038/nbt.1602)), which is incorporated by reference herein in its entirety for any purpose.
The terms “treat,” “treating” and “treatment” as used herein refer to ameliorating symptoms associated with lung cancer, including preventing or delaying the onset of symptoms and/or lessening the severity or frequency of symptoms of the lung cancer.
The term “effective amount” of a target RNA or an inhibitor of target RNA expression or activity is an amount sufficient to inhibit proliferation of cancer cells in an individual suffering from lung cancer. An effective amount of a compound for use in the pharmaceutical compositions disclosed herein is readily determined by a person skilled in the art, e.g., by taking into account factors such as the size and weight of the individual to be treated, the stage of the disease, the age, health and gender of the individual, the route of administration and whether administration is localized or systemic.
In addition to an isolated target RNA or a target RNA inhibitor, or a pharmaceutically acceptable salt thereof, the pharmaceutical compositions disclosed herein further comprise a pharmaceutically acceptable carrier, including but not limited to, water, buffered water, normal saline, 0.4% saline, 0.3% glycine, and hyaluronic acid. In some embodiments, the pharmaceutical compositions comprise an isolated target RNA or a target RNA expression inhibitor that is encapsulated, e.g., in liposomes. In some embodiments, the pharmaceutical compositions comprise an isolated target RNA or a target RNA expression inhibitor that is resistant to nucleases, e.g., by modification of the nucleic acid backbone as described above in Section 4.1.5. In some embodiments, the pharmaceutical compositions further comprise pharmaceutically acceptable excipients such as stabilizers, antioxidants, osmolality adjusting agents and buffers. In some embodiments, the pharmaceutical compositions further comprise at least one chemotherapeutic agent, including but not limited to, alkylating agents, anti-metabolites, epipodophyllotoxins, anthracyclines, vinca alkaloids, plant alkaloids and terpenoids, monoclonal antibodies, taxanes, topoisomerase inhibitors, platinum compounds, protein kinase inhibitors, and antisense nucleic acids.
Pharmaceutical compositions can take the form of solutions, suspensions, emulsions, tablets, pills, pellets, capsules, capsules containing liquids, powders, sustained-release formulations, suppositories, emulsions, aerosols, sprays, suspensions, or any other form suitable for use. Methods of administration include, but are not limited to, oral, parenteral, intravenous, oral, and by inhalation.
The following examples are for illustration purposes only, and are not meant to be limiting in any way.
5. EXAMPLES
5.1 Example 1
MicroRNAs from Primary Lung Tumors
Using microarray analysis, distinct microRNAs were demonstrated to be deregulated (e.g., either over-expressed or under-expressed) in primary lung tumors.
Total RNA was extracted from each of the primary tumors in Table 10 by preparation from frozen tissue samples as described below.
RNA Preparation from Frozen Tissue Samples
Archived or freshly snap-frozen tumor specimens were homogenized by mortar and pestle in TRIzol® Reagent, Invitrogen (Carlsbad, Calif.) and RNA was further extracted according to the manufacturer's protocol. All RNA samples were diluted in RNase-free water and stored at −80° C.
TABLE 10
|
|
Tumor
Smoking Risk
|
designation
Sex
Age
Factor
Cancer type
Stage
|
|
Adk-1
M
59
Smoker
Non Squamous,
YT2N2
|
adenocarcinoma
|
Adk-2
M
67
Smoker
Non Squamous,
PT2N0
|
adenocarcinoma
|
Adk-3
M
78
na
Non Squamous,
PT1N0
|
adenocarcinoma
|
Adk-8
F
51
na
Non Squamous,
PT3N0
|
adenocarcinoma
|
Adk-9
M
55
Smoker
Non Squamous,
PT1N0
|
adenocarcinoma
|
Adk-10
M
49
Smoker
Non Squamous,
PT3N0
|
adenocarcinoma
|
Adk-11
M
73
na
Non Squamous,
PT1N0
|
adenocarcinoma
|
Epi-4
M
78
Smoker
Squamous, Epidermoid
PT2NX
|
carcinoma
|
Epi-5
M
78
Smoker
Squamous, Epidermoid
PT2NX
|
carcinoma
|
Epi-7
F
84
Non-smoker
Squamous, Epidermoid
PT2NX
|
carcinoma
|
Normal-lung_1
M
81
na
Normal tissue from patient
PT2N0
|
Normal-lung_2
na
na
na
Normal tissue from Ambion
na
|
|
Epi4, Epi7, Epi5, Adk1, Adk3, Adk11, Adk8, Adk9 and Adk2 identify primary tumors resected from 10 patients. Epi (epidermoid) is squamous cell carcinoma, while Adk (adenocarcinoma) is non-squamous cell carcinoma.
In Table 10, above, “na” indicates that the information was not available. “Y” in the staging column indicates that the patient was treated before surgical resection. “P” indicates that the patient was not treated before surgical resection.
Staging is according to the “TNM” staging system for NSCLC. “T” categories for NSCLC indicate the following: (a) T1 indicates that the tumor is no larger than 3 centimeters across, has not reached the membranes that surround the lungs, and does not affect the main branches of the bronchi; (b) T2 tumors possess one or more of the following features: (i) larger than 3 centimeters across; (ii) involves a main bronchus, but is not closer than 2 cm to the carina (the point where the windpipe splits into the left and right main bronchi); (iii) has grown into the membranes that surround the lungs; or (iv) partially clogs the airways, but has not caused the entire lung to collapse or develop pneumonia; (c) T3 indicates a tumor of any size having one or more of the following features: (i) tumor has grown into the chest wall, the diaphragm, the membranes surrounding the space between the two lungs, or membranes of the sac surrounding the heart; (ii) tumor invades a main bronchus and is closer than 2 cm to the carina, but it does not involve the carina itself; or (iii) tumor has grown into the airways enough to cause an entire lung to collapse or to cause pneumonia in the entire lung. The “N” number indicates involvement of the lymph nodes as follows: (a) N0 indicates that the cancer has not spread to nearby lymph nodes; (b) N2 indicates spread to lymph nodes around the carina or in the space behind the breastbone and in front of the mediastinum. Affected lymph nodes are on the same side as the primary tumor; and (c) NX indicates that nearby lymph nodes could not be accessed.
Total RNA from normal lung tissue resected from a patient (in this case from a location in the lung as distal as possible from the tumor) and normal lung tissue from a location adjacent to a lung tumor (Ambion) were used as the control.
Total RNA Preparation and Analysis
Total RNA was isolated by using standard TRIzol® protocol (Invitrogen). Cells from two confluent 75 cm2 flasks were harvested (=approx 107 cells). Total RNA was prepared using TRIzol® Reagent, Invitrogen (Carlsbad, Calif.) according to the manufacturer's protocol. All RNA samples were diluted in RNase-free water and stored in −80° C. (−112° F.).
RNA quality was assessed by calculating OD 260/280 ratios. The quality of all RNA samples was high as assessed using an Agilent Bioanalyser 2100, as exemplified by the electropherogram shown in FIG. 1 obtained for total RNA from A549 human adenocarcinoma cell line. Similar electropherograms were obtained for total RNA from the other primary tumor samples as well.
MicroRNA Purification
MicroRNA purification was performed using a Flash PAGE Fractionator (Ambion). The Ambion gel purification protocol enriches for small RNAs less than 40 nucleotides (nt) long, including microRNAs. Briefly, a total RNA sample was loaded onto a pre-cast gel using the Flash PAGE Fractionator. The total RNA fraction smaller than 40 nt (the “microRNA fraction”) was recovered after gel migration and resuspended into nuclease free water.
Microarray Analysis
Probe Design and Spotting
The oligonucleotide probes used for microarray preparation had the configuration 5′—NH2—(C)6-(spacer)-(oligomer probe sequence)-3′. The 5′-amino group allowed chemical bonding onto the array support. Each also included an identical spacer sequence of 15 nt, as shown below, to prevent non-specific interactions of the oligonucleotide probes with the array support:
(SEQ ID NO: 1044)
|
5′AminoC6-TTGTAATACGACTCA-Oligo probe sequence
|
Probe sequences given in Table 1 and Table 2 omit the linker.
The probes were synthesized according to standard protocols by Eurofins MWG Operon (Ebersberg, Germany). Nexterion (Schott) microarray glass slides were used as the solid support for the microarray.
The oligonucleotide probe concentration used for the spotting was 25 μmol. The probes were spotted in duplicate using the Nexterion spotting buffer provided with the array glass support by Schott with 1% SDS (sodium dodecyl sulfate) added to allow larger spot sizes (e.g., 100-150 microns compared to 70-100 microns without SDS). The spotter used was the QArray mini (Genetix) equipped with Stealth SMP3 pins (Telechem). After deposition of one series of spots, the spotting needle was washed 5 times with 60 mM NaOH before spotting the next series of probes. Each slide is designed with 32 blocks of spotted probes, with each block being a 20×20 square of spotted probes. Each probe was spotted in duplicate. Spotted glass slides were stored at 4° C. until use.
MicroRNA Labelling
The labelling of the microRNA fraction was adapted from a published protocol developed at EMBL (Heidelberg, Germany) by the European Molecular Biology Group (Castoldi et al., “A sensitive array for microRNA expression profiling (miChip) based on locked nucleic acids (LNA),” RNA 2006 May; 12(5):913-20. Epub 2006 Mar. 15, incorporated herein by reference in its entirety). Briefly, the microRNA fraction was incubated for 6 hours at 4° C. with a mixture containing 10 μM of dye-labelled tetra-nucleotide (5′-rUrUrUrU-Cy5-3′) (or alternatively, 5′-rUrUrUrU-Cy3-3′) (Biospring, Germany) in Ambion buffer diluted to 1× with RNase free water, 8% polyethylene glycol (PEG), 2 mM adenosine triphosphate (ATP), and T4 RNA ligase (0.7 U/μl). The labelling reaction was run by heating the mixture for 15 minutes at 65° C. This procedure ligated the poly-U dye-labelled tail to the 3′ end of all the microRNAs. Labelled samples were stored at 4° C. before hybridization.
Array Hybridization
The labelled microRNA fraction was hybridized to the spotted arrays using a Discovery hybridization station (Ventana, Tucson, Ariz.). Briefly, 2 mL of a mixture of 1% BSA, 2×SSC, and 0.2% SDS was incubated with the chips for 30 min at 42° C. Then the chips were washed once using EZ Prep buffer (Ventana) and then three more times with Ribowash (Ventana). Next, 20 μl of the labelled microRNA mixture and 180 μl of ChipHybe Reagent (Ventana) were added to the array. The arrays were heated for 6 minutes at 37° C., then were incubated at 42° C. for 8 hours, after which the heating was stopped. The chips were washed once with Ribowash (Ventana) and then heated for 2 minutes at 37° C. The chips were washed again with Ribowash (Ventana) with one drop of CheapClean (Ventana) added, and incubated for 2 minutes at 37° C. The chips were washed two more times using Ribowash (Ventana). The chips were stored dry overnight. On the following day, the final washes were done according to Ventana's instructions for the Discovery hybridization station. The slides were washed twice with 2×SSC+0.2×SDS buffer and then one more time with 0.1×SSC. All the slides were dried using a speed centrifuge from Arrayit (TeleChem International, Sunnyvale, Calif.) at room temperature and kept in the dark before scanning.
As an alternative to the ChipHybe Reagent solution (solution 1), the following solution may be used for array hybridization (solution 2) to form probe:target RNA hybrids by mixing 2 parts of the 1.5×TMAC Hybridization Solution to 1 part (v:v) sample, so that the final component concentrations are 3M TMAC, 0.10% Sarkosyl, 50 mM Tris, and 4 mM EDTA, and incubating on the array at 42° C. for 8 hours:
|
1.5X TMAC Hybridization Solution
|
Amount/
|
Reagent
Catalog Number
Final Conc
250 mL
|
|
5M TMAC*
Sigma T3411
4.5M
225 mL
|
20% Sarkosyl
—
0.15%
1.88 mL
|
1M Tris-HCl, pH 8.0
Sigma T3038
75 mM
18.75 mL
|
0.5M EDTA, pH 8.0
Invitrogen
6 mM
3.0 mL
|
15575-020
|
H2O
—
—
1.37 mL
|
|
*TMAC is tetramethyl ammonium chloride
|
The number of technical replicates hybridized for each biological sample is shown below in Table 11.
TABLE 11
|
|
Squamous cell
|
Normal
carcinoma
Non-squamous carcinoma
|
Samples
Lung1
Lung2
Epi4
Epi5
Epi7
Adk1
Adk2
Adk3
Adk8
Adk9
Adk10
Adk11
|
|
G2
3
4
4
1
2
3
2
3
5
2
|
G3
2
2
1
2
|
|
Array Image Acquisition
The arrays were scanned using an Axon™ scanner (Molecular Devices, Sunnyvale, Calif.) and their Genepix™ software. The image was formatted in tif format, defined by an image color depth of 16 bits/pixel (1600*1600). At such setting, pixels can assume intensity values ranging from 0 to 65,535. Pixels exhibiting the maximum intensity value are “saturated” and were assigned the value of 65,535. The resolution of the array scan was set at 10 μm/pixel. For hybridization experiments using different fluorescent dyes (e.g., Cy5 and Cy3) the photomultiplier tube (PMT) was adjusted to the higher intensity spot (Cy3 is scanned at lower PMT settings than Cy5).
Array Image Analysis
The PMT of the laser scanner digitized the captured fluorescence intensity for each given “point” of a slide and stored the numerical value as a pixel corresponding to that point. A picture composed of such pixels was then analyzed.
The first task for image analysis was to detect the spot position, using a process called segmentation. Spots were segmented by circles of adaptable or fixed radius. To be reliably segmented and quantified, the spot diameter was required to be more than 5-6 pixels. Before segmentation an indexing grid was provided giving the approximate positions of the spots. The segmentation itself detected the limits of spots near the grid circles. Briefly, the Genepix software assigns a circle to each spot on the array (segmentation). The segmentation had to be conducted in a somewhat flexible way due to spotting imperfections and/or support deformation, as the spots were almost never on a perfectly rectangular grid.
After segmentation by the software, the circles were modified manually and adjusted onto the spots until all the spots on the array were clearly identified. At this stage, if the array presented high background noise preventing real spots from being distinguished from the background, the array was rejected for further analysis.
The second task of image analysis was to quantify spots and export the data into a result file. This was a relatively easy and well-defined task once the spots were located on the image. The statistical approach used most frequently to quantify spot intensity was the mean or median of pixels belonging to a spot. The median approach was more robust than the mean value in the presence of outlier pixels. In practice, however, there was little difference in the results obtained using mean or median.
Array Data Analysis
All the array data were analysed using the R bioconductor package (“Bioconductor: open software development for computational biology and bioinformatics,” Genome Biol. 2004; 5(10):R80. Epub 2004 Sep. 15, which is incorporated herein by reference in its entirety).
Array data were first tested for quality by comparing the spot intensities for the internal controls. (Table 12) One internal control (SEQ ID NO: 1046) was used as a labelling control (this synthetic RNA is added to the purified microRNA fraction before labelling), and 7 other internal controls (SEQ ID NOs: 1047 to 1052 and 1045) were used for the normalization of the data (these synthetic RNA controls are added to the total RNA fraction before hybridization at 520 fmol each/array).
TABLE 12
|
|
Internal controls added to total RNA or microRNA
|
fraction
|
|
|
CGCGCGUCGCUUUAUCUACUGU
SEQ ID NO: 1046; CTL30_COMP
|
|
UUAUCGUUCGAUAAGUCGCGUU
SEQ ID NO: 1047; CTL11_COMP
|
|
GAAGUUACUAUGUAGGCAACCU
SEQ ID NO: 1048; CTL23_COMP
|
|
CGCGGGACUAAUUGUUACCGGG
SEQ ID NO: 1049; CTL26_COMP
|
|
UCGCGUCGAACUCCGCAACCGA
SEQ ID NO: 1050; CTL29_COMP
|
|
ACCGAACGCCGUACCCAUCGGG
SEQ ID NO: 1051; CTL31_COMP
|
|
CGAGGGUAACGACUCUCGUGUC
SEQ ID NO: 1052; CTL36_COMP
|
|
GCGUACCGACGCGUAGACGGAC
SEQ ID NO: 1045; CTL13_COMP
|
|
TABLE 13
|
|
Probes for hybridization of control sequences in
|
microarray experiments
|
Sequence (5′-3′)
Sequence identification number
|
|
TTGTAATACGACTCAACAGTAGATAAAGCGACGCGCG
SEQ ID NO: 1054; CTL30
|
|
TTGTAATACGACTCAAACGCGACTTATCGAACGATAA
SEQ ID NO: 1055; CTL11
|
|
TTGTAATACGACTCAAGGTTGCCTACATAGTAACTTC
SEQ ID NO: 1056; CTL23
|
|
TTGTAATACGACTCACCCGGTAACAATTAGTCCCGCG
SEQ ID NO: 1057; CTL26
|
|
TTGTAATACGACTCATCGGTTGCGGAGTTCGACGCGA
SEQ ID NO: 1058; CTL29
|
|
TTGTAATACGACTCACCCGATGGGTACGGCGTTCGGT
SEQ ID NO: 1059; CTL31
|
|
TTGTAATACGACTCAGACACGAGAGTCGTTACCCTCG
SEQ ID NO: 1060; CTL36
|
|
TTGTAATACGACTCACCCGGTAACAATTAGACCCGCG
SEQ ID NO: 1061; CTL26_MUT
|
|
TTGTAATACGACTCAGTCCGTCTACGCGTCGGTACGC
SEQ ID NO: 1062; CTL13
|
|
TTGTAATACGACTCAGGCCGTCTACGCGTCGGTACGC
SEQ ID NO: 1053; CTL13_MUT
|
|
All sequences for which the intensity of the spot was higher than the mean local background intensity plus 1.5 times its standard deviation were categorized as expressed microRNAs. The following criteria were required to be met in order consider the array intensity data valid for further analysis:
- 1. Specificity of the hybridization controls had to be within acceptance criteria (e.g. CTL26 vs. its corresponding single base mutant, CTL26_MUT, or CTL13 vs. its corresponding single base mutant, CTL13_MUT).
- 2. Approximate equality of the signal intensity of the replicates of the positive controls
- 3. Approximate equality between median block signal intensities based on the positive controls for each block
- 4. Approximate equality between median array signals based on all sequences detected
- 5. Signal intensity for the purification and labelling control (CTL30).
Statistical normalization of the data was done by computing the Log 2ratio where the Log 2ratio equals average intensity signal of the duplicated spots/median intensity of all positives controls for the block. The normalization was done per block to avoid non-homogenous labelling of all blocks of the array. This block-by-block normalization has been shown to be more efficient then using overall normalization of the slide. The obtained values are Log 2 values.
The intensities of the spots for each oligonucleotide probe were compared in the sample from the primary lung tumors versus normal lung tissue, resulting in an evaluation of the relative expression for each microRNA.
The expression fold-change corresponds to 2(Log 2ratio). The Log 2ratio is the ratio between the two conditions compared, or log 2(Xcell-line/Xnormal), which is the same as (log 2Xcell-line−log 2Xnormal), where X is the measured intensity value. In cases where there was no signal from the “normal” condition, the lowest measured intensity value in the experiment was used as the baseline from which a fold-change expression value was calculated. A fold-change value of less than zero corresponds to a down-regulation of (1/fold-change) times.
Data are tabulated in Table 1. The numerical values set forth in Table 1 indicate the fold-change calculated by comparing the signal intensity measured for hybridization to a particular probe in each tumor cell sample with the signal intensity measured for hybridization to the same probe in the control sample (NHBE cells). When the signal detected for hybridization to a particular probe in both the control sample and the tumor cell sample was below the threshold value, the indication “nd” is given in the Table and no fold-change was calculated. Likewise, when hybridization to a particular array probe was detected in the control sample but not in a tumor cell sample, the fold-change calculation is preceded by “nd” in the Table. When no signal was detected in the control sample, the threshold value was retained for the fold-change calculation. This results in an underestimation of the fold-change in the tumor cell sample as compared to the control sample, which is indicated respectively by a “>” or “<” sign in Table 1 for up-regulation and down-regulation of a target RNA.
5.2 Example 2
Analysis of Target RNA from Lung Cancer Cell Lines
Cell Lines
Total RNA was prepared from three different lung cell lines that are commonly used in studies of lung cancer. The RNA was used for target RNA array profiling.
As set forth in Table 14 below, cell lines were selected for diversity, deriving from adenocarcinomas, squamous cell carcinomas and large cell carcinomas. All cell lines were purchased from LGC Promochem (ATCC) and cultured according to ATCC's guidelines.
TABLE 14
|
|
Cell Line
ATCC Number
Cancer type
|
|
NHBE
CC-2540
Normal bronchial epithelial
|
cells
|
BEA2B
CRL-9609
Immortalized bronchial
|
epithelial cells - normal
|
phenotype
|
A549
CCL-185
Adenocarcinoma
|
H1703
CRL-5889
Adenocarcinoma
|
H460
HTB-177
Carcinoma (big
|
neuroendocrine cells)
|
|
Microarray data acquisition and analysis were conducted as described in Example 1.
Total RNA from normal bronchial epithelial cells (NHBE, ATCC no. CC-2540) was used as a control.
Data are tabulated in Table 2. The tabulated values correspond to the fold-changes calculated by comparing the signal intensity measured for hybridization to a particular array probe in a primary tumor sample with the mean signal intensity for hybridization to the same probe in the control samples. When the signal was below the threshold value for both the control sample and the primary tumor sample, no fold-change was calculated (indicated by “nd” in Table 2). When hybridization to a particular probe was detected in the control sample, but not in a primary tumor sample, the fold-change calculation is preceded by “nd”. When no signal was detected for hybridization to an array probe in the control samples, the threshold value was retained for the fold-change calculation, which resulted in an underestimation of the fold-change in the primary tumor sample as compared to the control sample. This is indicated in Table 2 respectively by a “>” or “<” sign for up-regulated and down-regulated target RNAs.
5.3 Example 3
Analysis of Target RNA on Luminex Platform
The Luminex technology (Luminex Corp., Austin, Tex.) is based on liquid phase hybridization to probe-labelled beads, followed by flow cytometry detection of beads with differing ratios of fluorescent dyes. Beads with up to 100 different dye ratios are available, making it possible to interrogate a single sample for up to 100 analytes simultaneously.
Coupling of Probes to Luminex Beads
Aliquots of each 5′-amino-modified probe having sequences as set forth in Example 1 and Table 1 are prepared at a concentration of 0.1 nmol/μL in molecular biology grade water. The probes are coupled to the beads using carbodiimide chemistry according to the manufacturer's protocol (Luminex bead coupling protocol). The probe-coupled beads are stored at 4° C.
Total RNA Preparation for Luminex Analysis
Fifty fmoles of each of 7 internal controls (the same synthetic RNAs used for the array controls) are added to the total RNA fraction isolated from the biological samples. Prior to hybridization with Luminex beads, the total RNA preparation is treated to avoid the formation of dendrimers, which result from the circularization of a single RNA molecule, or concatenation to another RNA molecule. To avoid the formation of dendrimers, the RNA is pre-treated with calf intestinal phosphatase (CIP) to remove the 5′-phosphate groups. The CIP reagent can be obtained from Invitrogen (Carlsbad, Calif.) and the CIP reaction is run according to the manufacturer's protocol.
Bead Labelling and Hybridization
After CIP treatment, the total RNA fraction is then labelled with biotin using the Vantage microRNA Labelling Kit (Marligen). The labelled fraction is hybridized to the Luminex beads using the Marligen protocol. Briefly, the oligonucleotide beads are mixed with the Marligen hybridization solution (1.5×TMAC) and the labelled total RNA. The hybridization is performed at 60° C. for an hour in the dark. After hybridization, the beads are washed using the Luminex standard 6×SSPET wash buffer (sodium phosphate, sodium chloride, EDTA, Triton X-100, pH 7.4).
Detection of Bead Hybridization
The detection of the Luminex beads is done using streptavidin phycoerythrin (SAPE) (Europa Bioproducts, Cambridge, UK). The SAPE is added to the washed beads according to the Luminex protocol. The beads are then read using the Luminex IS-200 instrument using the high gain setting for better resolution
Data Acquisition and Analysis
The Luminex IS-200 reads at least 25 beads of each dye-ratio in the reaction mix. Each dye-ratio bead corresponds to a particular probe sequence, and the intensity value is returned as an average value of all read beads. The mean fluorescence intensity (MFI) data is normalized using synthetic RNA controls, and fold changes between normal and diseased samples are computed using the Bioplex software (Bio-Rad, Hercules, Calif.) and the R bioconductor package (Bioconductor: open software development for computational biology and bioinformatics, Genome Biol. 2004; 5(10):R80. Epub 2004 Sep. 15).
5.4 Example 4
Analysis of Target RNA from Additional Primary Lung Tumors
Three of the primary lung tumors analyzed in Example 1 were included in this analysis (Adk-9, Adk-10, and Epi-4). The microRNA fractions isolated from those tumors in Example 1 were used in the microarray experiment described below.
Patient Cohort
In addition to the three tumors listed above (and included in Table 15 in the first three lines), fifteen patients diagnosed with lung cancer were included in the cohort, nine men and six women. Normal tissue from an additional patient (Ksarc-17) was also included in the study. Because squamous cell lung cancer and non-squamous cell lung cancer are two of the most frequent lung cancer types (more than 70% of all lung cancers), four patients diagnosed with squamous cell carcinoma (Kmalp-21, Kmalp-25, Epi-42, and Kmalp-44) and seven patients diagnosed with non-squamous cell carcinoma (Adk-40, Adk-41, Adk-48, Adk-49, Adk-15, Adk-23, and Adk-29) were included, in addition to the previous squamous cell carcinoma (Epi-4) and non-squamous cell carcinoma (Adk-9, and Adk-10) patients. In addition, one patient diagnosed with a carcinoid (Car-13), one diagnosed with a carcinoma sarcomatoid (Ksarc-19), one diagnosed with a small cell lung cancer (Scc-27), and one diagnosed with a large cell neuroendocrine cancer (Lcnec-31) were also selected. Table 15 shows a list of the patients and various clinical characteristics of each patient.
TABLE 15
|
|
Clinical characteristics of patients in cohort.
|
Birth
|
year
|
Patient
Tissue
or
Smoking
TNM
Stage
|
ID
histology
collected
gender
Age
history
staging
group
|
|
Adk-9
adenocarcinoma
PT
M
1953
40 smokes/day
T1N0M0
IA
|
Adk-10
adenocarcinoma
PT
M
1959
25 smokes/day
T3N0M0
IIB
|
Epi-4
sqamous
PT
M
1930
30 smokes/day
T2NxM0
IIIA
|
Adk-29
adenocarcinome
PT & DNT
M
1932
? smokes/day
T4N2M1
IV
|
Adk-15
adenocarcinoma
PT & DNT
M
1947
? smokes/day
T2N0M0
IB
|
Adk-23
adenocarcinome
PT & DNT
F
1971
0
T3N0M0
IIB
|
Ksarc-19
carcinome
PT & DNT
M
1949
0
T4N1M0
IIIB
|
sarcomatoide
|
Kmalp-
Epidermoide
PT & DNT
M
1928
0
T2N0M0
IB
|
25
|
Kmalp-
Epidermoide
PT & DNT
F
1942
0
T3N1M0
IIIA
|
21
|
Car-13
Carcinoide
PT & DNT
F
1952
0
T3N1M0
IIIA
|
Lcnec-31
neuroendocrine
PT & DNT
M
1946
0
T3N2M0
IIIA
|
GC
|
Scc-27
petites cellules
PT & DNT
F
1943
0
T2N0M0
IB
|
Adk-40
Non Squamous,
PT
M
76
NA
T1aN0
IA
|
adenocarcinoma
|
Adk-41
Non Squamous,
PT
F
61
Smoker
T2N0M0
IB
|
adenocarcinoma
|
Adk-48
Non Squamous,
PT
F
56
NA
T1bN0M0
IA
|
adenocarcinoma
|
Adk-49
Non Squamous,
PT
M
53
NA
T3N2
IIIA
|
adenocarcinoma
|
Epi-42
Squamous,
PT
M
59
NA
T3N1M0
IIIA
|
Epidermoid
|
carcinoma
|
Kmalp-
Squamous,
PT
M
na
NA
T2bN0
IB
|
44
Epidermoid
|
carcinoma
|
Ksarc-17
Carcinome
DNT
M
53
NA
T2N0M0
IB
|
Sarcomatoide
|
|
PT = Primary Tumor
|
DNT = Distal Normal Tissue
|
NA = information not available
|
Five of the patients had very aggressive forms of lung cancer, Ksarc-19 (carcinoma sarcomatoide), Adk-9, Adk-10, Adk-29 (all adenocarcinoma), and Lcnec-31. Patient Ksarc-19 relapsed one month after surgery and died six months later. Patient Car-13 (carcinoide) had a slow growing form of lung cancer.
The primary tumors only were collected from six of the patients (as well as the four previous patients, for a total of 10 patients), while the primary tumor and distal normal tissue were collected from nine of the patients. Distal normal tissue only was used from one of the patients (Ksarc-17). The relative amount of tumor cells versus normal cells in primary tumors was determined to be between 90% and 100% for all patients. The distal normal tissue was collected from a location as far as possible from the primary tumor, and did not contain detectable tumor cells.
Tissue Samples
Archived or freshly snap-frozen specimens from lung primary tumors were used. Tissue samples were homogenized by mortar and pestle in TRIzol® Reagent (Invitrogen; Carlsbad, Calif.) and RNA was extracted according to manufacturer's protocol. RNA samples were diluted in RNase-free water and stored in −80° C. (−112° F.).
MicroRNA Preparation:
All samples were enriched for the microRNA fraction using a Flash PAGE Fractionator (Ambion). Briefly, a total RNA sample was loaded onto a pre-cast gel using the Flash PAGE Fractionator. The total RNA fraction smaller than 40 nt (the “microRNA fraction”) was recovered after gel migration and resuspended into nuclease free water.
Microarray Analysis
Probe Design and Spotting
The polynucleotide probes used for microarray preparation had the configuration 5′—NH2—(C)6-(spacer)-(oligomer probe sequence)-3′. The 5′-amino group allowed chemical bonding onto the array support. Each also included an identical spacer sequence of 15 nt, as shown below, to prevent non-specific interactions of the polynucleotide probes with the array support:
(SEQ ID NO: 1044)
|
5′AminoC6-TTGTAATACGACTCA-Oligo probe sequence.
|
Probe sequences given in the Tables herein omit the linker.
The probes were synthesized according to standard protocols by Eurofins MWG Operon (Ebersberg, Germany). Nexterion (Schott) microarray glass slides were used as the solid support for the microarray.
The polynucleotide probe concentration used for the spotting was 25 μmol. The probes were spotted in duplicate using the Nexterion spotting buffer provided with the array glass support by Schott with 1% SDS (sodium dodecyl sulfate) added to allow larger spot sizes (e.g., 100-150 microns compared to 70-100 microns without SDS). The spotter used was the QArray mini (Genetix) equipped with Stealth SMP3 pins (Telechem). After deposition of one series of spots, the spotting needle was washed 5 times with 60 mM NaOH before spotting the next series of probes. Each slide is designed with 48 blocks of spotted probes, with each block being a 20×18 square of spotted probes. Each probe was spotted in duplicate. Spotted glass slides were stored at 4° C. until use.
MicroRNA Labelling
The labelling of the microRNA fraction was adapted from a published protocol developed at EMBL (Heidelberg, Germany) by the European Molecular Biology Group (Castoldi et al., “A sensitive array for microRNA expression profiling (miChip) based on locked nucleic acids (LNA),” RNA 2006 May; 12(5):913-20. Epub 2006 Mar. 15, incorporated herein by reference in its entirety). Briefly, the microRNA fraction was incubated for 6 hours at 4° C. with a mixture containing 10 nM of dye-labelled tetra-nucleotide (5′-rUrUrUrU-Cy5-3′) (or alternatively, 5′-rUrUrUrU-Cy3-3′) (Biospring, Germany) in Ambion buffer diluted to 1× with RNase free water, 8% polyethylene glycol (PEG), 2 mM adenosine triphosphate (ATP), and T4 RNA ligase (0.7 U/μl). The labelling reaction was run by heating the mixture for 15 minutes at 65° C. This procedure ligated the poly-U dye-labelled tail to the 3′ end of all the microRNAs. Labelled samples were stored at 4° C. before hybridization.
Array Hybridization
Table 16 shows the number of array replicates carried out for each tumor sample.
TABLE 16
|
|
Number of Replicates for Sample
|
Sample
Tumor type
Number replicates
|
|
Adk-9
Non-squamous
1
|
Adk-10
Non-squamous
2
|
Epi-4
Squamous
2
|
Adk-29
Non-squamous
3
|
Adk-15
Non-squamous
3
|
Adk-23
Non-squamous
3
|
Ksarc-19
Squamous
2
|
Kmalp-25
Squamous
1
|
Kmalp-21
Squamous
3
|
Car-13
Carcinoid
3
|
Lcnec-31
Large cell neuroendocrine
2
|
Scc-27
Small cell
2
|
Adk-40
Non-squamous
2
|
Adk-41
Non-squamous
3
|
Adk-48
Non-squamous
2
|
Adk-49
Non-squamous
3
|
Epi-42
Squamous
3
|
Kmalp-44
Squamous
3
|
Ksarc-17
Normal
3
|
Adk-29
Normal
1
|
Adk-15
Normal
2
|
Adk-23
Normal
3
|
Ksarc-19
Normal
1
|
Kmalp-25
Normal
1
|
Kmalp-21
Normal
1
|
Lcnec31
Normal
1
|
Scc27
Normal
1
|
|
The labelled microRNA fraction was hybridized to the spotted arrays using a Discovery hybridization station (Ventana, Tucson, Ariz.). Briefly, 2 mL of a mixture of 1% BSA, 2×SSC, and 0.2% SDS was incubated with the chips for 30 min at 42° C. Then the chips were washed once using EZ Prep buffer (Ventana) and then three more times with Ribowash (Ventana). Next, 20 μl of the labelled microRNA mixture and 180 μl of ChipHybe Reagent (Ventana) were added to the array. The arrays were heated for 6 minutes at 37° C., then were incubated at 42° C. for 8 hours, after which the heating was stopped. The chips were washed once with Ribowash (Ventana) and then heated for 2 minutes at 37° C. The chips were washed again with Ribowash (Ventana) with one drop of CheapClean (Ventana) added, and incubated for 2 minutes at 37° C. The chips were washed two more times using Ribowash (Ventana). The chips were stored dry overnight. On the following day, the final washes were done according to Ventana's instructions for the Discovery hybridization station. The slides were washed twice with 2×SSC+0.2×SDS buffer and then one more time with 0.1×SSC. All the slides were dried using a speed centrifuge from Arrayit (TeleChem International, Sunnyvale, Calif.) at room temperature and kept in the dark before scanning.
Array Image Acquisition
The arrays were scanned using an Axon™ scanner (Molecular Devices, Sunnyvale, Calif.) and their Genepix™ software. The image was formatted in tif format, defined by an image color depth of 16 bits/pixel (1600*1600). At such setting, pixels can assume intensity values ranging from 0 to 65,535. Pixels exhibiting the maximum intensity value are “saturated” and were assigned the value of 65,535. The resolution of the array scan was set at 10 μm/pixel. For hybridization experiments using different fluorescent dyes (e.g., Cy5 and Cy3) the photomultiplier tube (PMT) was adjusted to the higher intensity spot (Cy3 is scanned at lower PMT settings than Cy5).
Array Image Analysis
The PMT of the laser scanner digitized the captured fluorescence intensity for each given “point” of a slide and stored the numerical value as a pixel corresponding to that point. A picture composed of such pixels was then analyzed. The first task for image analysis was to detect the spot position, using a process called segmentation. Spots were segmented by circles of adaptable or fixed radius. To be reliably segmented and quantified, the spot diameter was required to be more than 5-6 pixels. Before segmentation an indexing grid was provided giving the approximate positions of the spots. The segmentation itself detected the limits of spots near the grid circles. Briefly, the Genepix software assigns a circle to each spot on the array (segmentation). The segmentation had to be conducted in a somewhat flexible way due to spotting imperfections and/or support deformation, as the spots were almost never on a perfectly rectangular grid.
After segmentation by the software, the circles were modified manually and adjusted onto the spots until all the spots on the array were clearly identified. At this stage, if the array presented high background noise preventing real spots from being distinguished from the background, the array was rejected for further analysis.
The second task of image analysis was to quantify spots and export the data into a result file. This was a relatively easy and well-defined task once the spots were located on the image. The statistical approach used most frequently to quantify spot intensity was the mean or median of pixels belonging to a spot. The median approach was more robust than the mean value in the presence of outlier pixels. In practice, however, there was little difference in the results obtained using mean or median.
Array Data Analysis
All the array data were analysed using the R bioconductor package (“Bioconductor: open software development for computational biology and bioinformatics,” Genome Biol. 2004; 5(10):R80. Epub 2004 Sep. 15, which is incorporated herein by reference in its entirety).
Array data were first tested for quality by comparing the spot intensities for the internal controls. One internal control (SEQ ID NO: 1046; Table 17) was used as a labelling control (this synthetic RNA is added to the purified microRNA fraction before labelling), and 6 other internal controls (SEQ ID NOs: 1047 to 1052) were used for the normalization of the data (these synthetic RNA controls are added to the total RNA fraction before hybridization at 520 fmol each/array). The probe sequences that bind to the synthetic RNAs, and a mutant probe sequence, are also shown in Table 17 (SEQ ID NOs: 1054 to 1061).
TABLE 17
|
|
Control Sequences used in microarray experiments
|
Sequence (5′-3′)
Sequence identification number
|
|
CGCGCGUCGCUUUAUCUACUGU
SEQ ID NO: 1046; CTL30_COMP
|
|
UUAUCGUUCGAUAAGUCGCGUU
SEQ ID NO: 1047; CTL11_COMP
|
|
GAAGUUACUAUGUAGGCAACCU
SEQ ID NO: 1048; CTL23_COMP
|
|
CGCGGGACUAAUUGUUACCGGG
SEQ ID NO: 1049; CTL26_COMP
|
|
UCGCGUCGAACUCCGCAACCGA
SEQ ID NO: 1050; CTL29_COMP
|
|
ACCGAACGCCGUACCCAUCGGG
SEQ ID NO: 1051; CTL31_COMP
|
|
CGAGGGUAACGACUCUCGUGUC
SEQ ID NO: 1052; CTL36_COMP
|
|
TTGTAATACGACTCAACAGTAGATAAAGCGACGCGCG
SEQ ID NO: 1054; CTL30
|
|
TTGTAATACGACTCAAACGCGACTTATCGAACGATAA
SEQ ID NO: 1055; CTL11
|
|
TTGTAATACGACTCAAGGTTGCCTACATAGTAACTTC
SEQ ID NO: 1056; CTL23
|
|
TTGTAATACGACTCACCCGGTAACAATTAGTCCCGCG
SEQ ID NO: 1057; CTL26
|
|
TTGTAATACGACTCATCGGTTGCGGAGTTCGACGCGA
SEQ ID NO: 1058; CTL29
|
|
TTGTAATACGACTCACCCGATGGGTACGGCGTTCGGT
SEQ ID NO: 1059; CTL31
|
|
TTGTAATACGACTCAGACACGAGAGTCGTTACCCTCG
SEQ ID NO: 1060; CTL36
|
|
TTGTAATACGACTCACCCGGTAACAATTAGACCCGCG
SEQ ID NO: 1061; CTL26_MUT
|
|
All sequences for which the intensity of the spot was higher than the mean local background intensity plus 1.5 times its standard deviation were categorized as expressed microRNAs. The following criteria were required to be met in order consider the array intensity data valid for further analysis:
- 1. Specificity of the hybridization controls had to be within acceptance criteria (e.g. CTL26 vs. its corresponding single base mutant, CTL26_MUT).
- 2. Approximate equality of the signal intensity of the replicates of the positive controls
- 3. Approximate equality between median block signal intensities based on the positive controls for each block
- 4. Approximate equality between median array signals based on all sequences detected
- 5. Signal intensity for the purification and labelling control (CTL30).
Statistical normalization of the data was done by computing the Log 2ratio where the Log 2ratio equals average intensity signal of the duplicated spots/median intensity of all positives controls for the block. The normalization was done per block to avoid non-homogenous labelling of all blocks of the array. This block-by-block normalization has been shown to be more efficient then using overall normalization of the slide. The obtained values are Log 2 values.
The intensities of the spots for each polynucleotide probe were compared in the sample from the tumors versus normal tissue, resulting in an evaluation of the relative expression for each microRNA.
The expression fold-change corresponds to 2(Log 2ratio). The Log 2ratio is the ratio between the two conditions compared, or log 2(Xcell-line/Xnormal), which is the same as (log 2Xcell-line−log 2Xnormal), where X is the measured intensity value. In cases where there was no signal from the “normal” condition, the lowest measured intensity value in the experiment was used as the baseline from which a fold-change expression value was calculated. A fold-change value of less than zero corresponds to a down-regulation of (1/fold-change) times.
Results
The microarray data was analyzed to identify target RNAs that were present at increased levels in more than half of the tumor samples tested. Tables 18 and 19 show the target RNAs, in what percentage of tumor samples they were present in increased levels, and the average fold-increase in those tumor samples in which they were present at increased levels. Data for six of the tumors are shown in Table 18 and data for the remaining 13 tumors are shown in Table 19. Table 18 also shows the probe sequences used to detect the target RNAs.
The microarray data was further analyzed to identify target RNAs that are present at levels at least 5-fold higher than normal levels in less than 50% of the tumor samples. Tables 20 and 21 show the target RNAs, in what percentage of tumor samples they were present in increased levels, and the average fold-increase in those tumor samples in which they were present at increased levels. Data for six of the tumors are shown in Table 20 and data for the remaining 13 tumors are shown in Table 21. Table 20 also shows the probe sequences used to detect the target RNAs. Finally, Table 22 shows the pre-microRNA sequences and chromosomal location of the pre-microRNA gene for each of the target RNAs in Tables 18 to 21.
The microarray data was next analyzed to identify target RNAs that were present at least 5-fold decreased levels in more than half of the tumor samples tested. Tables 23 and 24 show the target RNAs, the probe sequences used to detect the target RNAs, and in what percentage of tumor samples they were present in increased levels. Data for six of the tumors are shown in Table 23 and data for the remaining 13 tumors are shown in Table 24. Table 25 shows the pre-microRNA sequences and chromosomal location of the pre-microRNA gene for each of the target RNAs in Tables 23 and 24.
Finally, Table 9, above, shows target RNAs that were present at higher levels in at least three of the five most aggressive cancers (Ksarc-19, Adk-9, Adk-10, Adk-29, and Lnec-31).
TABLE 18
|
|
Target RNAs present at increased levels in at least 50% of tumor samples
|
Fold
|
SEQ
% tumors
Chng
|
Gene
Probe sequence
ID NO
increased
Avg
ADK9
ADK10
Adk29
Adk15
Adk23
ADK48
|
|
10455-L5-1
TAACAACTGCAATTGCGCCAAACATCCCT
1063
58
6.4
2.05
−3.86
1.02
5.18
2.20
−3.86
|
CTCC
|
|
12947-L5-4
GTTCCCTTCTCCACAGCCTCTAAATCTCC
1064
63
5.0
3.17
2.58
−1.79
1.50
2.10
1.18
|
CATCCG
|
|
13098-L5-1
TGCCGGGGCGCTGTTGGCGGTTCCTCCGGG
1065
58
4.4
−2.86
−2.86
−2.86
1.70
−1.49
5.93
|
GGGT
|
|
13122-L5-1
TTAGGAAATTCCATCTCACCTGCTCCAGTCC
1066
58
11.5
1.32
1.17
1.40
1.68
1.56
2.09
|
|
13219-L5-1
CTCTGACTCCCTCACTCAGTCTCTCTGCTC
1067
68
7.8
1.54
−1.85
1.30
1.90
1.44
2.19
|
CAGC
|
|
13254-R5-1
CAATGAACCACTGAACCACTCATGCACTG
1068
63
5.0
2.21
6.72
2.48
2.40
1.52
4.02
|
AACC
|
|
13467-L5-1
GTGACAGTCAGACCCTCCTTGCTCCAAGT
1069
53
17.7
2.83
3.05
−1.83
3.62
2.22
1.35
|
CAAA
|
|
3923-R5-1
TCACAAAGGATCTCCTTCATCCCTCTCCAG
1070
58
5.3
−6.96
−3.57
−1.11
6.71
2.53
1.59
|
|
4440-L3-2*
TTTGACATTCAGAGCACTGGGCAGAAATCA
1071
68
6.9
2.32
−1.15
1.65
2.00
−1.34
1.29
|
CA
|
|
4479-R3-1
AGCCCCCTGCCCGGAAATTCAAAACAACTGC
1072
53
4.3
1.27
1.08
−1.38
1.11
1.55
1.75
|
|
5080-R3-1
CTTGCAAAGGGTCTCCTTCATCCCTCTCCA
1073
68
7.2
2.60
−3.84
1.58
8.83
4.24
−1.12
|
|
6216-L1-1
GACATTCAGAGCACTGGGCAGAAATCACATG
1074
53
8.0
−1.89
−1.89
1.27
2.22
−1.89
−1.89
|
|
6235-R5-2
TCTGCTCCAAAAATCCATTTAATATATTGT
1075
74
13.5
2.51
1.63
1.29
3.07
2.15
3.39
|
|
7426-L5-1
AGACGAACACCTCCTGCTGTGCTTGATTT
1076
63
5.1
2.59
−1.45
3.22
2.64
1.21
−1.45
|
|
7726-R3-2
CATCCCTCTCCAGAAGAGGAGAAGAGGAAA
1077
68
5.7
2.18
−2.52
1.66
7.34
3.64
−2.52
|
CA
|
|
8004-R3-2
GGAACTGCTTCTCCTTGCTCCAGTCATTGA
1078
63
11.0
−5.32
1.60
1.51
1.80
1.80
2.37
|
AG
|
|
836-R5-2
AAATAATCATTCCAAATGGTTCTCCCTGCT
1079
79
8.7
2.22
2.37
1.49
1.80
1.93
4.05
|
AT
|
|
9349-R5-2
GAACACAGTGATGCAGAGGACTTCCTGCT
1080
58
24.4
−1.44
4.53
1.39
7.28
1.65
−1.44
|
CCA
|
|
9594-R5-1
ACTTAGACTTCCTTCCCACTCCCTGCATCCT
1081
53
9.7
1.32
1.20
−1.03
1.68
1.46
1.95
|
|
miR-200a
ACATCGTTACCAGACAGTGTTA
1082
58
6.2
4.00
−1.98
−1.98
1.89
2.18
4.85
|
|
miR-200b
TCATCATTACCAGGCAGTATTA
1083
63
4.6
3.65
1.66
1.01
2.11
2.43
2.54
|
|
miR-200c
TCCATCATTACCCGGCAGTATTA
1084
68
3.6
3.05
1.53
−1.02
2.00
3.71
2.39
|
|
miR-205
CAGACTCCGGTGGAATGAAGGA
1085
53
21.2
6.16
−1.05
7.09
−1.05
−1.05
−1.05
|
|
miR-20b
CTACCTGCACTATGAGCACTTTG
1086
53
4.8
3.82
4.97
−2.24
5.93
1.03
2.35
|
|
miR-21
TCAACATCAGTCTGATAAGCTA
1087
68
6.7
10.37
4.28
−41.68
8.21
4.78
4.58
|
|
miR-298
TGGGAGAACCTCCCTGCTTCTGCT
1088
68
9.8
1.96
1.55
1.87
2.23
2.18
1.30
|
|
miR-720
TGGAGGCCCCAGCGAGA
1089
63
4.2
9.81
4.77
3.06
2.73
5.03
4.82
|
|
TABLE 19
|
|
Target RNAs present at increased levels in at least 50% of tumor samples (con't)
|
%
|
tumors
Fold
|
in-
Chng
|
Gene
creased
Avg
Adk40
Adk41
Adk49
Epi42
Ksarc19
Kmalp21
Kmalp25
EPI-4
Kmalp44
Scc27
Lcnec31
Car13
|
|
10455-
58
6.4
−3.86
−3.86
4.88
6.15
11.22
8.61
2.50
20.65
3.92
1.74
1.71
−3.86
|
L5-1
|
12947-
63
5.0
7.18
−2.89
1.75
2.00
10.83
4.19
2.17
15.66
4.39
3.14
2.39
−2.89
|
L5-4
|
13098-
58
4.4
6.04
2.12
4.93
7.99
2.92
2.06
1.19
5.45
5.13
1.99
1.68
−2.86
|
L5-1
|
13122-
58
11.5
−2.23
−3.30
11.06
3.00
45.07
8.66
12.05
25.75
4.32
8.92
4.14
−6.80
|
L5-1
|
13219-
68
7.8
2.12
−3.09
4.87
2.37
29.25
8.14
10.45
23.80
3.38
7.05
3.81
−5.56
|
L5-1
|
13254-
63
5.0
−5.53
−5.53
4.42
3.62
1.67
2.00
5.81
14.41
2.64
1.20
−1.16
−2.34
|
R5-1
|
13467-
53
17.7
−3.86
−3.86
6.58
−1.54
47.10
19.28
11.18
87.67
−1.56
6.95
4.54
−3.86
|
L5-1
|
3923-R5-1
58
5.3
1.69
1.36
5.55
6.66
7.94
6.74
2.87
12.31
3.49
1.89
1.78
−6.96
|
4440-
68
6.9
14.22
−2.38
4.89
5.53
4.84
4.40
4.36
20.54
7.80
5.37
9.54
−2.38
|
L3-2*
|
4479-R3-1
53
4.3
−14.83
1.85
−1.15
5.75
5.60
6.31
−14.83
10.98
1.91
4.07
1.95
2.02
|
5080-R3-1
68
7.2
−3.84
−1.79
8.12
10.22
12.60
9.22
3.75
18.91
6.17
2.71
2.74
−3.84
|
6216-L1-1
53
8.0
15.02
−1.89
2.61
−1.89
5.37
4.69
3.76
22.08
9.22
5.16
9.56
−1.89
|
6235-R5-2
74
13.5
−2.30
−1.76
11.09
4.52
53.43
16.58
19.84
39.60
6.59
11.81
11.43
−8.31
|
7426-L5-1
63
5.1
2.23
−1.45
6.10
−1.45
6.82
4.16
3.33
11.69
5.48
5.61
7.41
−1.45
|
7726-R3-2
68
5.7
−2.52
−2.52
8.06
9.94
8.81
7.20
3.54
11.79
2.24
2.37
2.77
−2.52
|
8004-R3-2
63
11.0
−1.69
−5.32
6.36
3.58
48.62
7.86
12.44
28.62
4.41
9.48
5.21
−5.32
|
836-R5-2
79
8.7
5.02
−2.64
5.63
4.02
40.75
6.59
10.21
26.72
4.38
8.08
5.16
−2.64
|
9349-R5-2
58
24.4
−1.44
−1.44
10.49
3.33
49.05
33.90
19.27
112.09
8.79
10.70
8.85
−1.44
|
9594-R5-1
53
9.7
−6.58
−6.58
4.10
2.60
30.50
7.67
10.86
24.28
3.32
6.82
4.54
−6.58
|
miR-200a
58
6.2
−1.98
−1.98
5.20
4.55
−1.98
1.86
1.17
3.60
3.49
4.09
3.32
26.93
|
miR-200b
63
4.6
−1.76
2.73
3.27
2.23
−4.79
1.16
1.30
2.97
2.05
4.07
2.98
24.67
|
miR-200c
68
3.6
−8.29
2.84
1.30
2.38
−8.29
−1.03
2.11
3.38
2.05
4.09
4.89
11.97
|
miR-205
53
21.2
−1.05
−1.05
8.11
13.68
3.20
27.74
56.45
30.05
46.50
−1.05
−1.05
−1.05
|
miR-20b
53
4.8
−2.24
2.99
8.37
4.56
−1.45
−1.10
1.71
−2.24
−2.24
6.46
3.10
−2.24
|
miR-21
68
6.7
−6.36
6.76
17.86
8.91
3.81
−41.68
4.64
1.92
7.46
3.38
1.19
1.41
|
miR-298
68
9.8
−2.56
−2.56
6.60
5.82
36.81
9.96
10.86
31.32
5.07
7.72
4.43
−2.56
|
miR-720
63
4.2
6.70
−1.87
2.31
−1.87
2.72
1.99
1.95
−1.87
4.11
1.35
−1.87
−1.87
|
|
TABLE 20
|
|
Target RNAs present at increased levels in less than 50% of tumor samples,
|
but with an average increase of at least 5-fold relative to normal levels
|
SEQ
Fold
|
ID
% tumors
Change
|
Gene
Probe sequence
NO
increased
Average
ADK9
ADK10
Adk29
Adk15
Adk23
|
|
10083-L5-1
CCCTCTTCCTTTCTACCCCCTCTCTCCACCC
1090
16
11.2
−1.64
−4.49
−10.22
−3.32
−1.50
|
|
10233-R5-1
ACCCTCTCCCCTTGGATCTGGAGCAGCAGGCAGTA
1091
16
13.1
−1.55
−7.07
−4.19
−1.46
−1.77
|
GA
|
|
10335-L5-2
CCACTCCCCTCCTTTTTAATTAGAAAGCAC
1092
16
5.3
−1.72
−8.23
−8.23
−2.21
−3.36
|
|
10357-R5-1
CTCTCCACTGTCTGAATATTCCATGTGTTTGTTT
1093
16
6.0
−1.13
−1.13
1.25
2.75
1.29
|
CCCTAG
|
|
10520-L5-1
CAGCATCTCCTTGCTACCTCCTC
1094
26
5.9
−1.42
−1.42
−1.42
−1.42
1.14
|
|
10844-R4-1
AGGGGGTAGCATATTCAGGACTCTACTTTCAAA
1095
26
5.4
−2.58
−2.58
−2.58
1.36
−2.00
|
|
11358-R5-2
ATGGAGGGTGGGAAACTAGGCTGACATGGCTC
1096
21
5.3
−2.77
−2.77
−2.77
1.77
−2.18
|
|
11444-L5-3
GCACTTGTGTTCAGGCACCCACTCCTCCAGCAAAG
1097
21
8.8
−1.20
−1.20
−1.20
−1.20
−1.20
|
|
11547-R4-1
GCCCCCTGCTCTGGCTGGTCAAACGGAACCAAGT
1098
16
7.6
−2.09
−2.09
−2.09
−2.09
−1.66
|
CCGTCT
|
|
11605-L5-4
TCCCTTCTTTAATTCCCTTCCCCTCAATTCCATAA
1099
26
5.0
−2.54
−2.54
−2.54
−2.54
−1.37
|
|
11688-R5-3
GAGACGCCGACTGGCTGAGACTCAAGGCGGGG
1100
32
6.0
−1.33
−1.33
−1.33
−1.33
−1.33
|
|
12699-R5-2
AGGGTGGTGGCGGTGGTGGCGGGAACGCTGGGGGG
1101
26
6.0
−1.96
−1.96
−1.96
1.14
−1.60
|
|
12707-L5-2
CATTCTCCTCTGCAATCCAACAACTCTAC
1102
42
5.0
−1.91
−1.91
−1.20
3.36
−1.40
|
|
12729-R5-1
CGACGAAAATGCAATTGTGTGCCTTCTCCCTCC
1103
16
11.8
−1.10
−5.55
−5.55
−1.51
−2.63
|
|
12730-R5-1
TTGTGCTCCGCTCTCCGGGAAATGCCATCACTAAT
1104
37
7.3
−3.66
−3.66
−2.24
1.55
−2.46
|
|
12888-L5-2
TTTCCTACATTGTATGGTTCTCCCAGCTCCT
1105
47
21.7
4.55
1.76
1.24
5.05
1.51
|
|
12907-L5-1
ATGCCCTCTCTACCACGTCCTAGACACTGAGCC
1106
26
6.4
−3.23
−3.23
−3.23
−1.53
−1.46
|
|
12912-L5-2
TCAAGTTTTCTGGCACCTTCCACCCACAGAGGCT
1107
37
5.3
−2.26
−2.26
−1.29
2.16
−2.26
|
|
12917-R5-2
GGACCTATGGGCCCTTCCCTTCCCCCAACATTG
1108
47
6.0
1.03
−3.76
−1.02
1.54
2.26
|
|
12958-R5-1
TCTTCCCCTGGGTGCATCTATAACGACTACAGA
1109
32
5.1
−1.32
−1.32
−1.32
−1.32
−1.32
|
|
12974-R5-2
ACCCTCTGTGCCCCCAAATTCCTAGTCCCTTGGT
1110
21
16.1
−1.94
−1.94
−1.94
−1.94
−1.30
|
|
12979-R5-2
TCCAGGTCCTTCCCCAGTAGCTAGATGAAAGAAAA
1111
42
16.3
−1.39
−1.39
1.39
6.66
4.45
|
|
12992-L5-1
CATACCTGCTTCCCTCCACCCCCATCTCTA
1112
16
6.7
−9.54
−2.35
−9.54
−2.64
−3.60
|
|
13001-L5-1
TTCCTAGATACCACTCCCAGCTCCA
1113
32
15.5
−1.83
−1.83
−1.09
1.61
1.27
|
|
13053-R5-4
GCCTTCCCTAAGATCAGGCTCATCAGGCAGCCCCA
1114
26
5.6
−1.32
−1.32
−1.32
−1.32
1.25
|
|
13070-R5-3
CTGTCTCCTCTCCCCAGTCCAAAGGACCTAATGC
1115
16
20.1
−1.13
−4.70
−4.70
−1.17
−2.22
|
|
13071-L5-3
AGAGAAGGGGTGAGGATCTCCAGGGGTGACTGCT
1116
32
7.2
−2.11
−2.11
−2.11
1.69
−2.11
|
|
13078-L5-1
GCCCTCATTTCATAAGCCTGCTAGACAGGAGA
1117
32
5.0
−1.28
−1.28
−1.28
−1.28
1.18
|
|
13185-L5-3
TTCTGTTTTTTTTCTTCCCTCTCTCCCCTCTT
1118
21
13.4
−1.02
−1.33
−6.52
−1.77
−1.16
|
|
13216-R5-2
ATATATTCCTCCTTTCTCCTCTCTGGCAGCTGA
1119
26
5.1
−1.79
−1.79
−1.79
−1.79
−1.03
|
|
13225-L5-1
CTGCCCACTTCTGGGACAGCCCCTTCCATCTTC
1120
16
5.9
−3.37
−3.37
−3.37
−1.24
−3.37
|
|
13235-R5-1
CCTGGGCTTTCTAGTCTCAGCTCTCCTCCAGCT
1121
42
5.1
1.75
2.72
−2.00
−2.00
−1.22
|
|
13245-L5-4
ATTCCAAATAGTCTTTCCCTTCTACTCCCTTTAAA
1122
16
12.2
−2.87
−2.87
−2.87
−2.87
−2.25
|
|
13252-L5-3
ACGTGCCTTCCTGACTGTGAGCTCCTTGAGAGC
1123
32
5.0
3.73
2.50
−1.79
3.92
1.23
|
|
13274-L5-3
CCTTCTCTTCTCCCGTGCTCCCACCCTCCCTCAGGG
1124
26
6.2
−1.53
−1.73
−2.51
−1.80
−1.69
|
|
13300-L5-1
TTACACACAGAATTATCTCCCCTCCTACTTACCC
1125
16
7.4
−1.04
−6.08
−6.08
−2.44
−3.08
|
|
13309-R5-1
TCCCCCTTGTCTTCAGCTACAATTTTTCTGTG
1126
16
8.2
1.66
−3.05
−3.05
−3.05
−3.05
|
|
13352-R5-1
CCGGAACCTCAGCGCTGCATCTGTGAAATGGGG
1127
37
5.8
−3.13
−3.13
−3.13
1.36
−2.38
|
|
13357-L5-4
AGCGGACCTTCTCCCCACACCTCCCTGCAGCCTC
1128
16
10.3
−1.89
−1.91
−6.27
−2.80
−2.38
|
|
13366-R5-3
CAGGCCTCACCCCAGTGCCCTCTCCTATTCCCAC
1129
16
6.5
−1.56
−5.82
−11.70
−1.40
−1.25
|
|
13373-R5-2
TGTGGGGGGAGGGTGGTCAGCAGGTGGGGCAG
1130
42
5.1
−1.86
−1.86
−1.86
3.87
−1.44
|
|
13375-R5-4
GTACCAGCTCTCAGACCCTCACCACAGCCTGGGGG
1131
32
5.8
−7.06
−7.06
−7.06
−2.47
−1.39
|
|
13398-R5-4
TTCTCTCTCCCTCCACCTTTTGTGCCACCACTT
1132
16
15.6
−5.01
−2.59
−5.01
−1.56
−2.35
|
|
13417-R5-4
TGCCCTTCCTTCTGTTAACACCAGCCAGATCCCC
1133
32
6.4
−1.82
−1.82
−1.82
2.57
1.34
|
|
13436-L5-1
AGCTCAATGAAGCCCCCAGCTAGGTCATGCCTC
1134
21
5.3
−2.80
−8.31
−20.29
−2.23
−2.79
|
|
13468-L5-1
CAAGTGGCCATCAGACCCTCTTTGCCCCAAGTC
1135
21
25.5
−1.16
−1.16
−1.16
−1.16
1.07
|
|
13470-R5-1
TCCCACCCTCTCCACCTCAGGGACCAGAATCCT
1136
21
13.2
−1.29
−3.12
−6.50
−1.24
−1.23
|
|
13473-L5-3
TATGTTTGCCCTTCTACCACCTATCCTGATACA
1137
21
9.2
−1.57
−1.57
−1.57
1.32
1.04
|
|
13500-L5-3
CCAAGATCTTCCAGGCCTCTCTCTCCATTGAGT
1138
37
6.4
−1.38
−1.38
−1.38
2.14
1.20
|
|
13522-L5-4
CTGCCTCACCTGAGCTCCCGTGCCTGTGCACCCTC
1139
16
5.3
−3.11
−3.11
−3.11
−3.11
−2.36
|
|
13523-R5-1
GTGGAATAGTAAGGCTTCTTCCCCTGCCTGGC
1140
26
5.3
−3.75
−3.75
−1.20
1.11
1.61
|
|
13545-L5-1
GCCTGTGGCGCAAGGGAGGCTGTGAGTCTGGGG
1141
21
5.3
−2.13
−2.13
−2.13
1.70
−2.13
|
|
227-L5-1
ACACCTGTCTCTCCCCAGTGCTTCCGCCCCTCA
1142
16
5.0
−2.46
−3.09
−2.60
−3.09
−3.20
|
|
3744-R5-1
CTTCTCCTTCCTCCCTGCTCCCCTCCCACTAATG
1143
37
6.7
−1.38
−2.00
−2.67
−1.30
−1.23
|
CCAAAT
|
|
3875-R5-2
GACTGATTCAACCTCTCTCTCCCACTTTA
1144
32
19.0
−2.72
−2.72
−2.72
1.47
−1.32
|
|
3926-L5-1
ACTGATAATTCATTAGCATTCTTGAACGTGCCCC
1145
16
5.1
−2.22
−2.22
−2.22
−2.22
−2.22
|
CACT
|
|
3992-R5-1
GCCCCTTTCTCTTCTGTCAGTATCTGAGCTGATG
1146
32
6.7
−1.27
−1.27
−1.27
−1.27
−1.27
|
GTTG
|
|
4203-R3-2
GCACATTCCCACTTCCCCAGAGGCAGGCTCCATAT
1147
16
6.0
−2.01
−2.01
−2.01
−1.45
−2.01
|
|
4261-R5-1
AATAACCCTCCTTCCTTGATAGATTTCAC
1148
21
6.4
−2.52
−2.52
−2.52
−2.52
−1.56
|
|
4291-R5-1
GATCAGGTAGTTACCAGGAGCCATGGGGGTGTACA
1149
37
6.0
−1.67
−1.67
−1.67
−1.25
−1.67
|
|
4790-L5-2
TAACCTGTCTCCCTCATTACTAGAATTCT
1150
21
12.6
−1.56
−1.56
−1.56
−1.56
−1.32
|
|
4958-L5-1
TAACCTGTCTCCCTCATTACTAGAATTCT
1151
32
5.0
−2.14
−2.14
−2.14
−1.00
−2.14
|
|
4988-R5-2
GAGAATTAATAAACCATGGCATCTTCTGAAAATGG
1152
16
5.3
−2.97
−3.81
−7.10
−2.52
−2.60
|
GG
|
|
5108-R5-2
CTCCTCCTCCCCGTCTTTGGATACCAAACAC
1153
21
16.5
−1.14
−1.67
−4.77
−1.11
−1.10
|
|
5232-L5-2
CCCTCTCCTCCCACACCGTCACTCACAATAACCC
1154
32
5.2
−1.81
−1.81
1.81
−1.34
−1.44
|
|
5392-R5-1
TCCTCCTCCTTCATTTGCAGGACATCAAGG
1155
42
7.0
−2.12
−2.12
−2.12
2.25
−1.14
|
|
5723-R5-1
CCCTCTCCGACAGTATCTCATTACAATAATTGCT
1156
16
6.9
−1.96
−3.89
−8.51
−5.58
−3.53
|
AATCTC
|
|
5836-L5-1
CCTCCTCCCCTTTCTCCAGCAGTAGCCTTCTTAA
1157
26
5.0
−2.14
−2.14
−2.14
1.48
−2.14
|
|
5842-R5-1
TCTTGGGAACCAAGGGGGCTACAG
1158
32
6.0
2.40
−5.08
−5.08
2.54
1.13
|
|
6037-R3-2
GCAATTCCCTTTCCTCCATCTCCAATTTTCCTC
1159
32
7.4
−1.71
−1.71
−1.71
−1.71
−1.32
|
|
6181-L5-1
CATGGTAAACTTAGATGACTCTTCCCCCTGGATTT
1160
26
8.6
−1.40
−1.40
−1.40
−1.40
−1.40
|
|
6233-L5-2
CAAAATTAGATTTCCACTTTATCCTTCTCCC
1161
16
10.1
−3.02
−3.02
−3.02
−1.89
−1.92
|
|
6395-L5-1
TCTCCCCTGCAGAGAGGAGGAAAGCCTGCCTCGGA
1162
21
8.4
−3.73
−3.73
−3.73
1.09
−1.93
|
AC
|
|
6405-R5-1
TCAAAGAAAAATAAGTGAAAGCATATCTCATCAT
1163
32
5.7
−2.10
−2.10
−2.10
−2.10
−2.10
|
GGGG
|
|
6474-L5-1
CCCTAATTAAAGCCATCCCCTCTTCCCCCTTCACC
1164
16
11.9
−11.16
−5.02
−11.16
−1.96
−1.85
|
|
6602-R3-1
AGAGCCCCAGTGGAAATCTCTCCTCCAAATCCAT
1165
32
8.8
−1.36
−1.36
−1.36
−1.36
−1.06
|
|
6681-R2-1
CCTGTTTTCTCCCCTCTCTCTCTGCCCCTCC
1166
16
5.0
−1.60
−2.15
−3.96
−1.87
−1.45
|
|
6683-R5-1
TCATCCCAAAATAAACTCTTCCTGCTCAAG
1167
37
11.9
−1.39
−1.39
−1.39
1.04
1.29
|
|
6752-R5-2
CCCTCCTTTCCCCACCTCAGTCGGGCCACTGCT
1168
16
6.4
−7.01
−7.01
−4.90
−2.94
−2.85
|
|
6803-R5-2
GCTCCCTCTCTGGTTGGACCTCACCCAAA
1169
21
12.2
1.30
−2.22
−1.17
−1.05
−1.19
|
|
6864-R4-1
GACACACAATTACACTCCCCTGGAG
1170
21
12.5
−1.50
−1.50
−1.50
−1.50
−1.50
|
|
6872-L5-1
AAGACTCTGTCACAGTCTGTGACCCGGTGGGG
1171
42
5.2
−1.96
−1.96
−1.96
−1.00
−1.96
|
|
6906-L5-1
TCTTCTCCCCAACCAGCCAGCTCTCCTGG
1172
21
8.0
−2.17
−2.17
−2.17
−2.17
−2.17
|
|
6930-R5-1
TTAATCCTTCTCTCCCCTCTGATCTTGCAG
1173
16
14.8
−1.27
−1.66
−4.45
−1.91
−1.65
|
|
7631-L3-2
CCTAGACGCCAGCTGCCTGCATGAAGCCTGCCCAA
1174
26
5.2
−2.68
−2.68
−2.68
1.68
2.02
|
|
7764-R3-2
CCCTCTCTGCCTCTCTCATCACCAATAACAGAC
1175
16
9.3
−1.03
−3.64
−3.64
−1.33
1.24
|
|
7849-L2-2
GAAATATCAAGACAAATAAGATGTTTGGGGGCACA
1176
16
6.1
−2.04
−2.04
−2.04
−1.42
−2.04
|
|
8316-R5-1
CAGGGTATCCTCTCCCCACGTGATGCC
1177
42
20.3
2.51
−1.81
−1.81
1.36
1.12
|
|
8433_C-R4-1
AAACCAAAAAAAAAAAATTAAAAAGCGACGAAA
1178
16
14.3
−1.03
−2.46
−5.42
−1.38
−1.21
|
ATGCAATTGTGTGCCTTCTCCCTCC
|
|
8433-L3-1
AAATGGCTCCTTTCCCCTTTCCCTCCACCG
1179
16
6.9
−1.70
−1.71
−5.48
−2.04
−1.62
|
|
8452-L3-1
ATGGCCACATACATGGCTGGGGTGTTGAA
1180
21
7.6
−1.08
−1.08
−1.08
−1.08
−1.08
|
|
8724-R5-2
GGCCAAGCTTGGAACCTCTCCCTGCCAGCA
1181
16
6.0
−1.71
−2.12
−4.29
−1.92
−1.69
|
|
8746-R5-1
TAAGCGCAGGATGGGGGTATTCAAGTCCAAAGC
1182
37
5.4
−2.03
−2.03
−2.03
1.54
−2.03
|
|
8808-R5-1
GACCCCTTTCTCCCAGCCTGTTTCTGCAA
1183
21
8.4
−1.07
−2.31
−4.54
−4.54
−2.03
|
|
8832-R5-1
TGGAGTACCACCTGTTTTTCCCCCACTT
1184
32
6.0
−1.37
−1.37
−1.37
−1.37
−1.06
|
|
8879-L5-1
TGGGGGCTGGGGCGCAGGTCGAGAGCCCAGGGG
1185
32
5.2
−1.79
−1.79
−1.79
−1.30
−1.79
|
|
9485-L5-1
TGCTGCACTCCATCCTCCCACAATGGCCCCATTGT
1186
26
5.2
−3.02
−3.02
−3.02
1.26
−3.02
|
TCCCAG
|
|
9507-L5-1
GTCTCCCTCATCCATCATCCACCA
1187
26
6.0
−1.45
−1.45
−1.45
−1.45
1.16
|
|
9798-L5-1
CTCTATATATACCTGGTATGACTTCTTTGGGG
1188
42
9.9
−1.40
−1.40
−1.40
3.74
1.36
|
GGAAAGAAAAGCAC
|
|
999996-L4-1
GGGAGGAGTCAGGTGTGTGCTGTGGGTTGGGGGA
1189
21
5.3
−4.63
−4.63
−4.63
1.35
−1.12
|
AGAC
|
|
999999-R4-1
CCCCTTGTCACCCCCAGCCCCTTCCTGGCCAGG
1190
16
5.2
−1.71
−9.15
−23.66
−3.15
−2.48
|
ACCCCAGCGAGGCCCAGAGAA
|
|
miR-103
TCATAGCCCTGTACAATGCTGCT
1191
26
5.0
1.81
−3.09
1.10
1.01
1.33
|
|
miR-1202
CTCCCCCACTGCAGCTGGCAC
1192
16
5.4
−1.58
−7.52
−7.52
−5.40
−4.07
|
|
miR-1249
TGAAGAAGGGGGGGAAGGGCGT
1193
32
5.0
−2.26
−2.26
−2.26
1.48
−1.92
|
|
miR-1275
GACAGCCTCTCCCCCAC
1194
16
12.7
1.07
−1.12
−12.61
−1.07
−2.42
|
|
miR-129-3p
ATGCTTTTTGGGGTAAGGGCTT
1195
11
21.4
−1.00
−1.00
−1.00
−1.00
−1.00
|
|
miR-1321
ATCACATTCACCTCCCTG
1196
16
5.9
−2.14
−2.14
−2.14
−1.05
−2.14
|
|
miR-1323
AGAAAATGCCCCTCAGTTTTGA
1197
47
5.0
2.09
−1.57
−3.13
1.70
−1.05
|
|
miR-141
CCATCTTTACCAGACAGTGTTA
1198
42
5.6
4.01
−1.96
−1.37
2.58
3.17
|
|
miR-143
GAGCTACAGTGCTTCATCTCA
1199
42
5.8
1.65
−4.11
1.63
1.38
1.30
|
|
miR-182
AGTGTGAGTTCTACCATTGCCAAA
1200
37
8.7
−1.00
−1.00
−1.00
2.28
1.51
|
|
miR-183
AGTGAATTCTACCAGTGCCATA
1201
21
10.0
−1.00
−1.00
−1.00
−1.00
−1.00
|
|
miR-198
GAACCTATCTCCCCTCTGGACC
1202
21
12.6
−4.73
−4.73
−4.73
−1.31
−2.54
|
|
miR-19a
TCAGTTTTGCATAGATTTGCACA
1203
47
5.0
2.88
−1.76
−1.23
2.71
−1.03
|
|
miR-30c-1*
GGAGTAAACAACCCTCTCCCAG
1204
26
11.2
−1.05
−8.25
−8.25
−1.14
−1.53
|
|
miR-375
TCACGCGAGCCGAACGAACAAA
1205
32
16.2
−1.60
4.80
−1.60
2.88
−1.60
|
|
miR-376c
ACGTGGAATTTCCTCTATGTT
1206
16
62.7
−1.12
−1.12
−1.12
−1.12
−1.12
|
|
miR-429
ACGGTTTTACCAGACAGTATTA
1207
16
8.1
3.25
−1.00
−1.00
−1.00
−1.00
|
|
miR-483-5p
CTCCCTTCTTTCCTCCCGTCTT
1208
42
10.1
2.71
−1.10
−3.38
2.43
1.23
|
|
miR-516a-5p
GAAAGTGCTTCTTTCCTCGAGAA
1209
47
8.8
2.57
−1.65
−1.65
1.35
−1.19
|
|
miR-7
ACAACAAAATCACTAGTCTTCCA
1210
21
86.3
−1.00
−1.00
1.53
−1.00
1.56
|
|
TABLE 21
|
|
Target RNAs present at levels at least 5-fold higher than normal
|
levels in less than 50% of tumor samples (con't)
|
|
|
Fold
|
% tumors
Change
|
Gene
increased
Average
ADK48
Adk40
Adk41
Adk49
Epi42
Ksarc19
|
|
10083-L5-1
16
11.2
−3.12
−10.22
−10.22
−4.85
1.60
14.20
|
10233-R5-1
16
13.1
−1.29
−15.77
−1.70
1.17
1.33
17.61
|
10335-L5-2
16
5.3
−2.42
−8.23
−8.23
−8.23
1.82
5.00
|
10357-R5-1
16
6.0
−1.13
12.33
−1.13
1.73
−1.13
2.98
|
10520-L5-1
26
5.9
−1.42
−1.42
−1.42
−1.42
−1.42
7.33
|
10844-R4-1
26
5.4
5.98
4.89
1.80
4.75
6.90
1.69
|
11358-R5-2
21
5.3
4.38
−2.77
1.50
7.69
5.96
1.31
|
11444-L5-3
21
8.8
−1.20
−1.20
−1.20
−1.20
−1.20
13.50
|
11547-R4-1
16
7.6
−2.09
−2.09
−2.09
−2.09
1.98
2.11
|
11605-L5-4
26
5.0
−2.54
−2.54
−2.54
−2.54
−2.54
7.43
|
11688-R5-3
32
6.0
6.88
2.76
1.49
5.01
7.47
1.72
|
12699-R5-2
26
6.0
1.74
7.41
5.23
5.07
7.67
1.00
|
12707-L5-2
42
5.0
−1.91
−1.91
−1.91
6.52
−1.91
7.16
|
12729-R5-1
16
11.8
−5.55
−5.55
−5.55
−5.55
−5.55
15.59
|
12730-R5-1
37
7.3
−1.10
−3.66
−3.66
3.20
−1.72
8.17
|
12888-L5-2
47
21.7
−1.64
−1.64
−1.64
7.18
1.22
43.87
|
12907-L5-1
26
6.4
−3.23
−3.23
−3.23
−1.68
4.63
10.17
|
12912-L5-2
37
5.3
−2.26
−2.26
−2.26
−1.02
−2.26
7.22
|
12917-R5-2
47
6.0
−3.76
−3.76
−3.76
−3.76
2.93
14.76
|
12958-R5-1
32
5.1
−1.32
−1.32
−1.32
−1.32
−1.32
6.38
|
12974-R5-2
21
16.1
−1.94
−1.94
−1.94
−1.94
−1.94
24.20
|
12979-R5-2
42
16.3
−1.39
−1.39
−1.39
−1.39
−1.39
10.78
|
12992-L5-1
16
6.7
−9.54
−9.54
−9.54
−4.91
1.18
9.52
|
13001-L5-1
32
15.5
−1.83
−1.83
−1.83
1.30
−1.83
42.81
|
13053-R5-4
26
5.6
−1.32
−1.32
−1.32
−1.32
−1.32
3.53
|
13070-R5-3
16
20.1
−1.56
−1.56
−4.70
−1.74
−2.22
28.78
|
13071-L5-3
32
7.2
9.95
11.19
−2.11
2.59
8.14
1.71
|
13078-L5-1
32
5.0
−1.28
−1.28
−1.28
−1.28
−1.28
5.67
|
13185-L5-3
21
13.4
1.19
−10.17
−4.63
−2.11
1.40
22.48
|
13216-R5-2
26
5.1
−1.79
−1.79
−1.79
−1.79
−1.79
9.13
|
13225-L5-1
16
5.9
−3.37
−3.37
−3.37
−1.14
−1.38
3.98
|
13235-R5-1
42
5.1
−2.00
6.84
−2.00
−2.00
−2.00
4.04
|
13245-L5-4
16
12.2
−2.87
−2.87
−2.87
−2.87
−2.87
14.29
|
13252-L5-3
32
5.0
7.58
−3.66
−3.66
3.75
−1.66
−1.06
|
13274-L5-3
26
6.2
−1.00
−1.48
−2.00
1.50
1.33
13.34
|
13300-L5-1
16
7.4
−1.75
−6.08
−6.08
−1.13
−2.47
5.40
|
13309-R5-1
16
8.2
−3.05
−3.05
−3.05
−3.05
−3.05
9.45
|
13352-R5-1
37
5.8
6.85
7.65
−3.13
4.84
4.78
1.36
|
13357-L5-4
16
10.3
−4.08
−13.36
−13.36
−1.26
−1.04
13.07
|
13366-R5-3
16
6.5
−3.19
−11.70
−11.70
1.49
−4.14
6.00
|
13373-R5-2
42
5.1
8.95
6.03
4.53
2.23
6.76
1.51
|
13375-R5-4
32
5.8
1.45
−1.36
3.34
5.09
3.16
2.32
|
13398-R5-4
16
15.6
−1.64
−5.01
−5.01
−5.01
−5.01
24.60
|
13417-R5-4
32
6.4
−1.82
−1.82
−1.82
2.73
11.74
7.23
|
13436-L5-1
21
5.3
10.40
−20.29
−20.29
3.70
−3.72
−1.06
|
13468-L5-1
21
25.5
−1.16
−1.16
−1.16
−1.16
−1.16
25.58
|
13470-R5-1
21
13.2
−6.50
−6.50
−6.50
1.75
2.16
22.13
|
13473-L5-3
21
9.2
−1.57
−1.57
−1.57
−1.57
−1.57
12.99
|
13500-L5-3
37
6.4
−1.38
−1.38
−1.38
−1.38
−1.38
11.94
|
13522-L5-4
16
5.3
−3.11
−3.11
−3.11
3.37
−3.11
2.60
|
13523-R5-1
26
5.3
−3.75
−3.75
−3.75
1.01
−3.75
7.12
|
13545-L5-1
21
5.3
1.56
5.75
4.10
4.33
7.14
1.80
|
227-L5-1
16
5.0
−1.10
−8.03
−2.54
−1.26
−1.22
3.33
|
3744-R5-1
37
6.7
1.22
−1.55
−1.88
2.15
1.70
17.73
|
3875-R5-2
32
19.0
−2.72
−2.72
−2.72
−2.72
−2.72
47.37
|
3926-L5-1
16
5.1
−2.22
−2.22
−2.22
−2.22
5.38
1.86
|
3992-R5-1
32
6.7
−1.27
−1.27
−1.27
−1.27
−1.27
11.59
|
4203-R3-2
16
6.0
−2.01
−2.01
−2.01
−2.01
−2.01
7.42
|
4261-R5-1
21
6.4
1.22
−2.52
−2.52
1.50
4.19
5.56
|
4291-R5-1
37
6.0
6.21
9.19
5.89
2.44
7.75
−1.03
|
4790-L5-2
21
12.6
−1.56
−1.56
−1.56
−1.56
−1.56
21.19
|
4958-L5-1
32
5.0
4.94
6.00
4.13
4.23
6.24
−2.14
|
4988-R5-2
16
5.3
1.08
−25.28
−3.70
−1.17
1.20
5.54
|
5108-R5-2
21
16.5
−2.27
−7.21
−7.21
1.49
1.77
31.12
|
5232-L5-2
32
5.2
−1.81
−1.81
−1.81
−1.81
5.58
6.39
|
5392-R5-1
42
7.0
−2.12
−2.12
−2.12
3.87
4.77
15.89
|
5723-R5-1
16
6.9
−2.80
−8.51
−8.51
−2.09
1.62
8.94
|
5836-L5-1
26
5.0
1.59
6.47
4.54
2.07
7.39
1.66
|
5842-R5-1
32
6.0
−1.05
−5.08
1.12
−1.02
2.33
2.71
|
6037-R3-2
32
7.4
−1.71
−1.71
−1.71
−1.71
−1.71
16.51
|
6181-L5-1
26
8.6
−1.40
−1.40
−1.40
−1.40
−1.40
16.60
|
6233-L5-2
16
10.1
−3.02
−3.02
−3.02
−3.02
−3.02
10.71
|
6395-L5-1
21
8.4
−3.73
−3.73
−3.73
1.35
4.16
7.80
|
6405-R5-1
32
5.7
6.13
7.07
4.77
5.11
6.86
−2.10
|
6474-L5-1
16
11.9
−3.05
−11.16
−11.16
−11.16
−4.35
14.82
|
6602-R3-1
32
8.8
−1.36
−1.36
−1.36
−1.36
−1.36
19.18
|
6681-R2-1
16
5.0
−1.47
−1.37
−1.55
−1.23
1.40
5.10
|
6683-R5-1
37
11.9
−1.39
−1.39
−1.39
1.48
−1.39
26.81
|
6752-R5-2
16
6.4
−2.32
−7.01
−1.56
−7.01
−1.38
7.39
|
6803-R5-2
21
12.2
1.33
1.11
−1.53
1.68
1.59
9.14
|
6864-R4-1
21
12.5
2.22
−1.50
−1.50
1.54
1.44
2.95
|
6872-L5-1
42
5.2
5.15
7.34
4.47
4.25
5.82
1.59
|
6906-L5-1
21
8.0
−2.17
−2.17
−2.17
−2.17
−2.17
14.47
|
6930-R5-1
16
14.8
−2.83
−10.13
−10.13
1.07
1.26
22.64
|
7631-L3-2
26
5.2
−2.68
−2.68
−2.68
−1.18
7.17
3.13
|
7764-R3-2
16
9.3
−3.64
−3.64
−3.64
−3.64
−3.64
12.47
|
7849-L2-2
16
6.1
1.61
6.57
4.84
1.03
6.78
1.71
|
8316-R5-1
42
20.3
−1.81
−1.81
−1.81
−1.81
−1.81
66.20
|
8433_C-R4-1
16
14.3
−1.74
−5.42
−5.42
−1.36
−2.50
18.24
|
8433-L3-1
16
6.9
1.35
−8.08
−8.08
−4.05
1.17
8.10
|
8452-L3-1
21
7.6
−1.08
11.39
4.06
4.04
11.10
−1.08
|
8724-R5-2
16
6.0
−2.90
−9.03
−4.67
1.24
1.37
6.87
|
8746-R5-1
37
5.4
6.65
6.64
4.26
4.91
6.70
1.49
|
8808-R5-1
21
8.4
−4.54
−4.54
−4.54
−4.54
−4.54
12.95
|
8832-R5-1
32
6.0
−1.37
−1.37
−1.37
−1.37
−1.37
4.44
|
8879-L5-1
32
5.2
5.93
6.75
2.28
1.04
6.13
−1.79
|
9485-L5-1
26
5.2
−3.02
−3.02
−3.02
2.49
3.21
3.66
|
9507-L5-1
26
6.0
−1.45
−1.45
−1.45
−1.45
−1.45
8.15
|
9798-L5-1
42
9.9
14.66
15.37
4.13
9.21
16.73
1.77
|
999996-L4-1
21
5.3
6.41
−1.05
5.20
4.33
1.88
1.23
|
999999-R4-1
16
5.2
9.26
−23.66
−1.25
2.35
−7.93
1.60
|
miR-103
26
5.0
−1.99
−6.84
1.87
3.43
2.56
1.28
|
miR-1202
16
5.4
−7.52
−7.52
−7.52
−7.52
1.62
6.96
|
miR-1249
32
5.0
5.38
5.84
2.27
4.52
8.04
1.49
|
miR-1275
16
12.7
−12.61
−4.87
−12.61
−1.62
1.01
9.83
|
miR-129-3p
11
21.4
−1.00
−1.00
−1.00
−1.00
11.04
−1.00
|
miR-1321
16
5.9
−2.14
−2.14
−2.14
−2.14
−2.14
8.17
|
miR-1323
47
5.0
1.07
1.16
−3.13
4.58
11.61
4.63
|
miR-141
42
5.6
1.66
−1.96
1.02
5.85
1.14
−1.96
|
miR-143
42
5.8
4.04
−4.11
2.93
5.90
5.59
−4.11
|
miR-182
37
8.7
−1.00
−1.00
−1.00
11.30
−1.00
−1.00
|
miR-183
21
10.0
−1.00
−1.00
−1.00
8.60
−1.00
−1.00
|
miR-198
21
12.6
−4.73
−4.73
−4.73
−2.51
1.98
21.91
|
miR-19a
47
5.0
1.80
−1.76
7.21
8.91
6.26
−1.04
|
miR-30c-1*
26
11.2
−2.57
−8.25
−3.89
1.91
1.94
22.43
|
miR-375
32
16.2
−1.60
−1.60
−1.60
−1.60
−1.60
−1.60
|
miR-376c
16
62.7
−1.12
−1.12
−1.12
−1.12
−1.12
−1.12
|
miR-429
16
8.1
−1.00
−1.00
−1.00
−1.00
−1.00
−1.00
|
miR-483-5p
42
10.1
1.50
−1.21
−3.38
1.14
2.56
9.82
|
miR-516a-
47
8.8
6.97
−1.65
−1.65
1.17
−1.65
9.91
|
5p
|
miR-7
21
86.3
−1.00
−1.00
−1.00
4.57
−1.00
−1.00
|
|
Gene
Kmalp21
Kmalp25
EPI-4
Kmalp44
Scc27
Lcnec31
Car13
|
|
10083-L5-1
6.04
−1.20
13.39
−1.15
1.20
−1.16
−10.22
|
10233-R5-1
6.52
−1.39
15.23
1.27
1.51
1.10
−6.54
|
10335-L5-2
2.55
−1.85
8.20
−8.23
−1.15
−1.71
−8.23
|
10357-R5-1
−1.13
1.86
−1.13
−1.13
1.37
−1.13
−1.13
|
10520-L5-1
3.18
4.71
10.86
−1.42
3.49
1.34
−1.42
|
10844-R4-1
1.36
1.08
−2.58
4.49
1.09
−2.58
−2.58
|
11358-R5-2
−1.16
1.17
−2.77
2.99
1.18
−2.77
−2.77
|
11444-L5-3
5.64
−1.20
13.27
−1.20
2.62
−1.20
−1.20
|
11547-R4-1
5.05
1.30
15.60
−2.09
1.36
−1.23
−2.09
|
11605-L5-4
3.53
1.60
9.69
−2.54
2.07
1.86
−2.54
|
11688-R5-3
1.11
−1.33
−1.33
4.67
−1.33
−1.33
−1.33
|
12699-R5-2
1.66
1.16
−1.96
4.62
−1.16
1.61
−1.96
|
12707-L5-2
4.03
2.78
−1.91
7.26
4.33
4.33
−1.91
|
12729-R5-1
5.64
−1.24
14.17
1.67
1.74
1.06
−5.55
|
12730-R5-1
6.34
1.57
23.70
5.24
2.24
2.37
−3.66
|
12888-L5-2
23.04
11.51
82.88
1.23
11.54
5.75
−1.64
|
12907-L5-1
3.99
1.05
11.02
2.09
1.42
1.32
−3.23
|
12912-L5-2
2.14
2.86
14.96
−2.26
3.88
4.19
−2.26
|
12917-R5-2
7.83
2.46
16.79
2.54
2.64
2.10
−3.76
|
12958-R5-1
4.19
1.98
12.26
−1.32
2.45
3.54
−1.32
|
12974-R5-2
12.93
1.29
29.06
−1.94
1.81
1.64
−1.94
|
12979-R5-2
36.28
4.84
58.47
1.46
5.16
4.12
−1.39
|
12992-L5-1
3.16
−2.51
7.29
−1.36
−1.30
−1.84
−3.31
|
13001-L5-1
17.02
13.68
4.38
−1.83
8.78
6.48
−1.83
|
13053-R5-4
13.64
2.00
6.49
−1.32
2.42
1.51
−1.32
|
13070-R5-3
10.28
−1.18
21.26
1.71
1.74
1.44
−4.70
|
13071-L5-3
−1.39
1.41
−2.11
9.31
−1.31
−2.11
1.49
|
13078-L5-1
3.96
2.12
9.20
−1.28
4.09
4.68
−1.28
|
13185-L5-3
9.50
−1.19
19.78
1.34
1.88
1.66
−1.67
|
13216-R5-2
3.36
1.72
8.24
−1.79
2.44
2.56
−1.79
|
13225-L5-1
4.43
1.04
9.41
−3.37
1.69
1.75
−3.37
|
13235-R5-1
10.73
2.12
9.58
1.76
2.43
2.20
−2.00
|
13245-L5-4
12.06
1.04
10.37
−2.87
1.47
1.29
−2.87
|
13252-L5-3
−1.78
1.28
1.36
−3.66
1.14
1.12
−3.66
|
13274-L5-3
3.11
2.88
9.05
1.27
2.80
1.56
−1.16
|
13300-L5-1
3.67
−1.28
13.10
−6.08
1.07
−1.03
−6.08
|
13309-R5-1
2.79
1.01
12.42
−3.05
1.39
−3.05
−3.05
|
13352-R5-1
−1.04
−1.01
−3.13
7.39
1.08
−1.49
3.02
|
13357-L5-4
4.68
−1.56
13.01
−1.17
1.17
−1.45
−13.36
|
13366-R5-3
3.36
−1.62
10.24
−4.94
−1.07
−1.49
−11.70
|
13373-R5-2
4.97
1.11
−1.86
3.80
−1.32
−1.06
−1.86
|
13375-R5-4
−1.53
−1.93
4.20
16.42
−1.56
−3.11
−7.06
|
13398-R5-4
7.38
−1.41
14.84
−5.01
1.57
1.33
−5.01
|
13417-R5-4
4.35
−1.82
9.97
−1.82
−1.82
1.33
−1.82
|
13436-L5-1
2.55
−2.03
4.35
−1.04
−1.31
−2.32
−20.29
|
13468-L5-1
42.79
−1.16
31.50
−1.16
2.25
−1.16
−1.16
|
13470-R5-1
9.28
−1.38
19.17
1.62
1.31
1.04
−6.50
|
13473-L5-3
5.85
1.57
15.53
−1.57
2.39
1.37
−1.57
|
13500-L5-3
6.95
2.11
14.71
−1.38
2.73
3.87
−1.38
|
13522-L5-4
1.14
1.10
9.89
−3.11
1.73
1.65
−3.11
|
13523-R5-1
4.25
1.30
11.04
1.81
2.32
1.90
−3.75
|
13545-L5-1
−1.46
1.04
−2.13
−2.13
−2.13
−2.13
−2.13
|
227-L5-1
5.25
−1.86
5.98
1.00
−1.14
−1.09
−4.63
|
3744-R5-1
4.94
4.32
12.79
1.63
2.72
1.99
−2.37
|
3875-R5-2
21.41
1.80
36.52
3.32
2.67
2.60
−2.72
|
3926-L5-1
2.06
1.37
7.91
−2.22
1.57
−1.06
−2.22
|
3992-R5-1
6.64
2.32
12.31
−1.27
3.77
3.55
−1.27
|
4203-R3-2
3.12
−2.01
7.32
−2.01
−1.16
−2.01
−2.01
|
4261-R5-1
9.03
1.23
6.64
−2.52
1.69
1.33
−2.52
|
4291-R5-1
1.01
−1.67
−1.67
4.73
−1.67
−1.67
−1.67
|
4790-L5-2
7.09
1.61
19.81
−1.56
2.37
1.17
−1.56
|
4958-L5-1
−1.19
−1.04
−2.14
4.24
−2.14
−2.14
−2.14
|
4988-R5-2
3.48
−2.05
6.82
1.28
1.05
−1.34
−8.12
|
5108-R5-2
11.82
1.05
21.13
1.91
2.06
1.54
−1.29
|
5232-L5-2
2.75
2.65
1.47
−1.81
2.30
−1.81
−1.81
|
5392-R5-1
6.70
1.74
16.76
3.71
1.91
1.15
−2.12
|
5723-R5-1
2.94
−1.53
8.79
1.02
1.08
−1.42
−8.51
|
5836-L5-1
−1.54
−2.14
−2.14
4.43
−2.14
−2.14
−2.14
|
5842-R5-1
9.50
1.02
16.41
−1.31
−1.32
−1.44
−5.08
|
6037-R3-2
6.11
1.91
14.55
−1.71
2.97
2.07
−1.71
|
6181-L5-1
5.10
1.57
15.61
−1.40
2.68
2.92
−1.40
|
6233-L5-2
4.99
−1.05
14.68
−3.02
1.54
1.57
−3.02
|
6395-L5-1
6.46
−1.04
15.00
−3.73
1.67
1.45
−3.73
|
6405-R5-1
1.46
−2.10
−2.10
4.48
−2.10
−2.10
−2.10
|
6474-L5-1
7.02
−1.48
13.75
−4.80
1.09
−1.19
−11.16
|
6602-R3-1
6.22
3.09
17.33
−1.36
3.82
2.93
−1.36
|
6681-R2-1
2.76
−1.63
6.93
−1.55
1.43
−1.17
−3.04
|
6683-R5-1
6.23
10.02
25.16
5.08
6.03
4.31
−1.39
|
6752-R5-2
3.11
−1.67
8.79
−7.01
1.18
−1.03
−7.01
|
6803-R5-2
18.88
1.50
18.71
1.83
1.99
1.71
−11.71
|
6864-R4-1
1.88
1.78
42.80
−1.50
2.10
1.47
−1.50
|
6872-L5-1
6.06
−1.96
−1.96
3.74
−1.96
−1.96
−1.96
|
6906-L5-1
3.55
1.13
12.00
−2.17
2.01
1.54
−2.17
|
6930-R5-1
6.91
−1.19
14.99
1.28
1.74
1.04
−10.13
|
7631-L3-2
5.17
1.30
8.27
−2.68
1.40
1.50
−2.68
|
7764-R3-2
4.37
−1.09
11.00
−3.64
1.53
1.54
−3.64
|
7849-L2-2
−1.05
−2.04
−2.04
−2.04
−1.29
−2.04
−2.04
|
8316-R5-1
16.64
2.12
60.43
6.75
3.99
3.79
−1.81
|
8433_C-R4-1
6.98
−1.37
17.79
1.52
1.68
1.01
−5.42
|
8433-L3-1
3.41
−1.39
9.18
−1.06
1.19
1.05
−3.51
|
8452-L3-1
−1.08
−1.08
−1.08
−1.08
−1.08
−1.08
−1.08
|
8724-R5-2
3.34
−1.55
7.87
1.04
1.14
−1.14
−9.03
|
8746-R5-1
1.68
1.04
−2.03
4.06
−2.03
−2.03
−2.03
|
8808-R5-1
5.01
1.08
13.67
1.70
1.57
1.02
−4.54
|
8832-R5-1
3.33
2.34
19.28
−1.37
3.13
3.30
−1.37
|
8879-L5-1
−1.07
−1.79
−1.79
4.14
−1.79
−1.79
−1.79
|
9485-L5-1
4.65
−1.18
11.90
−3.02
1.00
−1.56
−3.02
|
9507-L5-1
1.99
2.56
14.45
−1.45
2.84
1.67
−1.45
|
9798-L5-1
4.26
−1.40
−1.40
10.93
−1.40
−1.40
−1.40
|
999996-L4-1
−1.40
−1.10
−4.63
5.08
−1.06
−2.07
−1.67
|
999999-R4-1
1.32
−2.72
3.99
−7.30
−1.89
−2.94
−23.66
|
miR-103
−1.00
1.19
1.66
1.80
3.59
1.79
12.88
|
miR-1202
2.14
−2.10
7.21
1.01
−1.32
−1.79
−7.52
|
miR-1249
−1.12
1.02
−2.26
4.17
1.10
−2.26
−2.26
|
miR-1275
7.58
−2.54
20.69
−1.44
−1.20
−1.52
−12.61
|
miR-129-3p
−1.00
−1.00
−1.00
−1.00
−1.00
−1.00
31.72
|
miR-1321
2.93
1.49
6.53
−2.14
1.63
−2.14
−2.14
|
miR-1323
4.00
1.86
8.00
4.21
3.41
1.75
−3.13
|
miR-141
−1.96
1.49
−1.96
1.83
3.28
3.22
16.77
|
miR-143
4.76
−4.11
−4.11
4.40
−4.11
−4.11
7.28
|
miR-182
3.30
2.12
−1.00
−1.00
4.01
7.56
30.62
|
miR-183
1.85
−1.00
−1.00
−1.00
3.52
2.83
25.18
|
miR-198
7.44
−1.47
19.01
1.51
1.52
1.17
−4.73
|
miR-19a
1.14
1.68
4.45
−1.76
3.38
2.05
−1.76
|
miR-30c-1*
8.60
−1.36
21.06
1.72
1.31
−1.01
−8.25
|
miR-375
−1.60
1.32
−1.60
−1.60
10.44
12.39
58.80
|
miR-376c
−1.12
2.50
−1.12
−1.12
15.41
−1.12
170.06
|
miR-429
−1.00
−1.00
−1.00
−1.00
3.48
1.76
17.65
|
miR-483-5p
7.11
1.75
52.02
2.12
1.94
1.66
−3.38
|
miR-516a-
4.22
2.90
39.38
5.18
4.21
3.86
−1.65
|
5p
|
miR-7
−1.00
−1.00
−1.00
−1.00
11.46
7.18
321.94
|
|
TABLE 22
|
|
Chromosomal locations and pre-microRNA sequences for target RNAs in Tables 18 to 21.
|
SEQ
|
ID
|
Gene
Chr location
Pre-microRNA sequence
NO
|
|
10083-L5-1
14q12
GGGTGGAGAGAGGGGGTAGAAAGGAAGAGGGACATATGGGAGCCTCTTCCCCCATGCCCGAAAGCTTCTCCCATTT
1211
|
|
10233-R5-1
9q34.13
ACCTTCTGCCTTTGAGACCTGGAAGCCACAGCACTGGTGGACATAAATTCTACTGCCTGCTGCTCCAGATCCAAGGGGAGAGGGT
1212
|
|
10335-L5-2
15q26.1
TCTTAGTGCTTTCTAATTAAAAAGGAGGGGAGTGGTGATCTTTTTGCTCTCTAAGTTCTGTTTCCTCTGAGTGGAAAGCAGAGGG
1213
|
|
10357-R5-1
3p25.3
CTCTCTCTTGCTGAACTCTGTGTCCAGGGTTCTCTAGCCCTCTAGGGAAACAAACACATGGAATATTCAGACAGTGGAGAG
1214
|
|
10455-L5-1
17q23.2
GGAGAGGGATGTTTGGCGCAATTGCAGTTGTTAAAATAGAACAGGCTTCTGAATTGTGGCCAGAACATAATGAATCCCATTTCT
1215
|
|
10520-L5-1
3p23
AGTCCACAGAGAAGGCTGGAGGAGGTAGCAAGGAGATGCTGTAACAGCTGCTACAGCCTTAAAACAAAGTTGGTGTCTCTCTGGACT
1216
|
|
10844-R4-1
8p12
GGGTGGGTGGCAGATGTCTTACTCTGCCTTTTAGAAACACATGTTTGAAAGTAGAGTCCTGAATATGCTACCCCCT
1217
|
|
11358-R5-2
1q23.3
GTGAGAGGGTAAAGTAGTATGCTGTGGGTCAGAATTACTAGGGAAGTTCTGAGCCATGTCAGCCTAGTTTCCCACCCTCCAT
1218
|
|
11444-L5-3
15q22.2
GAATAGTTGGAAGGTCACCTTTGCTGGAGGAGTGGGTGCCTGAACACAAGTGCAGTCCTATTAGTAAGCCAGGACCTTCAGCTCCTCAGTTGAAAGGGAAATAACTATTC
1219
|
|
11547-R4-1
6p12.2
TGCCAGCCCTGCTGTAGCTGGTTGAAGGGGACCAAACCTCTCAGGAAGACGGACTTGGTTCCGTTTGACCAGCCAGAGCAGGGGGCA
1220
|
|
11605-L5-4
1p31.3
GGCCCTGTGCATAATAAATCTTTATGGAATTGAGGGGAAGGGAATTAAAGAAGGGAAGAGAAGAGCAAACCCACTACAGAGTTTATGACCATCTATTCTTAATATTAT
1221
|
ATTAGAACTGGGCC
|
|
11688-R5-3
11q13.4
CGCCCACTAAACCGGATGTGACGTTGACCTACCTTAGTCACATTGTTAGGGAAGGAAGTGTGCCGCGCCTACCTATCTGCCCCGCCTTCCACCACCGCCACCACCCTC
1222
|
GAGTCTCAGCCAGTCGGCGTCTCCATCCTGGCG
|
|
12699-R5-2
1q22
CTGGGACGGGCGGGGCGCCGAGGCCCAGGGCGCCTGAGGGGCGCAGAGGTGTCAGCGTGCAACCGCCGCCCCCCAGCGTTCCCG
1223
|
AAAGCCCGG
|
|
12707-L5-2
7q32.1,
GATTGTAGAGTTGTTGGATTGCAGAGGAGAATGTTCGATTCATCTTTTCAGTAACTTTAAAATC
1224
|
17q23.2
|
|
12729-R5-1
17q25.3
AAATTAAAGAAAAAAAATTCTCCACCAAAAGCGCCGCAGTGACAGTTCCCAACATTTTCTGCCTTTCTTCTTCCCCTCCCTGCACCACTACACAGGGCGCCGGGCTCGGG
1225
|
GGAGGGAGAAGGCACACAATTGCATTTTCGTCGCTTTTTAATTTTTTTTTTTTGGTTT
|
|
12730-R5-1
17q25.3
CCCGGCTCGGCCCCGCGTCTCTCCAGCTCCTCCGGCTCCTTTTAGTGCATAAATTAGTGATGGCATTTCCCGGAGAGCGGAGCACAA
1226
|
|
12888-L5-2
2q32.3
TCCTCCAGGAGCTGGGAGAACCATACAATGTAGGAAAAATATAGTTTAATTGAATGGTACTCTGGTCTTCTGGAGGA
1227
|
|
12907-L5-1
17q12
GGCTCAGTGTCTAGGACGTGGTAGAGAGGGCATGAGCACAGTGGAAGCAAAAATGCCAGTTCAGTGCTTAGTGCTGACTTTACCACC
1228
|
GTTCTTCATGGCAACTGAACT
|
|
12912-L5-2
1p36.33
CCCACCTACAGCCTCTGTGGGTGGAAGGTGCCAGAAAACTTGAAGAGTGGCTCTGGCCAGCTCTCTGGGCCCAGTTGGCACCAGGTG
1229
|
GTTGCAGAGAAAGGGTGGG
|
|
12917-R5-2
1p34.1
GGACCTGGGGGCTTCTCTGACCCTTGAACAGCTTATACTATGAGACCTTGGGAACCTCCTCCATGCAGACACACAAGGCTCAATGTTG
1230
|
GGGGAAGGGAAGGGCCCATAGGTCC
|
|
12947-L5-4
6p21.1
GCCTTGTCTGAAGGGAGAGGCCCTGGCATGCGGATGGGAGATTTAGAGGCTGTGGAGAAGGGAACTTGGGGCTTTCCTTCCTTCGTG
1231
|
GCCTCACTCCCCTGGGGCCTCTCTCTATGGAGGGGGC
|
|
12958-R5-1
6q23.3
GTTAGGGCCTGGAATCCCTCTGTCGGGCATCTGTTAGAGTCTGTGGATGGCACTCTGTAGTCGTTATAGATGCACCCAGGGGAAGATTCTCTCAGGCATGAT
1232
|
|
12974-R5-2
Xq27.3
ATTCTCTGCATGTTTACCTTGTTCTCTCTGTTGTTTTGGTGTTAAAAGTTAAATAACTCTGAACCAAGGGACTAGGAATTTGGGGGCACAGAGGGT
1233
|
|
12979-R5-2
3p21.1
TTTGGGTCCTTTGTCCAGAGTGTGAGGATGTTGGTGAAGGCCATGCCCTGACTAGATTCAGGGATCCTTTTCTTTCATCTAGCTACTGGGGAAGGACCTGGA
1234
|
|
12992-L5-1
9q31.3
TAGAGATGGGGGTGGAGGGAAGCAGGTATGATTTCAGGGGCAGCAGGAGATTCTCTTCTGTTTCCCTCTCTCCCAGCTCTA
1235
|
|
13001-L5-1
12q13.13
TGGAGCTGGGAGTGGTATCTAGGAATTTCTCCTTCTAGTTTTTACCTTCTTAGTTTTA
1236
|
|
13053-R5-4
19q13.33
ACCCATCTGTAAAGTGGGACAATCTTCTTGCCTCCTAGGATGGCCATGGAGCTCAGTGCAGGGGTTGGGGCTGCCTGATGAGCCTGATCTTAGGGAAGGC
1237
|
|
13070-R5-3
5q35.1
CTGCTCTCCTTGACCTGGTAGGAAGGTGATTTGATGGTTTTCAAACACATGCTGTTTCTCTCTTTCATCAGGGTAGCTGGGTGGGTGGC
1238
|
ATTAGGTCCTTTGGACTGGGGAGAGGAGACAG
|
|
13071-L5-3
7p22.3
TACATGTGCCGAGATGTGAGCAGTCACCCCTGGAGATCCTCACCCCTTCTCTGTAGAACGAGGAGTTGGGCTGCCAGGGATTGGGGT
1239
|
CTGGGCGCGTTGCTGGTGTGTGTG
|
|
13078-L5-1
2p13.1
TCTCCTGTCTAGCAGGCTTATGAAATGAGGGCCCATCCTTTGGTCAAGGCTTGTTTGAAGGAGA
1240
|
|
13098-L5-1
11q24.1
ACCCCCCGGAGGAACCGCCAACAGCGCCCCGGCACCATCAAGCATGGATCGGCGCTGGACGTGCTCCTCTCCATGGGGT
1241
|
|
13122-L5-1
2p11.2
GGACTGGAGCAGGTGAGATGGAATTTCCTAAAGGTCCAGATATTTAGGACCCTGGACCCATCTCACCCGCTGCCTCTGTCC
1242
|
|
13185-L5-3
3q13.31
GGGGAAGAAGAGCAAAGAGGGGAGAGAGGGAAGAAAAAAAACAGAATAAGTTGGTCGTATTGAAGCTTCTCCATCAACCCTAGAACAATTAGCTTCCACC
1243
|
|
13216-R5-2
1p21.1
TGAGTAAATAATCTTCAAATGTATGGCTTTTTATTCCTGGTGAGAGCATCATACTGAGAGAAACAGTGCTTCAGCTGCCAGAGAGGAGA
1244
|
AAGGAGGAATATATAGAAACATCCAAACTT
|
|
13219-L5-1
11q22.1
GCTGGAGCAGAGAGACTGAGTGAGGGAGTCAGAGAGTTAAGAGAATTAGTACAGGTGAGATTGTACTGATTATCTTAACTCTCTGACC
1245
|
CCCTCACTCAGTAAAGATCAGATTGTGCCAGGC
|
|
13225-L5-1
11q23.3
GAAGATGGAAGGGGCTGTCCCAGAAGTGGGCAGGAAGAACCAGGCTGTTATGCCATGTGGGCATGTGGCACAACAGCCTCGTTCTTC
1246
|
CTGCCCACTTCTGGGGCACCTTGTTTCCCTCT
|
|
13235-R5-1
11p11.2
CTTTCTGCTTGGCTGTTATATGAACCTGCCCTGGGCTTTCTAGTCTCAGCTCTCCTGACCAGCTGAGCTGGAGGAGAGCTGAGACTAG
1247
|
AAAGCCCAGGGCAGGTCCAACTGAAAA
|
|
13245-L5-4
1q24.1
AAGACATTACTTTGAATATATTTTAAAGGGAGTAGAAGGGAAAGACTATTTGGAATGCTTTATTAAAATAGTCTTTCCCTTCTACTCCTTT
1248
|
TAAAATATATTCAAAGAAAGTT
|
|
13252-L5-3
1q25.2
CTTTGGCACAGTCCGTGCTCTCAAGGAGCTCACAGTCAGGAAGGCACGTGGAATTTCAGCCTGGAGTTCCAAGTGCTGCCCTCAGGG
1249
|
AGTGCTGGGCCTGAGCTGGGGTGAGGCTGCAGGG
|
|
13254-R5-1
1q25.3
CTCACACATGGTACGTTTTCAATGAGCTGATTTTGTTTCTCCACTCAATGCAGTAATTGAGCTTCTTTGGTTCAGTGCATGAGTGGTTCA
1250
|
GTGGTTCATTGGGCATCCTGGTTGAGGG
|
|
13274-L5-3
12q13.13
AGGTGGTGGTGGGGAGGACCCTGAGGGAGGGTGGGAGCACGGGAGAAGAGAAGGCATACCCAACCTGACCTACTTACCTGTCCCCT
1251
|
ACCCCACAGAGGGCTTCCCTGGAGGCCGCCATTGC
|
|
13300-L5-1
14q24.2
GGGTAAGTAGGAGGGGAGATAATTCTGTGTGTAACTCACAACCCTTCTGCCCTTTTATCTCTGGGGCCCGAATTTCCATGTGGGGGAT
1252
|
AAAAGAAGTCACCCTTCCTCATCCCCC
|
|
13309-R5-1
1p32.2
ATAGATTTACACTCCCTGTCCTCCACAAGCTCACAGAAAAATTGTAGCTGAAGACAAGGGGGAAGAACCTA
1253
|
|
13352-R5-1
19q12
CACTTTTTATGACATCACATTGTTGACCTCAATCTGAGGAGATGGGGGAGCTAGCCCCATTTCACAGATGCAGCGCTGAGGTTCCGGGATGTGAGGTGAGGTGA
1254
|
|
13357-L5-4
19q13.2
TCAGGGTTTGGTGTACAATTGTGGGAGGCTGCAGGGAGGTGTGGGGAGAAGGTCCGCTTTAGAGCTTGGTCCCTCTGTGCTCACCTC
1255
|
CCAGCCCCAAGCCCCCAGCACCGGATCCTG
|
|
13366-R5-3
19p13.2
GGGCCGGTGAAGGCCCCGCCTGGGTCCCATACCCGGGGTTGGGGGTCAGAAGCCGCTCGGTCTCTGTGGGAATAGGAGAGGGCACTGGGGTGAGGCCTG
1256
|
|
13373-R5-2
20q13.33
TCCCTGCACCCCTGCCTGTACAGGTGAGTGGGAGCCGGTGGGGCTGGAGTAAGGGCACGCCCGGGGCTGCCCCACCTGCTGACCA
1257
|
CCCTCCCCCCACAGCACCCTGTGCCGGGGC
|
|
13375-R5-4
20q13.33
ACCCTCTCAGGACCCCTCCTAAGGGGTAGGCAGGGGCTGGGGTTTCAGGTTCTCAGTCAGAACCTTGGCCCCTCTCCCCAGACCCCC
1258
|
AGGCTGTGGTGAGGGTCTGAGAGCTGGTAC
|
|
13398-R5-4
2q35
ATCCTCATTCATTCACAGGAGACCTACCGCAGAAGAGACCCTAGAACATCCTTGGTTCAAAGTGAGTCTAGTCTGCAAAGTGGTGGCA
1259
|
CAAAAGGTGGAGGGAGAGAGAA
|
|
13417-R5-4
3q13.2
CCATGATTCCTTTAACAACATGTTTCCAGCATTCCCAGGTAGGCCAAGGTGTCCTACAGAAAAACCTTGGGTTAGACCTACAGGGGATC
1260
|
TGGCTGGTGTTAACAGAAGGAAGGGCA
|
|
13436-L5-1
3p12.1
GAGGCATGACCTAGCTGGGGGCTTCATTGAGCTGTGGTCACCGGAGCTCAGAGGCTGCTCCTCCTAGGCACCCTAGCTCTTAGGACT
1261
|
CAGTTCTCTGAAGCTCACCAAGGGCATCTATCTT
|
|
13467-L5-1
5q35.2
TTTGACTTGGAGCAAGGAGGGTCTGACTGTCACTTGGAGCTAAACCAGTCTCCAAGTGGCCATCAGACCCTCTTTGCCCCAAGTCAGT
1262
|
|
13468-L5-1
5q35.2
GACTTGGGGCAAAGAGGGTCTGATGGCCACTTGGAGACTGGTTTAGCTCCAAGTGACAGTCAGACCCTCCTTGCTCCAAGTCAA
1263
|
|
13470-R5-1
5q13.2
GGTCAGTCTAGCTTGCTCTTGAAGCTCTCCAGAGACAAAGAAGCCTGTAGCAAATCACAATGAGGATTCTGGTCCCTGAGGTGGAGAG
1264
|
GGTGGGAGCCCCACTGTTTGCCC
|
|
13473-L5-3
5q13.3
TATATAGAGAGACATATGTATCAGGATAGGTGGTAGAAGGGCAAACATAGAAAACACCACCCTAGCCAGGTTGCCCTGAATGGCCCCA
1265
|
GTGTCTAGCATAGTGCTTTATG
|
|
13500-L5-3
7q32.3
CTGGTGTGGACCTCACTCAATGGAGAGAGAGGCCTGGAAGATCTTGGAACAGGAACATCCAGCCCTGCTTCTCTCTTAATCTCAGCCCACACTCAGAG
1266
|
|
13522-L5-4
8p21.1
AGTGCAGTGGTGTGATCATAGCCAATAGAGGGTGCACAGGCACGGGAGCTCAGGTGAGGCAGGGAGCTGAGCTCACCTGACCTCCC
1267
|
ATGCCTGTGCACCCTCTATTATATCACTCGTAT
|
|
13523-R5-1
8p12
GGCCATAGCTGCTGGGTCCCTAAGGCACCTCTCATCAGTTAGGTCAATGTGCCAGGCAGGGGAAGAAGCCTTACTATTCCACTGCATCTGTGGCCT
1268
|
|
13545-L5-1
Xq28
CCCCAGACTCACAGCCTCCCTTGCGCCACAGGCCTGTGTCCTGACTGGGACTCTTGGGACGCCAGCAAGCCCGTTACCAATGCGCGA
1269
|
GAGGCCATGCAGCAGGCGGATGACTGGCTGGGCA
|
|
227-L5-1
3q27.2
TGAGGGGCGGAAGCACTGGGGAGAGACAGGTGTGAGCTTCCCACGTGGTGATCAGCTCACACCTGTCTTGTGTTCTTGGTATTCACA
1270
|
GACTCTCA
|
|
3744-R5-1
19p13.12
CTTCTCTTATTCTCCCTGTTTTCATCCTACTTTTAAGTAATAAATTTGGCATTAGTGGGAGGGGAGCAGGGAGGAAGGAGAAG
1271
|
|
3875-R5-2
5p15.1
GGCTCGGTTTCAAATCTCTCCTAATCCACTAATGAACCTTTATTAAAGTGGGAGAGAGAGGTTGAATCAGTC
1272
|
|
3923-R5-1
19p12
GGCTCTGCACCAGGCGTTTCTTCTTGTGTTTCCTCTTCTCTTCTGGAGAGGGATGAAGGAGATCCTTTGTGAGAGGC
1273
|
|
3926-L5-1
3q27.3
AGTGGGGGCACGTTCAAGAATGCTAATGAATTATCAGTTTTCTTTAAGCCTCATTAGATTTCTTGATAGCAAAACCTCCCATT
1274
|
|
3992-R5-1
2p22.3
GTCTCTGGCTTCTGTTTCTTATGCTGCTGTTGATTTTTTCCAACCATCAGCTCAGATACTGACAGAAGAGAAAGGGGC
1275
|
|
4203-R3-2
11q23.3
AGCAATTCCAACTGCCCCATTTATATTCCTAAGTAGAGGACTTGTTAATATGGAGCCTGCCTCTGGGGAAGTGGGAATGTGCT
1276
|
|
4261-R5-1
1q23.3
GTAAATTTCAACCTATTTTTAAGGGTTATTTTCACTCAAGTGAAATCTATCAAGGAAGGAGGGTTATTTTTAC
1277
|
|
4291-R5-1
3p14.3
GGTTAAAATGGATTGCCAGGAAACACCTGAAGGGTACAAAGTCATGTACACCCCCATGGCTCCTGGTAACTACCTGATC
1278
|
|
4440-L3-2*
11q14.1
CATGTGATTTCTGCCCAGTGCTCTGAATGTCAAAGTGAAGAAATTCAATGAAGCACGGGTAAACGGCGGGAGTAACTATG
1279
|
|
4440-L3-2*
7q11.22
GTGATGTGATTTCTGCCCAGTGCTCTGAATGTCAAACTGAAGAAATTCAGTGAAATGCGGGTAAACGGCGGGAGTAACTATGAC
1280
|
|
4479-R3-1
1p32.3
CCCAAGCTCCTTCCTGGAGGACTTAACACTGTGTTGAGCAGTTGTTTTGAATTTCCGGGCAGGGGGCTGCAAAAGGG
1281
|
|
4790-L5-2
2q11.2,
CCCAGAATTCTAGTAATGAGGGAGACAGGTTATGCCAAGCCTGCTTCTCCCAGGATGCACTGGGAGCCTGGG
1282
|
2q14.1
|
|
4958-L5-1
6p21.1
CCCCATTTTCAGAAGATGCCATGGTTTATTAATTCTCTGCAGAAGCAATAAGAACTGGGTATTGGCTTAATTTGGGG
1283
|
|
4988-R5-2
14q24.3
CTTTTTCTCTCTGCTGGGAAACCTTGCTTGACTTCATGTCCAGTGTTTGGTATCCAAAGACGGGGAGGAGGAG
1284
|
|
5080-R3-1
11q23.3
GGCGTTTCTTCTTGTGTTTCCTCTTCTCCTTTTCTGGAGAGGGATGAAGGAGACCCTTTGCAAGAGGCATGTT
1285
|
|
5108-R5-2
2p13.1
CCAATGCCTCTCACCTCCTCACTTGTGGCACCTTCGCTTTTGATCCGAAGTGCGGGGTTATTGTGAGTGACGGTGTGGGAGGAGAGGG
1286
|
|
5232-L5-2
9q21.13,
GGAGCCCTTGATGTCCTGCAAATGAAGGAGGAGGATGTCCTTAAGTTCCTTGCAGCAGGAACCCACTTAGGTGGCACC
1287
|
1q23.2
|
|
5392-R5-1
2q24.2
CTCTCTCTCTCAGTTACTCACAAAACATGGCTGTCTTATTCAGAGATTAGCAATTATTGTAATGAGATACTGTCGGAGAGGG
1288
|
|
5723-R5-1
4p15.31
CCTCTGCCTGGCTTTCTTTGTAAAGCCATTAAACTACATTAAGAAGGCTACTGCTGGAGAAAGGGGAGGAGG
1289
|
|
5836-L5-1
11q23.2
GCCATGGGCCTCCATAGTTTCCTGTAGCCCCCTTGGTTCCCAAGAATAGTTTTGGAATGGGGCGTGCTGTGATAATGGGGGTTAATGGT
1290
|
|
5842-R5-1
1p33
GGCCACTTGGGTGCATTGGACTTGAACTTCTTTTTTGTCTCCCCTTTAGGGGGGATATAGATTTTCATTTCTCTTTCATAACGGGCC
1291
|
|
6037-R3-2
16q21
GCAGGATCCCTCTTTTCATCTGAAAATTACCACTAATTTGCAATTAGTTGGAGGAAAATTGGAGATGGAGGAAAGGGAATTGC
1292
|
|
6181-L5-1
1q41, 5q23.1
AAATCCAGGGGGAAGAGTCATCTAAGTTTACCATGCAGTTGTTTACCAAAAATAGAGGAGGAGAGTCTTAACTTTTGCTCTTGGATTT
1293
|
|
6216-L1-1
11q14.1
CATGTGATTTCTGCCCAGTGCTCTGAATGTCAAAGTGAAGAAATTCAATGAAGCACGGGTAAACGGCGGGAGTAACTATG
1294
|
|
6233-L5-2
6q16.2
GGAAATGGGAGAAGGATAAAGTGGAAATCTAATTTTGAGAAATAAGGATTAAAGGTTCCATTATTCATGCTGTTTTC
1295
|
|
6235-R5-2
15q26.2
TCTGTTTTTATCAGTTTAATATATGATACATCTTCTATCCAAGGACAATATATTAAATGGATTTTTGGAGGAGA
1296
|
|
6395-L5-1
14q11.2
GTTCCGAGGCAGGCTTTCCTCCTCTCTGCAGGGGAGAGGCTCCCTCACACAAGAGGAGGATTACACTGGCTCTGAGC
1297
|
|
6405-R5-1
8q21.11
TCAAATGAGAAACTAAGTACATTTCTTTTCAACAGGCAATTTACCCCATGATGAGATATGCTTTCACTTATTTTTCTTTGA
1298
|
|
6474-L5-1
1p34.1
GGTGAAGGGGGAAGAGGGGATGGCTTTAATTAGGGCTTCTTGGCCTCGTCAGTCCTGGGGTTGGTCGGGGTAATCCAGTTAGAGTCC
1299
|
CAGCCTTTCATCTCAGCTGGCC
|
|
6602-R3-1
3p14.1
CAGAGTCTAAATGGAAGAGTCCTCCGTATTTACCCAGCTCATCTCCTGTGTAATGGATTTGGAGGAGAGATTTCCACTGGGGCTCTG
1300
|
|
6681-R2-1
11q12.2
TGTGCTCTCATTGTTATTCCAAAAGTCTCTGTCTAGATCACTGGAGGGGCAGAGAGAGAGGGGAGAAAACAGGGAGATACA
1301
|
|
6683-R5-1
12q23.2
GTTCTAGTTCCAGGATGCTGATACTTTAAGCCCGAGGCTCTAACTTGAGCAGGAAGAGTTTATTTTGGGATGAAGAAT
1302
|
|
6752-R5-2
Xq13.1
CCCTCCCAGTTCCCATAGCAACTGGGCTGTAGCAGCCAGAACTTGATTGAGCCCAGCAGTGGCCCGACTGAGGTGGGGAAAGGAGGG
1303
|
|
6803-R5-2
22q12.3
GCCACCTTTCATGGTGAGGATGCCTGCCACCTTCAGGATCACATCTTTGGGTGAGGTCCAACCAGAGAGGGAGC
1304
|
|
6864-R4-1
3q26.2
ATCTGTGTTTGGCTACAGGTGGGCACTCTAAGGGGTCAGTCTCCAGGGGAGTGTAATTGTGTGTCTCCTGGGGCTTGTTTGCAGAATG
1305
|
ACCTAAAGCTGAAGCCCCAGCT
|
|
6872-L5-1
2q37.2
CCCCACCGGGTCACAGACTGTGACAGAGTCTTATTGCCTGTCTCTGGGAATTCATTTTCTGTCTCTCCTCTGTTCCACCTCTCTGGGG
1306
|
|
6906-L5-1
6p21.1
CCAGGAGAGCTGGCTGGTTGGGGAGAAGACACTAACCCTGTGAGTCTGACCTCAGCCAGCTAACCTGCCCTGG
1307
|
|
6930-R5-1
9p21.3
TGTCATTTGTCCATTTTCTCTTCTGACCCAGTGGTATTCTGCAAGATCAGAGGGGAGAGAAGGATTAATGTCA
1308
|
|
7426-L5-1
2q22.3
AAATCAAGCACAGCAGGAGGTGTTCGTCTCCCAGGTAATGGGTAAATGATGAGCAGATGAGCCATCCTTCTATTGATTT
1309
|
|
7631-L3-2
1q23.3
GTGGCGATTGGGCAGGCTTCATGCAGGCAGCTGGCGTCTAGGGCTGTCAGACGCAATCAGTGTTTGCATGGCACCTGCGGCCAC
1310
|
|
7726-R3-2
1q21.3,
CATTTCACATCCATGAAGTAGGAATTGGGGCTCTGCACCAGGCGTTTCTTCTTGTGTTTCCTCTTCTCCTCTTCTGGAGAGGGATG
1311
|
12p13.32,
|
1q32.1
|
|
7764-R3-2
5q11.2
TGCTATCTCGCCTCACACATCAACACACGTGCCAGACAGATTCTGACTGCAAAGTCTGTTATTGGTGATGAGAGAGGCAGAGAGGGCA
1312
|
|
7849-L2-2
16p13.2
CATCCCATGGTGTGCCCCCAAACATCTTATTTGTCTTGATATTTCTTTCACAGAAATACATATGACAGATAAGGAGTCACTAGAGGATG
1313
|
|
8004-R3-2
Xq28
GGGGCTGCCATCCTGCTGTCCGTCATCTGTGTGGTGCTGGTCACGGCCTTCAATGACTGGAGCAAGGAGAAGCAGTTCC
1314
|
|
8316-R5-1
14q24.3
GTCAGGCTGCTGTATTCTCTTACACAGATGCCAGTAAGAACAAAGGCATCACGTGGGGAGAGGATACCCTGAT
1315
|
|
836-R5-2
3q26.2
AAATAAGCCATTCCAAACCATTCTCTGATTTGCTGTGAGTGGCAGAATCATTCACCGTGGTGAATCATAGCAGGGAGAACCATTTGGAA
1316
|
TGATTATTT
|
|
8433_C-R4-1
17q25.3
AAATTAAAGAAAAAAAATTCTCCACCAAAAGCGCCGCAGTGACAGTTCCCAACATTTTCTGCCTTTCTTCTTCCCCTCCCTGCACCACTA
1317
|
GGAGGGAGAAGGCACACAATTGCATTTTCGTCGCTTTTTAATTTTTTTTTTTTGGTTT
|
|
8433-L3-1
17q25.3
CGGTGGAGGGAAAGGGGAAAGGAGCCATTTTCTGCTGCACATCAGTCAGTGCCTGCGCCCTCCCTCCCTCCGCCG
1318
|
|
8452-L3-1
18q21.33
TTCAACACCCCAGCCATGTATGTGGCCATCCAGGCCTTGCTGTCCCTGTAAGCCTCTGGCCATACCACTGGCATCGTGATGGA
1319
|
|
8724-R5-2
15q23
GGCCCAGAAGATGAAAAGCTGAAGTCCTTTCCCTTCCAGCTGAAGCCAGGTGTGATGCTGGCAGGGAGAGGTTCCAAGCTTGGCC
1320
|
|
8746-R5-1
8p21.1
TAAGGCAGGATGATTCGGGAAATGGACTATTTAAAGCAAGCTGCTTTGGACTTGAATACCCCCATCCTGCGCTTA
1321
|
|
8808-R5-1
3p14.3
CCGATTATGGCTTTCTTCTCCTGCCCTTTCAGTAGTGATTTGCAGAAACAGGCTGGGAGAAAGGGGTCTTTGG
1322
|
|
8832-R5-1
9q33.2
TTCTGAGATATGATCTGTTGGATTCTCTACTACCAAAGTGGGGGAAAAACAGGTGGTACTCCAGAA
1323
|
|
8879-L5-1
11q13.1
CCCCTGGGCTCTCGACCTGCGCCCCAGCCCCCAGTACCTCGTCCGGAGCACTGTGAGGGAGCTGCAGCAGGACTCAAGGCAGCCCA
1324
|
GGGG
|
|
9349-R5-2
21q22.11
GGACACTCTGAACCCCAAGTGGAATTCCAACTGCCAGTTCTTCATCCGAGACCTGGAGCAGGAAGTCCTCTGCATCACTGTGTTC
1325
|
|
9485-L5-1
11q23.3
CTGGGAACAATGGGGCCATTGTGGGAGGATGGAGTGCAGCAGACTGCTGGCACAGCCAAGCGCACCACGGTGGGACCTCACCCAG
1326
|
|
9507-L5-1
16q22.3
GGTGTTTGGATGGATGAGGATGGTGGATGATGGATGAGGGAGACGGAGGATTCCCTTATTAAAGCATCAAATTCTTCCCTAAATATC
1327
|
|
9594-R5-1
2q12.1
TTCCAGCTATTTAGTAACTCTTCCAAAACACTGTCAGCACCCATGCTAGGATGCAGGGAGTGGGAAGGAAGTCTAAGTAGGGAA
1328
|
|
9798-L5-1
5q12.3
GTGCTTTTCTTTCCCCCCAAAGAAGTCATACCAGGTATATATAGAGAGATCTATAATGCCCTTCTGTTGGGGGAATGAAAGCAC
1329
|
|
999996-L4-1
17q21.2
GTCTTCCCCCAACCCACAGCACACACCTGACTCCTCCCTTCCAGGGAAAAGACCTCAGGGCTGCTGGTGAGTCAGAAATAGGAAGAC
1330
|
|
miR-103
20p13
TTGTGCTTTCAGCTTCTTTACAGTGCTGCCTTGTAGCATTCAGGTCAAGCAGCATTGTACAGGGCTATGAAAGAACCA
1331
|
|
miR-103
5q35.1
TACTGCCCTCGGCTTCTTTACAGTGCTGCCTTGTTGCATATGGATCAAGCAGCATTGTACAGGGCTATGAAGGCATTG
1332
|
|
miR-1202
6q25.3
CCTGCTGCAGAGGTGCCAGCTGCAGTGGGGGAGGCACTGCCAGGGCTGCCCACTCTGCTTAGCCAGCAGGTGCCAAGAACAGG
1333
|
|
miR-1249
22q13.31
GGGAGGAGGGAGGAGATGGGCCAAGTTCCCTCTGGCTGGAACGCCCTTCCCCCCCTTCTTCACCTG
1334
|
|
miR-1275
6p21.31
CCTCTGTGAGAAAGGGTGTGGGGGAGAGGCTGTCTTGTGTCTGTAAGTATGCCAAACTTATTTTCCCCAAGGCAGAGGGA
1335
|
|
miR-129-3p
11p11.2
TGCCCTTCGCGAATCTTTTTGCGGTCTGGGCTTGCTGTACATAACTCAATAGCCGGAAGCCCTTACCCCAAAAAGCATTTGCGGAGGG
1336
|
CG
|
|
miR-1321
Xq21.2
ACATTATGAAGCAAGTATTATTATCCCTGTTTTACAAATAAGGAAATAAACTCAGGGAGGTGAATGTGATCAAAGATAG
1337
|
|
miR-1323
19q13.41
ACTGAGGTCCTCAAAACTGAGGGGCATTTTCTGTGGTTTGAAAGGAAAGTGCACCCAGTTTTGGGGATGTCAA
1338
|
|
miR-141
12p13.31
CGGCCGGCCCTGGGTCCATCTTCCAGTACAGTGTTGGATGGTCTAATTGTGAAGCTCCTAACACTGTCTGGTAAAGATGGCTCCCGGG
1339
|
TGGGTTC
|
|
miR-143
5q33.1
GCGCAGCGCCCTGTCTCCCAGCCTGAGGTGCAGTGCTGCATCTCTGGTCAGTTGGGAGTCTGAGATGAAGCACTGTAGCTCAGGAAG
1340
|
AGAGAAGTTGTTCTGCAGC
|
|
miR-182
7q32.2
GAGCTGCTTGCCTCCCCCCGTTTTTGGCAATGGTAGAACTCACACTGGTGAGGTAACAGGATCCGGTGGTTCTAGACTTGCCAACTAT
1341
|
GGGGCGAGGACTCAGCCGGCAC
|
|
miR-183
7q32.2
CCGCAGAGTGTGACTCCTGTTCTGTGTATGGCACTGGTAGAATTCACTGTGAACAGTCTCAGTCAGTGAATTACCGAAGGGCCATAAA
1342
|
CAGAGCAGAGACAGATCCACGA
|
|
miR-198
3q13.33
TCATTGGTCCAGAGGGGAGATAGGTTCCTGTGATTTTTCCTTCTTCTCTATAGAATAAATGA
1343
|
|
miR-19a
13q31.3
GCAGTCCTCTGTTAGTTTTGCATAGTTGCACTACAAGAAGAATGTAGTTGTGCAAATCTATGCAAAACTGATGGTGGCCTGC
1344
|
|
miR-200a
1p36.33
CCGGGCCCCTGTGAGCATCTTACCGGACAGTGCTGGATTTCCCAGCTTGACTCTAACACTGTCTGGTAACGATGTTCAAAGGTGACCC
1345
|
GC
|
|
miR-200b
1p36.33
CCAGCTCGGGCAGCCGTGGCCATCTTACTGGGCAGCATTGGATGGAGTCAGGTCTCTAATACTGCCTGGTAATGATGACGGCGGAGC
1346
|
CCTGCACG
|
|
miR-200c
12p13.31
CCCTCGTCTTACCCAGCAGTGTTTGGGTGCGGTTGGGAGTCTCTAATACTGCCGGGTAATGATGGAGG
1347
|
|
miR-205
1q32.2
AAAGATCCTCAGACAATCCATGTGCTTCTCTTGTCCTTCATTCCACCGGAGTCTGTCTCATACCCAACCAGATTTCAGTGGAGTGAAGT
1348
|
TCAGGAGGCATGGAGCTGACA
|
|
miR-20b
Xq26.2
AGTACCAAAGTGCTCATAGTGCAGGTAGTTTTGGCATGACTCTACTGTAGTATGGGCACTTCCAGTACT
1349
|
|
miR-21
17q23.1
TGTCGGGTAGCTTATCAGACTGATGTTGACTGTTGAATCTCATGGCAACACCAGTCGATGGGCTGTCTGACA
1350
|
|
miR-298
20q13.32
TCAGGTCTTCAGCAGAAGCAGGGAGGTTCTCCCAGTGGTTTTCCTTGACTGTGAGGAACTAGCCTGCTGCTTTGCTCAGGAGTGAGCT
1351
|
|
miR-30c-1*
1p34.2
ACCATGCTGTAGTGTGTGTAAACATCCTACACTCTCAGCTGTGAGCTCAAGGTGGCTGGGAGAGGGTTGTTTACTCCTTCTGCCATGGA
1352
|
|
miR-375
2q35
CCCCGCGACGAGCCCCTCGCACAAACCGGACCTGAGCGTTTTGTTCGTTCGGCTCGCGTGAGGC
1353
|
|
miR-376c
14q32.31
AAAAGGTGGATATTCCTTCTATGTTTATGTTATTTATGGTTAAACATAGAGGAAATTCCACGTTTT
1354
|
|
miR-429
1p36.33
CGCCGGCCGATGGGCGTCTTACCAGACATGGTTAGACCTGGCCCTCTGTCTAATACTGTCTGGTAAAACCGTCCATCCGCTGC
1355
|
|
miR-483-5p
11p15.5
GAGGGGGAAGACGGGAGGAAAGAAGGGAGTGGTTCCATCACGCCTCCTCACTCCTCTCCTCCCGTCTTCTCCTCTC
1356
|
|
miR-516a-5p
19q13.41
TCTCAGGTTGTGACCTTCTCGAGGAAAGAAGCACTTTCTGTTGTCTGAAAGAAAAGAAAGTGCTTCCTTTCAGAGGGTTACGGTTTGAGA
1357
|
|
miR-516a-5p
19q13.41
TCTCAGGCTGTGACCTTCTCGAGGAAAGAAGCACTTTCTGTTGTCTGAAAGAAAAGAAAGTGCTTCCTTTCAGAGGGTTACGGTTTGAGA
1358
|
|
miR-7
19p13.3
AGATTAGAGTGGCTGTGGTCTAGTGCTGTGTGGAAGACTAGTGATTTTGTTGTTCTGATGTACTACGACAACAAGTCACAGCCGGCCTC
1359
|
ATAGCGCAGACTCCCTTCGAC
|
|
miR-7
9q21.32
TTGGATGTTGGCCTAGTTCTGTGTGGAAGACTAGTGATTTTGTTGTTTTTAGATAACTAAATCGACAACAAATCACAGTCTGCCATATGG
1360
|
CACAGGCCATGCCTCTACAG
|
|
miR-7
15q26.1
CTGGATACAGAGTGGACCGGCTGGCCCCATCTGGAAGACTAGTGATTTTGTTGTTGTCTTACTGCGCTCAACAACAAATCCCAGTCTAC
1361
|
CTAATGGTGCCAGCCATCGCA
|
|
miR-720
3q26.1
CCGGATCTCACACGGTGGTGTTAATATCTCGCTGGGGCCTCCAAAATGTTGTGCCCAGGGGTGTTAGAGAAAACACCACACTTTGAGA
1362
|
TGAATTAAGAGTCCTTTATTAG
|
|
TABLE 23
|
|
Target RNAs present at at least 5-fold decreased levels in at least 50% of tumor samples
|
% of down-
|
Gene
Probe sequence
SEQ ID NO
expressed
ADK9
ADK10
Adk29
Adk15
Adk23
ADK48
|
|
10010_B-L4-1
GCCGAGCCCCCGCCCCCGCCGGGATGCTGCCCTCCGGAAGGAGGGGCGCTGCCC
1363
67
−4.54
−4.10
−6.89
−5.28
−3.68
−2.54
|
|
10010_D-L4-1
TGGCGCCCTCCCCCGCCCGGGGCTCAGCCTCTCACCTG
1364
61
−4.69
−6.39
−10.13
−3.34
−2.75
−1.75
|
|
10010-R2-2
CTCGCCGGCTCCAAACTTTCCCCAACTCCAGG
1365
67
−10.92
−10.92
−7.27
−7.12
−4.44
−2.95
|
|
10030-R5-1
CCGTGGATGTCAACTCAGCTGCCTTCCGCC
1366
67
−6.81
−6.81
−6.81
−2.13
−3.82
−2.13
|
|
10145-L5-2
TCAAAAAATTCTTTTTCCTTTGCTCTCTCTTCTGT
1367
56
−2.03
−2.03
−2.03
−2.03
−1.18
−2.03
|
|
10231-R3-1
TGAACTTTAGCTGGGCCGCCGCCTGTCAGC
1368
72
−6.47
−4.83
−7.60
−4.34
−5.39
−1.70
|
|
10260-L5-2
ACCTATTGTTCGCCAGGGCCCCCACCCGATGT
1369
67
−13.31
−13.31
−3.91
−3.96
−6.75
−4.01
|
|
10333-L5-1
TGCCCTGCCCACCCCCTCCCCTGCCCCG
1370
78
−5.25
−5.14
−8.87
−5.02
−3.91
−2.93
|
|
10342-R2-2
CCCGCCGCCGGAGCATCTCGAAGTTAATTAAA
1371
56
−4.63
−3.69
−4.92
−3.66
−4.90
−1.74
|
|
10345-R5-1
ACCCTTCTCTCAAAAGCGACCCCTCCCATCCAGTCC
1372
72
−4.22
−4.59
−10.15
−5.45
−4.10
−2.11
|
|
10374-R3-2
GACACCGCCCGCTACTTTGTTAATGAAAAGCCCCC
1373
67
−33.82
−4.71
−10.79
−4.92
−11.40
−1.26
|
|
10435-R5-1
TGCTAATTGTGCCCTGTTGTCTTTCTTAAACT
1374
56
−2.03
−2.03
−2.03
1.07
−1.10
−2.03
|
|
10533-R5-2
TAACTGTCCTGAGCCCCTTCTTTATATTGC
1375
56
−2.60
−2.60
−2.60
−1.21
−1.46
−2.60
|
|
10543-R5-2
GCCTTCACCCTTCCCATCCTGGCTCATGAAT
1376
56
−2.16
−2.16
−2.16
−2.16
−1.24
−2.16
|
|
10578-R5-1
CCACCCCCTCTACGGTCCCCACCAGCCCCG
1377
78
−5.22
−4.46
−6.46
−4.96
−4.51
−1.76
|
|
10818-L5-1
CTCAGTGATGACAAATGACCGCTGTCAGCCGCC
1378
83
−21.17
−21.17
−8.42
−4.40
−9.89
−1.24
|
|
11370-L5-5
CCCTCCGCCCCCACACTGCATCCTTGCCCAGTTTGG
1379
78
−6.80
−4.03
−7.05
−3.30
−2.15
−2.30
|
|
11605-L5-4
TCCCTTCTTTAATTCCCTTCCCCTCAATTCCATAA
1380
61
−2.54
−2.54
−2.54
−2.54
−1.37
−2.54
|
|
12184-L4-1
GACCTCAGCGTGCCCCCTTTCAACCACAGACGAATATTGTGTACAA
1381
56
−2.73
−2.21
−3.89
−3.08
−1.99
1.08
|
|
12184-L5-3
TGACCTCAGCGTGCCCCCTTTCAACCACAGACG
1382
61
−5.57
−5.57
−5.57
−5.57
−2.34
−1.75
|
|
12224-L4-1
CAAGGCGTCGCCATGAAAATCCACCCCATGGAGTAGCA
1383
78
−3.22
−3.22
−3.22
−3.22
−2.54
−3.22
|
|
12361-R5-1
ATGTAAATGTGCCATATTGCCGCCCATCT
1384
67
−3.34
−4.62
−6.42
−3.65
−3.60
−1.50
|
|
12691-R5-1
CCCCGCCCCTGGCGCGCCCCCGACAGGC
1385
78
−67.73
−7.29
−9.93
−7.32
−3.57
−2.81
|
|
12692-L5-1
GACCCGGCCCCGCAGCCAGCACCCGGCCACCGCGC
1386
89
−7.80
−7.12
−6.21
−7.94
−5.87
−2.09
|
|
12693-L5-1
GTCGCGGCCGCCCGGCCCTCCCGGTCCCCTCCCC
1387
61
−84.98
−6.22
−8.38
−2.30
−2.98
−1.86
|
|
12694-R5-1
TCAGCCCCCAGCGCCCCCCGGAGTTCTTGGA
1388
78
−6.01
−5.88
−9.37
−6.86
−6.32
−2.41
|
|
12696-R5-2
AACCCGGGCTCCCCCACCCGCTCCCTGA
1389
61
−4.33
−3.38
−7.14
−5.25
−4.53
−1.41
|
|
12697-R5-1
CCGGTGTGCGCCCCCTCCTACCTCTGCCGGCC
1390
67
−4.28
−5.08
−27.65
−4.83
−3.72
−1.76
|
|
12699-L5-1
GGCGCCCTGGGCCTCGGCGCCCCGCCCGTCCCAG
1391
50
−4.46
−29.74
−4.16
−3.65
−2.69
−1.18
|
|
12701-L5-1
AAATCCTCGCCATCCTCCACCCCCAGCCCCGG
1392
78
−4.43
−12.74
−7.02
−6.42
−4.98
−1.97
|
|
12703-L5-3
AGCCGAGCCCCCGCCCCCGCCGGGATGCTGCCCTC
1393
61
−4.17
−3.97
−5.50
−4.94
−3.05
−1.64
|
|
12704-L5-2
CTGGCGCCCTCCCCCGCCCGGGGCTCAGCCTC
1394
72
−4.44
−5.86
−10.21
−3.67
−2.76
−2.08
|
|
12713-R5-1
CTCTCGCGACCGACCTGCCGCCGACCGCCACAG
1395
83
−7.39
−6.52
−7.89
−5.40
−7.13
−1.82
|
|
12722-L5-1
AAACAAAGTACTTCCGACCTCCCCGCCCGCCCGC
1396
56
−4.21
−4.38
−5.37
−2.81
−2.86
−2.02
|
|
12723-R5-2
CCCCAGCCCCTTCCTGGCCAGGACCCCAGCGAGG
1397
72
−18.13
−18.13
−18.13
−3.62
−3.52
−4.66
|
|
12725-R5-1
CCACCCCCTCAAGCCCCCAGGAGCTTCCTTAAC
1398
67
−22.87
−22.87
−22.87
−4.18
−9.94
−1.79
|
|
12731-L5-1
CAGCCGCGCCGGCCGCCAGCGCCCCGGCGCGC
1399
72
−14.83
−14.83
−14.83
−4.58
−3.87
1.02
|
|
12900-R5-3
GTGCCCGTGCCCTAAGCGACCCTCCACTCCCTCAA
1400
56
−8.25
−1.80
−8.25
−1.90
−3.08
−2.33
|
|
12904-R5-2
CTGCCTCCCTGACCCCAAAACACACCTGACTGCC
1401
61
−2.67
−4.87
−4.22
−2.80
−2.26
−9.55
|
|
12910-R5-2
GCTCCATTTCCCCACTGAAATGACAAAATCCA
1402
61
−4.61
−4.61
−4.61
−4.61
−4.61
−1.30
|
|
12925-L5-3
GAACACCTCCTCCTTTTCCCTTTGGTGAATAAAGA
1403
61
−2.02
−2.02
−2.02
−2.02
−1.68
−2.02
|
|
12932-L5-3
GACTCCCTTCCACCCCCATTTCCCACCTACTAAT
1404
67
−8.22
−8.22
−8.22
−3.88
−4.15
−8.22
|
|
12939-L5-2
CTGATTCAAAACCCACCTCTACAACTTAATAGCT
1405
72
−2.19
−2.19
−2.19
−2.19
−2.19
−2.19
|
|
12947-R5-3
GCCCCCTCCATAGAGAGAGGCCCCAGGGGAGTGA
1406
72
−28.53
−28.53
−28.53
−5.22
−4.41
−2.39
|
|
12975-L5-1
GGAGTCTACAACATCCCTCCCGCCT
1407
50
−2.29
−3.08
−4.02
−2.31
−2.47
−1.53
|
|
12981-L5-1
AATGATGTCACCTTGGTCTGGTTGCCCCCACCC
1408
61
−4.08
−4.08
−4.08
−4.08
−2.35
−1.27
|
|
12981-R5-1
GGGTGAAGACAGACAGAACCCAGACCCTCCCATAG
1409
50
−2.22
−9.73
−9.73
−2.36
−3.84
1.96
|
|
12998-R5-1
CAGGCCCCAGTGCCACCGCCAAGGCTATC
1410
89
−12.85
−12.85
−12.85
−12.85
−10.71
−3.87
|
|
13004-R5-1
CTCCAACCCCCGCAATTCTCGCTCCCTTCACCTGA
1411
56
−2.79
−4.11
−6.82
−4.51
−3.96
−2.17
|
|
13047-R5-2
GCACAGCAGACCCCATGCACTAGCCCCGGGCAC
1412
50
−2.69
−2.69
−2.69
1.15
−1.55
1.18
|
|
13050-R5-4
ACGCACCCCTATCTCCCACCCCCCGCAAGCCAAGCA
1413
78
−4.94
−6.60
−11.56
−5.96
−5.41
−2.49
|
|
13052-L5-1
TCCCCGGACCTAAGCATCTCCCCCACCCGCCAACC
1414
61
−2.01
−3.27
−4.41
−3.51
−3.73
−1.83
|
|
13066-R5-2
GGAGGTAGCCCCCAAATCTAGTTGAACCAATTC
1415
61
−2.42
−2.42
−2.42
−2.42
−2.42
−2.42
|
|
13072-L5-2
GGATTTCACCAAACGTATAGCCCCCACCAGTA
1416
78
−6.78
−30.88
−30.88
−7.56
−5.70
−2.19
|
|
13075-L5-1
TGAAAGCTGAAGTCCAGCCCAGCCCTCT
1417
56
−6.29
−6.29
−6.29
−2.93
−2.98
−2.05
|
|
13089-L5-2
ATCACCAACAACCTTGCCCCACTCCAAGCCCTG
1418
61
−2.76
−2.76
−2.76
−2.76
−2.23
−2.76
|
|
13091-L5-2
CCTGAGAACCCCCGACCCTCAAGTGTTCAGCAGGC
1419
78
−3.59
−8.53
−11.47
−12.31
−8.16
−1.70
|
|
13093-L5-2
CGACCCCGCAGAACCCCACCGCGCCCCGCGCAG
1420
67
−4.46
−10.00
−7.28
−7.97
−7.96
−1.06
|
|
13095-R5-1
GCAGGACCCACCTCCCTACTCCTGGCCCAGGT
1421
67
−10.16
−10.16
−4.31
−2.54
−5.00
−2.96
|
|
13097-L5-2
AGCCTCAGCCCCACCTCCAGCCCCACCCTAGGG
1422
56
−3.53
−3.87
−4.76
−4.17
−3.23
−1.41
|
|
13110-R5-1
AACAGCAGACAGGGTCCCAGGGCCCTCCCTTGT
1423
56
−4.98
−4.98
−4.98
−1.26
−2.35
−1.54
|
|
13115-L5-3
ACCCCCTCCAGGGCCGACCACCCCAACCCAAAC
1424
78
−8.12
−18.66
−32.34
−7.11
−5.65
−2.64
|
|
13119-R5-2
GACTCTGCCGCTCCCGCCCGGCCACCTCCCTGT
1425
61
−3.93
−3.70
−4.56
−3.71
−3.93
−1.95
|
|
13124-L5-1
TCCTCCCCTCCGCGAAAGCCTAAACTTACCCCTCA
1426
50
−2.05
−2.84
−5.18
−3.12
−2.71
−1.10
|
|
13129-L5-3
AGCCTTCCTGTCCCCTGGCCCCCGACCTGCTCCA
1427
78
−2.06
−2.16
−2.55
−2.91
−3.95
−6.35
|
|
13130-L5-1
AGCCCGCCCCAACCCACCTCGATCTTTTCCTC
1428
56
−2.86
−5.27
−3.54
−2.26
−1.75
−2.84
|
|
13135-R5-1
CGAGGAGGCCCTGAGCACTGCCCACCCCCACACC
1429
72
−4.99
−4.99
−6.04
−4.00
−7.63
−1.74
|
|
13136-L5-3
ACACTTGCCCCTGCCAGCCCTGGTCAGGGCCACCCT
1430
78
−6.86
−6.86
−6.86
−6.86
−2.82
−2.13
|
|
13137-L5-1
GCTCTAACCCCCGCAACCCCACCTCCCCATGCC
1431
61
−2.47
−3.81
−5.83
−3.96
−3.31
−1.66
|
|
13138-R5-1
TTCGCCACGCCCCGCCACCCGAGCTGCCTCCC
1432
78
−5.42
−5.75
−7.42
−6.65
−4.73
−2.51
|
|
13163-R5-1
AGACCAAAGCCCTCCCACCCCTTCCCCTCCCAGC
1433
72
−5.88
−16.87
−21.10
−2.25
−2.25
−2.13
|
|
13164-L5-1
GAAAACAAACATCTAATAAACTCTCAGGATACC
1434
50
−5.10
−5.10
−5.10
−1.16
−2.10
−1.52
|
|
13166-L5-1
TCAGAGGACCCCCCGACCCACCCCGCGAGGC
1435
83
−6.08
−6.39
−9.71
−13.71
−5.78
−2.21
|
|
13181-L5-1
GAACAGTCACTGCCTGCCCCAACCTCTTTCAGGA
1436
67
−7.92
−7.92
−4.10
−1.01
−3.99
−7.92
|
|
13184-L5-1
CAAAAAATAAACCAAAAACCCACCACCTAATG
1437
56
−2.31
−2.31
−2.31
−1.65
−2.31
−2.31
|
|
13186-R5-2
ACATTCATCTCTGTCAGATCCCTCCCTCACCA
1438
67
−4.00
−9.93
−26.53
−3.44
−2.79
−1.55
|
|
13195-L5-3
TCTATATTCCCCCTCCATGACCATTTGTATTAG
1439
78
−3.32
−11.15
−8.93
−3.70
−2.85
−5.82
|
|
13199-R5-1
GCTGGGGGATTCTGCCCATGCTTCACCTCCC
1440
50
−2.48
−8.02
−5.59
−2.40
−6.24
1.53
|
|
13202-L5-1
GGGTCTCCTGCCACCTCCTCTGAGAAGCCCCACCA
1441
61
−10.20
−10.20
−10.20
−4.67
−4.70
−3.14
|
|
13202-R5-2
GGTGGGGAGACTGGGAGAGAGCCCTCCTAATG
1442
56
−3.89
−14.39
−14.39
−2.07
−2.32
−1.06
|
|
13209-L5-2
TAACTCGCCTGCTGCCCCGGCGGCCTGCCCGCCG
1443
61
−45.23
−4.90
−5.49
−3.79
−3.36
−1.44
|
|
13209-R5-3
TGGTCGCCGCCGCAGGCGCCTGAAGGGCACGGCGG
1444
61
−12.46
−12.46
−3.05
−3.57
−6.27
1.13
|
|
13211-L5-1
ACGCGCCCCGCCGCTCTCTGACCGACCGGAGGCGC
1445
61
−7.25
−6.22
−5.47
−5.00
−4.38
−1.43
|
|
13220-L5-3
CCTGTAGCTGCCACTGCCCCTTCCTCACTCAACC
1446
72
−5.92
−19.89
−9.41
−4.26
−3.98
−1.61
|
|
13229-L5-1
ACCCGTCCCTGCCCCTTTACCCCTTGGGCCAGCA
1447
61
−5.10
−4.62
−6.00
−4.16
−3.60
−1.59
|
|
13230-L5-4
TAGCTCCAGTGCCTCCAGCTCCAACCACCTGAA
1448
50
−2.05
−2.05
−2.05
−2.05
−1.39
−2.05
|
|
13231-L5-2
GGGGCCGCTCCCCAGCACCGACGCCAGCATCATCG
1449
56
−16.99
−16.99
−3.88
−4.81
−8.33
1.00
|
|
13237-L5-4
ACCCCCTCCAGGGCCGACCACCCCAACCCAAACAA
1450
72
−35.36
−16.82
−35.36
−6.88
−5.65
−2.41
|
|
13239-L5-2
CAGAGCTCCCCCCATCTCCCCAGACTTACCCCT
1451
72
−4.10
−15.67
−39.77
−6.16
−5.51
−1.58
|
|
13240-L5-2
AATCGCCGTCCCCGCCGCGGCATTCCCGGCCCCAA
1452
72
−60.67
−6.31
−7.99
−5.64
−4.93
−1.84
|
|
13241-L5-2
ACACCCCTCCAAAACCACACAGAGCAAGCAAGG
1453
72
−10.26
−10.26
−10.26
−3.74
−4.35
−10.26
|
|
13251-R5-2
TTGTGCCCCCTCCTCTGCCATGGCTGGTCCCTGG
1454
78
−5.70
−7.57
−14.60
−5.42
−4.16
−2.77
|
|
13259-R5-1
GCCAGAATTACCACTGTATCTGTCCCCACCCC
1455
72
−3.29
−3.29
−3.29
−3.29
−2.05
−3.29
|
|
13267-L5-1
CACTCCCTGCTGGCCCCCACCTCACCTATGGTG
1456
61
−1.87
−2.26
−13.85
−2.21
−3.68
1.35
|
|
13281-L5-3
CACCCCCACCCCACAGGACAGAGGAAGTGACGAG
1457
56
−3.70
−9.33
−5.75
−7.17
−4.05
−6.04
|
|
13283-L5-3
GGACCCCTGCCTTCCTTGCTGCCACCCTTTGCACA
1458
50
−3.60
−7.29
−3.33
−3.32
−2.19
−1.11
|
|
13285-L5-3
GCTATGCACCCAGCCGCCCAGCTCAGCCCCTGC
1459
78
−6.84
−6.59
−7.59
−4.39
−4.35
−1.93
|
|
13287-L5-3
GGAGCCACCCCACCCTCCTCCCAAGACCCACAT
1460
56
−3.34
−3.34
−4.88
−3.81
−2.82
−2.04
|
|
13291-L5-1
CCCAAGCGCCCCTTCCTCCCTCCTTCCCTCCCG
1461
50
−2.07
−2.35
−3.92
−2.62
−2.12
−1.10
|
|
13293-L5-1
TGCCTGGCCAGGCCTCCGCCCCTTGGCTCGCCAC
1462
61
−3.68
−3.42
−6.95
−3.41
−3.34
−1.42
|
|
13298-R5-1
CAGGGCTTCAGCCTCCCCACAGCCCCACACTT
1463
78
−14.82
−14.82
−14.82
−8.93
−8.41
−4.71
|
|
13303-L5-3
CCTCCCCTGAACCCAGTTGCCACAACTTTCCAC
1464
50
−2.57
−7.48
−4.39
−2.24
−5.82
−1.05
|
|
13308-L5-1
CACTCACATCAGCCCATCCACCTCCACCTCTCCAC
1465
50
−14.43
−3.76
−3.43
−2.63
−5.96
−3.88
|
|
13310-R5-1
ATCCATTGCCACTACCACCACCAATAATTAAAA
1466
56
−6.22
−6.22
−6.22
−6.22
−4.23
−6.22
|
|
13312-L5-2
TGCCACCCCACCCCTCCCCCACAGCCCAGCCC
1467
72
−3.89
−4.71
−7.40
−5.54
−3.94
−2.64
|
|
13313-L5-2
CCTGTCTCCCATGCCGTGTCCCTCCCACTAACC
1468
61
−3.49
−4.79
−7.64
−2.95
−2.68
−1.55
|
|
13316-R5-2
CCACCACCTTGCTGCTGGCCCACAGCACCAGGCC
1469
50
−4.30
−4.30
−2.50
−2.88
−4.30
−1.25
|
|
13326-L5-2
CAGAGATTCCGGCTTCCCCCCACCCGCCCTTC
1470
67
−4.02
−4.30
−8.40
−5.02
−4.30
−2.41
|
|
13328-R5-2
TCACCTGCCCCCACATCTGCAACACACAAGAGT
1471
72
−14.53
−14.53
−14.53
−4.04
−7.65
−4.27
|
|
13332-L5-1
CCATACTCTCCAGCTGTCTTCCCTCCCAA
1472
50
−4.39
−4.39
−3.09
−1.46
−2.15
−1.38
|
|
13334-L5-3
TCCTGGCAGGACTCCCCTCCCCTCCCACTGTG
1473
72
−3.05
−5.00
−8.54
−3.73
−3.16
−2.05
|
|
13335-L5-3
ACCTCAGCCTCCACTGCCCTCCTGCCGCATCCTAT
1474
61
−4.66
−4.99
−9.25
−3.74
−2.81
−2.08
|
|
13337-L5-2
TCTTTTTCTGACATTCCCTCCCCCAACATGGAA
1475
67
−3.58
−4.94
−25.53
−3.71
−3.28
−1.08
|
|
13339-L5-1
GACTGAGGGTTTAAAGAAGATGGTGTCCGCCGC
1476
78
−45.98
−6.02
−7.34
−3.40
−4.61
−1.22
|
|
13343-L5-1
CCTCCACCCCTCCCGCAGCGCCCCTCCCCCTCA
1477
50
−3.99
−5.54
−7.36
−3.68
−3.31
−1.90
|
|
13349-L5-2
CACCACCTGTGTGGGCTATCCCAGCCGCCTCC
1478
83
−7.08
−7.21
−6.98
−4.08
−4.09
−1.92
|
|
13353-L5-2
GCTTCGGCCACAGAAATGTTCGCCCTCTGAAATC
1479
50
−2.24
−2.24
−2.24
−1.67
−1.24
−2.24
|
|
13354-L5-1
CTGCCCCACAAAGCTCCTGGAACCCCCTCAGT
1480
72
−17.63
−17.63
−17.63
−4.43
−9.91
−1.86
|
|
13355-L5-2
TGACCACACCCACCCCTATCCTTTCCTGCAGTGTG
1481
78
−5.51
−5.51
−5.51
−5.51
−3.48
−5.51
|
|
13356-L5-2
GGCCCCTGGCCTCCCTGCCACCCAGCACGGTG
1482
56
−8.37
−4.34
−4.14
−2.41
−4.28
1.04
|
|
13358-L5-2
CCTCCTCACCACCCCCTCCACACTCCTGGGGAAGT
1483
78
−23.01
−23.01
−23.01
−5.08
−7.50
−6.25
|
|
13361-L5-1
GGGAAGCAGAGTCAGTGACCCCAGCCCTGCACAC
1484
83
−12.93
−12.93
−12.93
−9.37
−12.93
−3.94
|
|
13363-L5-2
GGCCCCCACCGTCACCTGCTGACACCCTCACATCC
1485
83
−20.98
−20.98
−20.98
−5.06
−8.92
−6.01
|
|
13364-L5-2
TCCCAGGACCCTTCCTGAGCCTCAGCCCATT
1486
78
−7.47
−7.47
−7.47
−7.47
−7.47
−7.47
|
|
13365-L5-3
TCCCCAGAGCCCGCCCCAACCCACCTCGATCTTTT
1487
56
−3.16
−5.55
−6.40
−2.46
−1.71
−2.63
|
|
13370-L5-2
CATGCCCCACCCTCACCTCTGCTCCACATACT
1488
50
−3.37
−4.07
−4.87
−4.29
−3.66
−2.25
|
|
13373-L5-4
GCCCTTACTCCAGCCCCACCGGCTCCCACTCACCT
1489
56
−7.98
−7.98
−3.68
−2.29
−4.40
−1.07
|
|
13374-R5-1
AGCCTTCCTGTCCCCTGGCCCCCGACCTGC
1490
78
−5.54
−4.92
−5.77
−5.78
−4.29
−2.09
|
|
13375-L5-3
GAGAACCTGAAACCCCAGCCCCTGCCTACCCCTTAG
1491
72
−4.07
−4.48
−7.27
−6.24
−3.83
−1.92
|
|
13376-R5-1
TCTGCTGCAGGTAGTCTGAATGTCCCCCCAACATC
1492
78
−4.80
−21.42
−28.03
−11.86
−5.27
−3.27
|
|
13380-R5-3
AACTCCCAGCCCCGGAAGAATGCACACGCAGGAG
1493
61
−10.07
−10.07
−10.07
−3.28
−5.31
1.13
|
|
13385-L5-1
AATGACTCCTCCGGCGCCACCTACAGT
1494
50
−3.98
−3.98
−3.98
−1.32
−1.86
−3.98
|
|
13396-L5-2
GACCTGCCCCGCCCCACTCGGGCTCCTTACCG
1495
78
−4.91
−4.88
−2.43
−5.34
−3.01
−2.26
|
|
13403-L5-1
TCCCCCCAACCTGGGGCCAGGCCCACCTGGT
1496
67
−2.41
−11.03
−7.77
−2.10
−2.32
−1.72
|
|
13412-L5-1
AGTCAAGATGGCGCCCCCTGGTCCCAG
1497
61
−2.15
−8.32
−5.84
−5.72
−4.18
−2.68
|
|
13423-L5-3
GCCCTCCCCTGACTCCCTGAAGCTATTTGTTT
1498
72
−5.62
−16.59
−20.12
−2.22
−2.23
−1.92
|
|
13425-L5-3
TGCCCTCCCAGTCATATGCGCCGCATCAAGGTT
1499
72
−5.55
−18.57
−19.05
−2.11
−2.19
−1.90
|
|
13430-L5-3
TTCTTACCTCCCCCCAACCCCCATCCCAGTTACC
1500
72
−2.66
−5.22
−11.00
−5.21
−4.82
−2.37
|
|
13431-L5-3
CGACACCCACTCACTGCCGCTGCCGCACTCACAGC
1501
72
−6.02
−7.11
−7.16
−4.36
−6.77
−1.47
|
|
13432-R5-1
ACCTCCCCAAACTCCACGTAATCACCTACTATT
1502
50
−2.31
−4.47
−3.97
−1.94
−3.01
1.02
|
|
13456-R5-2
CAGATGCCCCGCTATGAAATCTTTTCCAACC
1503
50
−1.49
−5.78
−14.18
−2.24
−1.86
1.34
|
|
13458-R5-2
CCTCCTCGGCACTCCCTCTACCTCACTGTCCAC
1504
56
−9.56
−4.35
−9.56
−2.05
−1.81
−2.58
|
|
13461-L5-4
TCCCCAGCCCCGTCCCCACCCCCTAGAGAAAGTGAA
1505
78
−4.88
−5.69
−6.76
−5.00
−4.09
−2.33
|
|
13463-L5-2
ATCCAGGACTCGGACCAGCCCCCCAGCCTGAG
1506
78
−5.87
−22.46
−12.28
−4.92
−5.26
−2.41
|
|
13489-L5-1
GGGGGAAAGCCTGTGGTCAAGCCAAGGAACAAGA
1507
61
−2.32
−2.32
−2.32
−1.56
−2.32
−2.32
|
|
13497-L5-1
TGTGCCCCCCTCGCTCCCAGCCCCCAGGGGACCGC
1508
72
−6.04
−9.24
−13.05
−5.73
−5.31
−2.89
|
|
13513-L5-1
ATCCTCCCTGGGTGGTGCTACTCTCACCAAAG
1509
50
−3.48
−3.48
1.08
−3.48
−3.48
−3.48
|
|
13519-L5-1
ACCTTAGCTCTACCCAACCTCGCTTCCCACCCCC
1510
72
−8.34
−8.34
−8.34
−6.17
−4.60
−2.83
|
|
13525-L5-2
CCATGCTCTCGCGTGATCTCCCCTACCGCCATCGT
1511
78
−3.26
−11.76
−11.76
−3.63
−4.94
−3.67
|
|
25-R5-1
TTCCCAGAGCCTCACCCCCTCTTTTTCTAACC
1512
50
−2.21
−2.37
−8.78
−2.46
−2.10
−1.26
|
|
266-R5-2
GTCGCCCCCTCCCCCAAGTTGAGACTTGCA
1513
78
−3.86
−6.49
−10.77
−4.19
−3.42
−2.49
|
|
2786-L5-3
CACCTCCCGCTCAACTGCCCATACTAATGCTTTT
1514
61
−7.14
−7.14
−7.14
−5.01
−4.23
−7.14
|
|
2811-R5-1
CCACAGCCACCCCGTGCCACTGTGTCCCAACCC
1515
67
−5.19
−5.19
−5.19
−5.19
−5.19
−5.19
|
|
2819-R5-4
CAGCCTGCCACCGCCGCTTTTGAAAGAAGCACTTCA
1516
78
−8.91
−8.06
−8.93
−4.59
−8.36
−1.88
|
|
3717-L5-2
CCGCCCTCCCCATAGCCTCACCCCAAACCCA
1517
61
−161.90
−6.67
−8.36
−1.07
−3.17
−1.51
|
|
3732-R5-1
TCCCTTTCCCTGCCAGCAAACCCCACCACCCTAAG
1518
50
−13.70
−5.71
−2.96
−2.29
−2.86
−1.31
|
|
3799-R5-1
CTGAAGATGCTCCCAGAGGCCCCCCGCCGGCC
1519
67
−3.62
−5.47
−7.63
−3.60
−3.29
−2.20
|
|
3897-R5-2
CCGACCCGCCCGTCAGCCGCCTCCCCCTCAG
1520
72
−6.31
−6.25
−5.66
−5.22
−5.39
−1.95
|
|
3942-L5-1
TCCCTTCACTCCAGTTGCCAAACAGATCCCCCCACTCCC
1521
61
−2.19
−6.40
−7.64
−1.72
−2.42
−2.05
|
|
3952-L3-1
GAGCACTCAATCTGACACCCCTCGCCGGGG
1522
72
−7.09
−7.09
−7.09
−2.41
−4.47
1.53
|
|
3953-R3-2
ACTCCAGCCTCCGCCGCCTCAGCTTCCCGAGC
1523
67
−155.65
−4.18
−6.49
−3.80
−5.23
−1.96
|
|
3966-L5-1
ACCCCAGAGCTGTCGCCGCCGCTGCCGCCTTCGCC
1524
78
−8.01
−6.99
−8.17
−5.56
−7.00
−1.82
|
|
3995-L2-2
CTATAAAACTTCGAAAAGTCCCTCCTCCTCACGT
1525
50
−1.95
−3.65
−12.55
−2.00
−2.04
7.12
|
|
4013-L4-1
CTATGGCACTTGCATGGTTGAGCTATCAGCAGGGGGACCAT
1526
67
−2.19
−2.19
−2.19
1.07
−2.19
−2.19
|
|
4026-R5-1
GAGAGAAAGCCCCCCTTTGTCTGGCTTTG
1527
83
−81.69
−81.69
−18.32
−7.08
−6.50
−3.10
|
|
4026-R5-2
GGCGAGAGAGAAAGCCCCCCTTTGTCTGGC
1528
72
−7.22
−14.47
−19.24
−5.56
−6.21
−3.11
|
|
410-R5-1
CCAGCTCCACTACTCCGTCCCCGAGGAAGCAAAACACGGCACC
1529
67
−5.18
−5.18
−5.18
−5.18
−3.55
−5.18
|
|
4130-L5-1
TCAGCCAGCACGCCGTCCATGTCCACCAGCACCC
1530
78
−18.42
−18.42
−13.52
−4.27
−4.12
−1.61
|
|
4143-R5-2
TCAGCGTCTTGCTCTCCTCCTGGTAACAGCAGCC
1531
67
−3.75
−3.75
−3.75
−3.75
−3.75
−3.75
|
|
4258-L5-1
CCTAGAGAACATATATCTGGTGCCTCTCCTCTTTTCCCGT
1532
56
−2.02
−2.02
−2.02
−1.46
−1.05
−2.02
|
|
4315_C-L4-1
GCAGCCCCTCCTCCGAGAGGTTGGGGGTCGCGGCCGCCCGGCCCTCCCGGTCCCCTCCCC
1533
72
−3.12
−84.00
−7.08
−2.18
−2.69
−2.05
|
|
4315_D-R4-1
GGAAAGTCAGCCCCCAGCGCCCCCCGGAGTTCTTGG
1534
72
−6.78
−6.28
−7.97
−6.33
−6.20
−2.25
|
|
4315_E-R4-1
CCCCCACCAAACCTATTCCCGCATCCTCCCCGGCTCTGG
1535
50
−4.86
−4.04
−4.85
−3.23
−4.16
−1.61
|
|
4315_F-R4-1
AACCCGGGCTCCCCCACCCGCTCCCTGAGC
1536
67
−4.81
−4.70
−9.00
−5.38
−5.04
−2.05
|
|
4315_I-L4-1
ACACCTCTGCGCCCCTCAGGCGCCCTGGGCCTCGGCGCCCCGCCCGTCCCAG
1537
56
−3.26
−4.17
−7.04
−2.60
−2.59
−1.37
|
|
4315_K-L4-1
TCCCAGGGGGCCCTGAACTTGTCAAATCCTCGCCATCCTCCACCCCCAGCCCCGG
1538
67
−5.56
−4.67
−6.69
−5.88
−4.81
−1.81
|
|
4315-R3-2
TCCCCGGCCCTCTCCATTCTCGGCTCCGGAGCA
1539
56
−3.38
−3.19
−12.44
−3.43
−6.47
−1.41
|
|
4338-L5-2
CCTGGGGGTGGGCGGGAGCTGGCCCCACTGC
1540
50
−2.07
−2.07
−2.07
−1.43
−2.07
1.59
|
|
4340-R3-1
ATTTTCCAGCCCCTTGTCCCCAGGCCAAAC
1541
61
−5.28
−5.28
−5.28
−2.61
−3.21
−5.28
|
|
4346-L5-1
TTCTTCCCCCGCCCTCGCCGCGGCCGCGCACCGG
1542
67
−3.82
−4.80
−7.88
−4.88
−3.22
−2.13
|
|
4361-R5-1
CTCAGCGTCTCCCTCCCTCATGTGCACATGT
1543
67
−2.26
−2.85
−16.06
−2.89
−2.23
−16.06
|
|
4498-L3-2
GAGATCCAGACGGCCGTGCGCCTGCTGCTGCCT
1544
56
−2.36
−9.82
−2.18
−1.93
−6.91
1.37
|
|
4516-L5-1
TCCATCACCCCCCAGGCTGACTCTGGCTCCTGCCTGGCTCTGCC
1545
72
−14.82
−14.82
−14.82
−4.16
−7.74
−1.36
|
|
454-R5-1
CCAGCTCCACTACTCCGTCCCCGAGGAGGCCAAACACGGCACC
1546
67
−2.62
−2.62
−2.62
−2.62
−2.62
−2.62
|
|
4593-R5-1
CTATAGCAGATGACATAACTCCCCCGGCATCAG
1547
50
−1.18
−1.22
−2.44
−1.60
−4.72
−1.09
|
|
4610-R5-1
CCTCTGGCCCCTGCCTAATTGGCTGC
1548
72
−7.69
−7.69
−7.69
−7.69
−4.10
−7.69
|
|
4610-R5-2
GCCCTCTGGCCCCTGCCTAATTGGCTG
1549
56
−3.23
−3.23
−3.23
−3.23
−1.70
−3.23
|
|
4642-R3-2
CAGCGCTCCCCTTCCTTATTTGAGATCTGTGCA
1550
67
−10.25
−10.25
−10.25
−10.25
−5.81
1.30
|
|
4666-R5-1
GACTCCCCCCAACACCTGCGGGTGGCAC
1551
78
−3.26
−6.47
−13.10
−5.57
−5.25
−2.30
|
|
4792-L5-2
AAGCCAGTTACAGCCCCCACTGCCCCCATAAC
1552
61
−4.51
−4.61
−6.34
−4.01
−4.00
−1.49
|
|
4801-L5-2
GAACTCTGCCTCCTGTTTGCTACAAAAACA
1553
61
−4.53
−4.53
−4.53
−4.53
−2.36
−4.53
|
|
4813-R3-1
GATTTTACAATCGGGCTGTTAACCCTCCCG
1554
61
−3.33
−3.33
−3.33
−3.33
−2.04
−1.06
|
|
4875-R2-2
CACAGCCCCTTCCTGTGACTTCACAC
1555
67
−2.71
−25.83
−7.24
−2.30
−2.06
−1.91
|
|
4912-L5-2
TACCCCTGGCCCCCAGCTGTGATTGTCTAA
1556
78
−19.46
−19.46
−5.35
−5.07
−7.98
−1.65
|
|
4929-R4-1
GACGCTGACCCACCGCAGCCCGCACTGTT
1557
89
−11.74
−11.74
−11.74
−8.30
−7.20
−11.74
|
|
5032-R5-1
CGCACCCGTCCCGTTCGTCCCCGGACGT
1558
72
−13.13
−13.13
−13.13
−8.64
−6.34
−13.13
|
|
5048-L5-1
CGCCGCTCCTTGTACGCGTACTTCTGCTGCACACC
1559
61
−11.59
−11.59
−11.59
−3.55
−5.68
−1.14
|
|
5071-R5-2
GACCCCCGCCCCAGTCCCAGCCCAATTAATA
1560
72
−6.98
−7.41
−8.60
−7.82
−3.38
−3.14
|
|
5107-L5-1
AACTCCCCTTTGACCCCCCAGTACAAACTG
1561
61
−2.41
−26.66
−26.66
−3.80
−3.15
1.08
|
|
5210-L5-1
AAAGCTGCCCCATGGGGATCCAACCCCA
1562
67
−1.97
−7.99
−7.99
−3.58
−4.09
−7.99
|
|
5342-L5-1
CCACCAAACCAAATGCCGCTGCTCTCCTTCCA
1563
56
−4.62
−3.77
−3.56
−3.08
−2.92
−1.28
|
|
5491-R5-1
GCCGTCGCCCACCAGATCACTCATCAGGCCATGGTGGCA
1564
72
−5.64
−4.77
−6.07
−3.45
−4.72
−1.52
|
|
5521-L5-2
AGGTCTGTCTTGGGTGGGCCCTCCCCAGAGCAC
1565
50
−7.60
−7.60
−7.60
−2.62
−1.22
−2.35
|
|
554-R5-1
GGAAAGAGAACAGAGAGAGCCCTCCCAGCAGCC
1566
67
−5.86
−17.89
−18.96
−2.04
−2.19
−1.95
|
|
5554-R5-2
CCCCACCCCCTCATCAGCTGCTCCCAGATC
1567
61
−3.72
−3.98
−5.48
−4.08
−2.80
−1.59
|
|
5638-R5-2
GGCCCTCCCCCTGCCTGTGATAGGCTG
1568
78
−5.39
−15.00
−20.91
−2.61
−2.48
−2.16
|
|
5640-L3-1
GCCATGGAACACCGTGCCTGCCCCTCTCGAGA
1569
61
−2.75
−4.95
−5.84
−2.71
−2.38
−1.80
|
|
5749-R5-1
ATCATAATCCCCCTTTTGACTTTACATGATC
1570
56
−3.50
−3.50
−3.50
−1.35
−1.84
−3.50
|
|
5757-L5-1
TGCTTTATTGACTAATGAACCTACCGTGCCGCCAAC
1571
89
−22.78
−22.78
−22.78
−4.38
−4.58
−5.43
|
|
5854-R5-2
GCCCTCCCTCTCCGAAAGAATGTGTCACCCGGG
1572
72
−4.59
−14.74
−16.09
−1.96
−1.94
−2.01
|
|
5956-L5-1
GCCTGCTCTGCCAACCCCAAATCCGTCAAGACGCATAG
1573
50
−1.50
−3.54
−8.83
−2.47
−1.20
−8.83
|
|
5995-R5-1
CCCCCTTGAGGTTCCTACTGAAATCTGACAATCAG
1574
78
−2.29
−2.29
−2.29
−2.29
−2.29
−2.29
|
|
6008-R5-1
ACCCCCACCTTTTTCCTGTACCTTACCCGGAG
1575
83
−9.71
−9.71
−9.71
−9.71
−5.88
−3.27
|
|
6008-R5-2
CAACAATACCCCCACCTTTTTCCTGTACCTTA
1576
78
−5.41
−5.41
−5.41
−5.41
−5.41
−5.41
|
|
6016-R2-1
AAACTCCAGCAGCCCCGTCAGCCTCCTGCT
1577
61
−3.58
−3.27
−3.65
−3.22
−2.34
−3.50
|
|
6023-L5-1
AAGGCAGAGCCAGATGACTGGTCCAACCCCCCAGAGACC
1578
72
−4.72
−19.11
−19.11
−5.65
−9.37
−1.46
|
|
6087-L4-1
CTGTCTCCATTACTGCCTGCCACCTTCTCCATC
1579
78
−8.97
−8.97
−8.97
−6.19
−5.07
−8.97
|
|
6096-R5-1
CTTTCCCTTATGTTTTAATCCTGCCCCGT
1580
89
−12.65
−12.65
−12.65
−2.15
−6.96
−12.65
|
|
6192-L5-1
AATCCGTGAAGATAAAAAACCACCCACCCAGCAC
1581
50
−13.47
−13.47
−2.70
−1.88
−6.10
1.34
|
|
6198-R5-2
GCCGCCGCCGCCGCGTCTTCCCGCGAAGCCT
1582
67
−4.03
−2.96
−5.71
−4.41
−4.65
−1.50
|
|
6242-R5-1
CCCCCACAGTGGCATATGTGACAAACCCAAAGCCCCTGG
1583
67
−5.90
−5.90
−5.90
−5.90
−4.69
−5.90
|
|
6287-L3-2
GCCCCGCCCCACCTTTCGGGGCTCACCTGGC
1584
72
−19.21
−19.21
−4.59
−4.31
−2.70
−1.67
|
|
6385-R5-2
GGCCCTGCCCACGGACCGACTCCCGCGGCCC
1585
67
−9.70
−9.70
−9.70
−9.70
−5.59
−3.26
|
|
6409-L3-1
CGTTCCCAACCGCACGCGCCGCCTTCTGGAAC
1586
72
−8.06
−7.09
−6.76
−4.68
−5.18
−1.54
|
|
6434-R5-1
TGCAGCCCTCCCACCAGCCAGCTGCAGTGC
1587
67
−4.42
−12.82
−29.88
−2.13
−2.32
−1.24
|
|
6490-R5-3
CCCCATCCCCCATATGACGCTTCCCCCTCCTAAC
1588
67
−3.39
−4.20
−23.58
−4.26
−6.83
−1.35
|
|
6496-R5-2
CCCCCTCCCCCACCCACCACTTCCCCTAGA
1589
67
−44.85
−14.21
−9.47
−4.89
−3.70
−2.49
|
|
6584-L5-1
GTCGGCCCTGCCTCCTCCTCCTCTCACCAAGC
1590
56
−13.67
−5.50
−13.67
−2.42
−2.29
1.17
|
|
6590-L5-1
GGTTAATGAGAAACCAAATAAACAGCCTCTGCCCCAGCTG
1591
56
−4.65
−4.65
−4.65
−4.65
−2.56
−4.65
|
|
6642-R5-1
GTCCTCCCCTCCCCTCGAGGTGTCACACA
1592
56
−4.01
−5.51
−6.59
−3.85
−2.99
−1.63
|
|
669-R5-2
CCAGCCCTGAGCCACCCTCCCGGGAAACCCCACA
1593
67
−10.57
−10.57
−10.57
−1.47
−6.18
−2.07
|
|
6718-L3-2
GCCTCCACCACCATAGGGGCCAGAGCTTCTGCCT
1594
72
−3.98
−3.98
−3.98
−3.98
−3.30
−3.98
|
|
6839-L3-1
GCCCGCTGGGCCCTGCCACCCCCACCCCT
1595
72
−5.32
−4.50
−6.48
−4.99
−4.55
−2.17
|
|
6880-L3-2
ACCTCCCCCGCGAAGACATCCACATTCTGCA
1596
61
−2.19
−4.09
−5.43
−2.08
−4.56
−1.52
|
|
6908-L3-2
AGAGGCTACTGGGGGAACAAGACTGGCAAGCC
1597
50
−2.84
−2.84
−2.84
−1.73
−2.84
4.40
|
|
6984-R4-1
CCCCCTGCCCAAGCATTTGCTTGGGCACCAAAGTCCCTGCAA
1598
67
−3.05
−18.59
−18.59
−4.32
−7.50
−1.51
|
|
7029-R5-1
CAAGAGCCCTGCCCCAGCAGCAGCCGCAC
1599
67
−10.64
−10.64
−3.52
−2.90
−2.27
−3.48
|
|
7061-R5-2
TCATGGAAACCCCACCCTTCCCATGCCCAACC
1600
56
−3.93
−4.19
−5.53
−4.35
−3.52
−2.45
|
|
7066-R5-1
TAGCCTGAAAAAAGATGCCCCCACCAGCCCTGCC
1601
78
−6.87
−6.68
−11.13
−7.24
−11.42
−2.31
|
|
7069-R5-1
CTCGGGCCCGGCCCCCTCCGAGCTCAACAGGCTCCCA
1602
78
−6.84
−7.03
−9.92
−5.66
−4.77
−2.63
|
|
7113-R5-1
CGCCTAATTAGCCCCCCTGCTCCGGAGGCCTCACC
1603
78
−10.08
−16.70
−18.94
−7.28
−6.96
−3.32
|
|
7126-L3-1
GCACACCCGCTCTCCGGCCCGCGCCCCTG
1604
61
−3.58
−3.60
−3.88
−3.21
−4.09
−1.48
|
|
7141-R5-1
ACCCCAATCCTTGTTATGTAACCTACCACCTACCCCTT
1605
72
−2.31
−2.31
−2.31
−2.31
−2.31
−2.31
|
|
7221-R5-1
GGAGAGAAACCCCGGCCACTTCCCACCACCCTGGTGGC
1606
56
−2.57
−2.97
−3.51
−3.96
−6.16
−1.10
|
|
7313-L5-2
CTGCCTCTGCCCTGATCATCAAAGCCCTCAAGGA
1607
61
−2.26
−2.26
−2.26
−2.26
−1.58
−2.26
|
|
7352-R3-2
GCCCCTGCCAGAATCCTCTAACAGCTCTAATTGG
1608
50
−2.04
−2.07
−2.22
−2.46
−1.45
−3.40
|
|
7356_A-R4-1
CAGAGCCCGCTCTCGCGACCGACCTGCCGCCGACCGCCACAG
1609
67
−7.83
−6.39
−7.11
−4.76
−6.17
−1.56
|
|
7356-L5-1
ATCCGGGCTGCCACCGCGACATAGCCTCGCCCCC
1610
56
−3.91
−3.91
−6.19
−3.02
−2.48
−1.08
|
|
7367-L1-1
AGGGTTAGAGCTGCCCCCTCTGGGGACCG
1611
50
−5.61
−1.12
−5.61
−1.54
−2.24
−5.61
|
|
7384-R3-1
CTCGCAAAGGATCTCCTTCATCCCTCCCCA
1612
61
−3.15
−7.30
−4.15
−3.12
−2.40
−1.29
|
|
7411-R3-2
AGTCCCCTGCCTCATCTGCCACCCCTAATGAC
1613
50
−2.55
−2.66
−13.01
−2.77
−1.83
−3.86
|
|
7569-L5-2
TTCAGGCCACAAAGCTACCCCCAAGACAG
1614
67
−3.93
−3.93
−3.93
−3.93
−3.93
2.42
|
|
7571-L5-1
CAGGGCTAACAGGGCTCCCCCACCCCTAAG
1615
56
−3.75
−4.46
−6.71
−5.25
−4.30
−1.32
|
|
7572-R5-2
ATCACCCTTCCCCCTCCCAAATAAAGCCAAA
1616
50
−22.49
−4.07
−6.89
−3.47
−2.12
−1.57
|
|
7660-L5-1
GCCTCCGCCTGGCCCGAGCGATAAAGCTC
1617
56
−3.55
−7.83
−4.16
−3.75
−3.08
−1.29
|
|
7702-L2-1
CCCAGAGAACCGGAATTCCTCCCCGCCCC
1618
78
−6.38
−6.47
−8.59
−5.58
−4.12
−2.55
|
|
7736-L5-1
ATCCCCACCACCCACCAGAAGGCGACGGTCTCC
1619
50
−10.35
−10.35
−2.65
−4.09
−5.59
−2.98
|
|
7743-L5-1
GAGCTCCCCAGCCAGCTCCAGTTCGACCTGCCTT
1620
67
−7.13
−7.13
−7.13
−7.13
−5.90
−7.13
|
|
7781-R5-2
AGCCTGTGCCTGCCGCTGTCTAGTACTGGT
1621
72
−22.71
−12.29
−6.84
−3.46
−3.67
−1.44
|
|
7824-R5-1
TGCCAGCTTCATCGCCGCCTCACACACACA
1622
72
−10.99
−8.91
−14.45
−5.40
−5.99
4.65
|
|
7846-L5-2
GTCCTCCTCCATCCCATCCCTTCCACCAGCCCT
1623
50
−2.66
−2.66
−2.66
−2.66
−1.45
−2.66
|
|
7883-R5-1
CTCTCCCCTCCCGCCCTCTCACCCTCCCAACCTTATTTAGAAAC
1624
50
−3.69
−4.72
−7.94
−3.56
−2.66
−2.03
|
|
78-R4-1
CCAGAGCTTCTCAAGGGGGACTACAACTCCCAAGGTACATACAA
1625
50
−2.39
−2.39
−2.39
1.35
−2.39
1.44
|
|
7949-R5-1
GATGCGCGCGCCGACCGCCGCCAGCTGCAATTCATAC
1626
72
−4.04
−3.23
−5.42
−3.02
−5.45
−1.05
|
|
7971-L5-1
TGTCACTCCCCTGCCGCTCCCTGGGTGCAGGCT
1627
61
−7.45
−7.45
−7.45
−3.26
−5.59
−2.17
|
|
8016-L3-1
TCAGCGCAACAAGCCCCGCAGTCACCCCTCT
1628
50
−3.02
−3.60
−2.40
−2.98
−2.70
1.10
|
|
8062-R5-1
GGGCAAAGGTCACGGGGTCCAAGGCCTTAAGCACCTCCGCCA
1629
50
−7.61
−7.61
−2.06
−1.46
−1.16
−2.34
|
|
8077-R3-1
CCATTCCCCACCCTCAGGTAGTAAAAATA
1630
67
−2.08
−10.66
−3.95
−3.94
−2.28
−10.66
|
|
8089-L5-1
TAGAGACCCTTATAAGCTCAGGGCCACCCCCTCCC
1631
78
−12.58
−12.58
−12.58
−4.10
−6.46
−4.03
|
|
8239-R5-1
TGATTTTCTTCCCACTTCACCTCCCTCTGAGCTCTCCA
1632
56
−7.85
−7.85
−7.85
−2.34
−5.84
−2.52
|
|
8250-R5-2
CCGACCCGCCCGTCAGCCGCCTCTCCCTCAG
1633
72
−8.36
−6.52
−12.10
−5.21
−5.60
−2.31
|
|
8281-L5-2
CAGCCCCTCCCCAGCTGCAGCTGAGGGC
1634
61
−2.82
−7.08
−8.59
−2.10
−2.55
−1.83
|
|
8298-R5-1
GATGCTGGCGTCCGCCGCAGCCTCTCGCCCCATCCCGG
1635
72
−7.60
−6.38
−5.79
−4.53
−4.42
−1.51
|
|
8329-L5-1
TCCTTCCAAACGCCCACCCTGGGTCAGCTC
1636
72
−7.14
−7.14
−7.14
−4.59
−3.30
−7.14
|
|
8336-R5-2
CCTCCCCACTCAGTCCCCACACCCCCAGCCA
1637
56
−3.54
−3.08
−4.97
−3.00
−3.92
−1.33
|
|
8394-L5-2
TGGGGCCCCCGCCCTGCCCATCTCCGACTATCC
1638
50
−3.26
−3.15
−4.42
−4.40
−2.96
−1.58
|
|
8564-L5-1
ACCCCAGTTGCCAAACAGACCTCCCACCCCCT
1639
72
−9.90
−9.90
−9.90
−2.63
−4.92
−3.12
|
|
8564-R5-2
AGGGGCTGGGGGAATCCCAGCAGGGGAA
1640
50
−6.82
−6.82
−6.82
−1.12
−3.67
3.00
|
|
8898-R5-1
CAGCCGAGGCGGACGCCCGCTCCCGCCACCATG
1641
72
−5.76
−6.58
−7.08
−4.99
−4.72
−2.23
|
|
9021-L5-2
GAAACAAACACCCAAGCTCCCCACACCA
1642
50
−9.46
−9.46
−9.46
−4.34
−5.86
1.27
|
|
9068-R5-2
GTCTGCCCTCCCTCTTGATCAAGACTGCTCT
1643
67
−6.33
−16.55
−18.60
−2.35
−2.21
−1.89
|
|
9087-L5-2
AGGAAAAGAAACCCTCCCAGTCCATTCCCT
1644
72
−6.46
−10.39
−14.13
−5.66
−5.34
−1.11
|
|
9134-R5-1
GAAAGGGTTATCCGCCTGGTTGCGGGGCTGC
1645
50
−2.19
−2.19
−2.19
−1.49
−2.19
1.49
|
|
9217-L3-2
CGCTAAACTGACGATCCCCGCCGTGACTAAAGCCA
1646
72
−4.02
−10.70
−3.72
−4.17
−2.98
−1.46
|
|
9245-R5-1
TCTCATTAGCCAGCCACTCGCTCCCAAG
1647
67
−7.70
−7.70
−7.70
−5.35
−4.29
−7.70
|
|
9287-L5-2
GATATTCAGAGCCCTCCCCAGCCCACACA
1648
67
−4.67
−9.40
−29.04
−1.28
−2.93
−1.16
|
|
9369-L5-1
TCACACATTCTTCCACAGAGGGAAATCAGGGGA
1649
50
−2.53
−2.53
−2.53
1.38
−2.53
1.22
|
|
9384-R5-2
AAACCAGCTAGCAAACCGCTCCGTCCGTATTG
1650
78
−15.00
−15.00
−15.00
−15.00
−7.95
−4.59
|
|
9387-R2-2
TCCATCCTTGCCGTCGCCTTCATCTCAAAGCCATC
1651
67
−7.04
−4.60
−3.03
−4.14
−4.99
3.25
|
|
9564-R5-2
GCCGCCCGCCGGGCACCGGGCCGGGCCTGGGC
1652
50
−3.25
−3.61
−4.38
−3.31
−2.97
−1.18
|
|
9605-R5-1
GCCCCCAAGTGAAAAACAGAGCAAAACTCATTTCCTGA
1653
50
−2.11
−2.11
−2.11
−1.42
−2.11
−2.11
|
|
9691-L5-1
CATTTCATCCGCATCTCCCTCTTGGCCCCTTGC
1654
56
−3.33
−6.89
−4.05
−5.66
−2.65
−4.01
|
|
9770-R5-2
CACCTGTTGCCAACCCCAGCCCTATAA
1655
67
−16.08
−16.08
−16.08
−3.95
−7.31
−1.78
|
|
9774-R2-2
CCGCCCCCTCACCGCCTCCTGCTCCCATCAGGC
1656
83
−7.02
−6.70
−13.75
−8.18
−5.97
−2.86
|
|
9812-L3-1
AAGCTCTATTTATCTGGGCTCCCCAGCTTGCT
1657
56
−1.83
−8.36
−8.36
−2.32
−2.02
−2.57
|
|
9866-L5-1
TAGGAGAGGGGCTCCATTGCCAGCCCCAGCCC
1658
94
−11.22
−11.22
−11.22
−11.22
−5.31
−3.72
|
|
999997-R4-1
TCCTCACTGGGCCCCACCAAAACTGTGCCACCCCCTCAAGCCCCCA
1659
72
−4.04
−4.22
−40.37
−2.33
−5.94
−1.62
|
GGAGCTTCCTTAAC
|
|
let-7b
TGAGGTAGTAGGTTGTGTGGTT
1660
56
−1.48
−6.50
−2.74
−2.48
−2.61
−1.23
|
|
let-7c
TGAGGTAGTAGGTTGTATGGTT
1661
50
−1.39
−5.08
−2.46
−2.14
−2.43
−1.26
|
|
let-7e
TGAGGTAGGAGGTTGTATAGTT
1662
50
−1.27
−4.56
−2.29
−2.10
−2.25
−1.06
|
|
miR-100
AACCCGTAGATCCGAACTTGTG
1663
50
−1.16
−15.70
−1.03
−3.27
−2.27
−15.70
|
|
miR-101
TACAGTACTGTGATAACTGAA
1664
50
−1.54
−12.44
−3.65
−2.51
−5.38
1.25
|
|
miR-1182
GAGGGTCTTGGGAGGGATGTGAC
1665
50
−2.49
−6.37
−2.91
−2.61
−4.75
1.04
|
|
miR-1207-5p
TGGCAGGGAGGCTGGGAGGGG
1666
50
−2.88
−9.91
−5.91
−3.63
−2.81
−1.28
|
|
miR-1224-5p
GTGAGGACTCGGGAGGTGG
1667
61
−8.27
−8.27
−8.27
−2.05
−4.54
−8.27
|
|
miR-1225-5p
GTGGGTACGGCCCAGTGGGGGG
1668
72
−32.61
−32.61
−32.61
−32.61
−14.04
−2.24
|
|
miR-1228*
GTGGGCGGGGGCAGGTGTGTG
1669
67
−3.86
−3.61
−6.14
−5.78
−2.67
−2.95
|
|
miR-1234
TCGGCCTGACCACCCACCCCAC
1670
61
−2.04
−2.04
−2.04
−1.47
−2.04
1.67
|
|
miR-125a-5p
TCCCTGAGACCCTTTAACCTGTGA
1671
72
−3.80
−7.98
−2.23
−5.05
−2.99
−2.20
|
|
miR-126
TCGTACCGTGAGTAATAATGCG
1672
83
−6.57
−7.43
−7.29
−5.33
−20.83
−2.68
|
|
miR-1268
CGGGCGTGGTGGTGGGGG
1673
56
−10.67
−10.67
−10.67
−5.01
−5.42
−3.17
|
|
miR-130b
CAGTGCAATGATGAAAGGGCAT
1674
50
1.68
−2.21
−2.21
1.20
−1.89
−2.21
|
|
miR-140-3p
TACCACAGGGTAGAACCACGG
1675
67
−4.44
−4.44
−4.44
−2.32
−2.82
−4.44
|
|
miR-145
GTCCAGTTTTCCCAGGAATCCCT
1676
61
−5.21
−7.10
−4.29
−4.12
−3.15
−1.88
|
|
miR-149*
AGGGAGGGACGGGGGCTGTGC
1677
56
−3.51
−2.89
−6.31
−3.80
−2.13
−2.15
|
|
miR-150
TCTCCCAACCCTTGTACCAGTG
1678
61
−3.14
−3.14
−3.14
−3.14
−3.14
1.10
|
|
miR-181b
AACATTCATTGCTGTCGGTGGGT
1679
50
−2.73
−2.73
−2.73
2.75
−1.22
−2.73
|
|
miR-181d
AACATTCATTGTTGTCGGTGGGT
1680
56
−2.47
−2.47
−2.47
−1.78
−1.37
−2.47
|
|
miR-185*
AGGGGCTGGCTTTCCTCTGGTC
1681
78
−10.19
−10.19
−10.19
−2.49
−2.10
2.05
|
|
miR-214
ACAGCAGGCACAGACAGGCAGT
1682
56
−4.43
−4.43
−4.43
−3.17
−2.21
−1.30
|
|
miR-23a*
GGGGTTCCTGGGGATGGGATTT
1683
78
−3.92
−3.92
−3.92
−3.92
−2.50
−3.92
|
|
miR-30a
TGTAAACATCCTCGACTGGAAG
1684
56
−19.76
1.09
−4.20
−1.92
−2.01
1.15
|
|
miR-30d
TGTAAACATCCCCGACTGGAAG
1685
50
1.47
1.77
−16.33
1.08
−1.97
2.70
|
|
miR-320a
AAAAGCTGGGTTGAGAGGGCGA
1686
56
−9.70
−9.70
−4.14
−1.93
−2.89
−2.92
|
|
miR-320b
AAAAGCTGGGTTGAGAGGGCAA
1687
50
−2.05
−5.08
−6.60
−1.99
−3.25
−3.07
|
|
miR-335
TCAAGAGCAATAACGAAAAATGT
1688
67
−3.24
−3.24
−3.24
1.00
−2.68
−3.24
|
|
miR-34a
TGGCAGTGTCTTAGCTGGTTGT
1689
50
3.37
−2.08
1.99
2.04
−1.20
−2.08
|
|
miR-34b*
TAGGCAGTGTCATTAGCTGATTG
1690
67
1.46
−3.29
−1.58
1.09
−2.68
−3.29
|
|
miR-34c-5p
AGGCAGTGTAGTTAGCTGATTGC
1691
94
−2.54
−2.54
−2.54
−2.54
−2.54
−2.54
|
|
miR-371-5p
ACTCAAACTGTGGGGGCACT
1692
56
−3.87
−3.87
−3.87
−3.87
−3.87
−3.87
|
|
miR-373*
ACTCAAAATGGGGGCGCTTTCC
1693
72
−2.95
−3.88
−34.48
−2.43
−4.31
1.09
|
|
miR-451
AAACCGTTACCATTACTGAGTT
1694
94
−5.28
−7.77
−12.78
−4.68
−16.47
1.61
|
|
miR-486-3p
CGGGGCAGCTCAGTACAGGAT
1695
72
−2.72
−10.16
−10.16
−2.65
−5.72
1.09
|
|
miR-491-3p
CTTATGCAAGATTCCCTTCTAC
1696
72
−2.34
−2.34
−2.34
−2.34
−1.30
−2.34
|
|
miR-498
TTTCAAGCCAGGGGGCGTTTTTC
1697
83
−5.68
−5.82
−9.56
−7.20
−4.74
−1.67
|
|
miR-557
GTTTGCACGGGTGGGCCTTGTCT
1698
56
−2.45
−5.53
−10.00
−2.80
−1.94
1.01
|
|
miR-638
AGGGATCGCGGGCGGGTGGCGGCCT
1699
78
−9.64
−8.70
−11.76
−7.11
−6.51
−2.43
|
|
miR-663
AGGCGGGGCGCCGCGGGACCGC
1700
61
−15.30
−15.30
−5.72
−3.78
−7.09
−3.77
|
|
miR-671-5p
AGGAAGCCCTGGAGGGGCTGGAG
1701
56
−2.58
−9.36
−9.36
−2.04
−1.63
−3.08
|
|
miR-744
TGCGGGGCTAGGGCTAACAGCA
1702
67
−3.86
−14.84
−3.85
−4.06
−6.80
−1.26
|
|
miR-885-3p
AGGCAGCGGGGTGTAGTGGATA
1703
83
−7.91
−26.07
−17.77
−5.03
−5.01
−1.60
|
|
miR-92a-2*
GGGTGGGGATTTGTTGCATTAC
1704
56
−2.01
−4.24
−5.49
−2.24
−6.01
−2.74
|
|
miR-92b*
AGGGACGGGACGCGGTGCAGTG
1705
50
−11.88
−11.88
−7.35
−2.61
−5.68
−1.07
|
|
miR-98
TGAGGTAGTAAGTTGTATTGTT
1706
50
−1.51
−4.47
−2.57
−1.99
−2.20
1.13
|
|
miR-99a
AACCCGTAGATCCGATCTTGTG
1707
50
−1.63
−10.35
1.26
−4.62
−4.12
−3.20
|
|
TABLE 24
|
|
Target RNAs present at at least 5-fold decreased levels in at least 50% of tumor samples (con't)
|
Gene
Adk40
Adk41
Adk49
Epi42
Ksarc19
Kmalp21
Kmalp25
EPI-4
Kmalp44
Scc27
Lcnec31
Car13
|
|
10010_B-L4-1
−8.97
−3.24
−2.01
−1.22
−1.01
1.17
−4.47
1.82
−4.06
−1.50
−2.18
−10.58
|
10010_D-L4-1
−6.36
−2.67
1.05
1.34
1.42
−1.02
−4.33
1.72
−3.11
−1.85
−2.76
−2.21
|
10010-R2-2
−10.92
−10.92
−10.92
−10.92
1.41
1.26
−2.35
1.55
−1.11
−1.47
−1.43
−10.92
|
10030-R5-1
−1.67
−6.81
−6.81
−6.81
1.05
−1.33
−1.91
3.13
−6.81
−1.68
−1.42
−6.81
|
10145-L5-2
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5640-L3-1
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|
5749-R5-1
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|
5757-L5-1
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|
5854-R5-2
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|
5956-L5-1
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|
5995-R5-1
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|
6008-R5-1
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|
6008-R5-2
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|
6016-R2-1
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|
6023-L5-1
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|
6087-L4-1
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1.95
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|
6096-R5-1
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|
6192-L5-1
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4.14
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|
6198-R5-2
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|
6242-R5-1
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3.61
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|
6287-L3-2
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|
6385-R5-2
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|
6409-L3-1
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|
6434-R5-1
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|
6490-R5-3
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|
6496-R5-2
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4.50
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|
6584-L5-1
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6.84
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|
6590-L5-1
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1.66
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6.29
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1.13
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|
6642-R5-1
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3.00
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3.60
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|
669-R5-2
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3.58
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|
6718-L3-2
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1.66
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|
6839-L3-1
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1.05
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2.43
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|
6880-L3-2
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2.00
1.81
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3.05
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|
6908-L3-2
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3.97
6.90
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1.57
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3.32
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|
6984-R4-1
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1.15
3.57
1.76
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5.19
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|
7029-R5-1
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1.54
1.33
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3.16
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|
7061-R5-2
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1.10
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1.94
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|
7066-R5-1
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1.47
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|
7069-R5-1
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1.34
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1.59
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|
7113-R5-1
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1.60
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1.53
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|
7126-L3-1
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1.09
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1.21
1.28
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2.92
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|
7141-R5-1
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5.66
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1.32
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|
7221-R5-1
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|
7313-L5-2
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1.59
5.74
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2.36
2.07
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|
7352-R3-2
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1.09
1.44
1.44
1.64
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2.77
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1.60
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|
7356_A-R4-1
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|
7356-L5-1
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1.37
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2.37
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|
7367-L1-1
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2.85
2.74
1.81
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3.71
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|
7384-R3-1
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1.34
3.85
1.12
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2.45
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|
7411-R3-2
−13.01
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1.17
1.26
1.15
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2.04
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1.08
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|
7569-L5-2
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2.37
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|
7571-L5-1
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1.02
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1.30
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2.12
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|
7572-R5-2
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6.19
2.41
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5.40
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|
7660-L5-1
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1.08
1.23
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2.32
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|
7702-L2-1
−33.45
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1.18
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1.73
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|
7736-L5-1
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1.09
2.15
1.62
1.20
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4.30
1.24
1.39
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|
7743-L5-1
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2.34
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|
7781-R5-2
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1.05
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|
7824-R5-1
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|
7846-L5-2
1.10
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5.00
2.15
1.24
4.64
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2.08
1.99
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|
7883-R5-1
−4.16
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3.79
1.59
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3.80
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|
78-R4-1
−2.39
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6.26
2.28
1.91
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1.00
3.43
1.26
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|
7949-R5-1
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1.15
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1.16
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1.33
|
7971-L5-1
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1.29
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2.29
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1.31
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|
8016-L3-1
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1.05
1.08
1.03
2.34
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3.25
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|
8062-R5-1
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2.18
2.59
1.56
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2.34
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1.60
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|
8077-R3-1
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1.52
1.52
2.13
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4.22
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|
8089-L5-1
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1.14
1.34
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1.73
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|
8239-R5-1
−7.85
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1.38
3.30
1.25
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4.30
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−1.16
−1.28
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|
8250-R5-2
−8.86
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1.20
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1.31
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|
8281-L5-2
−4.41
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2.18
1.25
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2.00
−2.11
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|
8298-R5-1
−2.06
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1.18
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1.41
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|
8329-L5-1
−7.14
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1.64
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−7.14
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|
8336-R5-2
−7.05
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1.44
1.78
−1.12
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2.53
−1.47
−1.45
−2.17
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|
8394-L5-2
−33.24
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−1.40
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1.26
1.30
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2.74
−2.20
−1.19
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|
8564-L5-1
−9.90
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−9.90
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2.20
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3.01
−9.90
−2.15
−2.29
−3.34
|
8564-R5-2
3.57
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2.65
4.26
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−1.65
−6.82
−1.16
−1.87
−3.25
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|
8898-R5-1
−15.47
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−2.03
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1.04
−1.40
−4.53
1.61
−2.95
−1.90
−2.58
−1.63
|
9021-L5-2
−9.46
−4.89
−1.02
1.42
1.38
1.13
−1.84
4.21
−1.28
−1.21
−2.15
−9.46
|
9068-R5-2
−10.19
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−1.93
2.59
1.47
−1.63
−3.56
1.03
−4.24
−2.77
−4.29
−2.77
|
9087-L5-2
−5.65
−2.03
−2.17
1.21
−1.62
−4.32
−4.61
−1.82
−3.78
−3.28
−6.39
1.58
|
9134-R5-1
−2.19
1.85
−1.06
5.55
1.62
1.08
1.58
−2.19
−2.19
1.28
−2.19
−2.19
|
9217-L3-2
−25.69
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−2.14
−1.16
−1.07
1.71
−3.81
1.45
−2.41
−2.14
−2.41
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|
9245-R5-1
−7.70
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−7.70
−7.70
1.21
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−1.48
−7.70
1.20
−1.58
−1.57
−7.70
|
9287-L5-2
−8.66
−10.47
−2.11
1.95
1.22
1.28
−5.10
2.39
−5.82
−4.19
−6.03
−2.02
|
9369-L5-1
−2.53
2.54
3.26
5.80
−1.36
1.32
−1.20
−2.53
3.39
−2.53
−2.53
−2.53
|
9384-R5-2
−15.00
−15.00
−3.18
−1.02
−1.40
−1.71
−4.41
1.20
−4.03
−2.13
−2.58
−15.00
|
9387-R2-2
−2.27
−11.24
1.24
−1.66
−1.77
−2.13
−2.67
1.46
−18.94
−3.05
−3.88
−1.22
|
9564-R5-2
−21.32
−1.78
−1.27
1.30
−1.36
−1.75
−2.96
1.23
−1.50
−1.51
−2.02
−8.68
|
9605-R5-1
−2.11
−2.11
2.05
9.59
3.34
1.71
1.35
1.73
−2.11
2.19
1.04
−2.11
|
9691-L5-1
−13.91
−7.43
−3.19
−1.18
1.46
−1.16
−1.81
3.62
−1.45
−1.71
−1.56
−13.91
|
9770-R5-2
−16.08
−16.08
−1.38
−6.49
−1.54
−1.04
−3.18
2.79
−16.08
−2.24
−1.93
−16.08
|
9774-R2-2
−20.32
−5.37
−3.62
−1.47
−1.04
−2.24
−5.14
1.19
−4.78
−2.77
−3.92
−3.06
|
9812-L3-1
−8.36
−8.36
1.41
−3.81
−1.10
−1.30
−1.61
2.18
−8.36
−1.63
−1.54
−8.36
|
9866-L5-1
−11.22
−11.22
−11.22
−11.22
−1.94
−4.41
−3.65
1.13
−11.22
−2.98
−2.07
−11.22
|
999997-R4-1
−40.37
−3.22
−2.37
1.31
−1.44
1.32
−5.01
3.93
−3.66
−3.76
−5.46
−40.37
|
let-7b
−4.92
1.02
2.03
1.30
−4.60
−2.75
−2.04
−2.69
−1.28
−1.09
−2.68
1.40
|
let-7c
−6.31
−1.05
1.94
1.37
−4.31
−2.44
−1.65
−3.04
−1.21
−1.03
−2.43
1.67
|
let-7e
−22.08
1.03
2.47
1.47
−4.26
−2.47
−1.58
−2.23
−1.12
−1.04
−2.53
2.01
|
miR-100
−15.70
−1.06
2.47
1.30
−1.44
−2.47
−2.17
−1.90
−1.30
−1.64
−1.79
−15.70
|
miR-101
−12.44
−1.03
1.43
1.63
−3.70
−2.97
−2.13
−12.44
−1.45
−1.11
−1.92
1.97
|
miR-1182
−12.48
−2.69
1.05
1.43
2.25
−1.41
−1.78
−1.07
−12.48
−1.46
−2.26
2.67
|
miR-1207-5p
−7.81
−1.85
−1.68
1.60
1.80
−1.18
−2.41
2.42
−1.87
−1.78
−2.38
−2.36
|
miR-1224-5p
−8.27
−4.01
1.20
1.73
3.06
−1.10
−2.00
2.05
−8.27
−1.44
−1.68
−8.27
|
miR-1225-5p
−32.61
−3.21
−16.64
1.04
1.24
−1.74
−5.01
1.53
−3.91
−5.58
−5.48
−32.61
|
miR-1228*
−9.13
−2.28
−2.02
−1.49
1.07
1.35
−3.26
2.11
−3.56
−1.07
−1.87
−3.42
|
miR-1234
−2.04
3.94
4.09
6.04
1.42
1.35
−2.04
−2.04
−2.04
−2.04
−2.04
−2.04
|
miR-125a-5p
−12.05
−1.57
2.48
−1.11
−2.90
−3.80
−2.32
−36.39
−1.43
−2.16
−3.93
1.84
|
miR-126
−41.23
−1.60
−1.58
1.20
−9.24
−16.81
−5.80
−17.32
−3.33
−5.96
−5.54
−2.23
|
miR-1268
−10.67
−10.67
−10.67
1.26
1.67
−1.01
−1.65
4.86
−1.28
1.79
−1.47
−10.67
|
miR-130b
−2.21
−2.21
5.25
5.24
−1.32
−2.21
1.17
−2.21
−2.21
1.98
1.45
−2.21
|
miR-140-3p
−4.44
−4.44
1.97
2.44
−1.38
−2.55
−1.53
−4.44
−1.28
−1.52
−2.25
−4.44
|
miR-145
−31.48
−1.89
1.24
−1.28
−2.10
−1.49
−2.04
−13.08
1.01
−3.26
−2.80
1.20
|
miR-149*
−61.43
−1.79
−1.40
1.02
1.46
1.72
−2.47
3.20
−2.22
1.19
−1.22
−2.53
|
miR-150
−3.14
−3.14
3.09
4.65
1.17
−1.40
−1.27
−3.14
−3.14
2.18
−3.14
−3.14
|
miR-181b
−2.73
−2.73
4.73
−1.14
1.39
−1.40
−1.08
−2.73
−1.49
1.49
−1.51
−2.73
|
miR-181d
−2.47
−2.47
1.60
3.76
1.17
1.29
−2.47
−2.47
−2.47
1.49
1.28
−2.47
|
miR-185*
−10.19
−10.19
1.73
−3.97
−1.15
−2.49
−2.41
−10.19
−10.19
−1.56
−2.19
−10.19
|
miR-214
−4.43
−4.43
2.00
2.45
−1.27
1.26
−1.06
−4.43
1.76
−1.08
−2.47
−4.43
|
miR-23a*
−3.92
−3.92
−3.92
−3.92
2.27
1.12
1.28
−3.92
−3.92
−1.18
−3.92
−3.92
|
miR-30a
−19.76
−1.04
−1.44
1.58
−3.89
−3.05
−4.56
−7.27
−1.86
−1.24
−2.08
5.69
|
miR-30d
−1.08
−16.33
1.01
−5.75
−3.77
−3.17
−4.86
−16.33
−7.71
−1.17
−2.19
12.09
|
miR-320a
−3.29
−2.05
1.23
1.49
5.76
2.18
−1.27
−9.70
1.23
1.59
−1.65
−3.76
|
miR-320b
−10.09
−2.35
1.00
1.90
5.22
2.10
−1.35
4.46
−1.05
1.28
−1.58
−10.09
|
miR-335
−3.24
−3.24
1.22
3.13
−3.24
−3.24
−1.26
−3.24
−3.24
5.52
1.37
−3.24
|
miR-34a
−2.08
−2.08
5.16
−2.08
−1.23
−2.08
1.19
−2.08
−2.08
−2.08
−1.15
1.18
|
miR-34b*
−3.29
−3.29
5.13
−3.29
−3.29
−3.29
−1.55
−3.29
−3.29
−3.29
−1.06
−3.29
|
miR-34c-5p
−2.54
−2.54
5.54
−2.54
−2.54
−2.54
−2.54
−2.54
−2.54
−2.54
−2.54
−2.54
|
miR-371-5p
−3.87
−3.87
−1.81
−1.51
1.98
1.65
−1.03
−1.06
−3.87
1.10
−1.83
−3.87
|
miR-373*
−34.48
−13.72
−1.65
−8.74
1.28
2.21
−3.58
5.31
−16.32
−2.81
−4.50
−34.48
|
miR-451
−14.34
−2.32
−4.25
−2.09
−10.15
−7.99
−3.72
−9.47
−9.88
−7.90
−2.86
−3.23
|
miR-486-3p
−10.16
−10.16
−2.27
1.10
−1.59
−1.36
−3.64
1.72
−10.16
−2.14
−1.92
−10.16
|
miR-491-3p
−2.34
−2.34
−2.34
2.06
1.33
−2.34
2.23
−2.34
−2.34
1.67
−2.34
−2.34
|
miR-498
−28.12
−3.04
−1.96
1.11
−1.41
−2.01
−3.75
1.36
−3.41
−2.64
−4.35
−28.12
|
miR-557
−10.00
−1.36
−1.92
1.93
1.16
−1.55
−2.17
1.60
−1.32
−2.10
−2.21
−1.67
|
miR-638
−5.13
−5.73
−2.92
−1.37
−1.87
−2.89
−5.04
−1.34
−4.22
−3.54
−4.11
−1.97
|
miR-663
−15.30
−15.30
−2.65
−1.03
−1.31
−1.69
−3.07
1.69
−1.47
−1.68
−1.53
−15.30
|
miR-671-5p
−9.36
−9.36
1.12
2.50
1.56
1.06
−2.25
2.06
−1.39
−1.18
−2.06
−9.36
|
miR-744
−14.84
−14.84
−3.03
1.02
−1.26
−1.33
−3.71
2.36
−1.77
−2.34
−2.27
−14.84
|
miR-885-3p
−26.07
−26.07
−2.17
−1.16
−1.96
−2.54
−4.68
−1.16
−3.53
−3.27
−3.46
−10.53
|
miR-92a-2*
−8.53
−2.11
1.23
1.61
1.34
1.10
−2.40
2.65
−1.15
−1.39
−1.82
−8.53
|
miR-92b*
−11.88
−11.88
−1.16
1.21
1.35
1.19
−2.46
3.28
−1.42
−1.41
−1.46
−11.88
|
miR-98
−45.32
1.35
2.78
1.82
−4.33
−2.12
−1.37
−9.42
1.07
1.08
−2.69
1.84
|
miR-99a
−10.35
1.22
3.06
1.55
−1.32
−4.39
−1.67
−10.35
−1.21
−1.78
−2.15
−10.35
|
|
TABLE 25
|
|
Pre-microRNA sequences and chromosomal locations of target RNAs in Table 23 and 24
|
SEQ ID
|
Gene
Chrom loc'n
Pre-microRNA sequence
NO
|
|
10010_B-L4-1
7q32.1
GGGCAGCGCCCCTCCTTCCGGAGGGCAGCATCCCGGCGGGGGCGGGGGCTCGGCTTTGATGCCAGGGCACCTTTTGTCCCTGGAGACGCTCTGCCAGCCAG
1708
|
GTGCGTGGAGGGAGTGCAGCCC
|
|
10010_D-L4-1
7q32.1
CAGGTGAGAGGCTGAGCCCCGGGCGGGGGAGGGCGCCAGGCCTGGGGCATTAACCGTCCCGGGGACCCTTTTGGCCTG
1709
|
|
10010-R2-2
7q32.1, 17q23.2
CCGGGCGCCCCCGAGAGCCGGCCCTCCCTTCCTCCGTGACAGGTGGGCCTGGAGTTGGGGAAAGTTTGGAGCCGGCGAGGGGCGCCGGG
1710
|
|
10030-R5-1
10q24.1
GGATGCAACCGTGGAAGCCGGTGCCGTTGAGGATCTGCCACAGGCGGAAGGCAGCTGAGTTGACATCCACGGGCATCC
1711
|
|
10145-L5-2
5p15.33
GGTCCAGATAACAGAAGAGAGAGCAAAGGAAAAAGAATTTTTTGAAGATCAAAAGTGGCTGTTCATTTTGTTATCTGACC
1712
|
|
10231-R3-1
9p11.2
GGCGGCTGCGGAGGCTGGCGCGGGCTGCTGCACCTTTAACGCTTTCTGGCGCTGACAGGCGGCGGCCCAGCTAAAGTTCACAGCGCC
1713
|
|
10260-L5-2
22q13.1
GTGGGAGACATCGGGTGGGGGCCCTGGCGAACAATAGGTGGGCCCAGCTGGGGCCCCCTCCTGCCTGCCTCACCGC
1714
|
|
10333-L5-1
11q12.2
CGGGGCAGGGGAGGGGGTGGGCAGGGCACAAGCCTCCCACTGTGCCGTGTCCCCACCCTCCCCCGTTCCCCG
1715
|
|
10342-R2-2
19q12
CCCACGCACGGAGGGTCGCCAGGAAAGTGGACATTACCGCTTTAATTAACTTCGAGATGCTCCGGCGGCGGG
1716
|
|
10345-R5-1
20p12.3
ACCCTCAAGCTCTCAAGTGGTGACCACCGTCCTTCCGGCCAGGTAGGACTGGATGGGAGGGGTCGCTTTTGAGAGAAGGGT
1717
|
|
10374-R3-2
16q12.1
CAGGGGATTTGTTACCGCTGATGTGTGGCCCGTCCGAATGAAGGGGGCTTTTCATTAACAAAGTAGCGGGCGGTGTCATCTTCCCCTG
1718
|
|
10435-R5-1
5q35.1
GAGGCTGCTTAATGAGGTGCCCTTTTCAAAATGTCATCTTAATCTTTTATTAGTTTAAGAAAGACAACAGGGCACAATTAGCATGCAACTC
1719
|
|
10533-R5-2
20q12
TAATTGCCTGAATCGCCGGGTTACATATCTGTTAGGAAATCTCTTGGCAATATAAAGAAGGGGCTCAGGACAGTTA
1720
|
|
10543-R5-2
1p31.1
GCCTTAACCTTTTTATCATTTATCTTCTTGTATTAATGTCACTGAATTATTAATTCATGAGCCAGGATGGGAAGGGTGAAGGC
1721
|
|
10578-R5-1
1p22.3
CCGCCAGCTTTGTAGCGGTTCCTGCTTACAAAAGGGCTCTTCTTGGAAACGGGGCTGGTGGGGACCGTAGAGGGGGTGG
1722
|
|
10818-L5-1
8q24.3
GGCGGCTGACAGCGGTCATTTGTCATCACTGAGCTGCCCAAACTCCTCAGACTGCACTGCGGATGGCTGCTTAGGGTGACTTATGGCCCTGTCGGGCTGCC
1723
|
|
11370-L5-5
12q13.2
GTCCAGTTCTCAGGGGACAATACTGATGGCAGCCAAACTGGGCAAGGATGCAGTGTGGGGGCGGAGGGGGCATGACCTCTATTC
1724
|
AAGTTCTGTGTCTTGGCCCCTGGCTGAGGTATTGAGTGTGAGGAAGGGAACACTGGGC
|
|
11605-L5-4
1p31.3
GGCCCTGTGCATAATAAATCTTTATGGAATTGAGGGGAAGGGAATTAAAGAAGGGAAGAGAAGAGCAAACCCACTACAGAGTTTAT
1725
|
GACCATCTATTCTTAATATTATATTAGAACTGGGCC
|
|
12184-L4-1
3p14.1
TTGTACACAATATTCGTCTGTGGTTGAAAGGGGGCACGCTGAGGTCAAGTGATGTAGTGTTTTCCATTTTTCCATATGAGTCTCACA
1726
|
GTGTGCGA
|
|
12184-L5-3
3p14.1
TTGTACACAATATTCGTCTGTGGTTGAAAGGGGGCACGCTGAGGTCAAGTGATGTAGTGTTTTCCATTTTTCCATATGAGTCTCACA
1727
|
GTGTGCGA
|
|
12224-L4-1
4q27
TTGCTACTCCATGGGGTGGATTTTCATGGCGACGCCTTGTTATCTTGGTTATTGTTGCCATAGGACTTTCCAAAGCACCACATGGTT
1728
|
TGGTAA
|
|
12361-R5-1
6q23.3
GGTCCACTGTCAGAGAGAGATGTGCCACTGTGCACTCTCTGAGCAGATGGGCGGCAATATGGCACATTTACATGGACC
1729
|
|
12691-R5-1
1q22
CCCACGCGTCGCGCGCTCCCGACCGGAGCGGGACGGGGCCTGTCGGGGGCGCGCCAGGGGCGGGG
1730
|
|
12692-L5-1
1q22
GCGCGGTGGCCGGGTGCTGGCTGCGGGGCCGGGTCCTCATTCTGCTCAGTCCTTGCTGCCCTTGTCTTCTCCTCCCCGCCAAGC
1731
|
CGCCGTGT
|
|
12693-L5-1
1q22
GGGGAGGGGACCGGGAGGGCCGGGCGGCCGCGACCCCCAACCTCTCGGAGGAGGGGCTGCCGCTCGCCGCTCCGCTCTTTGT
1732
|
TGTTTGGGGCTCCGCGCCTCCCCCTCTCTCCCTCCTC
|
|
12694-R5-1
1q22
GGGGACGTGGCCCCTCCCCCCCGGAGCGGGACTCCAAGAACTCCGGGGGGCGCTGGGGGCTGACTTTCC
1733
|
|
12696-R5-2
1q22
GATCAGGTTCCCCTCCCCCGCATACACCTGGGCGCAGGTGAAAGCTCAGGGAGCGGGTGGGGGAGCCCGGGTT
1734
|
|
12697-R5-1
1q22
CGGGAGCCTCCTTTCTGTCCTCTCTACTCCGTGCGGGCCTGGGCCGGCAGAGGTAGGAGGGGGCGCACACCGGGCAGGAGGC
1735
|
TGCC
|
|
12699-L5-1
1q22
CTGGGACGGGCGGGGCGCCGAGGCCCAGGGCGCCTGAGGGGCGCAGAGGTGTCAGCGTGCAACCGCCGCCCCCCAGCGTTCC
1736
|
CGCCACCACCGCCACCACCCTCAAAGCCCGG
|
|
12701-L5-1
1q22
CCGGGGCTGGGGGTGGAGGATGGCGAGGATTTGACAAGTTCAGGGCCCCCTGGGATCCTTTCCCTACTCCCTGGTCTTGTTGGA
1737
|
CACCCTGTTTACCTGCCCTAATTGCCCCGG
|
|
12703-L5-3
7q32.1
GGGCAGCGCCCCTCCTTCCGGAGGGCAGCATCCCGGCGGGGGCGGGGGCTCGGCTTTGATGCCAGGGCACCTTTTGTCCCTGG
1738
|
AGACGCTCTGCCAGCCAGGTGCGTGGAGGGAGTGCAGCCC
|
|
12704-L5-2
7q32.1
CAGGTGAGAGGCTGAGCCCCGGGCGGGGGAGGGCGCCAGGCCTGGGGCATTAACCGTCCCGGGGACCCTTTTGGCCTG
1739
|
|
12713-R5-1
8q24.3
CGGAGGTCGCTCGCTCGCTCGCTCGGCTCGCTGACTCGCCGGAGCGCTCTGTGGCGGTCGGCGGCAGGTCGGTCGCGAGAGCGGGCTCTG
1740
|
|
12722-L5-1
13q31.3
GCGGGCGGGCGGGGAGGTCGGAAGTACTTTGTTTTTTATGCTAATGAGGGAGTGGGGCTTGTCCGTATTTACGTTGAGGCGGGAG
1741
|
CCGCCGCCCTTCATTCACCCACATGGTCCTTCGAGGTGCCGCCGCCGCCGCCCGACCTGC
|
|
12723-R5-2
17q25.3
CCCTTTGCACCTCCCGGGATTGGGCGGTCAGGGCCAGGGCCCCTTGAGAGTCTGGGAATCCCTTCTCTGGGCCTCGCTGGGGTC
1742
|
CTGGCCAGGAAGGGGCTGGGGGTGACAAGGGG
|
|
12725-R5-1
17q25.3
TCTTCCTCCACCCTGCCCCACCCCTAGGTCTCTTTATTGATTCAAAGGTTAAGGAAGCTCCTGGGGGCTTGAGGGGGTGGCACAGTTTTGGTGGGGCCC
1743
|
AGTGAGGA
|
|
12731-L5-1
17q25.3
GCGCGCCGGGGCGCTGGCGGCCGGCGCGGCTGCAGACGCTGCTAGCTCCCGCCGGCGCCCAGCTGCCGCCCCGGCCGAAGCGCCCCCGCCGC
1744
|
|
12900-R5-3
17p13.3
GTTCGCGTGACCCTCAGCGCCCTCCCCACCCGGCAGGCCCTTTCCCGCCGAATGGGTGCGGCTGGATTATTGAGGGAGTGGAGGGTCGCTTAGGGCACGG
1745
|
GCAC
|
|
12904-R5-2
17q11.2
GGCGTCCTGCCCATACTGTTGTCCCTGTTTTGGGGGCATGTGGGAGCCAACACAGGGGAGTCAGGTGTGTGGTAGGCAGTCAGG
1746
|
TGTGTTTTGGGGTCAGGGAGGCAGGTTTGGGCCTGGGAGGCC
|
|
12910-R5-2
22q12.3
GGCCCATGGTCACTCCCCAGCAAATGACAGCTCAGTGGCTATAATTAATGTCAAATTGGATTTTGTCATTTCAGTGGGGAAATGGAG
1747
|
CTGTGGGCT
|
|
12925-L5-3
1q23.3
GGCAGGTGGAACCAGCATATTCTTTATTCACCAAAGGGAAAAGGAGGAGGTGTTCAGGATGTTACCTCAATTTCCAGGTCTCCCTC
1748
|
TCATGTGTTGGTTTCTCCTGCT
|
|
12932-L5-3
18q21.31
CAAGTGAAGAGTGAAGGTATTAGTAGGTGGGAAATGGGGGTGGAAGGGAGTCTTGAGCTTTATTTGATCCAATTGTCACTCTATCT
1749
|
ACTGCTTAACTTTGCTTCCTTTTCTTG
|
|
12939-L5-2
13q22.3
AAGTCATATAGCTATTAAGTTGTAGAGGTGGGTTTTGAATCAGAGCTGAATCTAAAGTTCACCTTTTCTAAAACACTCTAAAAGCTAA
1750
|
GTGATTT
|
|
12947-R5-3
6p21.1
GCCTTGTCTGAAGGGAGAGGCCCTGGCATGCGGATGGGAGATTTAGAGGCTGTGGAGAAGGGAACTTGGGGCTTTCCTTCCTTCG
1751
|
TGGCCTCACTCCCCTGGGGCCTCTCTCTATGGAGGGGGC
|
|
12975-L5-1
3p26.2
AGGCGGGAGGGATGTTGTAGACTCCTCACTCCATGAGCATACAGTATTTTCTCGCCT
1752
|
|
12981-L5-1
3p14.1
GGGTGGGGGCAACCAGACCAAGGTGACATCATTCCCAAGGGGACACTGAAGGAAAACTATGGGAGGGTCTGGGTTCTGTCTGTCTTCACCC
1753
|
|
12981-R5-1
3p14.1
GGGTGGGGGCAACCAGACCAAGGTGACATCATTCCCAAGGGGACACTGAAGGAAAACTATGGGAGGGTCTGGGTTCTGTCTGTCTTCACCC
1754
|
|
12998-R5-1
9q33.3
TAGGCCGAAGTACCTCTCCAAGGTTATTTGAGAGGCGCTGATAGCCTTGGCGGTGGCACTGGGGCCTG
1755
|
|
13004-R5-1
12q13.2
CCTTGACTTCCCTTTCTTCTCACTTCGGACTGCTCACTTGCCTTGTTCAGCCCTGAATCATCAGGTGAAGGGAGCGAGAATTGCGG
1756
|
GGGTTGGAGTTAGGTAGAGGGATTTAAGG
|
|
13047-R5-2
10q26.3
ACCTCAGTGTTGATAGCAGATCTCATTATAGTCGGTGCATTTGGCTACCGACCTGCAGCCAGCAGTGCCCGGGGCTAGTGCATGG
1757
|
GGTCTGCTGTGCCACTGTGGT
|
|
13050-R5-4
19p13.12
AGGCCGTCCGCAGACCCAGGTCAGGGGCGAAGGCGCGCTCGCCCATCCCTGGTCGTCACTGCTTGGCTTGCGGGGGGTGGGAG
1758
|
ATAGGGGTGCGT
|
|
13052-L5-1
19q13.33
GGTTGGCGGGTGGGGGAGATGCTTAGGTCCGGGGAATCTCTGAGATTCTCGGCTTCCCCTCTCCCCTCACCCTCCTCCTCAGGCC
1759
|
CCAGGCAGCCCCGGGGCATGCTGGGAACCCAGGCCTGGGCTCCGGGCCAGG
|
|
13066-R5-2
5q33.2
CAGCCACCAGAGCAGATGAGCTGTCACCTTTAAATCACAATTCTGAAGCTCTGGAAGAGAGAATAGAATTGGTTCAACTAGATTTGG
1760
|
GGGCTACCTCCATCTGCTCAAGTTTGGCTG
|
|
13072-L5-2
7q22.1
GGAGGATACTGGTGGGGGCTATACGTTTGGTGAAATCCATCAGTGATATTCAAGCCAAGCAAATAATCACCCACTAATTTGTGTTTT
1761
|
CC
|
|
13075-L5-1
2p21
AGAGGGCTGGGCTGGACTTCAGCTTTCACCTAGGAAATGAGTCTTGCTGCCCTTT
1762
|
|
13089-L5-2
10q24.2
CACTAGCCCAGGGCTTGGAGTGGGGCAAGGTTGTTGGTGATATGGCTTCCTCTCCCTTCCTGCCCTGGCTAGGCCCTGGAGCGAC
1763
|
TG
|
|
13091-L5-2
9q34.11
TGCAGCCTGGGCCTGCTGAACACTTGAGGGTCGGGGGTTCTCAGGAAATCCCTGAGAGCTCAAAGGATGGCCTGAGGGGCCTGG
1764
|
TGGCA
|
|
13093-L5-2
11q13.1
CTGACTTCTGCGCGGGGCGCGGTGGGGTTCTGCGGGGTCGGAAAGACTCCCCAGATCCCCGCGCGGCCCCAGACCCAG
1765
|
|
13095-R5-1
1p36.11
GGGCAGGGCAGCTTCACCTGGCTCTGCAGCTCCTGAGCCTGGGTGGGCTAACCTGGGCCAGGAGTAGGGAGGTGGGTCCTGCC
1766
|
ACTGCCC
|
|
13097-L5-2
11q23.3
GTGGACAACCCTAGGGTGGGGCTGGAGGTGGGGCTGAGGCTGAGTCTTCCTCCCCTTCCTCCCTGCCCAGGGGTCCAC
1767
|
|
13110-R5-1
16p13.3
AGTTGGGGGTCCAGGAGGCTCCAGGGTGAGCCCACTCCTCCCCCTAGATACAAGGGAGGGCCCTGGGACCCTGTCTGCTGTTCC
1768
|
TCCTGGACTCCTGCT
|
|
13115-L5-3
1q21.3
AGGGAAAGGCAAGGGTAGCCATTGTTTGGGTTGGGGTGGTCGGCCCTGGAGGGGGTTTGTTTGCTTATTCCCCTCTGTGCTTCAC
1769
|
CCCTACCCAGCTTCCCGCCAGAAAGCCCTG
|
|
13115-L5-3
1q21.3
GGCAAGGGTAGCCATTGTTTGGGTTGGGGTGGTCGGCCCTGGAGGGGGTTTGTTTGCTTATTCCCCTCTGTGCTTCACCCCTACC
1770
|
CAGCTTCCCGCC
|
|
13119-R5-2
17q21.32
TCTCCGTGCACGCTGCTGACCGGCTCGGCGACTGCCTCCCTGCTGTGAGCAGGAGAACAGGAAGTCTGCCCGACAGGGAGGTGG
1771
|
CCGGGCGGGAGCGGCAGAGTCGGCGTTGAGA
|
|
13124-L5-1
1q22
TGAGGGGTAAGTTTAGGCTTTCGCGGAGGGGAGGAGACATGGAGCCTGGGAACTCCTTGTTCTCCCCTCTGCTGCCTCTCCCCAC
1772
|
CCCTTA
|
|
13129-L5-3
20q13.33
TGGCGCTGCTCTGCTGTTCCTCTGTCTCCCAGACTCTGGGTGGATGGAGCAGGTCGGGGGCCAGGGGACAGGAAGGCTAGGGCC
1773
|
|
13129-L5-3
20q13.33
CCAGACTCTGGGTGGATGGAGCAGGTCGGGGGCCAGGGGACAGGAAGGCTAGGGCCCCAGAGACCTGTCCTGGGCCCCATGTC
1774
|
CAGCTCTGCCCTTAGTGCTTGG
|
|
13130-L5-1
19p13.3
CCAAGCAGCTTATCGAGGAAAAGATCGAGGTGGGTTGGGGCGGGCTCTGGGGATTTGGTCTCACAGCCCGGATCCCAGCCCACT
1775
|
TACCTTGGTTACTCTCCTTCCTTCTAGGG
|
|
13130-L5-1
19p13.3
GAGGAAAAGATCGAGGTGGGTTGGGGCGGGCTCTGGGGATTTGGTCTCACAGCCCGGATCCCAGCCCACTTACCTTGGTTACTCT
1776
|
CCTT
|
|
13135-R5-1
1q42.12
CATGAGTCTGCACCTCCAGGCAGGCTCTGTGCAGTACTCACCCCCTCCGTCTGCTCCCTCCAAGGTGTGGGGGTGGGCAGTGCTC
1777
|
AGGGCCTCCTCGGAGCCAAAGGACAGCATG
|
|
13136-L5-3
5p15.33
GAGGAGGGAGCCCCCCATAGGGTGGCCCTGACCAGGGCTGGCAGGGGCAAGTGTGGACGCCCGGCCCCTTGCCCAGGCTGGG
1778
|
ACCACTCTGAGGGACAACTCATCCTT
|
|
13137-L5-1
5p15.2
GGCATGGGGAGGTGGGGTTGCGGGGGTTAGAGCTGTGGGTGATCAGAAGGGAAGGGCTTCATTTCTACGCTCTGCCTCCGCTAC
1779
|
CTCTTCCCCACCACCCCTAATCCC
|
|
13138-R5-1
5q22.3
ATCCGTCGCAGCAGTCGCTGCAGCCGCTGCAGTCCGAGCCGACTAAGGGCGGGAGGCAGCTCGGGTGGCGGGGCGTGGCGAAC
1780
|
AGCGCGGCCGGAT
|
|
13163-R5-1
19q13.32
GCTGGGATCTCCGGGGTCTTGGTTCAGGGCCGGGGCCTCTGGGTTCCAAGCACCAGTGAGGAGAGTGCTGGGAGGGGAAGGGG
1781
|
TGGGAGGGCTTTGGTCTTGTGGGAGGGAGAGAAGGAGGGGAGGT
|
|
13164-L5-1
10q23.33
GGTATCCTGAGAGTTTATTAGATGTTTGTTTTCATTCCTTTTGCAATGGCCTATGGTATATTATGTATCAACATTTAATGTGATGAAAA
1782
|
CGTCTCACTTATATTCTTCAGGATACT
|
|
13166-L5-1
20p11.1
GCCTCGCGGGGTGGGTCGGGGGGTCCTCTGACGCGGCAGGCACCCCTCGCTCTCGCCTCCTGTGGT
1783
|
|
13181-L5-1
1p21.3
TCCTGAAAGAGGTTGGGGCAGGCAGTGACTGTTCAGACGTCCAATCTCTTTGGGACGCCTCTTCAGCGCTGTCTTCCCTGCCTCTG
1784
|
CCTTTAGGA
|
|
13184-L5-1
9q33.3
CATTAGGTGGTGGGTTTTTGGTTTATTTTTTGCTTTTTCAATATGGAAAATAGCTTGTGGACTATCACTAACACCTCTGTG
1785
|
|
13186-R5-2
3q25.2
GCATGCACAGTCATTTTTGTTTAAGAGTAATATTTTTAATGTAATAGATTGTAAGACGTGGTGAGGGAGGGATCTGACAGAGATGAA
1786
|
TGTGCCAAGC
|
|
13195-L5-3
3p21.1
AAAAAAAAAAAAGATACTAATACAAATGGTCATGGAGGGGGAATATAGAGAAGATCAATTTTGTACAGAAAAACCATTGGTTAGTATT
1787
|
TTTTTTTCTTTT
|
|
13199-R5-1
10q26.13
AGGTGCTGGGAGAAGCTGCCAGTGTTTCTCAACATGTCTGCCTCCCTGGGAGGTGAAGCATGGGCAGAATCCCCCAGCTTCCCA
1788
|
|
13202-L5-1
10p15.3
TGGTGGGGCTTCTCAGAGGAGGTGGCAGGAGACCCGAGCCTGCCAAGGTTGCACCTAAGGTCACGGGCAGCATTAGGAGGGCTC
1789
|
TCTCCCAGTCTCCCCACCCCCCCATCCCCCCTCCC
|
|
13202-R5-2
10p15.3
TGGTGGGGCTTCTCAGAGGAGGTGGCAGGAGACCCGAGCCTGCCAAGGTTGCACCTAAGGTCACGGGCAGCATTAGGAGGGCTC
1790
|
TCTCCCAGTCTCCCCACCCCCCCATCCCCCCTCCC
|
|
13209-L5-2
10q22.1
GGGAGCCGCCGGCGGGCAGGCCGCCGGGGCAGCAGGCGAGTTACCTCAACTCCCGGCCGCTCCGGAGGTTGCCGGGCACCGA
1791
|
GGAGCCGCCGTGCCCTTCAGGCGCCTGCGGCGGCGACCA
|
|
13209-R5-3
10q22.1
GGGAGCCGCCGGCGGGCAGGCCGCCGGGGCAGCAGGCGAGTTACCTCAACTCCCGGCCGCTCCGGAGGTTGCCGGGCACCGA
1792
|
GGAGCCGCCGTGCCCTTCAGGCGCCTGCGGCGGCGACCA
|
|
13211-L5-1
10q23.1
GCGCCTCCGGTCGGTCAGAGAGCGGCGGGGCGCGTCTGCAGCCCTCCAAGCCGCCTCCTGCGCGCCGGGTCCCCGCGCCCGC
1793
|
TGCTGCTGCTGCTGCCCGCCGCCTGCGTGC
|
|
13220-L5-3
1p13.3
CCAGACCCAAACTAGGTTGAGTGAGGAAGGGGCAGTGGCAGCTACAGGAATAGCCTGTGATGCCTCTGTCCCTCTGAAGATGTCC
1794
|
CAATGTCCCGTGGCCTG
|
|
13229-L5-1
11p15.5
TGCTGGCCCAAGGGGTAAAGGGGCAGGGACGGGTGGCCCCAGGAAGAAGGGCCTGGTGGAGCCGCTCTTCTCCCTGCCCACAG
1795
|
AGACTGGCGGAGCTGC
|
|
13230-L5-4
11p13
AGCTTTGTGTTCGTAATGGCTCAGTTCAGGTGGTTGGAGCTGGAGGCACTGGAGCTAAGACTGTGGGCTCAGGGCCTCAAGTCCC
1796
|
TAGAATCACACCACACTTCCAAATCATTAAGCTC
|
|
13231-L5-2
11p13
AGGAACAGGACGATGATGCTGGCGTCGGTGCTGGGGAGCGGCCCCCGGGTGGGCCTCTGCTCTGGCCCCTCCTGGGGCCCGCA
1797
|
CTCTCGCTCTGGGCCCGCTCCTCTTCC
|
|
13237-L5-4
1q21.3
AGGGAAAGGCAAGGGTAGCCATTGTTTGGGTTGGGGTGGTCGGCCCTGGAGGGGGTTTGTTTGCTTATTCCCCTCTGTGCTTCAC
1798
|
CCCTACCCAGCTTCCCGCCAGAAAGCCCTG
|
|
13237-L5-4
1q21.3
GGCAAGGGTAGCCATTGTTTGGGTTGGGGTGGTCGGCCCTGGAGGGGGTTTGTTTGCTTATTCCCCTCTGTGCTTCACCCCTACC
1799
|
CAGCTTCCCGCC
|
|
13239-L5-2
1q23.3
CTGAGGACAGGGGTAAGTCTGGGGAGATGGGGGGAGCTCTGCTGAGGGTGCACAAGGCCCTGGCTCTACACACATCCCTGTCTT
1800
|
ACAGAG
|
|
13240-L5-2
11q12.2
GCAGTGTGATTTGGGGCCGGGAATGCCGCGGCGGGGACGGCGATTGGTCCGTATGTGTGGTGCCACCGGCCGCCGGCTCCGCC
1801
|
CCGGCCCCCGCCCCACACGCCGCAT
|
|
13241-L5-2
11q12.3
CTCTGTTACCTTGCTTGCTCTGTGTGGTTTTGGAGGGGTGTGGAAAGAGGCAGAACATTCGTTCACTTTCCTGCCTTCCTCTGCAC
1802
|
CAGCTAAAAAGTTTGCAGAGAC
|
|
13251-R5-2
1q25.2
GGCTGGGACCACCTCCTTGTGCCCCCTCCTCTGCCATGGCACCTGGCTGTCACCTGCCTGACCTCAGCCAGGGACCAGCCATGG
1803
|
CAGAGGAGGGGGCACAAGGAGGTGGTCCAAAGGCCCA
|
|
13259-R5-1
12q24.11
CAGGTATGCTCTGTGACAAGATTTGCAGCATTTTAGAGAGCCCCTGGCCTGCTGGGGTGGGGACAGATACAGTGGTAATTCTGGC
1804
|
AGAAGATGAGGCCT
|
|
13267-L5-1
1q42.13
CACCATAGGTGAGGTGGGGGCCAGCAGGGAGTGGGCTGGGCTGGGCTGGGCCAAGGTACAAGGCCTCACCCTGCATCCCGCAC
1805
|
CCAGGCTTCAACGTGG
|
|
13281-L5-3
12p13.31
GCCGCCCCCACCCTGTCCCTCGTCACTTCCTCTGTCCTGTGGGGTGGGGGTGCAGGCGCTTCTCCTTTAGCTGTGCCGCACTTCT
1806
|
CCCTACAGGCCAGGAGAAACAGAACACCGTGTGCAC
|
|
13283-L5-3
1p36.11
GGGCACGGGGGTTGGGTGTGCAAAGGGTGGCAGCAAGGAAGGCAGGGGTCCTAAGGTGTGTCCTCCTGCCCTCCTTGCTGTAGA
1807
|
CTTTGGCCTGAGCAAAGAGGCC
|
|
13285-L5-3
1p36.32
CTGGGGGTGACCCCGTGCAGGGGCTGAGCTGGGCGGCTGGGTGCATAGCCCATCTGTAGCCTAAGCAATGGTGCAAAGCCCCCA
1808
|
CGCCTTGGTTTCCTCTCCTGAACGCGGGCACACAGAG
|
|
13287-L5-3
1p35.2
TCCGCCGAATAACTCCATGTGGGTCTTGGGAGGAGGGTGGGGTGGCTCCTCTGCAGTGAGTAGGTCTGCCTGGAGCTACTCCAC
1809
|
CATCTCCCCCAGCCCCTGTATGGCTGGGAGGGGAA
|
|
13291-L5-1
1p34.3
CGGGAGGGAAGGAGGGAGGAAGGGGCGCTTGGGCAGAACCAAGGGTGGCAGATTATCCTAGGGACTCTTGGGGCAGAACCAGA
1810
|
CGCCTCTGCGTCCTCCCCTCTCCCC
|
|
13293-L5-1
14q32.2
GTGGCGAGCCAAGGGGCGGAGGCCTGGCCAGGCAGAGGCTCCGAGGCCAGCCAGGCCTCCTAACCCTCCACC
1811
|
|
13298-R5-1
1p34.1
GTACTCCCTCACAGCTGCATTTCAGTGCCTGGCTCTGACCTGGCCACAGCACACACCATTGCTAAGTGTGGGGCTGTGGGGAGGC
1812
|
TGAAGCCCTGCACCCACTCCAGGCTGAAGGCAGT
|
|
13303-L5-3
14q32.13
TGGGAAGAGGGACATCGTGGAAAGTTGTGGCAACTGGGTTCAGGGGAGGCCAGGAGCCTGCCAGCTGTGGCCTCTAAAAAAATA
1813
|
AAACCCAGGTGCTCACTGGCCCTGCCTTCCCAC
|
|
13308-L5-1
15q23
GTGGAGAGGTGGAGGTGGATGGGCTGATGTGAGTGTGTGTGTGTAGACAGCCTTTCTGACAAACAAGGCTGTATTCACCAAGGAT
1814
|
CTCCTGGCGGGTATCTCAAATTCCATCATTCATC
|
|
13310-R5-1
15q23
TTTTGGTAATTTAGACTGGAAATGGCAATGGTAATTCAGAAAAAGAAATAAATTTTAATTATTGGTGGTGGTAGTGGCAATGGATTTT
1815
|
CAAAGA
|
|
13312-L5-2
15q24.1
GTGAGTGGGGCTGGGCTGTGGGGGAGGGGTGGGGTGGCAGGGAACAGGCAGACCATCCCTTCTACCCACAGGATCCTGCTGCT
1816
|
GCAGACAG
|
|
13313-L5-2
15q24.1
CTGATTAGGGTTAGTGGGAGGGACACGGCATGGGAGACAGGGAGATTTGCCTGTTGCCCTGAGCCTGACTGAGCTTCCTTTCTCC
1817
|
CTAGCAC
|
|
13316-R5-2
16p12.3, 16p1311
GCTCAATGCCTCCAACGCAGTCAGCTGGGTCTCAGCCACGTACAACCTCACGGTGGAGGAGCCCATCGTGGGCCTGGTGCTGTG
1818
|
GGCCAGCAGCAAGGTGGTGGCGCCCGGGCA
|
|
13316-R5-2
16p13.11
ATCCGGCTCAATGCCTCCAACGCAGTCAGCTGGGTCTCAGCCACGTACAACCTCACGGTGGAGGAGCCCATCGTGGGCCTGGTG
1819
|
CTGTGGGCCAGCAGCAAGGTGGTGGCGCCCGGGC
|
|
13326-L5-2
17p12
TGCCATCGAAGGGCGGGTGGGGGGAAGCCGGAATCTCTGTCCACATGCTCCAGGCACCTAGCTGCTCTGAGGGGCAGAGAGCAG
1820
|
AGGTGGTGCTCCCCCCCATCAGCATTTTGAGTTGGCT
|
|
13328-R5-2
17p11.2
AGCTTGTATCACCTGCCACTTGCACCTGTATCACACCTGTGTGTTACACCTGTCACTCCTGTGTGTCACTCTTGTGTGTTGCAGATG
1821
|
TGGGGGCAGGTGAGCATCTGC
|
|
13332-L5-1
17q21.31
TTGGGAGGGAAGACAGCTGGAGAGTATGGTCACAGCAGCATCCTCCTCTGTTTTCTTTCCTAGAT
1822
|
|
13332-L5-1
17q21.31
TTGGGAGGGAAGACAGCTGGAGAGTATGGTCACAGCAGCATCCTCCTCTGTTTTCTTTCCTAG
1823
|
|
13334-L5-3
17q21.31
TGGGGCAGACAGGGCACAGTGGGAGGGGAGGGGAGTCCTGCCAGGAGGGCCACCTGGTGACTCCACATCCTTTCTCACCCCCC
1824
|
AGA
|
|
13335-L5-3
17p13.2
TGGCTGGGAGAGGAGCATAGGATGCGGCAGGAGGGCAGTGGAGGCTGAGGTACGGATTTCTAGGCCCGCCCTACCCTCCTCTCT
1825
|
GCCCCTAGTGCCCGTGGCCAA
|
|
13337-L5-2
17q24.3
ATCACGGGTTCCATGTTGGGGGAGGGAATGTCAGAAAAAGAATGTCCGTTCAACATTCCCTCTCCACCCTTAAATCTCTATGTGA
1826
|
|
13339-L5-1
17p13.1
GCGGCGGACACCATCTTCTTTAAACCCTCAGTCCGTATTGGTCTCTATGGCATCCATAGAGGCCATTCGGCTCTGAGGTCCTCAGT
1827
|
AAAGAAACTTAGATGGTATTACTGTGT
|
|
13343-L5-1
17q25.3
TGAGGGGGAGGGGCGCTGCGGGAGGGGTGGAGGGCCCAGGGAAGGGTGAGGGGCCGGGAGCCACTCTGCCCGGCACTCTCC
1828
|
GCCCAGAAACAGCCCAACGCCCCTTTCTTTCCCCTTT
|
|
13349-L5-2
18q23
AGAGGAAGGAGGCGGCTGGGATAGCCCACACAGGTGGTGGGAGTCTGTCCTCTCCCTGCCAGGGTGCAGGACAGCAGGTCTCAA
1829
|
TCTCGCCCAGTGGGACTCAGTGGTCCCTCATTCA
|
|
13353-L5-2
19p13.3
ACAGGCCTGGATTTCAGAGGGCGAACATTTCTGTGGCCGAAGCTCCCAGTGCGTTTGCAGTCCTTGGAGACGGCCGCAGACACAT
1830
|
TTGTTCTTGGCCTGTCTCCAGGTCTGTA
|
|
13354-L5-1
19q13.11
ACTGAGGGGGTTCCAGGAGCTTTGTGGGGCAGCATTGGGAGTGTGAACCCCCATCCAGGTTCTCACCTCTCAAACTTCCTCAGAT
1831
|
GCTGAGCCCCACTTAT
|
|
13355-L5-2
19q13.12
GTTTCCCATTCACACTGCAGGAAAGGATAGGGGTGGGTGTGGTCAGAGGACCCTCACATGGCTCCACTCTAGAAGCTGGCATGGG
1832
|
CAGCTC
|
|
13356-L5-2
19q13.2
TGGTGAGCACCGTGCTGGGTGGCAGGGAGGCCAGGGGCCCACCTAGTGCCACCTTTCCGTGACTCCTGCTGTCTCCCTGCAGCC
1833
|
CGTCGGGGATGAGAGCCAGG
|
|
13358-L5-2
19q13.32
CGGCCAGTGACTTCCCCAGGAGTGTGGAGGGGGTGGTGAGGAGGAGCACCTGGGCTCTCTACCCCTCTCCTCACAGAAGTACCT
1834
|
GAAACTAGGTC
|
|
13361-L5-1
19q13.33
GTGTGCAGGGCTGGGGTCACTGACTCTGCTTCCCCTGCCCTGCATGGTGTCCCCACAGGGACAGCATGGACAGTGTCAAGCAGA
1835
|
GTGCGGCCCTGTGCCTCCTTCGACTGTACA
|
|
13363-L5-2
19q13.42
AGTCGGGTGGGATGTGAGGGTGTCAGCAGGTGACGGTGGGGGCCACGCTGACAGCCGCACCTGCCTCTCACCCACAGTGCAAC
1836
|
CAGAGACCCCTCTA
|
|
13364-L5-2
19q13.43
AGGTGGAATGGGCTGAGGCTCAGGAAGGGTCCTGGGATACAAATGCTCACTCTATGGGTCTCTCCCTGAGCAGGACATTGGTTACC
1837
|
|
13365-L5-3
19p13.3
CCAAGCAGCTTATCGAGGAAAAGATCGAGGTGGGTTGGGGCGGGCTCTGGGGATTTGGTCTCACAGCCCGGATCCCAGCCCACT
1838
|
TACCTTGGTTACTCTCCTTCCTTCTAGGG
|
|
13365-L5-3
19p13.3
GAGGAAAAGATCGAGGTGGGTTGGGGCGGGCTCTGGGGATTTGGTCTCACAGCCCGGATCCCAGCCCACTTACCTTGGTTACTCT
1839
|
CCTT
|
|
13370-L5-2
20q13.12
TACCGCAAGTATGTGGAGCAGAGGTGAGGGTGGGGCATGCATGTGGTTAAGCCACCAACCCCACCAGACCTTTCCGCCACACTCT
1840
|
CATCCTGCAGGTAC
|
|
13373-L5-4
20q13.33
TCCCTGCACCCCTGCCTGTACAGGTGAGTGGGAGCCGGTGGGGCTGGAGTAAGGGCACGCCCGGGGCTGCCCCACCTGCTGAC
1841
|
CACCCTCCCCCCACAGCACCCTGTGCCGGGGC
|
|
13374-R5-1
20q13.33
TGGCGCTGCTCTGCTGTTCCTCTGTCTCCCAGACTCTGGGTGGATGGAGCAGGTCGGGGGCCAGGGGACAGGAAGGCTAGGGCC
1842
|
|
13374-R5-1
20q13.33
CCAGACTCTGGGTGGATGGAGCAGGTCGGGGGCCAGGGGACAGGAAGGCTAGGGCCCCAGAGACCTGTCCTGGGCCCCATGTC
1843
|
CAGCTCTGCCCTTAGTGCTTGG
|
|
13375-L5-3
20q13.33
ACCCTCTCAGGACCCCTCCTAAGGGGTAGGCAGGGGCTGGGGTTTCAGGTTCTCAGTCAGAACCTTGGCCCCTCTCCCCAGACCC
1844
|
CCAGGCTGTGGTGAGGGTCTGAGAGCTGGTAC
|
|
13376-R5-1
2p25.1
CCAGAGAGGAAAGCTGCAGGTGCTGATGTTGGGGGGACATTCAGACTACCTGCAGCAGAGCCCATGGCT
1845
|
|
13380-R5-3
2q21.2
TAATCTCCAGTGAAAAATAAGCATGAGTGTGAGGCTGAAAAGGCTGGAATCATTCTCCTGCGTGTGCATTCTTCCGGGGCTGGGAG
1846
|
TT
|
|
13385-L5-1
21q22.3
ACTGTAGGTGGCGCCGGAGGAGTCATTTCCCATCACTAATGGCTTCTCTTGCACACCCAG
1847
|
|
13396-L5-2
22q11.21
GGGACAGCGGTAAGGAGCCCGAGTGGGGCGGGGCAGGTCCCTGCAGGGACTGTGACACTGAAGGACCTGCACCTTCGCCCACA
1848
|
GAAAGACTCCTAGCCAGGAGGGCCTGC
|
|
13403-L5-1
22q13.1
ACCAGGTGGGCCTGGCCCCAGGTTGGGGGGACACGGGTGGGTCCCGGCACCCCTCCCCTGACCACCGTGCCTCTCCCAGGA
1849
|
|
13412-L5-1
2p16.3
CTGGGACCAGGGGGCGCCATCTTGACTCATGGTCCAAGATGGCGACCTGGAACGCTGAGCG
1850
|
|
13423-L5-3
3p24.3
AACTAGGCTCCTAAAAACAAATAGCTTCAGGGAGTCAGGGGAGGGCAGAAATAGATGGCCTTCCCCTGCTGGGAAGAAAGTGGGT
1851
|
CAAGGGGGAAAGGGTG
|
|
13425-L5-3
3q26.33
CCTGTTGATTCCCAAGAACCTTGATGCGGCGCATATGACTGGGAGGGCACCTAGAGCATTTCTGGGTGAATAAGGCCCCTCCATC
1852
|
CCTCAACAGCAGCACAAGTGTGTGTGAAAAAGGA
|
|
13430-L5-3
3p21.31
CCTAGGAAAGGCTGCTGGTAACTGGGATGGGGGTTGGGGGGAGGTAAGAAGTCTCTGACTCCTCCTCTACCTCATCCCAGTTCCA
1853
|
TCACCTGAAGTGGACCTCTTGGGAC
|
|
13431-L5-3
3p21.31
GCCTCTTCCTGTCTCTGCTGTGAGTGCGGCAGCGGCAGTGAGTGGGTGTCGACGCGGCGGAATGCCCGTCGCTGCTGCTGCTGC
1854
|
TGCCCGACGGGCCTGGGG
|
|
13432-R5-1
3p14.2
TGCTTTCTGCATTCTTCTCCCTCCCCGGTCTCTTGTGACAAGCCATACTGTTAAATATCAGAATAGTAGGTGATTACGTGGAGTTTG
1855
|
GGGAGGTGGTAGGAAGTGCCAGAAACTGTAAA
|
|
13456-R5-2
4q12
CCAGGAGCTACCAAGCAGAGGTTTATTCAGTCTCCAGAAGGCTATGCAGGTTGGAAAAGATTTCATAGCGGGGCATCTG
1856
|
|
13458-R5-2
4p16.1
GCTGGAGCCTTCCCCTCCCCTCCTCGGCACTTCCCCCACCTCACTGCCCGGGTGCCCACAAGACTGTGGACAGTGAGGTAGAGG
1857
|
GAGTGCCGAGGAGGGCACAGCTGTGCCTCAGA
|
|
13461-L5-4
5p15.33
TCCGGGAATCTGGAGGTTTCTAGCACTTTCACTTTCTCTAGGGGGTGGGGACGGGGCTGGGGAGAGAATCCCCCAGCCCTGTTCC
1858
|
CTCCATCCTGGCTCCAAATCCCAGTTACTCCCCGGA
|
|
13463-L5-2
5p15.33
GGGGACCTCAGGCTGGGGGGCTGGTCCGAGTCCTGGATCCTCAGGGACTCTGGGAAGCTGGAGCTCTAGCACCCTCCTCCC
1859
|
|
13489-L5-1
6p21.2
TCTTGTTCCTTGGCTTGACCACAGGCTTTCCCCCCAGCCAGGGGCTTCCTCCCCTCACTCCCCTCCCTGGGCTCTGCCTCCCAATC
1860
|
AGAACCACCTCGAGC
|
|
13497-L5-1
7q22.1
GCGGTCCCCTGGGGGCTGGGAGCGAGGGGGGCACAGATCTGATGTGCCCCCCACCCTCTCACAGGACTGG
1861
|
|
13513-L5-1
7q11.22
CTTTGGTGAGAGTAGCACCACCCAGGGAGGATTCAGGCATTAATCATCCCTGGCAGAGTGCTCCCTGGAAGTTTACTCTGAAGAC
1862
|
|
13519-L5-1
8q24.21
GGGGGTGGGAAGCGAGGTTGGGTAGAGCTAAGGTATCAGCAGGACATAGTAACAAATTAAAATATTATCTCTGGCAAATGATAATA
1863
|
TAGATCTAAACTTTCAGTCCCAAACTCAA
|
|
13525-L5-2
8q11.23
GGCCAGAAGACGATGGCGGTAGGGGAGATCACGCGAGAGCATGGCCTCCACCTCTCCTCCCCACCGCCATCTCCACGTTCTCGC
1864
|
|
25-R5-1
2q31.1
TCCCGCAGCCGGTGACTGGAGCCCACCTCTGCAGAGACAAAGGTTAGAAAAAGAGGGGGTGAGGCTCTGGGAAAGCAGAATGCG
1865
|
GGG
|
|
266-R5-2
12q14.3
GTTGCTATTTCCCTCAGTTGAGGGCGAAGTTAGCAAATCCGTAGCTGCAAGTCTCAACTTGGGGGAGGGGGCGAC
1866
|
|
2786-L5-3
2q31.1
AAGCCCTAGAGATCAAAAGCATTAGTATGGGCAGTTGAGCGGGAGGTGAATATTTAACGCTTTTGTTCATCAATAACTCGTTGGCTT
1867
|
|
2811-R5-1
17q25.2
AGCATGGAACAAGCCAGAATCCCTCTCTTACCCCGAGAGCTGGTCCCTCCAGGTCAGGGTTGGGACACAGTGGCACGGGGTGGC
1868
|
TGTGGGTGGCTTGCACTGCCG
|
|
2819-R5-4
15q22.2
AATGCCAGTGAGTTTGAAAGGCACTTTGTCCAATTAGAAGTGTGGAGAAATATTCATCCTGTCCATGACAAAGATGAAGTGCTTCTT
1869
|
TCAAAAGCGGCGGTGGCAGGCTG
|
|
3717-L5-2
1q21.3
TGTGAGTGGGTTTGGGGTGAGGCTATGGGGAGGGCGGGGTGCCGCCTTGCCCAGCCCCTGAGGGCCCCAGCCCAGTACA
1870
|
|
3732-R5-1
Xp22.12
TCTCTTTCTCTTTTTGTAAATATACCGTCATATATAAGCTAAAATTTCTCTTAGGGTGGTGGGGTTTGCTGGCAGGGAAAGGGA
1871
|
|
3799-R5-1
11q13.1
GAATTTGCCCTACGGTGTGACCCCAGCCTCTCCCTCTGGCCACAGCCAGGGCCGGCGGGGGGCCTCTGGGAGCATCTTCAGCAA
1872
|
GTTC
|
|
3897-R5-2
9q12, 9p11.2
CGGAGCCGCCCGCGCCAGCCTCTCCATCTCGCAAGTTTTAATTAACGCTGAGGGGGAGGCGGCTGACGGGCGGGTCGG
1873
|
|
3942-L5-1
1p31.3
GGGAGTGGGGGGATCTGTTTGGCAACTGGAGTGAAGGGATTGCCCTCCCCCTGCTGGGATCCCCCCAGCCC
1874
|
|
3952-L3-1
1p36.32
CCCCGGCGAGGGGTGTCAGATTGAGTGCTCTGTGCGCATGTGCGAAGGTGTCCAAACTGACAATGCTGGGG
1875
|
|
3953-R3-2
9q33.3
GCTCCTGCTCCGCCGCGGGAGCTGCTCCGGCGGCCGCAGGGCTCGCTCGGGAAGCTGAGGCGGCGGAGGCTGGAGT
1876
|
|
3966-L5-1
3q27.2
GGCGAAGGCGGCAGCGGCGGCGACAGCTCTGGGGTTTGCGTCTCGGGGTGTGTCGGCCGCCGCTGCTGCTTGGGCC
1877
|
|
3995-L2-2
7p21.1
TGGCCTGACGTGAGGAGGAGGGACTTTTCGAAGTTTTATAGGAAAGTTTCCGCTTTCCAGTCCCCCTCCCCCGTCCCA
1878
|
|
4013-L4-1
15q22.2
ATGGTCCCCCTGCTGATAGCTCAACCATGCAAGTGCCATAGGAAACAGACTTTGGCATTTGAGCTGCTCACAGTCTGGGTCAT
1879
|
|
4026-R5-1
10q24.32
GGCTCTGGGAAAGCCTTCCTTTCCCGGCTGGCCTGGCATTCAAAGCCAGACAAAGGGGGGCTTTCTCTCTCGCC
1880
|
|
4026-R5-2
10q24.32
GGCTCTGGGAAAGCCTTCCTTTCCCGGCTGGCCTGGCATTCAAAGCCAGACAAAGGGGGGCTTTCTCTCTCGCC
1881
|
|
410-R5-1
5q31.3
CCAGCTCCGCCAGCTCCAGCCCCAGGTCCTGAGCGATGCGGCCCACGAAGGTGCCGTGTTTTGCTTCCTCGGGGACGGAGTAGT
1882
|
GGAGCTGG
|
|
4130-L5-1
17p11.2
GGGTGCTGGTGGACATGGACGGCGTGCTGGCTGACTTCGAGGGCGGATTCCTCAGGAAGTTCCGCGCGCGCTTTCCCGACCAGC
1883
|
CCT
|
|
4143-R5-2
22q12.3
TCAGCGTCAGGAACTTCATCCTGGCAGCCGACCTCATGAAGAGCATCTGGCTGCTGTTACCAGGAGGAGAGCAAGACGCTGA
1884
|
|
4258-L5-1
2q31.1
ACGGGAAAAGAGGAGAGGCACCAGATATATGTTCTCTAGGCCTTTTAGAAAACATGGGGTTTTTCCTTTGGCCACGT
1885
|
|
4315_C-L4-1
1q22
GGGGAGGGGACCGGGAGGGCCGGGCGGCCGCGACCCCCAACCTCTCGGAGGAGGGGCTGCCGCTCGCCGCTCCGCTCTTTGT
1886
|
TGTTTGGGGCTCCGCGCCTCCCCCTCTCTCCCTCCTC
|
|
4315_D-R4-1
1q22
GGGGACGTGGCCCCTCCCCCCCGGAGCGGGACTCCAAGAACTCCGGGGGGCGCTGGGGGCTGACTTTCC
1887
|
|
4315_E-R4-1
1q22
TCCCCGCCACCCTTGGAGCACCTCAGCGTTCTTAGGGGAAGCCAGAGCCGGGGAGGATGCGGGAATAGGTTTGGTGGGGG
1888
|
|
4315_F-R4-1
1q22
GATCAGGTTCCCCTCCCCCGCATACACCTGGGCGCAGGTGAAAGCTCAGGGAGCGGGTGGGGGAGCCCGGGTT
1889
|
|
4315_I-L4-1
1q22
CTGGGACGGGCGGGGCGCCGAGGCCCAGGGCGCCTGAGGGGCGCAGAGGTGTCAGCGTGCAACCGCCGCCCCCCAGCGTTCC
1890
|
CGCCACCACCGCCACCACCCTCAAAGCCCGG
|
|
4315_K-L4-1
1q22
CCGGGGCTGGGGGTGGAGGATGGCGAGGATTTGACAAGTTCAGGGCCCCCTGGGATCCTTTCCCTACTCCCTGGTCTTGTTGGA
1891
|
CACCCTGTTTACCTGCCCTAATTGCCCCGG
|
|
4315-R3-2
1q22
GCTCCCCGGCTCCCTCACTGCGGCAGCCGCGGCCCCATAAATCGTGAGAGCGACGTGCTCCGGAGCCGAGAATGGAGAGGGCC
1892
|
GGGGAGC
|
|
4338-L5-2
1p34.3
GCTGAGCAGTGGGGCCAGCTCCCGCCCACCCCCAGGAGACTGGTGAGGAGAGCTGTCCGGCTGAGCAGC
1893
|
|
4340-R3-1
10q21.3
GCTCTGCTTCCAGGCTGTATTTTTAGGCTGGCATTTAGGTTTGGCCTGGGGACAAGGGGCTGGAAAATGCAAGGC
1894
|
|
4346-L5-1
2p23.2
CCGGTGCGCGGCCGCGGCGAGGGCGGGGGAAGAAAAACACCCTGTTTCCTCTCCGGCCCCCACCGCGGATCATGTACCAGG
1895
|
|
4361-R5-1
Xp11.22
TGCTGGAGGTAAGGGTTTTCTGAAGCCTGGTGCCATGGCCACATGTGCACATGAGGGAGGGAGACGCTGAGGCTAGCA
1896
|
|
4498-L3-2
6p22.2
TTCCCCAGGCAGCAGCAGGCGCACGGCCGTCTGGATCTCCCTGGAGGTGATGGTCGAGCGCTTGTCATAATGCGCCAGGCGGGA
1897
|
|
4516-L5-1
10q11.22, 16q22.3
GGCAGAGCCAGGCAGGAGCCAGAGTCAGCCTGGGGGGTGATGGAGCTGAGGCCATCACCGGTCTGACAGTGGACCAGTATGGC
1898
|
ATGCT
|
|
454-R5-1
5q31.3
CCAGCTCCGCCAGCTCCAGCCCCAGGTCCTGCGCGATCCGGCCCACGAAGGTGCCGTGTTTGGCCTCCTCGGGGACGGAGTAGT
1899
|
GGAGCTGG
|
|
4593-R5-1
15q23
CAATCAATTAGCACATGAGTAATACCAAGCCCATTAGGACAAACTGATGCCGGGGGAGTTATGTCATCTGCTATAGAAATGATTG
1900
|
|
4610-R5-1
8p12
GCCCAGTTAATTGGTCTCTCAACCTACATTAGCTGTTGCATTGCAGCCAATTAGGCAGGGGCCAGAGGGC
1901
|
|
4610-R5-2
8p12
GCCCAGTTAATTGGTCTCTCAACCTACATTAGCTGTTGCATTGCAGCCAATTAGGCAGGGGCCAGAGGGC
1902
|
|
4642-R3-2
11q24.1
CAGCCTGCCTTTCACATATCCGAGCCCTCTGTGACACATCAGATTTAATGAGACTGCACAGATCTCAAATAAGGAAGGGGAGCGCTG
1903
|
|
4666-R5-1
1q21.3
GCCGGCTCCAACCCAGAGGCCCGGAATAGGCGCGGAGTTATAAATAGTGCCACCCGCAGGTGTTGGGGGGAGTCGGC
1904
|
|
4792-L5-2
2q31.1
GGCTTGGTTATGGGGGCAGTGGGGGCTGTAACTGGCTTCGTATGTGGCCATTTCCTGCCTTTGGTGCAGTTAAACCAAGCC
1905
|
|
4801-L5-2
1q32.2
ATTAATGTTTTTGTAGCAAACAGGAGGCAGAGTTCTCCAAAGGCTCTCATCTCTGTGCTTCCAGAAAATATTGAT
1906
|
|
4813-R3-1
16q22.3
ATGACATCTGATTGATAGCTTGGGCCAAAAAGGTTGGCAGGCCTGAAGGGGCGGGAGGGTTAACAGCCCGATTGTAAAATCAATG
1907
|
TCAT
|
|
4875-R2-2
3p22.1
TGTGAAGCCACAGGAAGGGGCTCTGTGACATCACAGGTAGGGGCAGTGTGAAGTCACAGGAAGGGGCTGTGGGAAGTCACA
1908
|
|
4912-L5-2
12q13.2
CTTGTTAGACAATCACAGCTGGGGGCCAGGGGTAAATTTAGCCTTTGTTCAGCCCCCAGTTATGTGTGGGATGCAGG
1909
|
|
4929-R4-1
17q25.3
GACGAACCTTGGCCGCAGTCCTTGCGAACTGTTCGCAAAACAGTGCGGGCTGCGGTGGGTCAGCGTC
1910
|
|
5032-R5-1
14q32.31
GGGCGCTCCAGTCTCGACGTTCCCGGGGTAGAGAGCAACGTCCGGGGACGAACGGGACGGGTGCGCCC
1911
|
|
5048-L5-1
11q13.1
GGTGTGCAGCAGAAGTACGCGTACAAGGAGCGGCGGGCCAAGCTGTACGTGTGTGAGGAGTGCGGCTGCACATC
1912
|
|
5071-R5-2
17q12
GATTCCTGCTCCCAGAGCCATAAAGTGGGAGCCCCCATTTATTAATTGGGCTGGGACTGGGGCGGGGGTC
1913
|
|
5107-L5-1
11q23.3
CAGTTTGTACTGGGGGGTCAAAGGGGAGTTCTTTTCCGAAGAATTCTGGGAGAGACGCCAACTAGAGCAAGCTG
1914
|
|
5210-L5-1
1p31.3
TGGGGTTGGATCCCCATGGGGCAGCTTTTGGACCACCAGTGTTAACCCAGGAATTGGAGCGATCTAAACCCTA
1915
|
|
5342-L5-1
8p21.2
TGGAAGGAGAGCAGCGGCATTTGGTTTGGTGGTGGGCAGATTTTCTTTTACGACTGCTAAATGCCTGCCTTTCTCCCCA
1916
|
|
5491-R5-1
6p21.33
GCCTCCCCTTCCAGGTCATTACCTGCGGCCGCGGAGGCAACAGCTGCCACCATGGCCTGATGAGTGATCTGGTGGGCGACGGC
1917
|
|
5521-L5-2
5q31.3
AGAGGGTGTGCTCTGGGGAGGGCCCACCCAAGACAGACCTCATGGCCTTCAGTCCCAGCCTTCCTCAGGGTCCATCCTCT
1918
|
|
554-R5-1
14q24.3
GGAGAGAGGCGCAGACAAGAGAAAATAAGCCTGCCCAGCAATCATGTCTGGGGCTGCTGGGAGGGCTCTCTCTGTTCTCTTTCC
1919
|
|
5554-R5-2
1p34.3
CCCCACCAACCACCAGTGCTCAGGACTTCTGCAAATCCCATTCGGATCTGGGAGCAGCTGATGAGGGGGTGGGG
1920
|
|
5638-R5-2
6q23.2
GGCTTTGCCCTTTTCGGTGACACAGGCTGTTGCTATTCCAAGCAGCCTATCACAGGCAGGGGGAGGGCC
1921
|
|
5640-L3-1
1p34.1
TCTCGAGAGGGGCAGGCACGGTGTTCCATGGCAAGACGGCGGTTGATGTATAGGCGTGGCATGAAGCTGGGCTTGCTGCTCTCA
1922
|
GA
|
|
5749-R5-1
18q23
ACAGGCTCATCCCTCTGAACAGATGAGATTAGTCGATCATGTAAAGTCAAAAGGGGGATTATGATGCTTGT
1923
|
|
5757-L5-1
19q12
GTTGGCGGCACGGTAGGTTCATTAGTCAATAAAGCATTGCCACGCGTTTTATTGAATTGTAACCCTATTTTGCCCTGAT
1924
|
|
5854-R5-2
11p14.1
GCCCTCCCTCCCACCGCACTTACACCTGAACTTGTCTCCAGCACTGCGGACACCCGGGTGACACATTCTTTCGGAGAGGGAGGGC
1925
|
|
5956-L5-1
1q41
CTATGCGTCTTGACGGATTTGGGGTTGGCAGAGCAGGCTGCCCCTGCTTTCTATCCCCATTCAGTCCACTTATAG
1926
|
|
5995-R5-1
7q11.22
CCTGCTTGATTTGCTTAATGGAAGCTGACAGTGAAGTTCAACCCTGATTGTCAGATTTCAGTAGGAACCTCAAGGGGG
1927
|
|
6008-R5-1
4p15.32
CGACTTTATCACCCATCGGTTATCTGTGTCGCCTGAAGGAACTCCGGGTAAGGTACAGGAAAAAGGTGGGGGTATTGTTG
1928
|
|
6008-R5-2
4p15.32
CGACTTTATCACCCATCGGTTATCTGTGTCGCCTGAAGGAACTCCGGGTAAGGTACAGGAAAAAGGTGGGGGTATTGTTG
1929
|
|
6016-R2-1
1q23.3
TTTCTGTATATGTTTCTGGAGTCCTGAGCCTGAGCTAAACAAAAGCAGGAGGCTGACGGGGCTGCTGGAGTTTGCAGAGA
1930
|
|
6023-L5-1
Xp11.4
GGTCTCTGGGGGGTTGGACCAGTCATCTGGCTCTGCCTTCCTCAGGGCAGAGCTGGCTGCTGGTGAGGCCAGGAGGCC
1931
|
|
6087-L4-1
9q33.1
GATGGAGAAGGTGGCAGGCAGTAATGGAGACAGAATTTCTGTTAACTGCTGTAATTAATGTTATGTCTCATC
1932
|
|
6096-R5-1
3q29
GCCATTTGGTACCTGATGTGATCGGGCTTTTTCCTGTCGTGTGAAAAAACGGGGCAGGATTAAAACATAAGGGAAAGGTGGT
1933
|
|
6192-L5-1
11q25
GTGCTGGGTGGGTGGTTTTTTATCTTCACGGATTTATGGAGTCCTTAAAACATCTGTTCCGTTCTGATTCCCCCGCTCAGTAC
1934
|
|
6198-R5-2
1q25.3
GCCGCCAGCACCCGCGGTGCCGCGGGGCCGCTCCGAGGAGCCTGAGAGACCCACGGAGGCTTCGCGGGAAGACGCGGCGGCG
1935
|
GCGGC
|
|
6242-R5-1
8q21.13
CCCTCACGAACTGTGCGGTAATGAGAAATCCAAACACCAGGTGCTCCAGGGGCTTTGGGTTTGTCACATATGCCACTGTGGGGG
1936
|
|
6287-L3-2
1p34.1
AGCAGCCAGGTGAGCCCCGAAAGGTGGGGCGGGGCAGGGGCGCTCCCAGCCCCACCCCGGGATCTGGTGACGCT
1937
|
|
6385-R5-2
11q13.1
GGCTCCGTCGACGTTCGGAGCCTGCTGGCCCGTCGGGCAGCTGTCGGGCCGCGGGAGTCGGTCCGTGGGCAGGGCC
1938
|
|
6409-L3-1
11q13.1
GTTCCAGAAGGCGGCGCGTGCGGTTGGGAACGCGGAGCGGACGGATTCGATTCAACGGGGTTCCGGACCGCGCTGCGCTATGG
1939
|
AGC
|
|
6434-R5-1
15q25.2
GTGGGCTGCATGTTCCCGCATTGCTGGTGAGGGTGCACGATCTGGCACTGCAGCTGGCTGGTGGGAGGGCTGCATCCTAC
1940
|
|
6490-R5-3
1q21.3
TCCTTCCCCCTTCGTGGCTTGCGGTCTCTCTTCCCCGCCTCGGCCCCCAGGAAGTGTGAGTGCTGGGGGTGGTGAGGTTAGGAG
1941
|
GGGGAAGCGTCATATGGGGGATGGGG
|
|
6496-R5-2
5q31.1
CTCCCTCAGGCCCCGCCTGCACCTTTCCCAGCCCCCAGGACTCTAGGGGAAGTGGTGGGTGGGGGAGGGGG
1942
|
|
6584-L5-1
12q24.23
GCTTGGTGAGAGGAGGAGGAGGCAGGGCCGACCGCCACCCGCCTGTCTGCCATCTGGTCCCCTTCCCCTCCCTCCTCTCATTGC
1943
|
|
6590-L5-1
Xq13.1
CAGCTGGGGCAGAGGCTGTTTATTTGGTTTCTCATTAACCAAAGGAAGTGCCTGGATCAGATGGAGCCTCTGCTGCTTGACTG
1944
|
|
6642-R5-1
14q11.2
ACACTCTCCTCTTGTCTCCTTGTAATCAATTCATTGTCATCAGAAATGTGTGACACCTCGAGGGGAGGGGAGGACGTGT
1945
|
|
669-R5-2
11q13.1
CCAGCGGCCACCTTTCCTCCCTGCCCCATTGGGACAGTCGAGACTGGATCTGTGGGGTTTCCCGGGAGGGTGGCTCAGGGCTGG
1946
|
|
6718-L3-2
3p22.1
CTTTGGAGGCAGAAGCTCTGGCCCCTATGGTGGTGGAGGCCAATACTTTGCCAAACCACAAAACCAAGGTGGCTATGGCGGTTCC
1947
|
AGTAG
|
|
6839-L3-1
3p21.31
AGGGGTGGGGGTGGCAGGGCCCAGCGGGCTGGCAGGCAAACCCTGGTTTTGGCCCAGGGACCTATAATCAGCTCCTGCCCCT
1948
|
|
6880-L3-2
1q42.13
GGCTTGCAGAATGTGGATGTCTTCGCGGGGGAGGTGGCCACGTTCTCCTGTGAGGTGTCTCACGCGGGTGGGCC
1949
|
|
6908-L3-2
4q28.3
TGTGGGGCTTGCCAGTCTTGTTCCCCCAGTAGCCTCTGTGCACGGGGACAATGGAGAGCTTGGGCAGGATGATAGCCCCACG
1950
|
|
6984-R4-1
1q21.3
CCCCACTCCCTTGCAGGCTGCAGGCACTAGGGCTCTCAGGAATTGCAGGGACTTTGGTGCCCAAGCAAATGCTTGGGCAGGGGG
1951
|
|
7029-R5-1
Xq28
CAGGAGCGTGATGCCTACTTGGGTCAGCGGCTGCACAGCAGGTGCGGCTGCTGCTGGGGCAGGGCTCTTG
1952
|
|
7061-R5-2
1p13.3
TCATGGCAGCGACCCACCTCCAGTCCCCTGGACAATCGGGTACAAGAGACTTAAGGTTGGGCATGGGAAGGGTGGGGTTTCCATGA
1953
|
|
7066-R5-1
15q23
CAAGGTCTTTGGTCTTGGAGGAAGGTGTGCTACTGGAAGAGGCCACCGAGGCAGGGCTGGTGGGGGCATCTTTTTTCAGGCTACG
1954
|
GGCCTTG
|
|
7069-R5-1
3p21.31
CTCAGGGAGCCCCAAAGGGTTTATGGGTCTCCCAATGAATGGGAGCCTGTTGAGCTCGGAGGGGGCCGGGCCCGAG
1955
|
|
7113-R5-1
18q21.2
CGTCTTGCTGGCTCCCCAAGGCTTCCAGGCATTTGCCCATCTGGTGAGGCCTCCGGAGCAGGGGGGCTAATTAGGCG
1956
|
|
7126-L3-1
5q31.1
CAGGGGCGCGGGCCGGAGAGCGGGTGTGCAAAGTGGGCGCAGGGCCCTGGGGCCGCGCCCCTTGCTCTGCCGGCTCGACTCT
1957
|
TG
|
|
7141-R5-1
9p22.2
ACTCCACTCTTTGTTGCAACTTGCTGACTCGGGTGTCCCTTGCCAAAAAGGGGTAGGTGGTAGGTTACATAACAAGGATTGGGGT
1958
|
|
7221-R5-1
8p21.3
GGAGATGTGCGCCCCCTCTGCCACGCCCCCACCTTCCTGGCAGGTGGTGGGCCACCAGGGTGGTGGGAAGTGGCCGGGGTTTC
1959
|
TCTCC
|
|
7313-L5-2
2q33.2, 20q13.2
CTTGGTGGTTCCTTGAGGGCTTTGATGATCAGGGCAGAGGCAGAAGGCACCACCTCAATCTGGGCCTGTCTGTTCTGAATGGTCA
1960
|
GTTTCACTGTAATCCTCAGG
|
|
7352-R3-2
1q25.2
GCCTCTGTGCGCATGGATATAATCAGCTTTGATAGGCAGAGGCTGAGGCTGTTTTTCCAATTAGAGCTGTTAGAGGATTCTGGCAG
1961
|
GGGC
|
|
7356_A-R4-1
8q24.3
CGGAGGTCGCTCGCTCGCTCGCTCGGCTCGCTGACTCGCCGGAGCGCTCTGTGGCGGTCGGCGGCAGGTCGGTCGCGAGAGCG
1962
|
GGCTCTG
|
|
7356-L5-1
8q24.3
GGGGGCGAGGCTATGTCGCGGTGGCAGCCCGGATGGGCCGGCAGGGCCGGGAGTAACGGGACGTCGCCGCGGAGCTTCTTCC
1963
|
CCC
|
|
7367-L1-1
6p21.33
CGGTCCCCAGAGGGGGCAGCTCTAACCCTAAACAAGTGCTCAACCCTTGAATGGGCCTGGATGGCTCCCCTGGGGACTG
1964
|
|
7384-R3-1
12q12
GGCATTTCTTCTTGTGTTTCCTCTTCTCCTCTTCTGGGGAGGGATGAAGGAGATCCTTTGCGAGAGGCATGTT
1965
|
|
7411-R3-2
18q22.3
GAGTGTGAACTGGCTCCAGCTGTGACAATAAAACAGCAGGTGGCTGCTGTCATTAGGGGTGGCAGATGAGGCAGGGGACTAACAT
1966
|
TC
|
|
7569-L5-2
11q23.2
GGCCTGTCTTGGGGGTAGCTTTGTGGCCTGAAAACAAATCATCCTTCACAGCTTGCTCCCAAGTCCAATAAGCC
1967
|
|
7571-L5-1
2p21
CTTAGGGGTGGGGGAGCCCTGTTAGCCCTGTAAATAAAGTTTAACGAGGTGAACAATGGCTGGCTCTGTCCCTGAG
1968
|
|
7572-R5-2
11q12.1
ATCACCTTTCCCCCTCCCATGTGCTTTCCTTCATTTGAGATCTTTTGACCTTTGGCTTTATTTGGGAGGGGGAAGGGTGAT
1969
|
|
7660-L5-1
19q13.32
GAGCTTTATCGCTCGGGCCAGGCGGAGGCCGGGCGGCCCCGTGGCTTCCGGAGGCGCCCGGGCGGGATGAGCTC
1970
|
|
7702-L2-1
10q21.2
GGGGCGGGGAGGAATTCCGGTTCTCTGGGACTTTCCAAAAAAGGCGAAGATCCGGTGCCGGCGGCTCCGCCTCCCTAGCCCT
1971
|
|
7736-L5-1
8q24.21
GGAGACCGTCGCCTTCTGGTGGGTGGTGGGGATGGACTTCTCCTCCGTCTACCATGAGGGGAAGTCTCT
1972
|
|
7743-L5-1
20q12
AAGGCAGGTCGAACTGGAGCTGGCTGGGGAGCTCATTAGCACCTCGCCAGAGCCGAGGGCTGCCTGCCTT
1973
|
|
7781-R5-2
17q12
AGCCTGTTCCGTGCTCGCTAACTATAAACTATCTGATTTATATTCATTAACCAGTACTAGACAGCGGCAGGCACAGGCT
1974
|
|
7824-R5-1
6q16.2
CCTGGATGCTGTTTCATTATGTAGAGTCAGGCAAAAGACAGACGGATGTGTGTGTGAGGCGGCGATGAAGCTGGCACCAGG
1975
|
|
7846-L5-2
17q12
GCCCTGGCAGGGCTGGTGGAAGGGATGGGATGGAGGAGGACTCACTTCCCAGCCTCTGCCTTCCCCTTCCTCCCTCCCTCCCCT
1976
|
GGGC
|
|
7883-R5-1
11q14.2
CTCTCCGTGCTTCTCGGCCCGCCGCCCTTCCTGTCTCGGGGACACGGTTTCTAAATAAGGTTGGGAGGGTGAGAGGGCGGGAGG
1977
|
GGAGAG
|
|
78-R4-1
1q21.3
CCAAATTGAGAGCTCAAGGACTACAACTCCCAGTGTGCACCACAATTGCTTTGTATGTACCTTGGGAGTTGTAGTCCCCCTTGAGAA
1978
|
GCTCTGG
|
|
7949-R5-1
5q31.3
GGTGCGCGCGGTGGACGCCGATTCGGGCTACAATGCGTGGCTTTCGTATGAATTGCAGCTGGCGGCGGTCGGCGCGCGCATC
1979
|
|
7971-L5-1
9q31.3
AGCCTGCACCCAGGGAGCGGCAGGGGAGTGACACAGTGAGTCACAGACCACAACAAAGCCCTTCCTGGCATGTCGGGCT
1980
|
|
8016-L3-1
12q21.1
AGAGGGGTGACTGCGGGGCTTGTTGCGCTGAAGATTTACAATGTACTTCTTGCAGGCGGCTCAGCAACCCCCTCT
1981
|
|
8062-R5-1
11q23.2
GGGCAGGCGTCCTGCGGGCTCCAGGCTTCTCTGCCACAGCTGGCGGAGGTGCTTAAGGCCTTGGACCCCGTGACCTTTGCCC
1982
|
|
8077-R3-1
Xq22.3
CCAATTCTCACTTAGGTGTTAGGGATTTAATGATACTCCTCTGAAGAGTATTTTTACTACCTGAGGGTGGGGAATGG
1983
|
|
8089-L5-1
4p16.2
GGGAGGGGGTGGCCCTGAGCTTATAAGGGTCTCTAAGAGCCAGGAGACAGTCAGCCTGGCTACCTCTAATCTC
1984
|
|
8239-R5-1
Xp21.2
TGACTTTTCATCCCCTTCACACCCTCTGCATTTCCCTTTTGGAGAGCTCAGAGGGAGGTGAAGTGGGAAGAAAATCA
1985
|
|
8250-R5-2
9p11.2
CGGAGCCGCCCGCGCCAGCCTCTCCATCTCGCAAGTTTTAATTAACGCTGAGGGAGAGGCGGCTGACGGGCGGGTCGG
1986
|
|
8281-L5-2
11q13.4
CCAGCCCTCAGCTGCAGCTGGGGAGGGGCTGAAGGGTAGGGAGCCCTATCCCACCTGCATCAGAGGCCTGG
1987
|
|
8298-R5-1
22q13.1
GATGCCGGGCGCCCGCCGCAGCCGCTGCCGCCGGAGCCCGGGATGGGGCGAGAGGCTGCGGCGGACGCCAGCATC
1988
|
|
8329-L5-1
1p34.2
GAGCTGACCCAGGGTGGGCGTTTGGAAGGACTCAGCCTCCGTCCTGCCTGGTGCTGGGATCAGCTT
1989
|
|
8336-R5-2
Xq13.1
CCTCCCCAAGCAATCTGCTCACCCACTTGTTGTCATGGTGACTCTGGCTGGGGGTGTGGGGACTGAGTGGGGAGG
1990
|
|
8394-L5-2
7p13
GGGGCCAGGGATAGTCGGAGATGGGCAGGGCGGGGGCCCCACTGGCGAGGGGCCCTCGGCTTCTGGGGTCCCTGAGCCCC
1991
|
|
8564-L5-1
5q13.2
AGGGGGTGGGAGGTCTGTTTGGCAACTGGGGTGAAGGGATTGCCCTTCCCCTGCTGGGATTCCCCCAGCCCCT
1992
|
|
8564-R5-2
5q13.2
AGGGGGTGGGAGGTCTGTTTGGCAACTGGGGTGAAGGGATTGCCCTTCCCCTGCTGGGATTCCCCCAGCCCCT
1993
|
|
8898-R5-1
17p13.3
GGCGCTGTCGGCCGGGGCGGCCGCCGGCAACTCGTCCGTCTTGATAACCATGGTGGCGGGAGCGGGCGTCCGCCTCGGCTGTC
1994
|
CGCGCC
|
|
9021-L5-2
10q23.1
GATGGTGTGGGGAGCTTGGGTGTTTGTTTCCCATTTCACAAAACAAAGCAGCCAACCTTACATTCATC
1995
|
|
9068-R5-2
14q24.3
GTCTGCCTCTTTCTCTGCAGTAATTGCTTCCTGACATTTGTTTATTTTAATTAGGAGAGCAGTCTTGATCAAGAGGGAGGGCAGAC
1996
|
|
9087-L5-2
3p14.1
AGGAAGGGAATGGACTGGGAGGGTTTCTTTTCCTGATGGAAAGCCTATTTTTCTTATTGTGTTCCTTTTCT
1997
|
|
9134-R5-1
8q24.3
GCTGCTTTGGGGGTTTTCCGCCCTTCCGCGCGGCTGCAGCTCCCCACGGCAGCCCCGCAACCAGGCGGATAACCCTTTCCTCGGC
1998
|
|
9217-L3-2
2q31.2
TCCACTGTTGGCTTTAGTCACGGCGGGGATCGTCAGTTTAGCGCGGCCATCGCTAAAGGAGATCTGCACGCCGGGCAGAGTGGAA
1999
|
GTGGA
|
|
9245-R5-1
5q21.1
AGCCTAAATACATTAGCGAGCTGGTAAAGCTTTTAAGGCCTTCTTGGGAGCGAGTGGCTGGCTAATGAGAGGTT
2000
|
|
9287-L5-2
17q21.1
TGCATGTGTGGGCTGGGGAGGGCTCTGAATATCTCCTGGAACGGTACCCAGAGCCCTGTGGCTCTGCGCATGCG
2001
|
|
9369-L5-1
Xq26.3
TCCCCTGATTTCCCTCTGTGGAAGAATGTGTGAATTCACATGCATCCTGTCCTAACTGTGCAGGGGAAAATTCCAGTCAGGGGA
2002
|
|
9384-R5-2
16q22.3
AAACCAGTTAGTCAATTCGTTCAGGTCCCTAAGTGGCGATTTGTGGTAATGTCTACATCAATACGGACGGAGCGGTTTGCTAGCTG
2003
|
GTTT
|
|
9387-R2-2
3p21.1
TCTCCATCCTCTGTCTCCCTTGATCCTCTGTTCTCCCTGATGGCTTTGAGATGAAGGCGACGGCAAGGATGGAGG
2004
|
|
9564-R5-2
9q33.2
GGCGCCCGCCGGGCTGTCCGGAGCGGCCGATGGGGCCCGTGTGAGCGCGCCCAGGCCCGGCCCGGTGCCCGGCGGGCGGC
2005
|
|
9605-R5-1
Xp11.4
GTTCTCCTTGGAACTCAGAGCACATAGTGACTCCTTTTTCCTTTTGTGGTCAGGAAATGAGTTTTGCTCTGTTTTTCACTTGGGGGC
2006
|
|
9691-L5-1
14q24.3
GCAAGGGGCCAAGAGGGAGATGCGGATGAAATGGATGATTTAATGGGTCATCTCTCCTGTAGTTAATTTCTCTAGATCTCTTGT
2007
|
|
9770-R5-2
17q21.2
CACCTGTCATTCTGCAGCCCCCTCCCTAGCAAGCTCCAGTTATAGGGCTGGGGTTGGCAACAGGTG
2008
|
|
9774-R2-2
13q13.3
GCTTGTCCTAAAAGATCTTCCTTCTGTTTCCCTGGGTTTATCCACTTGGTTGGCCTGATGGGAGCAGGAGGCGGTGAGGGGGCGG
2009
|
GC
|
|
9812-L3-1
5p13.3
AGCAAGCTGGGGAGCCCAGATAAATAGAGCTTTCTGTTTCCTTTCCTGGAGTCTAAAATATCTGATCTGGAGGTTCCCTCCCTGCT
2010
|
|
9866-L5-1
11q13.1
GGGCTGGGGCTGGCAATGGAGCCCCTCTCCTAGCCTCCTCCATGGGGACTGGGGCTCCAGGGGCCCCATCCTGCTCAGCCTCCC
2011
|
|
999997-R4-1
17q25.3
TCTTCCTCCACCCTGCCCCACCCCTAGGTCTCTTTATTGATTCAAAGGTTAAGGAAGCTCCTGGGGGCTTGAGGGGGTGGCACAGT
2012
|
TTTGGTGGGGCCCAGTGAGGA
|
|
let-7b
22q13.31
CGGGGTGAGGTAGTAGGTTGTGTGGTTTCAGGGCAGTGATGTTGCCCCTCGGAAGATAACTATACAACCTACTGCCTTCCCTG
2013
|
|
let-7c
21q21.1
GCATCCGGGTTGAGGTAGTAGGTTGTATGGTTTAGAGTTACACCCTGGGAGTTAACTGTACAACCTTCTAGCTTTCCTTGGAGC
2014
|
|
let-7e
19q13.33
CCCGGGCTGAGGTAGGAGGTTGTATAGTTGAGGAGGACACCCAAGGAGATCACTATACGGCCTCCTAGCTTTCCCCAGG
2015
|
|
miR-100
11q24.1
CCTGTTGCCACAAACCCGTAGATCCGAACTTGTGGTATTAGTCCGCACAAGCTTGTATCTATAGGTATGTGTCTGTTAGG
2016
|
|
miR-101
9p24.1
ACTGTCCTTTTTCGGTTATCATGGTACCGATGCTGTATATCTGAAAGGTACAGTACTGTGATAACTGAAGAATGGTGGT
2017
|
|
miR-101
1p31.3
TGCCCTGGCTCAGTTATCACAGTGCTGATGCTGTCTATTCTAAAGGTACAGTACTGTGATAACTGAAGGATGGCA
2018
|
|
miR-1182
1q42.2
GGGACTTGTCACTGCCTGTCTCCTCCCTCTCCAGCAGCGACTGGATTCTGGAGTCCATCTAGAGGGTCTTGGGAGGGATGTGACT
2019
|
GTTGGGAAGCCC
|
|
miR-1207-5p
8q24.21
GCAGGGCTGGCAGGGAGGCTGGGAGGGGCTGGCTGGGTCTGGTAGTGGGCATCAGCTGGCCCTCATTTCTTAAGACAGCACTTC
2020
|
TGT
|
|
miR-1224-5p
3q27.1
GTGAGGACTCGGGAGGTGGAGGGTGGTGCCGCCGGGGCCGGGCGCTGTTTCAGCTCGCTTCTCCCCCCACCTCCTCTCTCCTCAG
2021
|
|
miR-1225-5p
16p13.3
GTGGGTACGGCCCAGTGGGGGGGAGAGGGACACGCCCTGGGCTCTGCCCAGGGTGCAGCCGGACTGACTGAGCCCCTGTGCC
2022
|
GCCCCCAG
|
|
miR-1228*
12q13.3
GTGGGCGGGGGCAGGTGTGTGGTGGGTGGTGGCCTGCGGTGAGCAGGGCCCTCACACCTGCCTCGCCCCCCAG
2023
|
|
miR-1234
8q24.3
GTGAGTGTGGGGTGGCTGGGGGGGGGGGGGGGGGGCCGGGGACGGCTTGGGCCTGCCTAGTCGGCCTGACCACCCACCCCAC
2024
|
AG
|
|
miR-125a-5p
19q13.33
TGCCAGTCTCTAGGTCCCTGAGACCCTTTAACCTGTGAGGACATCCAGGGTCACAGGTGAGGTTCTTGGGAGCCTGGCGTCTGGCC
2025
|
|
miR-126
9q34.3
CGCTGGCGACGGGACATTATTACTTTTGGTACGCGCTGTGACACTTCAAACTCGTACCGTGAGTAATAATGCGCCGTCCACGGCA
2026
|
|
miR-1268
15q11.2
TAGCCGGGCGTGGTGGTGGGGGCCTGTGGTCCCAGCTACTTTGGAGGCTGAG
2027
|
|
miR-130b
22q11.21
GGCCTGCCCGACACTCTTTCCCTGTTGCACTACTATAGGCCGCTGGGAAGCAGTGCAATGATGAAAGGGCATCGGTCAGGTC
2028
|
|
miR-140-3p
16q22.1
TGTGTCTCTCTCTGTGTCCTGCCAGTGGTTTTACCCTATGGTAGGTTACGTCATGCTGTTCTACCACAGGGTAGAACCACGGACAG
2029
|
GATACCGGGGCACC
|
|
miR-145
5q33.1
CACCTTGTCCTCACGGTCCAGTTTTCCCAGGAATCCCTTAGATGCTAAGATGGGGATTCCTGGAAATACTGTTCTTGAGGTCATGGTT
2030
|
|
miR-149*
2q37.3
GCCGGCGCCCGAGCTCTGGCTCCGTGTCTTCACTCCCGTGCTTGTCCGAGGAGGGAGGGAGGGACGGGGGCTGTGCTGGGGCA
2031
|
GCTGGA
|
|
miR-150
19q13.33
CTCCCCATGGCCCTGTCTCCCAACCCTTGTACCAGTGCTGGGCTCAGACCCTGGTACAGGCCTGGGGGACAGGGACCTGGGGAC
2032
|
|
miR-181b
9q33.3
CTGATGGCTGCACTCAACATTCATTGCTGTCGGTGGGTTTGAGTCTGAATCAACTCACTGATCAATGAATGCAAACTGCGGACCAAA
2033
|
CA
|
|
miR-181b
1q31.3
CCTGTGCAGAGATTATTTTTTAAAAGGTCACAATCAACATTCATTGCTGTCGGTGGGTTGAACTGTGTGGACAAGCTCACTGAACAA
2034
|
TGAATGCAACTGTGGCCCCGCTT
|
|
miR-181d
19p13.12
GTCCCCTCCCCTAGGCCACAGCCGAGGTCACAATCAACATTCATTGTTGTCGGTGGGTTGTGAGGACTGAGGCCAGACCCACCGG
2035
|
GGGATGAATGTCACTGTGGCTGGGCCAGACACGGCTTAAGGGGAATGGGGAC
|
|
miR-185*
22q11.21
AGGGGGCGAGGGATTGGAGAGAAAGGCAGTTCCTGATGGTCCCCTCCCCAGGGGCTGGCTTTCCTCTGGTCCTTCCCTCCCA
2036
|
|
miR-214
1q24.3
GGCCTGGCTGGACAGAGTTGTCATGTGTCTGCCTGTCTACACTTGCTGTGCAGAACATCCGCTCACCTGTACAGCAGGCACAGAC
2037
|
AGGCAGTCACATGACAACCCAGCCT
|
|
miR-23a*
19p13.12
GGCCGGCTGGGGTTCCTGGGGATGGGATTTGCTTCCTGTCACAAATCACATTGCCAGGGATTTCCAACCGACC
2038
|
|
miR-30a
6q13
GCGACTGTAAACATCCTCGACTGGAAGCTGTGAAGCCACAGATGGGCTTTCAGTCGGATGTTTGCAGCTGC
2039
|
|
miR-30d
8q24.22
GTTGTTGTAAACATCCCCGACTGGAAGCTGTAAGACACAGCTAAGCTTTCAGTCAGATGTTTGCTGCTAC
2040
|
|
miR-320a
8p21.3
GCTTCGCTCCCCTCCGCCTTCTCTTCCCGGTTCTTCCCGGAGTCGGGAAAAGCTGGGTTGAGAGGGCGAAAAAGGATGAGGT
2041
|
|
miR-320b
1q42.11
TGTTATTTTTTGTCTTCTACCTAAGAATTCTGTCTCTTAGGCTTTCTCTTCCCAGATTTCCCAAAGTTGGGAAAAGCTGGGTTGAGAG
2042
|
GGCAAAAGGAAAAAAAAAGAATTCTGTCTCTGACATAATTAGATAGGGAA
|
|
miR-320b
1p13.1
AATTAATCCCTCTCTTTCTAGTTCTTCCTAGAGTGAGGAAAAGCTGGGTTGAGAGGGCAAACAAATTAACTAATTAATT
2043
|
|
miR-335
7q32.2
TGTTTTGAGCGGGGGTCAAGAGCAATAACGAAAAATGTTTGTCATAAACCGTTTTTCATTATTGCTCCTGACCTCCTCTCATTTGCTA
2044
|
TATTCA
|
|
miR-34a
1p36.23
GGCCAGCTGTGAGTGTTTCTTTGGCAGTGTCTTAGCTGGTTGTTGTGAGCAATAGTAAGGAAGCAATCAGCAAGTATACTGCCCTA
2045
|
GAAGTGCTGCACGTTGTGGGGCCC
|
|
miR-34b*
11q23.1
GTGCTCGGTTTGTAGGCAGTGTCATTAGCTGATTGTACTGTGGTGGTTACAATCACTAACTCCACTGCCATCAAAACAAGGCAC
2046
|
|
miR-34c-5p
11q23.1
AGTCTAGTTACTAGGCAGTGTAGTTAGCTGATTGCTAATAGTACCAATCACTAACCACACGGCCAGGTAAAAAGATT
2047
|
|
miR-371-5p
19q13.41
GTGGCACTCAAACTGTGGGGGCACTTTCTGCTCTCTGGTGAAAGTGCCGCCATCTTTTGAGTGTTAC
2048
|
|
miR-373*
19q13.41
GGGATACTCAAAATGGGGGCGCTTTCCTTTTTGTCTGTACTGGGAAGTGCTTCGATTTTGGGGTGTCCC
2049
|
|
miR-451
17q11.2
CTTGGGAATGGCAAGGAAACCGTTACCATTACTGAGTTTAGTAATGGTAATGGTTCTCTTGCTATACCCAGA
2050
|
|
miR-486-3p
8p11.21
GCATCCTGTACTGAGCTGCCCCGAGGCCCTTCATGCTGCCCAGCTCGGGGCAGCTCAGTACAGGATAC
2051
|
|
miR-491-3p
9p21.3
TTGACTTAGCTGGGTAGTGGGGAACCCTTCCATGAGGAGTAGAACACTCCTTATGCAAGATTCCCTTCTACCTGGCTGGGTTGG
2052
|
|
miR-498
19q13.41
AACCCTCCTTGGGAAGTGAAGCTCAGGCTGTGATTTCAAGCCAGGGGGCGTTTTTCTATAACTGGATGAAAAGCACCTCCAGAGCT
2053
|
TGAAGCTCACAGTTTGAGAGCAATCGTCTAAGGAAGTT
|
|
miR-557
1q24.2
AGAATGGGCAAATGAACAGTAAATTTGGAGGCCTGGGGCCCTCCCTGCTGCTGGAGAAGTGTTTGCACGGGTGGGCCTTGTCTTT
2054
|
GAAAGGAGGTGGA
|
|
miR-638
19p13.2
GTGAGCGGGCGCGGCAGGGATCGCGGGCGGGTGGCGGCCTAGGGCGCGGAGGGCGGACCGGGAATGGCGCGCCGTGCGCCG
2055
|
CCGGCGTAACTGCGGCGCT
|
|
miR-663
20p11.1
CCTTCCGGCGTCCCAGGCGGGGCGCCGCGGGACCGCCCTCGTGTCTGTGGCGGTGGGATCCCGCGGCCGTGTTTTCCTGGTGG
2056
|
CCCGGCCATG
|
|
miR-671-5p
7q36.1
GCAGGTGAACTGGCAGGCCAGGAAGAGGAGGAAGCCCTGGAGGGGCTGGAGGTGATGGATGTTTTCCTCCGGTTCTCAGGGCTC
2057
|
CACCTCTTTCGGGCCGTAGAGCCAGGGCTGGTGC
|
|
miR-744
17p12
TTGGGCAAGGTGCGGGGCTAGGGCTAACAGCAGTCTTACTGAAGGTTTCCTGGAAACCACGCACATGCTGTTGCCACTAACCTCA
2058
|
ACCTTACTCGGTC
|
|
miR-885-3p
3p25.3
CCGCACTCTCTCCATTACACTACCCTGCCTCTTCTCCATGAGAGGCAGCGGGGTGTAGTGGATAGAGCACGGGT
2059
|
|
miR-92a-2*
Xq26.2
TCATCCCTGGGTGGGGATTTGTTGCATTACTTGTGTTCTATATAAAGTATTGCACTTGTCCCGGCCTGTGGAAGA
2060
|
|
miR-92b*
1q22
CGGGCCCCGGGCGGGCGGGAGGGACGGGACGCGGTGCAGTGTTGTTTTTTCCCCCGCCAATATTGCACTCGTCCCGGCCTCCG
2061
|
GCCCCCCCGGCCC
|
|
miR-98
Xp11.22
AGGATTCTGCTCATGCCAGGGTGAGGTAGTAAGTTGTATTGTTGTGGGGTAGGGATATTAGGCCCCAATTAGAAGATAACTATACA
2062
|
ACTTACTACTTTCCCTGGTGTGTGGCATATTCA
|
|
miR-99a
21q21.1
CCCATTGGCATAAACCCGTAGATCCGATCTTGTGGTGAAGTGGACCGCACAAGCTCGCTTCTATGGGTCTGTGTCAGTGTG
2063
|
|
5.5 Example 5
Analysis of Target RNA from Additional Lung Cancer Cell Lines
Total RNA was prepared from the eight cell lines (seven lung cancer cell lines and one normal lung cell line) listed in Table 26. Cell lines were purchased from LGC promochem (ATCC) and cultured according to ATCC guidelines.
TABLE 26
|
|
Normal lung and lung tumor cell lines
|
Cell line
ATCC number
Cancer type
|
|
H520
HTB-182
squamous cell carcinoma
|
H69
HTB-119
small cell lung cancer
|
H146
HTB-173
small cell lung cancer
|
H23
CRL-5800
adenocarcinoma; non-small cell lung
|
cancer
|
NHBE
CC-2540
normal Bronchial epithelial cells
|
H187
CRL-5804
small cell lung cancer
|
calu 1
HTB-54
epidermoid carcinoma
|
calu 3
HTB-55
anaplastic carcinoma
|
|
Microarray data acquisition and analysis were conducted as described in Example 4.
Total RNA from normal bronchial epithelial cells (NHBE) was used as a control.
The microarray data was analyzed to identify target RNAs that were present at increased levels in at least four of the cell lines tested. Table 27 shows the target RNAs, the probe sequences used to detect the target RNAs, and the fold-increase in each of the cell lines, relative to NHBE cells.
The microarray data was further analyzed to identify target RNAs that were present at increased levels in two or three of the cell lines, but for which the average increase in the level of the target RNA relative to NHBE cells was at least 5-fold. Table 28 shows the target RNAs, the probe sequences used to detect the target RNAs, and the fold-change in each of the cell lines, relative to NHBE cells. Table 29 shows the pre-microRNA sequences and chromosomal location of the pre-microRNA gene for each of the target RNAs in Tables 27 and 28.
The microarray data was then analyzed to identify target RNAs that were present at least 5-fold decreased levels in at least four of the cell lines. Table 30 shows the target RNAs, the probe sequences used to detect the target RNAs, and the fold-change in each of the cell lines relative to NHBE cells. Table 30 also shows the number of cell lines in which the same target RNA is present at least 2-fold increased levels. Table 31 shows the pre-microRNA sequences and chromosomal location of the pre-microRNA gene for each of the target RNAs in Table 30.
TABLE 27
|
|
Target RNAs present at increased levels in at least four cell lines
|
SEQ ID
Calu1
calu3
H146
H187
H23
H520
H69
|
Gene
Probe sequence
NO
FC
FC
FC
FC
FC
FC
FC
|
|
10083-L5-1
CCCTCTTCCTTTCTACCCCCTCTCTCCACCC
2064
−1.00
−1.00
6.68
2.01
4.16
4.70
19.19
|
|
10333-L5-1
TGCCCTGCCCACCCCCTCCCCTGCCCCG
2065
−8.68
−8.68
1.38
2.28
2.04
2.09
4.83
|
|
10398-R5-1
TTGCTACCCGTTTCCCCTCCTCTTGAAGTTGCTT
2066
−1.00
−1.00
3.24
1.35
20.09
10.86
13.61
|
|
13122-L5-1
TTAGGAAATTCCATCTCACCTGCTCCAGTCC
2067
−1.77
1.01
4.68
1.44
4.33
3.39
84.80
|
|
13124-L5-1
TCCTCCCCTCCGCGAAAGCCTAAACTTACCCCTCA
2068
−1.00
−1.00
5.38
−1.00
5.68
2.02
19.83
|
|
13163-R5-4
ACCTCCCCTCCTTCTCTCCCTCCCACAAGACCAA
2069
−1.18
−2.47
4.54
3.26
6.06
2.05
20.32
|
|
13185-L5-3
TTCTGTTTTTTTTCTTCCCTCTCTCCCCTCTT
2070
−1.99
−1.99
5.80
3.21
12.07
3.25
16.10
|
|
13195-L5-3
TCTATATTCCCCCTCCATGACCATTTGTATTAG
2071
−1.00
−1.00
2.03
−1.00
23.44
12.07
6.32
|
|
13219-L5-1
CTCTGACTCCCTCACTCAGTCTCTCTGCTCCAGC
2072
−1.00
1.77
7.06
2.04
9.36
3.89
89.50
|
|
13247-L5-2
CTTCCCCTCCCGACCTCAGAGCCCTGTTCTTCCT
2073
−1.00
−1.00
2.45
1.33
13.02
3.99
10.40
|
|
13334-L5-2
AGGACTCCCCTCCCCTCCCACTGTGCCCTGTC
2074
−2.05
−2.05
3.45
−1.05
7.61
2.31
8.48
|
|
13335-L5-3
ACCTCAGCCTCCACTGCCCTCCTGCCGCATCCTAT
2075
−2.19
−2.19
4.64
5.53
2.19
−1.17
7.44
|
|
25-R5-2
TTCTGCTTTCCCAGAGCCTCACCCCCTCTTTT
2076
−1.00
−1.00
3.62
−1.00
2.55
2.18
4.29
|
|
266-R5-2
GTCGCCCCCTCCCCCAAGTTGAGACTTGCA
2077
−2.31
−2.31
3.23
1.50
9.97
5.43
10.49
|
|
3249-L5-1
GCCGCCATCCCCGGAGCCGCCGCCGCCGCCGCC
2078
1.78
1.99
3.86
81.53
5.02
2.61
69.65
|
|
3371-L5-2
CTTTCCTTTCCTCCCCTCCACACCCCATGACTCCC
2079
−1.00
−1.00
4.01
1.42
12.35
5.21
16.88
|
|
3744-R5-1
CTTCTCCTTCCTCCCTGCTCCCCTCCCACTAATGC
2080
−2.39
5.28
7.66
12.05
14.66
5.31
107.49
|
CAAAT
|
|
4855-R5-1
CGGGTCTCCCGCTTCCCCCTCCTGCTCCAAGG
2081
−5.66
−8.69
3.89
3.18
3.61
2.49
9.85
|
|
5107-L5-1
AACTCCCCTTTGACCCCCCAGTACAAACTG
2082
−1.00
−1.00
5.89
−1.00
6.60
3.56
35.94
|
|
6235-R5-2
TCTGCTCCAAAAATCCATTTAATATATTGT
2083
−1.00
1.77
10.45
7.18
13.80
16.55
207.50
|
|
6474-L5-1
CCCTAATTAAAGCCATCCCCTCTTCCCCCTTCACC
2084
−1.00
−1.00
7.06
2.24
8.81
2.57
8.35
|
|
6490-R5-3
CCCCATCCCCCATATGACGCTTCCCCCTCCTAAC
2085
−2.09
−2.09
2.58
−2.09
9.85
6.98
8.49
|
|
6681-R2-1
CCTGTTTTCTCCCCTCTCTCTCTGCCCCTCC
2086
−2.21
−2.21
4.83
2.74
6.51
4.82
19.47
|
|
7572-R5-2
ATCACCCTTCCCCCTCCCAAATAAAGCCAAA
2087
1.39
−1.00
7.08
4.90
27.15
15.82
29.39
|
|
7883-R5-1
CTCTCCCCTCCCGCCCTCTCACCCTCCCAACCTTATTT
2088
−4.54
−2.60
2.34
3.18
3.80
1.61
6.57
|
AGAAAC
|
|
8004-R3-2
GGAACTGCTTCTCCTTGCTCCAGTCATTGAAG
2089
−1.00
2.87
4.28
1.99
9.46
6.50
113.48
|
|
836-R4-1
AAATAATCATTCCAAATGGTTCTCCCTGCTATGATTCAC
2090
−1.00
−1.00
3.82
−1.00
2.16
2.67
104.03
|
|
9594-R5-1
ACTTAGACTTCCTTCCCACTCCCTGCATCCT
2091
−1.81
1.65
3.62
1.98
6.80
5.25
59.46
|
|
let-7c
AACCATACAACCTACTACCTCA
2092
3.65
24.65
2.65
1.35
3.24
5.11
15.37
|
|
let-7d
AACTATGCAACCTACTACCTCT
2093
2.02
13.30
1.78
−1.94
1.37
4.41
8.00
|
|
miR-103
TCATAGCCCTGTACAATGCTGCT
2094
−1.00
−1.00
2.97
3.07
1.27
3.15
3.05
|
|
miR-106a
CTACCTGCACTGTAAGCACTTTT
2095
−1.00
−1.00
13.51
23.92
4.32
6.14
17.48
|
|
miR-107
TGATAGCCCTGTACAATGCTGCT
2096
−1.00
1.59
4.64
2.94
1.85
7.68
8.76
|
|
miR-16
CGCCAATATTTACGTGCTGCTA
2097
−1.00
1.78
6.76
13.51
3.05
1.91
2.91
|
|
miR-17
CTACCTGCACTGTAAGCACTTTG
2098
−1.00
−1.00
13.68
23.68
3.51
8.86
18.29
|
|
miR-200b
TCATCATTACCAGGCAGTATTA
2099
−1.00
6.04
6.46
36.53
−1.00
7.67
2.72
|
|
miR-200c
TCCATCATTACCCGGCAGTATTA
2100
−3.97
5.00
4.38
7.25
−3.97
1.02
2.02
|
|
miR-20a
CTACCTGCACTATAAGCACTTTA
2101
512.00
−1.00
6.67
5.00
1.25
2.43
5.02
|
|
miR-20b
CTACCTGCACTATGAGCACTTTG
2102
−1.00
−1.00
15.49
7.38
1.90
2.68
8.04
|
|
miR-298
TGGGAGAACCTCCCTGCTTCTGCT
2103
−1.00
−1.00
4.26
−1.00
3.08
2.00
49.37
|
|
miR-320a
TCGCCCTCTCAACCCAGCTTTT
2104
−1.00
−1.00
5.63
6.24
4.27
−1.00
9.68
|
|
miR-320b
TTGCCCTCTCAACCCAGCTTTT
2105
−1.00
−1.00
3.91
3.97
3.28
−1.00
3.98
|
|
miR-320d
TCCTCTCAACCCAGCTTTT
2106
−1.00
−1.00
2.33
2.66
2.54
−1.00
3.22
|
|
TABLE 28
|
|
target RNAs present at increased levels in two or three cell lines, but with
|
an average increase of at least 5-fold relative to normal levels
|
SEQ ID
Calu1
calu3
H146
H187
H23
H520
H69
|
Gene
Probe sequence
NO
FC
FC
FC
FC
FC
FC
FC
|
|
10233-R5-1
ACCCTCTCCCCTTGGATCTGGAGCAGCAGGCAGTAGA
2107
−2.04
−2.04
3.75
1.08
−1.08
−2.04
10.41
|
|
10335-L5-2
CCACTCCCCTCCTTTTTAATTAGAAAGCAC
2108
−1.00
−1.00
2.43
−1.00
2.56
1.35
12.59
|
|
12184-L4-1
GACCTCAGCGTGCCCCCTTTCAACCACAGACGAA
2109
−1.98
−1.98
2.91
−1.03
−1.63
−1.51
9.45
|
TATTGTGTACAA
|
|
12223-L5-1
GACATCAGACAGAGTTGTTTCTTCTCCCTCTA
2110
−4.85
−4.85
2.43
−1.45
−4.85
−3.28
7.69
|
|
12695-R5-2
CCCCCACCAAACCTATTCCCGCATCCTCCCCGG
2111
−2.87
−2.87
2.64
1.50
−1.43
−2.87
7.70
|
|
12721-R5-2
TCCACTCTGACCAGCTCACCCTCACTGGACTA
2112
−1.00
−1.00
2.69
−1.00
−1.00
−1.00
19.11
|
|
12729-R5-1
CGACGAAAATGCAATTGTGTGCCTTCTCCCTCC
2113
−1.00
−1.00
2.17
−1.00
−1.00
−1.00
16.72
|
|
12888-L5-2
TTTCCTACATTGTATGGTTCTCCCAGCTCCT
2114
−1.00
−1.00
1.29
−1.00
2.69
1.51
85.37
|
|
12911-L5-1
CAACTGACACCTCCTTCCTTTTCCTCCTTCGT
2115
−1.00
−1.00
7.10
2.04
−1.00
−1.00
10.36
|
|
12917-R5-2
GGACCTATGGGCCCTTCCCTTCCCCCAACATTG
2116
−1.00
−1.00
4.25
−1.00
2.62
−1.00
10.54
|
|
12947-R5-3
GCCCCCTCCATAGAGAGAGGCCCCAGGGGAGTGA
2117
−1.00
−1.00
1.37
−1.00
−1.00
4.78
8.65
|
|
12992-L5-1
CATACCTGCTTCCCTCCACCCCCATCTCTA
2118
−1.00
−1.00
5.12
1.36
1.24
−1.00
10.93
|
|
13001-L5-1
TTCCTAGATACCACTCCCAGCTCCA
2119
−1.00
−1.00
2.06
−1.00
1.28
2.46
11.10
|
|
13070-R5-3
CTGTCTCCTCTCCCCAGTCCAAAGGACCTAATGC
2120
−1.00
−1.00
5.17
1.43
1.89
−1.00
13.57
|
|
13115-L5-3
ACCCCCTCCAGGGCCGACCACCCCAACCCAAAC
2121
−1.00
−1.00
1.59
−1.00
10.07
13.09
12.60
|
|
13124-L5-2
GCTCCATGTCTCCTCCCCTCCGCGAAAGCCTAAAC
2122
−2.76
−2.76
4.56
−1.18
7.69
−1.73
20.66
|
|
13195-L5-2
CCCCCTCCATGACCATTTGTATTAGTATCTTTT
2123
−1.00
−1.00
−1.00
−1.00
12.25
13.17
10.79
|
|
13237-L5-4
ACCCCCTCCAGGGCCGACCACCCCAACCCAAACAA
2124
−1.00
−1.00
1.35
−1.00
8.49
13.59
14.13
|
|
13274-L5-3
CCTTCTCTTCTCCCGTGCTCCCACCCTCCCTCAGGG
2125
−4.16
−3.37
1.81
1.66
3.05
2.03
18.48
|
|
13278-R5-2
TCAGACTGTGCTCTCTCCATTCCCCAGGACTCC
2126
−1.00
−1.00
4.29
1.86
−1.00
−1.00
22.61
|
|
13287-L5-4
ACTGCAGAGGAGCCACCCCACCCTCCTCCCAAG
2127
−1.00
−1.00
4.08
−1.00
4.47
−1.00
8.90
|
|
13343-L5-4
CTCCCGGCCCCTCACCCTTCCCTGGGCCCTCCACCC
2128
−1.00
−1.00
4.67
1.44
−1.00
1.34
10.16
|
|
13357-L5-4
AGCGGACCTTCTCCCCACACCTCCCTGCAGCCTC
2129
−2.19
−2.19
3.44
1.44
−1.81
−2.19
15.06
|
|
13358-L5-2
CCTCCTCACCACCCCCTCCACACTCCTGGGGAAGT
2130
−1.00
−1.00
1.41
−1.00
5.44
10.83
5.16
|
|
13366-R5-3
CAGGCCTCACCCCAGTGCCCTCTCCTATTCCCAC
2131
−1.00
−1.00
2.14
1.46
−1.00
−1.00
19.41
|
|
13395-R5-2
CGTCAGACTGTGCTCTCTCCATTCCCCAGGACTC
2132
−1.00
−1.00
4.13
−1.00
−1.00
−1.00
25.57
|
|
13403-L5-2
CCCGTGTCCCCCCAACCTGGGGCCAGGCCCA
2133
−1.00
−1.00
1.56
−1.00
4.85
1.85
9.80
|
|
13467-L5-1
GTGACAGTCAGACCCTCCTTGCTCCAAGTCAAA
2134
−1.00
−1.00
2.40
1.94
9.75
−1.00
105.32
|
|
13470-R5-1
TCCCACCCTCTCCACCTCAGGGACCAGAATCCT
2135
−1.00
−1.00
5.33
1.97
−1.00
−1.00
12.11
|
|
13472-L5-1
CTCAGAGCACTGTGTGTGACGTCCTCCTGTCTGTC
2136
9.44
30.30
−1.00
−1.00
−1.00
−1.00
−1.00
|
|
13508-L5-3
GACAGGCTGCTCTCCTTCTGCTCTTAGCTTCCT
2137
−1.00
−1.00
2.96
−1.00
−1.00
−1.00
18.27
|
|
13530-L5-3
CCTTCCTCCTTCCCCTGGGTCCCCCTAAGTTCTCC
2138
−1.00
−1.00
8.37
5.70
1.56
1.34
16.94
|
|
13546-R5-2
TGCCTCCACCCTCTCCATCCCGTCACCCTCCCA
2139
−2.75
−2.75
3.08
6.44
−1.36
−2.04
8.01
|
|
3875-R5-2
GACTGATTCAACCTCTCTCTCCCACTTTA
2140
−1.00
−1.00
3.37
1.56
−1.00
−1.00
8.56
|
|
3923-R5-1
TCACAAAGGATCTCCTTCATCCCTCTCCAG
2141
−1.00
−1.00
1.18
3.17
−1.00
−1.00
8.48
|
|
5108-R5-2
CCCTCTCCTCCCACACCGTCACTCACAATAACCC
2142
−1.94
−1.94
4.49
1.77
1.53
−1.94
12.32
|
|
5192-L3-2
CATTTTTCCCCTTCCTTCCTCTATATCAGCAA
2143
−1.00
−1.00
1.79
−1.00
24.42
13.63
4.95
|
|
5306_B-R4-1
TCCACTCTGACCAGCTCACCCTCACTGGACTATGACCCC
2144
−1.00
−1.00
3.27
−1.00
−1.00
−1.00
16.02
|
|
5633-L5-1
CACTCCCTCCCTGGCTCCTGGAGACCCTCTCCAGG
2145
−1.00
−1.00
2.22
2.39
1.27
−1.00
45.28
|
ACTTG
|
|
5638-R5-2
GGCCCTCCCCCTGCCTGTGATAGGCTG
2146
−1.57
−2.40
3.23
−1.15
5.85
−1.33
8.54
|
|
5723-R5-1
CCTCCTCCCCTTTCTCCAGCAGTAGCCTTCTTAA
2147
−1.00
−1.00
4.87
1.40
3.97
−1.00
11.99
|
|
5735-L5-1
TGCTGTTTCCTCTGGCCTCAAGCCTGTGGGGG
2148
−1.00
−1.00
1.18
3.00
−1.00
−1.00
14.30
|
|
6183-R5-1
ACTTTTCTTAATGACTTTCCCCTCCTTAAG
2149
−1.00
−1.00
1.75
−1.00
18.55
12.12
10.01
|
|
6216-R5-1
TACTCCCGCCGTTTACCCGTGCTTCATTGAA
2150
−3.03
−3.03
2.63
13.19
1.06
−3.03
−1.10
|
|
6490-R5-3
CCCCATCCCCCATATGACGCTTCCCCCTCCTAAC
2151
−3.21
−4.42
−2.06
−1.29
5.92
3.87
5.51
|
|
6496-R5-2
CCCCCTCCCCCACCCACCACTTCCCCTAGA
2152
−2.49
−5.45
1.82
−1.65
4.91
−1.83
10.29
|
|
6584-L5-1
GTCGGCCCTGCCTCCTCCTCCTCTCACCAAGC
2153
−1.00
−1.00
3.33
−1.00
−1.00
−1.00
12.02
|
|
6647-R5-1
CCCCAGCTGGAGAATTTTTCCCCTCATTA
2154
−1.00
−1.00
−1.00
−1.00
12.90
5.66
6.72
|
|
6752-R5-2
CCCTCCTTTCCCCACCTCAGTCGGGCCACTGCT
2155
−1.00
−1.00
2.70
1.92
5.08
1.27
9.54
|
|
6803-R5-2
GCTCCCTCTCTGGTTGGACCTCACCCAAA
2156
−2.35
−2.35
5.77
3.27
−2.35
−2.35
13.06
|
|
6930-R5-1
TTAATCCTTCTCTCCCCTCTGATCTTGCAG
2157
−1.00
−1.00
7.92
1.50
2.40
−1.00
28.87
|
|
7113-R5-1
CGCCTAATTAGCCCCCCTGCTCCGGAGGCCTCACC
2158
1.06
−2.16
2.60
−2.16
1.12
−1.18
12.56
|
|
7192-R5-1
TTCCCCCTCTAAGTCTGCCTGGGCTCTTGGCACTG
2159
−1.00
−1.00
−1.00
−1.00
5.96
13.37
21.66
|
|
7384-R3-1
CTCGCAAAGGATCTCCTTCATCCCTCCCCA
2160
−1.00
−1.00
1.30
−1.00
2.58
−1.00
9.23
|
|
7571-L5-1
CAGGGCTAACAGGGCTCCCCCACCCCTAAG
2161
−2.26
−2.26
4.35
−2.26
−1.81
−2.26
6.92
|
|
836-R5-2
AAATAATCATTCCAAATGGTTCTCCCTGCTAT
2162
−1.00
−1.00
3.09
−1.00
2.40
1.86
51.66
|
|
8433_C-R4-1
AAACCAAAAAAAAAAAATTAAAAAGCGACGAAAATGC
2163
−1.00
−1.00
5.09
−1.00
−1.00
−1.00
16.86
|
AATTGTGTGCCTTCTCCCTCC
|
|
8433-L3-1
AAATGGCTCCTTTCCCCTTTCCCTCCACCG
2164
−1.00
−1.00
6.04
1.95
5.50
1.32
11.98
|
|
8724-R5-2
GGCCAAGCTTGGAACCTCTCCCTGCCAGCA
2165
−1.89
−1.89
2.12
1.04
−1.89
−1.89
7.98
|
|
8808-R5-1
GACCCCTTTCTCCCAGCCTGTTTCTGCAA
2166
−1.95
−1.95
2.65
1.01
−1.95
−1.95
9.58
|
|
8832-R5-1
TGGAGTACCACCTGTTTTTCCCCCACTT
2167
−1.00
−1.00
−1.00
−1.00
5.05
1.41
21.96
|
|
9349-R5-2
GAACACAGTGATGCAGAGGACTTCCTGCTCCA
2168
−1.00
−1.00
1.84
−1.00
1.99
1.61
85.75
|
|
let-7b
AACCACACAACCTACTACCTCA
2169
−1.24
11.28
1.29
1.73
−1.24
2.39
6.09
|
|
let-7e
AACTATACAACCTCCTACCTCA
2170
−1.27
12.32
1.35
−1.94
1.66
1.71
7.50
|
|
miR-1268
CCCCCACCACCACGCCCG
2171
−1.00
−1.00
2.84
−1.00
−1.00
1.37
11.23
|
|
miR-1274b
TGGCGCCCGAACAGGGA
2172
6.00
−1.00
9.59
−1.00
1.21
−1.00
−1.00
|
|
miR-15b
TGTAAACCATGATGTGCTGCTA
2173
−1.00
−1.00
2.40
1.66
−1.00
8.53
−1.00
|
|
miR-181a
ACTCACCGACAGCGTTGAATGTT
2174
−1.00
4.65
1.33
−1.00
1.20
−1.00
6.04
|
|
miR-198
GAACCTATCTCCCCTCTGGACC
2175
−1.00
−1.00
3.07
−1.00
−1.00
−1.00
17.81
|
|
miR-222
ACCCAGTAGCCAGATGTAGCT
2176
2.68
9.77
−1.96
−1.96
−1.00
−1.96
−1.96
|
|
miR-26a
AGCCTATCCTGGATTACTTGAA
2177
−1.00
4.43
1.73
6.73
1.20
−1.00
4.27
|
|
miR-30d
CTTCCAGTCGGGGATGTTTACA
2178
−1.00
9.69
1.71
7.03
−1.00
−1.00
−1.00
|
|
miR-720
TGGAGGCCCCAGCGAGA
2179
5.56
−1.00
4.48
−1.00
−1.00
−1.00
−1.00
|
|
miR-92a
ACAGGCCGGGACAAGTGCAATA
2180
−1.00
−1.00
3.74
10.88
−1.00
−1.00
7.26
|
|
miR-92b*
CACTGCACCGCGTCCCGTCCCT
2181
−1.00
−1.00
3.82
1.40
−1.00
−1.00
10.85
|
|
miR-936
CTGCGATTCCTCCCTCTACTGT
2182
−1.00
−1.00
3.62
1.32
1.90
1.69
18.17
|
|
miR-98
AACAATACAACTTACTACCTCA
2183
−1.00
17.16
1.88
−1.00
−1.00
1.89
10.57
|
|
TABLE 29
|
|
Chromosomal locations and pre-microRNA sequences for target RNAs in Tables 27 and 28.
|
Gene
Chrom. Loc'n
Pre-microRNA sequence
SEQ ID NO
|
|
10083-L5-1
14q12
GGGTGGAGAGAGGGGGTAGAAAGGAAGAGGGACATATGGGAGCCTCTTCCCCCATGCCCGAAAGCTTCTCCCATTT
2184
|
|
10333-L5-1
11q12.2
CGGGGCAGGGGAGGGGGTGGGCAGGGCACAAGCCTCCCACTGTGCCGTGTCCCCACCCTCCCCCGTTCCCCG
2185
|
|
10398-R5-1
Xq21.1
TTGCTGAAGTTCTACCTTCTCACAAGGTTGCTAAAGTGAAGCAACTTCAAGAGGAGGGGAAACGGGTAGCAA
2186
|
|
13122-L5-1
2p11.2
GGACTGGAGCAGGTGAGATGGAATTTCCTAAAGGTCCAGATATTTAGGACCCTGGACCCATCTCACCCGCTGCCTCTGTCC
2187
|
|
13124-L5-1
1q22
TGAGGGGTAAGTTTAGGCTTTCGCGGAGGGGAGGAGACATGGAGCCTGGGAACTCCTTGTTCTCCCCTCTGCTGCCTCTCCCCACCCCTTA
2188
|
|
13163-R5-4
19q13.32
GCTGGGATCTCCGGGGTCTTGGTTCAGGGCCGGGGCCTCTGGGTTCCAAGCACCAGTGAGGAGAGTGCTGGGAGGGGAAGGGGTGGGAGGGCTTTGGTCTTG
2189
|
TGGGAGGGAGAGAAGGAGGGGAGGT
|
|
13185-L5-3
3q13.31
GGGGAAGAAGAGCAAAGAGGGGAGAGAGGGAAGAAAAAAAACAGAATAAGTTGGTCGTATTGAAGCTTCTCCATCAACCCTAGAACAATTAGCT
2190
|
TCCACC
|
|
13195-L5-3
3p21.1
AAAAAAAAAAAAGATACTAATACAAATGGTCATGGAGGGGGAATATAGAGAAGATCAATTTTGTACAGAAAAACCATTGGTTAGTATTTTTTTTTCT
2191
|
TTT
|
|
13219-L5-1
11q22.1
GCTGGAGCAGAGAGACTGAGTGAGGGAGTCAGAGAGTTAAGAGAATTAGTACAGGTGAGATTGTACTGATTATCTTAACTCTCTGACCCCCTCA
2192
|
CTCAGTAAAGATCAGATTGTGCCAGGC
|
|
13247-L5-2
1q24.2
ATCTCACAGAGGAAGAACAGGGCTCTGAGGTCGGGAGGGGAAGGCGGCTCAGGACTTCTGGCTCCAGAGCCTCCTCTCCTTCCACCATAGTG
2193
|
CCTGCTCCAGAGGAGAC
|
|
13334-L5-2
17q21.31
TGGGGCAGACAGGGCACAGTGGGAGGGGAGGGGAGTCCTGCCAGGAGGGCCACCTGGTGACTCCACATCCTTTCTCACCCCCCAGA
2194
|
|
13335-L5-3
17p13.2
TGGCTGGGAGAGGAGCATAGGATGCGGCAGGAGGGCAGTGGAGGCTGAGGTACGGATTTCTAGGCCCGCCCTACCCTCCTCTCTGCCCCTAGTGCCCGTG
2195
|
GCCAA
|
|
25-R5-2
2q31.1
TCCCGCAGCCGGTGACTGGAGCCCACCTCTGCAGAGACAAAGGTTAGAAAAAGAGGGGGTGAGGCTCTGGGAAAGCAGAATGCGGGG
2196
|
|
266-R5-2
12q14.3
GTTGCTATTTCCCTCAGTTGAGGGCGAAGTTAGCAAATCCGTAGCTGCAAGTCTCAACTTGGGGGAGGGGGCGAC
2197
|
|
3249-L5-1
1q22
GGCGGCGGCGGCGGCGGCTCCGGGGATGGCGGCGGCTCCGCTGCTGCTGCTGCTGCTGCTCGTGCCCGTGCCGCTGCTGCCGCTGCT
2198
|
|
3371-L5-2
18q21.33
CTCAAGTGTGGGGAGTCATGGGGTGTGGAGGGGAGGAAAGGAAAGGTATTTTGTTTCTTTGTCTATACATTTCCTAGATTTCTATGCAGTTGGG
2199
|
|
3744-R5-1
19p13.12
CTTCTCTTATTCTCCCTGTTTTCATCCTACTTTTAAGTAATAAATTTGGCATTAGTGGGAGGGGAGCAGGGAGGAAGGAGAAG
2200
|
|
4855-R5-1
12q13.11
GGGTCCGGGTCTCTACCGCGCCCTCATGCAGGAGGCCCTTGGAGCAGGAGGGGGAAGCGGGAGACCCGGCAGCCC
2201
|
|
5107-L5-1
11q23.3
CAGTTTGTACTGGGGGGTCAAAGGGGAGTTCTTTTCCGAAGAATTCTGGGAGAGACGCCAACTAGAGCAAGCTG
2202
|
|
6235-R5-2
15q26.2
TCTGTTTTTATCAGTTTAATATATGATACATCTTCTATCCAAGGACAATATATTAAATGGATTTTTGGAGCAGA
2203
|
|
6474-L5-1
1p34.1
GGTGAAGGGGGAAGAGGGGATGGCTTTAATTAGGGCTTCTTGGCCTCGTCAGTCCTGGGGTTGGTCGGGGTAATCCAGTTAGAGTCCCAGCCT
2204
|
TTCATCTCAGCTGGCC
|
|
6490-R5-3
1q21.3
TCCTTCCCCCTTCGTGGCTTGCGGTCTCTCTTCCCCGCCTCGGCCCCCAGGAAGTGTGAGTGCTGGGGGTGGTGAGGTTAGGAGGGGGAAGCGTCATAT
2205
|
GGGGGATGGGG
|
|
6681-R2-1
11q12.2
TGTGCTCTCATTGTTATTCCAAAAGTCTCTGTCTAGATCACTGGAGGGGCAGAGAGAGAGGGGAGAAAACAGGGAGATACA
2206
|
|
7572-R5-2
11q12.1
ATCACCTTTCCCCCTCCCATGTGCTTTCCTTCATTTGAGATCTTTTGACCTTTGGCTTTATTTGGGAGGGGGAAGGGTGAT
2207
|
|
7883-R5-1
11q14.2
CTCTCCGTGCTTCTCGGCCCGCCGCCCTTCCTGTCTCGGGGACACGGTTTCTAAATAAGGTTGGGAGGGTGAGAGGGCGGGAGGGGAGAG
2208
|
|
8004-R3-2
Xq28
GGGGCTGCCATCCTGCTGTCCGTCATCTGTGTGGTGCTGGTCACGGCCTTCAATGACTGGAGCAAGGAGAAGCAGTTCC
2209
|
|
836-R4-1
3q26.2
AAATAAGCCATTCCAAACCATTCTCTGATTTGCTGTGAGTGGCAGAATCATTCACCGTGGTGAATCATAGCAGGGAGAACCATTTGGAATGATTATTT
2210
|
|
9594-R5-1
2q12.1
TTCCAGCTATTTAGTAACTCTTCCAAAACACTGTCAGCACCCATGCTAGGATGCAGGGAGTGGGAAGGAAGTCTAAGTAGGGAA
2211
|
|
let-7c
21q21.1
GCATCCGGGTTGAGGTAGTAGGTTGTATGGTTTAGAGTTACACCCTGGGAGTTAACTGTACAACCTTCTAGCTTTCCTTGGAGC
2212
|
|
let-7d
9q22.32
CCTAGGAAGAGGTAGTAGGTTGCATAGTTTTAGGGCAGGGATTTTGCCCACAAGGAGGTAACTATACGACCTGCTGCCTTTCTTAGG
2213
|
|
miR-103
20p13
TTGTGCTTTCAGCTTCTTTACAGTGCTGCCTTGTAGCATTCAGGTCAAGCAGCATTGTACAGGGCTATGAAAGAACCA
2214
|
|
miR-103
5q35.1
TACTGCCCTCGGCTTCTTTACAGTGCTGCCTTGTTGCATATGGATCAAGCAGCATTGTACAGGGCTATGAAGGCATTG
2215
|
|
miR-106a
Xq26.2
CCTTGGCCATGTAAAAGTGCTTACAGTGCAGGTAGCTTTTTGAGATCTACTGCAATGTAAGCACTTCTTACATTACCATGG
2216
|
|
miR-107
10q23.31
CTCTCTGCTTTCAGCTTCTTTACAGTGTTGCCTTGTGGCATGGAGTTCAAGCAGCATTGTACAGGGCTATCAAAGCACAGA
2217
|
|
miR-16
13q14.3
GTCAGCAGTGCCTTAGCAGCACGTAAATATTGGCGTTAAGATTCTAAAATTATCTCCAGTATTAACTGTGCTGCTGAAGTAAGGTTGAC
2218
|
|
miR-16
3q26.1
GTTCCACTCTAGCAGCACGTAAATATTGGCGTAGTGAAATATATATTAAACACCAATATTACTGTGCTGCTTTAGTGTGAC
2219
|
|
miR-17
13q31.3
GTCAGAATAATGTCAAAGTGCTTACAGTGCAGGTAGTGATATGTGCATCTACTGCAGTGAAGGCACTTGTAGCATTATGGTGAC
2220
|
|
miR-200b
1p36.33
CCAGCTCGGGCAGCCGTGGCCATCTTACTGGGCAGCATTGGATGGAGTCAGGTCTCTAATACTGCCTGGTAATGATGACGGCGGAGCCCTGCACG
2221
|
|
miR-200c
12p13.31
CCCTCGTCTTACCCAGCAGTGTTTGGGTGCGGTTGGGAGTCTCTAATACTGCCGGGTAATGATGGAGG
2222
|
|
miR-20a
13q31.3
GTAGCACTAAAGTGCTTATAGTGCAGGTAGTGTTTAGTTATCTACTGCATTATGAGCACTTAAAGTACTGC
2223
|
|
miR-20b
Xq26.2
AGTACCAAAGTGCTCATAGTGCAGGTAGTTTTGGCATGACTCTACTGTAGTATGGGCACTTCCAGTACT
2224
|
|
miR-298
20q13.32
TCAGGTCTTCAGCAGAAGCAGGGAGGTTCTCCCAGTGGTTTTCCTTGACTGTGAGGAACTAGCCTGCTGCTTTGCTCAGGAGTGAGCT
2225
|
|
miR-320a
8p21.3
GCTTCGCTCCCCTCCGCCTTCTCTTCCCGGTTCTTCCCGGAGTCGGGAAAAGCTGGGTTGAGAGGGCGAAAAAGGATGAGGT
2226
|
|
miR-320b
1q42.11
TGTTATTTTTTGTCTTCTACCTAAGAATTCTGTCTCTTAGGCTTTCTCTTCCCAGATTTCCCAAAGTTGGGAAAAGCTGGGTTGAGAGGGCAAAAGGAAAAAAA
2227
|
AAGAATTCTGTCTCTGACATAATTAGATAGGGAA
|
|
miR-320b
1p13.1
AATTAATCCCTCTCTTTCTAGTTCTTCCTAGAGTGAGGAAAAGCTGGGTTGAGAGGGCAAACAAATTAACTAATTAATT
2228
|
|
miR-320d
13q14.11
TTCTCGTCCCAGTTCTTCCCAAAGTTGAGAAAAGCTGGGTTGAGAGGA
2229
|
|
miR-320d
Xq27.1
TTCTCTTCCCAGTTCTTCTTGGAGTCAGGAAAAGCTGGGTTGAGAGGA
2230
|
|
10233-R5-1
9q34.13
ACCTTCTGCCTTTGAGACCTGGAAGCCACAGCACTGGTGGACATAAATTCTACTGCCTGCTGCTCCAGATCCAAGGGGAGAGGGT
2231
|
|
10335-L5-2
15q26.1
TCTTAGTGCTTTCTAATTAAAAAGGAGGGGAGTGGTGATCTTTTTGCTCTCTAAGTTCTGTTTCCTCTGAGTGGAAAGCAGAGGG
2232
|
|
12184-L4-1
3p14.1
TTGTACACAATATTCGTCTGTGGTTGAAAGGGGGCACGCTGAGGTCAAGTGATGTAGTGTTTTCCATTTTTCCATATGAGTCTCACAGTGTGCGA
2233
|
|
12223-L5-1
4q27
TAGAGGGAGAAGAAACAACTCTGTCTGATGTCTTCTGGGATGGCCTTAATACAGATAGCATTGTCTCTTCCATTTCTG
2234
|
|
12695-R5-2
1q22
TCCCCGCCACCCTTGGAGCACCTCAGCGTTCTTAGGGGAAGCCAGAGCCGGGGAGGATGCGGGAATAGGTTTGGTGGGGG
2235
|
|
12721-R5-2
12q13.13
TTCACCCATGACCCTTGTCCTCACCCCCACCCAAGGGGTCATAGTCCAGTGAGGGTGAGCTGGTCAGAGTGGA
2236
|
|
12729-R5-1
17q25.3
AAATTAAAGAAAAAAAATTCTCCACCAAAAGCGCCGCAGTGACAGTTCCCAACATTTTCTGCCTTTCTTCTTCCCCTCCCTGCACCACTAGGAGGGAGAAGGC
2237
|
ACACAATTGCATTTTCGTCGCTTTTTAATTTTTTTTTTTTGGTTT
|
|
12888-L5-2
2q32.3
TCCTCCAGGAGCTGGGAGAACCATACAATGTAGGAAAAATATAGTTTAATTGAATGGTACTCTGGTCTTCTGGAGGA
2238
|
|
12911-L5-1
22q12.3
ACGAAGGAGGAAAAGGAAGGAGGTGTCAGTTGGACTGCCCCAAGGCAACCCTTGAGCCATCAGGACAGCTCAACACCTCCTCTGTTTTCTTCTT
2239
|
TGT
|
|
12917-R5-2
1p34.1
GGACCTGGGGGCTTCTCTGACCCTTGAACAGCTTATACTATGAGACCTTGGGAACCTCCTCCATGCAGACACACAAGGCTCAATGTTGGGGGA
2240
|
AGGGAAGGGCCCATAGGTCC
|
|
12947-R5-3
6p21.1
GCCTTGTCTGAAGGGAGAGGCCCTGGCATGCGGATGGGAGATTTAGAGGCTGTGGAGAAGGGAACTTGGGGCTTTCCTTCCTTCGTGGCCTC
2241
|
ACTCCCCTGGGGCCTCTCTCTATGGAGGGGGC
|
|
12992-L5-1
9q31.3
TAGAGATGGGGGTGGAGGGAAGCAGGTATGATTTCAGGGGCAGCAGGAGATTCTCTTCTGTTTCCCTCTCTCCCAGCTCTA
2242
|
|
13001-L5-1
12q13.13
TGGAGCTGGGAGTGGTATCTAGGAATTTCTCCTTCTAGTTTTTACCTTCTTAGTTTTA
2243
|
|
13070-R5-3
5q35.1
CTGCTCTCCTTGACCTGGTAGGAAGGTGATTTGATGGTTTTCAAACACATGCTGTTTCTCTCTTTCATCAGGGTAGCTGGGTGGGTGGCATTAGG
2244
|
TCCTTTGGACTGGGGAGAGGAGACAG
|
|
13115-L5-3
1q21.3
AGGGAAAGGCAAGGGTAGCCATTGTTTGGGTTGGGGTGGTCGGCCCTGGAGGGGGTTTGTTTGCTTATTCCCCTCTGTGCTTCACCCCTACCC
2245
|
AGCTTCCCGCCAGAAAGCCCTG
|
|
13124-L5-2
1q22
TGAGGGGTAAGTTTAGGCTTTCGCGGAGGGGAGGAGACATGGAGCCTGGGAACTCCTTGTTCTCCCCTCTGCTGCCTCTCCCCACCCCTTA
2246
|
|
13195-L5-2
3p21.1
AAAAAAAAAAAAGATACTAATACAAATGGTCATGGAGGGGGAATATAGAGAAGATCAATTTTGTACAGAAAAACCATTGGTTAGTATTTTTTTTTCT
2247
|
TTT
|
|
13237-L5-4
1q21.3
GGCAAGGGTAGCCATTGTTTGGGTTGGGGTGGTCGGCCCTGGAGGGGGTTTGTTTGCTTATTCCCCTCTGTGCTTCACCCCTACCCAGCTTCC
2248
|
CGCC
|
|
13274-L5-3
12q13.13
AGGTGGTGGTGGGGAGGACCCTGAGGGAGGGTGGGAGCACGGGAGAAGAGAAGGCATACCCAACCTGACCTACTTACCTGTCCCCTACCCCACAGAGGGC
2249
|
TTCCCTGGAGGCCGCCATTGC
|
|
13278-R5-2
22q11.21
TGGTTCTCTGTGTTTTGTGGACTGTGCTCTCACTGTTCACCCAGCACTAGCAGTACCAGACGGTTCTGTGGAGTCCTGGGGAATGGAGAGAGCA
2250
|
CAGTCTGACGCCCTGCCAA
|
|
13278-R5-2
12q13.13
TGGTTCTCTGTGTTTTGTGGACTCTGCTCTCACTGTTCACCCAGCACTAGCAGTACCAGATGGTTCTGTGGAGTCCTGGGGAATGGAGAGAGCA
2251
|
CAGTCTGACTCCCTGCCAAGTAGCCAG
|
|
13287-L5-4
1p35.2
TCCGCCGAATAACTCCATGTGGGTCTTGGGAGGAGGGTGGGGTGGCTCCTCTGCAGTGAGTAGGTCTGCCTGGAGCTACTCCACCATCTCCCC
2252
|
CAGCCCCTGTATGGCTGGGAGGGGAA
|
|
13343-L5-4
17q25.3
TGAGGGGGAGGGGCGCTGCGGGAGGGGTGGAGGGCCCAGGGAAGGGTGAGGGGCCGGGAGCCACTCTGCCCGGCACTCTCCGCCCAGAA
2253
|
ACAGCCCAACGCCCCTTTCTTTCCCCTTT
|
|
13357-L5-4
19q13.2
TCAGGGTTTGGTGTACAATTGTGGGAGGCTGCAGGGAGGTGTGGGGAGAAGGTCCGCTTTAGAGCTTGGTCCCTCTGTGCTCACCTCCCAGCC
2254
|
CCAAGCCCCCAGCACCGGATCCTG
|
|
13358-L5-2
19q13.32
CGGCCAGTGACTTCCCCAGGAGTGTGGAGGGGGTGGTGAGGAGGAGCACCTGGGCTCTCTACCCCTCTCCTCACAGAAGTACCTGAAACTAG
2255
|
GTC
|
|
13366-R5-3
19p13.2
GGGCCGGTGAAGGCCCCGCCTGGGTCCCATACCCGGGGTTGGGGGTCAGAAGCCGCTCGGTCTCTGTGGGAATAGGAGAGGGCACTGGGGT
2256
|
GAGGCCTG
|
|
13395-R5-2
22q11.21
TGGTTCTCTGTGTTTTGTGGACTGTGCTCTCACTGTTCACCCAGCACTAGCAGTACCAGACGGTTCTGTGGAGTCCTGGGGAATGGAGAGAGCA
2257
|
CAGTCTGACGCCCTGCCAA
|
|
13403-L5-2
22q13.1
ACCAGGTGGGCCTGGCCCCAGGTTGGGGGGACACGGGTGGGTCCCGGCACCCCTCCCCTGACCACCGTGCCTCTCCCAGGA
2258
|
|
13467-L5-1
5q35.2
TTTGACTTGGAGCAAGGAGGGTCTGACTGTCACTTGGAGCTAAACCAGTCTCCAAGTGGCCATCAGACCCTCTTTGCCCCAAGTCAGT
2259
|
|
13470-R5-1
5q13.2
GGTCAGTCTAGCTTGCTCTTGAAGCTCTCCAGAGACAAAGAAGCCTGTAGCAAATCACAATGAGGATTCTGGTCCCTGAGGTGGAGAGGGTGG
2260
|
GAGCCCCACTGTTTGCCC
|
|
13472-L5-1
5p15.33
GACAGACAGGAGGACGTCACACACAGTGCTCTGAGGACCTCACTTGCCCTGTGGCGGCTGCCCTCCAAACACACTGTG
2261
|
|
13508-L5-3
7p14.1
GAGAGGTGTCTGTGAGGAAGCTAAGAGCAGAAGGAGAGCAGCCTGTCAGAAAACGGGCTGTCCCTCCCTCCCTAATCACAGCCCTACTCACAG
2262
|
CAAACTCCCTCCCTCTCCA
|
|
13530-L5-3
9q33.3
CTACAGCTTGGCAAAAAGGGAGAACTTAGGGGGACCCAGGGGAAGGAGGAAGGCCACCCCACTCCCTTCCTGCCATTCCTGTCATCCCAGCGAGGCCTCCG
2263
|
ACCCTGCAAAAGGCTGTGAG
|
|
13546-R5-2
Xq28
GGAAAGGACCAGGGATGGCCTGCACCCCTCGGGAAGCTTGGCCAAGGTGCCCTGGGAGGGTGCCCTGGGAGGGTGACGGGATGGAGAGGG
2264
|
TGGAGGCACCCTGCTGGAAGCCAG
|
|
3875-R5-2
5p15.1
GGCTCGGTTTCAAATCTCTCCTAATCCACTAATGAACCTTTATTAAAGTGGGAGAGAGAGGTTGAATCAGTC
2265
|
|
3923-R5-1
19p12
GGCTCTGCACCAGGCGTTTCTTCTTGTGTTTCCTCTTCTCTTCTGGAGAGGGATGAAGGAGATCCTTTGTGAGAGGC
2266
|
|
5108-R5-2
2p13.1
CCAATGCCTCTCACCTCCTCACTTGTGGCACCTTCGCTTTTGATCCGAAGTGCGGGGTTATTGTGAGTGACGGTGTGGGAGGAGAGGG
2267
|
|
5192-L3-2
5q35.1
GTCTTTGCTGATATAGAGGAAGGAAGGGGAAAAATGAGCGCATTAGTTCTCTTTTATTAAAAGAGTTATTTCAGCATGAC
2268
|
|
5306_B-R4-1
12q13.13
TTCACCCATGACCCTTGTCCTCACCCCCACCCAAGGGGTCATAGTCCAGTGAGGGTGAGCTGGTCAGAGTGGA
2269
|
|
5633-L5-1
15q25.2
CAAGTCCTGGAGAGGGTCTCCAGGAGCCAGGGAGGGAGTGACTAACTTCTGACTGCCTGGGGGCCTGAGAGAAGGCTGGGACTTG
2270
|
|
5638-R5-2
6q23.2
GGCTTTGCCCTTTTCGGTGACACAGGCTGTTGCTATTCCAAGCAGCCTATCACAGGCAGGGGGAGGGCC
2271
|
|
5723-R5-1
4p15.31
CCTCTGCCTGGCTTTCTTTGTAAAGCCATTAAACTACATTAAGAAGGCTACTGCTGGAGAAAGGGGAGGAGG
2272
|
|
5735-L5-1
5q31.1
CCCCCACAGGCTTGAGGCCAGAGGAAACAGCAACTTTCTTCGCTGGGAAAGTGTTGTGGGGCTCAAGCATTTGGGGG
2273
|
|
6183-R5-1
12q21.33
GATTCATCTATTCTTTTTCTCCTTCTTCAAAGATAACTCTGTAAGCACTTAAGGAGGGGAAAGTCATTAAGAAAAGTGGAATC
2274
|
|
6216-R5-1
11q14.1
CATGTGATTTCTGCCCAGTGCTCTGAATGTCAAAGTGAAGAAATTCAATGAAGCACGGGTAAACGGCGGGAGTAACTATG
2275
|
|
6490-R5-3
1q21.3
TCCTTCCCCCTTCGTGGCTTGCGGTCTCTCTTCCCCGCCTCGGCCCCCAGGAAGTGTGAGTGCTGGGGGTGGTGAGGTTAGGAGGGGGAAGCGTCATATGG
2276
|
GGGATGGGG
|
|
6496-R5-2
5q31.1
CTCCCTCAGGCCCCGCCTGCACCTTTCCCAGCCCCCAGGACTCTAGGGGAAGTGGTGGGTGGGGGAGGGGG
2277
|
|
6584-L5-1
12q24.23
GCTTGGTGAGAGGAGGAGGAGGCAGGGCCGACCGCCACCCGCCTGTCTGCCATCTGGTCCCCTTCCCCTCCCTCCTCTCATTGC
2278
|
|
6647-R5-1
1q23.3
CTCAGTATCTTCAGCTTGGGAAACTGACCTCGTTAATTTTAATGAGGGGAAAAATTCTCCAGCTGGGGCTGAG
2279
|
|
6752-R5-2
Xq13.1
CCCTCCCAGTTCCCATAGCAACTGGGCTGTAGCAGCCAGAACTTGATTGAGCCCAGCAGTGGCCCGACTGAGGTGGGGAAAGGAGGG
2280
|
|
6803-R5-2
22q12.3
GCCACCTTTCATGGTGAGGATGCCTGCCACCTTCAGGATCACATCTTTGGGTGAGGTCCAACCAGAGAGGGAGC
2281
|
|
6930-R5-1
9p21.3
TGTCATTTGTCCATTTTCTCTTCTGACCCAGTGGTATTCTGCAAGATCAGAGGGGAGAGAAGGATTAATGTCA
2282
|
|
7113-R5-1
18q21.2
CGTCTTGCTGGCTCCCCAAGGCTTCCAGGCATTTGCCCATCTGGTGAGGCCTCCGGAGCAGGGGGGCTAATTAGGCG
2283
|
|
7192-R5-1
9q33.1
TGTAGCAAATCCCATCCATCTGTTTGGCTGCTCTTGCCTCAGTGACAGTGCCAAGAGCCCAGGCAGACTTAGAGGGGGAAGTGCTTTGCA
2284
|
|
7384-R3-1
12q12
GGCATTTCTTCTTGTGTTTCCTCTTCTCCTCTTCTGGGGAGGGATGAAGGAGATCCTTTGCGAGAGGCATGTT
2285
|
|
7571-L5-1
2p21
CTTAGGGGTGGGGGAGCCCTGTTAGCCCTGTAAATAAAGTTTAACGAGGTGAACAATGGCTGGCTCTGTCCCTGAG
2286
|
|
836-R5-2
3q26.2
AAATAAGCCATTCCAAACCATTCTCTGATTTGCTGTGAGTGGCAGAATCATTCACCGTGGTGAATCATAGCAGGGAGAACCATTTGGAATGATTA
2287
|
TTT
|
|
8433_C-R4-1
17q25.3
AAATTAAAGAAAAAAAATTCTCCACCAAAAGCGCCGCAGTGACAGTTCCCAACATTTTCTGCCTTTCTTCTTCCCCTCCCTGCACCACTAGGAGGGAGAAGGCA
2288
|
CACAATTGCATTTTCGTCGCTTTTTAATTTTTTTTTTTTGGTTT
|
|
8433-L3-1
17q25.3
CGGTGGAGGGAAAGGGGAAAGGAGCCATTTTCTGCTGCACATCAGTCAGTGCCTGCGCCCTCCCTCCCTCCGCCG
2289
|
|
8724-R5-2
15q23
GGCCCAGAAGATGAAAAGCTGAAGTCCTTTCCCTTCCAGCTGAAGCCAGGTGTGATGCTGGCAGGGAGAGGTTCCAAGCTTGGCC
2290
|
|
8808-R5-1
3p14.3
CCGATTATGGCTTTCTTCTCCTGCCCTTTCAGTAGTGATTTGCAGAAACAGGCTGGGAGAAAGGGGTCTTTGG
2291
|
|
8832-R5-1
9q33.2
TTCTGAGATATGATCTGTTGGATTCTCTACTACCAAAGTGGGGGAAAAACAGGTGGTACTCCAGAA
2292
|
|
9349-R5-2
21q22.11
GGACACTCTGAACCCCAAGTGGAATTCCAACTGCCAGTTCTTCATCCGAGACCTGGAGCAGGAAGTCCTCTGCATCACTGTGTTC
2293
|
|
let-7b
22q13.31
CGGGGTGAGGTAGTAGGTTGTGTGGTTTCAGGGCAGTGATGTTGCCCCTCGGAAGATAACTATACAACCTACTGCCTTCCCTG
2294
|
|
let-7e
19q13.33
CCCGGGCTGAGGTAGGAGGTTGTATAGTTGAGGAGGACACCCAAGGAGATCACTATACGGCCTCCTAGCTTTCCCCAGG
2295
|
|
miR-1268
15q11.2
TAGCCGGGCGTGGTGGTGGGGGCCTGTGGTCCCAGCTACTTTGGAGGCTGAG
2296
|
|
miR-1274b
19q13.43
CTTCTTCACTCACGTCCCTGTTCGGGCGCCACTTGTGGCTGTCGGTTCGGGACTGAATGAAGAAGGA
2297
|
|
miR-15b
3q26.1
TTGAGGCCTTAAAGTACTGTAGCAGCACATCATGGTTTACATGCTACAGTCAAGATGCGAATCATTATTTGCTGCTCTAGAAATTTAAGGAAATTC
2298
|
AT
|
|
miR-181a
1q31.3
TGAGTTTTGAGGTTGCTTCAGTGAACATTCAACGCTGTCGGTGAGTTTGGAATTAAAATCAAAACCATCGACCGTTGATTGTACCCTATGGCTAA
2299
|
CCATCATCTACTCCA
|
|
miR-181a
9q33.3
AGAAGGGCTATCAGGCCAGCCTTCAGAGGACTCCAAGGAACATTCAACGCTGTCGGTGAGTTTGGGATTTGAAAAAACCACTGACCGTTGACTGTACCTTGG
2300
|
GGTCCTTA
|
|
miR-198
3q13.33
TCATTGGTCCAGAGGGGAGATAGGTTCCTGTGATTTTTCCTTCTTCTCTATAGAATAAATGA
2301
|
|
miR-222
Xp11.3
GCTGCTGGAAGGTGTAGGTACCCTCAATGGCTCAGTAGCCAGTGTAGATCCTGTCTTTCGTAATCAGCAGCTACATCTGGCTACTGGGTCTCTG
2302
|
ATGGCATCTTCTAGCT
|
|
miR-26a
3p22.2
GTGGCCTCGTTCAAGTAATCCAGGATAGGCTGTGCAGGTCCCAATGGGCCTATTCTTGGTTACTTGCACGGGGACGC
2303
|
|
miR-26a
12q14.1
GGCTGTGGCTGGATTCAAGTAATCCAGGATAGGCTGTTTCCATCTGTGAGGCCTATTCTTGATTACTTGTTTCTGGAGGCAGCT
2304
|
|
miR-30d
8q24.22
GTTGTTGTAAACATCCCCGACTGGAAGCTGTAAGACACAGCTAAGCTTTCAGTCAGATGTTTGCTGCTAC
2305
|
|
miR-720
3q26.1
CCGGATCTCACACGGTGGTGTTAATATCTCGCTGGGGCCTCCAAAATGTTGTGCCCAGGGGTGTTAGAGAAAACACCACACTTTGAGATGAATT
2306
|
AAGAGTCCTTTATTAG
|
|
miR-92a
13q31.3
CTTTCTACACAGGTTGGGATCGGTTGCAATGCTGTGTTTCTGTATGGTATTGCACTTGTCCCGGCCTGTTGAGTTTGG
2307
|
|
miR-92a
Xq26.2
TCATCCCTGGGTGGGGATTTGTTGCATTACTTGTGTTCTATATAAAGTATTGCACTTGTCCCGGCCTGTGGAAGA
2308
|
|
miR-92b*
1q22
CGGGCCCCGGGCGGGCGGGAGGGACGGGACGCGGTGCAGTGTTGTTTTTTCCCCCGCCAATATTGCACTCGTCCCGGCCTCCGGCCCCCCC
2309
|
GGCCC
|
|
miR-936
10q25.1
TCAAGGCCACTGGGACAGTAGAGGGAGGAATCGCAGAAATCACTCCAGGAGCAACTGAGAGACCTTGCTTCTACTTTACCAGGTCCTGCTGGC
2310
|
CCAGA
|
|
miR-98
Xp11.22
AGGATTCTGCTCATGCCAGGGTGAGGTAGTAAGTTGTATTGTTGTGGGGTAGGGATATTAGGCCCCAATTAGAAGATAACTATACAACTTACTAC
2311
|
TTTCCCTGGTGTGTGGCATATTCA
|
|
TABLE 30
|
|
Target RNAs present at at least 5-fold decreased levels in at least four cell lines
|
Number of
|
cell lines
|
Gene
with at
|
Down expressed in
calu3
H146
H187
H23
H520
least a 2-fold
|
Cell lines
Probe sequence
SEQ ID NO
Calu1 FC
FC
FC
FC
FC
FC
H69 FC
increase
|
|
10010_B-L4-1
GCCGAGCCCCCGCCCCCGCCGGGATGCTGCCCTCCGGAA
2312
−16.79
−8.41
−4.11
−2.74
−7.08
−22.10
−2.85
0
|
GGAGGGGCGCTGCCC
|
|
10010_D-L4-1
TGGCGCCCTCCCCCGCCCGGGGCTCAGCCTCTCACCTG
2313
−30.70
−30.70
−2.08
−4.60
−3.76
−16.38
−1.22
0
|
|
10138-L2-1
AGCCTGCTCCGCTCTCCCCTCCCACCAGAAAAAGT
2314
−7.46
−7.46
1.75
−1.81
1.87
−2.04
7.73
1
|
|
10231-R3-1
TGAACTTTAGCTGGGCCGCCGCCTGTCAGC
2315
−29.14
−29.14
−3.13
−4.48
−29.14
−29.14
−5.84
0
|
|
10242-R5-1
GAAGCCCTTCCGCTTCCACCCCGAACAC
2316
−25.94
−25.94
−14.00
−25.94
−25.94
−25.94
−8.13
0
|
|
10342-R2-2
CCCGCCGCCGGAGCATCTCGAAGTTAATTAAA
2317
−28.71
−3.68
−4.01
−2.19
−10.93
−50.54
−3.01
0
|
|
11370-L4-1
CCTCCGCCCCCACACTGCATCCTTGCCCAGTTTGGCTGCCA
2318
−5.20
−5.20
1.61
−2.49
−2.57
−2.80
3.46
1
|
TCAGTATTGTCCCCTGAGAACTGGAC
|
|
11370-L5-5
CCCTCCGCCCCCACACTGCATCCTTGCCCAGTTTGG
2319
−5.86
−5.86
1.74
1.95
1.55
−3.00
4.02
1
|
|
12223-L4-1
CCCAGAAGACATCAGACAGAGTTGTTTCTTCTCCCTCTA
2320
−5.20
−5.20
2.99
−2.63
−5.20
−5.20
5.56
2
|
|
12691-R5-1
CCCCGCCCCTGGCGCGCCCCCGACAGGC
2321
−46.43
−46.43
−6.02
−32.36
−46.43
−46.43
−3.50
0
|
|
12692-L5-1
GACCCGGCCCCGCAGCCAGCACCCGGCCACCGCGC
2322
−7.57
−7.57
1.00
−5.34
−7.57
−7.57
1.21
0
|
|
12693-L5-1
GTCGCGGCCGCCCGGCCCTCCCGGTCCCCTCCCC
2323
−34.28
−34.28
−4.19
−6.29
−2.25
−14.44
−1.05
0
|
|
12694-R5-1
TCAGCCCCCAGCGCCCCCCGGAGTTCTTGGA
2324
−85.43
−85.43
−17.02
−29.82
−85.43
−85.43
−6.11
0
|
|
12695-R5-1
AAACCTATTCCCGCATCCTCCCCGGCTCTGGC
2325
−44.55
−44.55
−3.70
−3.25
−13.08
−32.36
−1.29
0
|
|
12696-R5-1
CCGGGCTCCCCCACCCGCTCCCTGAGC
2326
−9.47
−9.47
1.52
−3.26
−4.38
−9.47
2.17
1
|
|
12696-R5-2
AACCCGGGCTCCCCCACCCGCTCCCTGA
2327
−38.89
−38.89
−2.62
−3.23
−12.87
−26.21
1.03
0
|
|
12697-R5-1
CCGGTGTGCGCCCCCTCCTACCTCTGCCGGCC
2328
−26.89
−26.89
−5.74
−13.37
−13.11
−5.78
−1.74
0
|
|
12699-L5-1
GGCGCCCTGGGCCTCGGCGCCCCGCCCGTCCCAG
2329
−9.80
−9.80
−2.20
−4.84
−9.80
−9.80
−1.77
0
|
|
12701-L5-1
AAATCCTCGCCATCCTCCACCCCCAGCCCCGG
2330
−24.62
−24.62
−2.85
−2.72
−5.56
−12.45
−1.45
0
|
|
12703-L5-3
AGCCGAGCCCCCGCCCCCGCCGGGATGCTGCCCTC
2331
−64.38
−60.80
−7.33
−2.94
−20.92
−66.02
−9.82
0
|
|
12704-L5-1
CCTCCCCCGCCCGGGGCTCAGCCTCTCACCTG
2332
−8.28
−8.28
1.19
−1.16
−1.79
−4.47
2.96
1
|
|
12704-L5-2
CTGGCGCCCTCCCCCGCCCGGGGCTCAGCCTC
2333
−7.28
−7.28
−1.14
−1.77
−1.61
−5.51
2.57
1
|
|
12713-R5-1
CTCTCGCGACCGACCTGCCGCCGACCGCCACAG
2334
−43.69
−9.13
−3.01
−2.22
−23.87
−33.93
−2.33
0
|
|
12722-L5-1
AAACAAAGTACTTCCGACCTCCCCGCCCGCCCGC
2335
−34.34
−6.02
−2.48
−2.05
−6.64
−8.13
−1.75
0
|
|
13004-R5-1
CTCCAACCCCCGCAATTCTCGCTCCCTTCACCTGA
2336
−35.18
−35.18
−5.05
−10.62
−35.18
−35.18
−2.20
0
|
|
13006-R5-4
CCCGGCTCTCCCTCCCCTGCGCCGCGCTCTCGCC
2337
−13.41
−29.15
−1.35
−3.15
−4.57
−3.39
1.17
0
|
|
13044-L5-3
CCCATCCCAGCTGTCCCTTTCTTTGCTTTCATCA
2338
−23.71
−23.71
−17.84
−12.27
−23.71
−23.71
−4.70
0
|
|
13044-L5-4
CCAGGGCTTCTCCCATCCCAGCTGTCCCTTTCTTTG
2339
−30.11
−30.11
−4.72
−5.11
−30.11
−30.11
−2.34
0
|
|
13047-R5-2
GCACAGCAGACCCCATGCACTAGCCCCGGGCAC
2340
−19.29
−19.29
−19.29
−19.29
−19.29
−19.29
−19.29
0
|
|
13052-L5-1
TCCCCGGACCTAAGCATCTCCCCCACCCGCCAACC
2341
−6.46
−6.46
1.30
−2.05
−2.52
−4.72
4.47
1
|
|
13093-L5-2
CGACCCCGCAGAACCCCACCGCGCCCCGCGCAG
2342
−45.57
−45.57
−16.39
−23.29
−45.57
−45.57
−10.53
0
|
|
13097-L5-2
AGCCTCAGCCCCACCTCCAGCCCCACCCTAGGG
2343
−7.94
−7.94
−1.16
−3.99
−5.23
−7.94
1.33
0
|
|
13106-R5-1
ATCAGAGGCCGACCCCGGCGTCCAGGCCGGCA
2344
−37.32
−37.32
−26.17
−37.32
−37.32
−37.32
−24.68
0
|
|
13106-R5-2
TGGACCAATCAGAGGCCGACCCCGGCGTCCAG
2345
−42.08
−42.08
−35.48
−42.08
−42.08
−42.08
−9.62
0
|
|
13111-L5-3
TCTCCGCCGGGCCTTCACCCTGCCCTGCTCTTCT
2346
−8.41
−8.41
1.41
1.94
−4.26
−6.40
−1.19
0
|
|
13119-R5-2
GACTCTGCCGCTCCCGCCCGGCCACCTCCCTGT
2347
−6.27
−5.25
−3.10
−2.23
−8.08
−8.44
−2.59
0
|
|
13129-L5-2
GTCCCCTGGCCCCCGACCTGCTCCATCCACCCA
2348
−10.72
−10.72
1.69
−2.03
−7.75
−4.28
4.56
1
|
|
13129-L5-3
GTCCCCTGGCCCCCGACCTGCTCCATCCACCCA
2349
−10.72
−10.72
1.69
−2.03
−7.75
−4.28
4.56
1
|
|
13129-L5-3
AGCCTTCCTGTCCCCTGGCCCCCGACCTGCTCCA
2350
−8.92
−15.69
−1.15
−1.02
−5.81
−15.69
3.68
1
|
|
13130-L5-1
AGCCCGCCCCAACCCACCTCGATCTTTTCCTC
2351
−2.96
−5.75
−1.02
−2.38
−7.72
−7.44
−1.49
0
|
|
13130-L5-2
TCCCCAGAGCCCGCCCCAACCCACCTCGATCT
2352
−19.17
−11.28
−2.91
−4.08
−19.00
−28.42
−1.70
0
|
|
13137-L5-1
GCTCTAACCCCCGCAACCCCACCTCCCCATGCC
2353
−6.42
−6.42
1.22
−1.92
−2.51
−6.42
2.70
1
|
|
13138-R5-1
TTCGCCACGCCCCGCCACCCGAGCTGCCTCCC
2354
−22.78
−6.06
−3.57
−2.48
−3.75
−4.73
−2.04
0
|
|
13161-L5-4
TCCGCCAGGGTCCGCGTGTCAGTCCCCTCTGGTGA
2355
−60.36
−106.72
−106.33
−4.55
−225.31
−225.31
−122.88
0
|
|
13209-R5-3
TGGTCGCCGCCGCAGGCGCCTGAAGGGCACGGCGG
2356
−23.10
−23.10
−23.10
−23.10
−23.10
−23.10
−14.65
0
|
|
13211-L5-1
ACGCGCCCCGCCGCTCTCTGACCGACCGGAGGCGC
2357
−33.55
−33.55
−13.40
−24.17
−33.55
−33.55
−8.31
0
|
|
13227-L5-1
CTCCTCGTCCCCCTTCCCACCTCGGTGTCTTGCTT
2358
−25.42
−25.42
−3.92
−12.50
−2.75
−12.60
−4.39
0
|
|
13227-L5-2
GGGCCCAGTCCTCCTCGTCCCCCTTCCCACCTCGG
2359
−24.86
−38.26
−4.08
−9.37
−2.60
−5.71
−1.14
0
|
|
13229-L5-1
ACCCGTCCCTGCCCCTTTACCCCTTGGGCCAGCA
2360
−6.14
−6.14
1.13
−3.09
−3.21
−4.58
2.42
1
|
|
13229-L5-2
CCTGGGGCCACCCGTCCCTGCCCCTTTACCCCTT
2361
−7.44
−7.44
−1.25
−7.44
−7.44
−7.44
3.22
1
|
|
13229-R5-3
GCAGCTCCGCCAGTCTCTGTGGGCAGGGAGAAG
2362
−29.88
−18.41
−18.21
−1.79
−29.88
−29.88
−6.56
0
|
|
13239-L5-2
CAGAGCTCCCCCCATCTCCCCAGACTTACCCCT
2363
−5.36
−5.36
−1.08
−3.59
−3.58
−5.36
3.91
1
|
|
13240-L5-2
AATCGCCGTCCCCGCCGCGGCATTCCCGGCCCCAA
2364
−28.53
−28.53
−2.82
−2.43
−28.53
−21.92
−1.98
0
|
|
13247-L5-3
TCCTGAGCCGCCTTCCCCTCCCGACCTCAGAGCCCT
2365
−13.68
−19.46
−1.59
−1.37
−1.28
−2.19
1.48
0
|
|
13267-L5-1
CACTCCCTGCTGGCCCCCACCTCACCTATGGTG
2366
−58.86
−58.86
−9.66
−17.90
−7.03
−39.11
−1.08
0
|
|
13276-L5-4
CCCCCATTGTGGCTGCTCCCACCCCACCTGCCTTCA
2367
−9.13
−3.05
−1.92
−2.52
−1.28
−2.58
−1.50
0
|
|
13281-L5-3
CACCCCCACCCCACAGGACAGAGGAAGTGACGAG
2368
−17.40
−17.40
−2.72
−9.25
−17.40
−17.40
−1.76
0
|
|
13283-L5-3
GGACCCCTGCCTTCCTTGCTGCCACCCTTTGCACA
2369
−5.08
−5.08
−1.49
−2.73
−5.08
−5.08
1.94
0
|
|
13285-L5-3
GCTATGCACCCAGCCGCCCAGCTCAGCCCCTGC
2370
−13.41
−13.41
−2.23
−7.03
−13.41
−13.41
−1.61
0
|
|
13289-L5-3
GCTCAAAGTTTGCCTCCCATGGCCCCTCTGCCC
2371
−5.97
−5.97
−1.04
−2.79
−5.97
−5.97
1.72
0
|
|
13291-L5-2
TGGTTCTGCCCAAGCGCCCCTTCCTCCCTCCTT
2372
−5.00
−5.00
1.36
−3.54
1.37
−2.63
3.53
1
|
|
13312-L5-2
TGCCACCCCACCCCTCCCCCACAGCCCAGCCC
2373
−6.79
−15.24
−1.49
−6.97
−1.11
−3.12
1.59
0
|
|
13325-R5-1
CTGCCTGGCGCTGGGCTCTTCCCCATGAGCG
2374
−8.15
−8.15
−1.33
−3.29
−8.15
−8.15
2.04
1
|
|
13325-R5-2
TCCAACACTGCCTGGCGCTGGGCTCTTCCCCA
2375
−8.85
−8.85
1.23
−1.20
−8.85
−8.85
2.07
1
|
|
13326-L5-1
TCCGGCTTCCCCCCACCCGCCCTTCGATGGCA
2376
−5.52
−5.52
1.33
−1.60
2.24
−1.93
2.59
2
|
|
13326-L5-2
CAGAGATTCCGGCTTCCCCCCACCCGCCCTTC
2377
−10.44
−14.87
−1.59
−3.94
−1.48
−5.00
1.20
0
|
|
13343-L5-1
CCTCCACCCCTCCCGCAGCGCCCCTCCCCCTCA
2378
−54.66
−54.66
−2.68
−1.95
−2.09
−4.50
−1.06
0
|
|
13349-L5-1
TGTGTGGGCTATCCCAGCCGCCTCCTTCCTCT
2379
−6.04
−6.04
1.05
−1.36
−6.04
−6.04
1.40
0
|
|
13349-L5-2
CACCACCTGTGTGGGCTATCCCAGCCGCCTCC
2380
−17.13
−17.13
−4.48
−12.67
−17.13
−17.13
−2.49
0
|
|
13365-L5-3
TCCCCAGAGCCCGCCCCAACCCACCTCGATCTTTT
2381
−12.64
−27.91
−4.88
−2.98
−22.68
−21.98
−1.53
0
|
|
13374-R5-1
AGCCTTCCTGTCCCCTGGCCCCCGACCTGC
2382
−20.45
−20.45
−2.48
−5.82
−13.37
−11.72
−1.59
0
|
|
13374-R5-2
GGCCCTAGCCTTCCTGTCCCCTGGCCCCCGA
2383
−5.79
−5.79
−1.35
−2.92
−4.80
−5.79
1.61
0
|
|
13375-L5-3
GAGAACCTGAAACCCCAGCCCCTGCCTACCCCTTAG
2384
−5.86
−5.86
1.24
−2.87
−5.86
−5.86
1.67
0
|
|
13396-L5-2
GACCTGCCCCGCCCCACTCGGGCTCCTTACCG
2385
−5.03
−10.37
−1.25
−2.62
−8.50
−7.78
1.54
0
|
|
13431-L5-3
CGACACCCACTCACTGCCGCTGCCGCACTCACAGC
2386
−23.38
−23.38
−2.69
−4.01
−23.38
−23.38
−4.52
0
|
|
13432-R5-4
TTTACAGTTTCTGGCACTTCCTACCACCTCCCCA
2387
−5.41
−5.41
−1.42
−1.80
−5.41
−5.41
2.00
1
|
|
13456-R5-2
CAGATGCCCCGCTATGAAATCTTTTCCAACC
2388
−16.80
−16.80
−13.79
−16.80
−16.80
−16.80
−16.80
0
|
|
13461-L5-4
TCCCCAGCCCCGTCCCCACCCCCTAGAGAAAGTGAA
2389
−19.96
−28.08
−3.31
−5.34
−4.75
−16.77
−1.67
0
|
|
13497-L5-1
TGTGCCCCCCTCGCTCCCAGCCCCCAGGGGACCGC
2390
−7.88
−20.24
−4.39
−3.42
−3.34
−3.05
−1.79
0
|
|
227-L5-1
ACACCTGTCTCTCCCCAGTGCTTCCGCCCCTCA
2391
−59.95
−93.40
−4.00
−10.53
−13.51
−33.21
−2.73
0
|
|
266-R4-1
GTCGCCCCCTCCCCCAAGTTGAGACTTGCAGCTAC
2392
−6.36
−14.52
−1.45
−2.41
1.12
−3.13
1.90
0
|
|
266-R5-1
CCCCTCCCCCAAGTTGAGACTTGCAGCTAC
2393
−7.35
−7.35
1.06
−2.08
1.10
−4.92
5.32
1
|
|
2819-R5-4
CAGCCTGCCACCGCCGCTTTTGAAAGAAGCACTTCA
2394
−8.56
−8.56
1.00
−5.87
−8.56
−8.56
−1.66
0
|
|
3009-L5-1
ACCTCGGTCTCCTCCACCAGACTTTAAACTCTC
2395
−17.19
−17.19
−5.92
−2.82
−7.48
−17.19
−4.70
0
|
|
3009-L5-2
CCAGTGATACCTCGGTCTCCTCCACCAGACTTT
2396
−19.46
−19.46
−4.10
−9.16
−10.45
−19.46
−5.93
0
|
|
3009-L5-3
TGTAATAACCAGTGATACCTCGGTCTCCTCCAC
2397
−23.73
−23.73
−3.74
−2.02
−7.39
−23.73
−5.75
0
|
|
3249-L4-1
GCGGAGCCGCCGCCATCCCCGGAGCCGCCGCCGCCGCCG
2398
−8.53
−6.22
−3.77
−2.41
−14.30
−15.31
−2.56
0
|
CC
|
|
3249-L5-2
AGCGGAGCCGCCGCCATCCCCGGAGCCGCCGCCG
2399
−94.34
−18.11
−4.95
−2.32
−23.40
−29.20
−2.57
0
|
|
3799-R5-1
CTGAAGATGCTCCCAGAGGCCCCCCGCCGGCC
2400
−7.96
−8.04
−1.30
1.45
−8.27
−13.22
1.59
0
|
|
3897-R5-2
CCGACCCGCCCGTCAGCCGCCTCCCCCTCAG
2401
−11.04
−14.48
−1.65
−2.21
−3.50
−5.62
−1.55
0
|
|
3953-R3-2
ACTCCAGCCTCCGCCGCCTCAGCTTCCCGAGC
2402
−34.43
−52.88
−3.53
−4.10
−15.19
−24.22
−5.59
0
|
|
3966-L5-1
ACCCCAGAGCTGTCGCCGCCGCTGCCGCCTTCGCC
2403
−12.50
−9.10
−4.67
−3.33
−12.90
−27.25
−3.64
0
|
|
4303-R1-1
AGTGCCCGCTCCTCCGACCTCCCTGCGCACC
2404
−16.94
−16.94
−1.82
−7.37
−13.90
−16.94
1.02
0
|
|
4315_C-L4-1
GCAGCCCCTCCTCCGAGAGGTTGGGGGTCGCGGCCGCCC
2405
−10.99
−17.02
−1.97
−1.53
−1.97
−2.96
1.32
0
|
GGCCCTCCCGGTCCCCTCCCC
|
|
4315_D-R4-1
GGAAAGTCAGCCCCCAGCGCCCCCCGGAGTTCTTGG
2406
−88.80
−88.80
−12.25
−8.23
−57.77
−88.80
−6.18
0
|
|
4315_E-R4-1
CCCCCACCAAACCTATTCCCGCATCCTCCCCGGCTCTGG
2407
−7.17
−8.95
−1.28
1.62
−3.51
−8.09
2.47
1
|
|
4315_F-R4-1
AACCCGGGCTCCCCCACCCGCTCCCTGAGC
2408
−19.29
−28.54
−1.97
−2.12
−6.85
−14.36
−1.32
0
|
|
4315_I-L4-1
ACACCTCTGCGCCCCTCAGGCGCCCTGGGCCTCGGCGCCC
2409
−30.88
−30.88
−4.30
−3.56
−30.88
−30.88
−1.71
0
|
CGCCCGTCCCAG
|
|
4315_K-L4-1
TCCCAGGGGGCCCTGAACTTGTCAAATCCTCGCCATCCTCC
2410
−7.44
−7.44
1.35
−1.81
−2.45
−3.94
1.80
0
|
ACCCCCAGCCCCGG
|
|
4440-R3-1
TACTCCCGCCGTTTACCCGCATTTCACTGAA
2411
−10.88
−1.67
−1.04
1.21
−4.04
−11.36
−1.05
0
|
|
4479-R3-1
AGCCCCCTGCCCGGAAATTCAAAACAACTGC
2412
−14.50
−20.12
−3.55
−6.32
−16.37
−20.12
−3.97
0
|
|
4593-R5-1
CTATAGCAGATGACATAACTCCCCCGGCATCAG
2413
−12.46
−12.46
1.06
1.11
−12.46
−12.46
−1.12
0
|
|
4829-R2-1
TCCCTTTGTGCTGCCCGAGTGCCTTCCCCCTG
2414
−9.27
−9.27
2.07
−1.01
−3.71
−2.66
6.01
2
|
|
4855-R5-2
GGGCTGCCGGGTCTCCCGCTTCCCCCTCCTGC
2415
−10.65
−15.12
1.25
1.03
1.70
−1.51
1.72
0
|
|
4884-R5-1
TCCCCAGTCTCCCTGTTTCAGCACCTGCCTCA
2416
−17.58
−17.58
−1.81
−2.95
−7.44
−9.96
1.51
0
|
|
4988-R4-1
CTCCTCCTCCCCGTCTTTGGATACCAAACACTGGAC
2417
−5.47
−5.47
1.61
−1.61
−1.44
−5.47
3.51
1
|
|
4988-R5-2
CTCCTCCTCCCCGTCTTTGGATACCAAACAC
2418
−9.43
−9.43
1.16
−2.18
−1.17
−9.43
4.95
1
|
|
5071-R5-1
CGCCCCAGTCCCAGCCCAATTAATAAATGGG
2419
−6.09
−6.09
1.41
2.38
−6.09
−6.09
1.59
0
|
|
5071-R5-2
GACCCCCGCCCCAGTCCCAGCCCAATTAATA
2420
−24.30
−13.23
−2.97
−3.00
−5.08
−18.13
−1.48
0
|
|
5640-L3-1
GCCATGGAACACCGTGCCTGCCCCTCTCGAGA
2421
−22.57
−22.57
−3.86
−4.16
−22.57
−22.57
−1.57
0
|
|
5707-L5-2
TCACCATGCGGCCCCGGTGGTCTTCACACAGCA
2422
−17.42
−17.42
−17.42
−17.42
−17.42
−17.42
−17.42
0
|
|
6198-R5-2
GCCGCCGCCGCCGCGTCTTCCCGCGAAGCCT
2423
−8.01
−10.31
−4.02
−2.44
−21.45
−23.60
−3.04
0
|
|
6216-R5-2
CATAGTTACTCCCGCCGTTTACCCGTGCTTC
2424
−15.09
−10.39
−1.12
1.09
−5.30
−18.03
−1.30
0
|
|
6825-R5-1
TCCTTCTGCTCAGCTGTTCCCGGTGCCAG
2425
−28.95
−28.95
−21.84
−14.99
−28.95
−28.95
−6.06
0
|
|
6880-L3-2
ACCTCCCCCGCGAAGACATCCACATTCTGCA
2426
−20.08
−29.17
−1.83
−9.68
−3.55
−29.17
−3.36
0
|
|
7061-R5-2
TCATGGAAACCCCACCCTTCCCATGCCCAACC
2427
−5.94
−5.94
−1.04
−4.28
−5.94
−5.94
1.37
0
|
|
7126-L3-1
GCACACCCGCTCTCCGGCCCGCGCCCCTG
2428
−25.95
−6.91
−4.10
−2.74
−11.10
−14.35
−2.85
0
|
|
7356_A-R4-1
CAGAGCCCGCTCTCGCGACCGACCTGCCGCCGACCGCCAC
2429
−18.01
−26.53
−3.41
−4.02
−22.46
−25.26
−3.07
0
|
AG
|
|
7702-L2-1
CCCAGAGAACCGGAATTCCTCCCCGCCCC
2430
−5.27
−5.27
−1.83
−2.91
−4.35
−5.27
2.04
1
|
|
7824-R5-1
TGCCAGCTTCATCGCCGCCTCACACACACA
2431
−8.78
−8.78
−2.70
−8.78
−8.78
−8.78
−3.37
0
|
|
7949-R5-1
GATGCGCGCGCCGACCGCCGCCAGCTGCAATTCATAC
2432
−24.23
−24.23
−3.02
−1.84
−24.23
−24.23
−2.16
0
|
|
8016-L3-1
TCAGCGCAACAAGCCCCGCAGTCACCCCTCT
2433
−54.19
−54.19
−16.08
−20.80
−54.19
−54.19
−6.74
0
|
|
8250-R5-2
CCGACCCGCCCGTCAGCCGCCTCTCCCTCAG
2434
−17.68
−16.09
−1.77
−1.62
−3.89
−4.78
1.33
0
|
|
8394-L5-1
CCGCCCTGCCCATCTCCGACTATCCCTGGCCCC
2435
−7.06
−7.06
1.08
−1.28
−7.06
−7.06
2.40
1
|
|
8898-R5-1
CAGCCGAGGCGGACGCCCGCTCCCGCCACCATG
2436
−10.42
−15.12
−2.07
−1.34
−12.35
−15.12
−1.31
0
|
|
9053-R3-1
TTCTTGCCCTCCAATCCCCGGGCTCCACCAGCC
2437
−10.59
−10.59
−1.97
−1.65
−8.41
−10.59
−2.27
0
|
|
9387-R2-2
TCCATCCTTGCCGTCGCCTTCATCTCAAAGCCATC
2438
−8.80
−8.80
−1.47
−8.80
−8.80
−8.80
−3.48
0
|
|
9691-L5-1
CATTTCATCCGCATCTCCCTCTTGGCCCCTTGC
2439
−8.33
−8.33
−2.45
−6.14
−8.33
−8.33
1.53
0
|
|
9774-R2-2
CCGCCCCCTCACCGCCTCCTGCTCCCATCAGGC
2440
−7.93
−16.14
−1.34
−2.55
−4.83
−3.47
1.40
0
|
|
miR-1228*
CACACACCTGCCCCCGCCCAC
2441
−15.38
−12.90
−2.54
−1.74
−4.13
−8.82
−1.45
0
|
|
miR-1275
GACAGCCTCTCCCCCAC
2442
−8.09
−8.09
2.33
−1.30
−2.96
−8.09
2.04
2
|
|
miR-1308
CCACTGAACCACCCATGC
2443
−18.92
−18.92
−5.22
−18.92
−4.03
−18.92
−5.64
0
|
|
miR-21
TCAACATCAGTCTGATAAGCTA
2444
−1.68
−23.57
−19.14
−23.57
1.39
−7.45
−2.50
0
|
|
miR-373*
GGAAAGCGCCCCCATTTTGAGT
2445
−48.87
−48.87
−48.87
−48.87
−48.87
−48.87
−21.32
0
|
|
miR-423-5p
AAAGTCTCGCTCTCTGCCCCTCA
2446
−9.88
−4.20
−6.30
−4.12
−7.70
−16.50
−3.64
0
|
|
miR-486-3p
ATCCTGTACTGAGCTGCCCCG
2447
−40.84
−40.84
−36.13
−40.84
−40.84
−40.84
−7.70
0
|
|
miR-612
AAGGAGCTCAGAAGCCCTGCCCAGC
2448
−5.79
−5.79
−3.09
−2.94
−5.79
−5.79
−1.13
0
|
|
miR-638
AGGCCGCCACCCGCCCGCGATCCCT
2449
−11.00
−23.12
−2.25
−1.89
−19.12
−23.12
−1.53
0
|
|
miR-663
GCGGTCCCGCGGCGCCCCGCCT
2450
−45.02
−45.02
−10.68
−32.17
−45.02
−45.02
−11.52
0
|
|
miR-744
TGCTGTTAGCCCTAGCCCCGCA
2451
−37.67
−37.67
−10.59
−19.87
−37.67
−37.67
−4.41
0
|
|
miR-923
AGTTTCTTTTCCTCCGCTGAC
2452
−3.90
−3.72
1.48
1.30
−6.06
−8.95
2.30
1
|
|
TABLE 31
|
|
Pre-microRNA sequences and chromosomal locations of target RNAs in Table 30
|
Gene Down
SEQ
|
expressed in
Chrom
ID
|
Cell lines
loc'n
Pre-microRNA sequence
NO
|
|
10010_B-L4-1
7q32.1
GGGCAGCGCCCCTCCTTCCGGAGGGCAGCATCCCGGCGGGGGCGGGGGCTCGGCTTTGATGCCAGGG
2453
|
CACCTTTTGTCCCTGGAGACGCTCTGCCAGCCAGGTGCGTGGAGGGAGTGCAGCCC
|
|
10010_D-L4-1
7q32.1
CAGGTGAGAGGCTGAGCCCCGGGCGGGGGAGGGCGCCAGGCCTGGGGCATTAACCGTCCCGGGGACC
2454
|
CTTTTGGCCTG
|
|
10138-L2-1
17q22
ACTTTTTCTGGTGGGAGGGGAGAGCGGAGCAGGCTCACGTGTAACCGCGCAGGAGCCTCCTCTGGCT
2455
|
TGAGCCCTTTCTTGGTAAGT
|
|
10231-R3-1
9p11.2
GGCGGCTGCGGAGGCTGGCGCGGGCTGCTGCACCTTTAACGCTTTCTGGCGCTGACAGGCGGCGGCC
2456
|
CAGCTAAAGTTCACAGCGCC
|
|
10242-R5-1
22q13.2
GGCAGGAAGGCCTCCGGCTTCACAAAGTGGCCCTGGGCATCCAGGAAGTGTTCGGGGTGGAAGCGGA
2457
|
AGGGCTTCTTCC
|
|
10342-R2-2
19g12
CCCACGCACGGAGGGTCGCCAGGAAAGTGGACATTACCGCTTTAATTAACTTCGAGATGCTCCGGCG
2458
|
GCGGG
|
|
11370-L4-1,
12g13.2
GTCCAGTTCTCAGGGGACAATACTGATGGCAGCCAAACTGGGCAAGGATGCAGTGTGGGGGCGGAGGGGGC
2459
|
11370-L5-5
ATGACCTCTATTCAAGTTCTGTGTCTTGGCCCCTGGCTGAGGTATTGAGTGTGAGGAAGGGAACACTGGGC
|
|
12223-L4-1
4q27
TAGAGGGAGAAGAAACAACTCTGTCTGATGTCTTCTGGGATGGCCTTAATACAGATAGCATTGTCTCTTCC
2460
|
ATTTCTG
|
|
12691-R5-1
1q22
CCCACGCGTCGCGCGCTCCCGACCGGAGCGGGACGGGGCCTGTCGGGGGCGCGCCAGGGGCGGGG
2461
|
|
12692-L5-1
1q22
GCGCGGTGGCCGGGTGCTGGCTGCGGGGCCGGGTCCTCATTCTGCTCAGTCCTTGCTGCCCTTGTCTTCTC
2462
|
CTCCCCGCCAAGCCGCCGTGT
|
|
12693-L5-1
1q22
GGGGAGGGGACCGGGAGGGCCGGGCGGCCGCGACCCCCAACCTCTCGGAGGAGGGGCTGCCGCTCGCCGCT
2463
|
CCGCTCTTTGTTGTTTGGGGCTCCGCGCCTCCCCCTCTCTCCCTCCTC
|
|
12694-R5-1
1q22
GGGGACGTGGCCCCTCCCCCCCGGAGCGGGACTCCAAGAACTCCGGGGGGCGCTGGGGGCTGACTTTCC
2464
|
|
12695-R5-1
1q22
TCCCCGCCACCCTTGGAGCACCTCAGCGTTCTTAGGGGAAGCCAGAGCCGGGGAGGATGCGGGAATAGGTT
2465
|
TGGTGGGGG
|
|
12696-R5-1,
1q22
GATCAGGTTCCCCTCCCCCGCATACACCTGGGCGCAGGTGAAAGCTCAGGGAGCGGGTGGGGGAGCCCGGGTT
2466
|
12696-R5-2
|
|
12697-R5-1
1q22
CGGGAGCCTCCTTTCTGTCCTCTCTACTCCGTGCGGGCCTGGGCCGGCAGAGGTAGGAGGGGGCGCACACCGG
2467
|
GCCAGGAGGCTGCC
|
|
12699-L5-1
1q22
CTGGGACGGGCGGGGCGCCGAGGCCCAGGGCGCCTGAGGGGCGCAGAGGTGTCAGCGTGCAACCGCCGCCCCC
2468
|
CAGCGTTCCCGCCACCACCGCCACCACCCTCAAAGCCCGG
|
|
12701-L5-1
1q22
CCGGGGCTGGGGGTGGAGGATGGCGAGGATTTGACAAGTTCAGGGCCCCCTGGGATCCTTTCCCTACTCCCTG
2469
|
GTCTTGTTGGACACCCTGTTTACCTGCCCTAATTGCCCCGG
|
|
12703-L5-3
7q32.1
GGGCAGCGCCCCTCCTTCCGGAGGGCAGCATCCCGGCGGGGGCGGGGGCTCGGCTTTGATGCCAGGGCACCTT
2470
|
TTGTCCCTGGAGACGCTCTGCCAGCCAGGTGCGTGGAGGGAGTGCAGCCC
|
|
12704-L5-1,
7q32.1
CAGGTGAGAGGCTGAGCCCCGGGCGGGGGAGGGCGCCAGGCCTGGGGCATTAACCGTCCCGGGGACCCTTTTG
2471
|
12704-L5-2
GCCTG
|
|
12713-R5-1
8q24.3
CGGAGGTCGCTCGCTCGCTCGCTCGGCTCGCTGACTCGCCGGAGCGCTCTGTGGCGGTCGGCGGCAGGTCGGT
2472
|
CGCGAGAGCGGGCTCTG
|
|
12722-L5-1
13q31.3
GCGGGCGGGCGGGGAGGTCGGAAGTACTTTGTTTTTTATGCTAATGAGGGAGTGGGGCTTGTCCGTATTTACG
2473
|
TTGAGGCGGGAGCCGCCGCCCTTCATTCACCCACATGGTCCTTCGAGGTGCCGCCGCCGCCGCCCGACCTGC
|
|
13004-R5-1
12g13.2
CCTTGACTTCCCTTTCTTCTCACTTCGGACTGCTCACTTGCCTTGTTCAGCCCTGAATCATCAGGTGAAGGGA
2474
|
GCGAGAATTGCGGGGGTTGGAGTTAGGTAGAGGGATTTAAGG
|
|
13006-R5-4
12q21.1
CCCTAACTTCCCTCTCTACACCCTCGCTCTTCCCACCGCTCCCGTCCTTCTCCCTAGCCGAGAACCGGTTGGA
2475
|
AGGCTCCCGCGGAAAGCGAGGCGAGAGCGCGGCGCAGGGGAGGGAGAGCCGGG
|
|
13044-L5-3,
10q21.3
CTGCAGCTAAGAGGGGTGTGATGAAAGCAAAGAAAGGGACAGCTGGGATGGGAGAAGCCCTGGGGGGAGCAGG
2476
|
13044-L5-4
GAGGCTCCCACATGTTGTACCCTCCGGTAACACTCAGGCCCTGGACAGTCAGCAG
|
|
13047-R5-2
10q26.3
ACCTCAGTGTTGATAGCAGATCTCATTATAGTCGGTGCATTTGGCTACCGACCTGCAGCCAGCAGTGCCCGGG
2477
|
GCTAGTGCATGGGGTCTGCTGTGCCACTGTGGT
|
|
13052-L5-1
19g13.33
GGTTGGCGGGTGGGGGAGATGCTTAGGTCCGGGGAATCTCTGAGATTCTCGGCTTCCCCTCTCCCCTCACCCT
2478
|
CCTCCTCAGGCCCCAGGCAGCCCCGGGGCATGCTGGGAACCCAGGCCTGGGCTCCGGGCCAGG
|
|
13093-L5-2
11813.1
CTGACTTCTGCGCGGGGCGCGGTGGGGTTCTGCGGGGTCGGAAAGACTCCCCAGATCCCCGCGCGGCCCCAGA
2479
|
CCCAG
|
|
13097-L5-2
11q23.3
GTGGACAACCCTAGGGTGGGGCTGGAGGTGGGGCTGAGGCTGAGTCTTCCTCCCCTTCCTCCCTGCCCAGGGG
2480
|
TCCAC
|
|
13106-R5-1,
14q11.2
TGGCTCTAGGCCACCCTGGCAGCTGGGCCGCACTCTGCCGGCCTGGACGCCGGGGTCGGCCTCTGATTGGTCCA
2481
|
13106-R5-2
|
|
13111-L5-3
16p13.3
AGCCTGTGGGAAAGAGAAGAGCAGGGCAGGGTGAAGGCCCGGCGGAGACACTCTGCCCACCCCACACCCTGCC
2482
|
TATGGGCCACACAGCT
|
|
13119-R5-2
17q21.32
TCTCCGTGCACGCTGCTGACCGGCTCGGCGACTGCCTCCCTGCTGTGAGCAGGAGAACAGGAAGTCTGCCCGA
2483
|
CAGGGAGGTGGCCGGGCGGGAGCGGCAGAGTCGGCGTTGAGA
|
|
13129-L5-2,
20q13.33
TGGCGCTGCTCTGCTGTTCCTCTGTCTCCCAGACTCTGGGTGGATGGAGCAGGTCGGGGGCCAGGGGACAGGA
2484
|
13129-L5-3
AGGCTAGGGCC
|
|
13129-L5-2,
20q13.33
CCAGACTCTGGGTGGATGGAGCAGGTCGGGGGCCAGGGGACAGGAAGGCTAGGGCCCCAGAGACCTGTCCTGG
2485
|
13129-L5-3
GCCCCATGTCCAGCTCTGCCCTTAGTGCTTGG
|
|
13130-L5-1,
19p13.3
CCAAGCAGCTTATCGAGGAAAAGATCGAGGTGGGTTGGGGCGGGCTCTGGGGATTTGGTCTCACAGCCCGGAT
2486
|
13130-L5-2
CCCAGCCCACTTACCTTGGTTACTCTCCTTCCTTCTAGGG
|
|
13137-L5-1
5p15.2
GGCATGGGGAGGTGGGGTTGCGGGGGTTAGAGCTGTGGGTGATCAGAAGGGAAGGGCTTCATTTCTACGCTCT
2487
|
GCCTCCGCTACCTCTTCCCCACCACCCCTAATCCC
|
|
13138-R5-1
5q22.3
ATCCGTCGCAGCAGTCGCTGCAGCCGCTGCAGTCCGAGCCGACTAAGGGCGGGAGGCAGCTCGGGTGGCGGGG
2488
|
CGTGGCGAACAGCGCGGCCGGAT
|
|
13161-L5-4
8p21.3
GGGAGAGAAGGGGCGACGAGATCACCAGAGGGGACTGACACGCGGACCCTGGCGGAACCCCACCCCCTTGCTT
2489
|
TCCGGTCCCCCAGTCGGTGCGTCCCTCCAGTGGCCTCTCAGCTCCTCCCCTCCC
|
|
13209-R5-3
10q22.1
GGGAGCCGCCGGCGGGCAGGCCGCCGGGGCAGCAGGCGAGTTACCTCAACTCCCGGCCGCTCCGGAGGTTGCC
2490
|
GGGCACCGAGGAGCCGCCGTGCCCTTCAGGCGCCTGCGGCGGCGACCA
|
|
13211-L5-1
10q23.1
GCGCCTCCGGTCGGTCAGAGAGCGGCGGGGCGCGTCTGCAGCCCTCCAAGCCGCCTCCTGCGCGCCGGGTCCC
2491
|
CGCGCCCGCTGCTGCTGCTGCTGCCCGCCGCCTGCGTGC
|
|
13227-L5-1,
11q25
AAGCAAGACACCGAGGTGGGAAGGGGGACGAGGAGGACTGGGCCCTATTTCTCCCATCTATGTAAAGGGAGGG
2492
|
13227-L5-2
ATATCAGGGAAGTCTCTGTCTGTGTACTCAAGTTTGGGATGCT
|
|
13229-L5-1,
11p15.5
TGCTGGCCCAAGGGGTAAAGGGGCAGGGACGGGTGGCCCCAGGAAGAAGGGCCTGGTGGAGCCGCTCTTCTCC
2493
|
13229-L5-2,
CTGCCCACAGAGACTGGCGGAGCTGC
|
13229-R5-3
|
|
13239-L5-2
1q23.3
CTGAGGACAGGGGTAAGTCTGGGGAGATGGGGGGAGCTCTGCTGAGGGTGCACAAGGCCCTGGCTCTACACAC
2494
|
ATCCCTGTCTTACAGAG
|
|
13240-L5-2
11q12.2
GCAGTGTGATTTGGGGCCGGGAATGCCGCGGCGGGGACGGCGATTGGTCCGTATGTGTGGTGCCACCGGCCGC
2495
|
CGGCTCCGCCCCGGCCCCCGCCCCACACGCCGCAT
|
|
13247-L5-3
1q24.2
ATCTCACAGAGGAAGAACAGGGCTCTGAGGTCGGGAGGGGAAGGCGGCTCAGGACTTCTGGCTCCAGAGCCTC
2496
|
CTCTCCTTCCACCATAGTGCCTGCTCCAGAGGAGAC
|
|
13267-L5-1
1q42.13
CACCATAGGTGAGGTGGGGGCCAGCAGGGAGTGGGCTGGGCTGGGCTGGGCCAAGGTACAAGGCCTCACCCTG
2497
|
CATCCCGCACCCAGGCTTCAACGTGG
|
|
13276-L5-4
12q13.13
GTGCTTTCTTGTCCAAGCAGTTGATGAAGGCAGGTGGGGTGGGAGCAGCCACAATGGGGGCTCTGCTGACCAT
2498
|
CTGCCCTTCCACCCTACAGCACCCGGCGACAGGACACCAGGT
|
|
13281-L5-3
12p13.31
GCCGCCCCCACCCTGTCCCTCGTCACTTCCTCTGTCCTGTGGGGTGGGGGTGCAGGCGCTTCTCCTTTAGCTG
2499
|
TGCCGCACTTCTCCCTACAGGCCAGGAGAAACAGAACACCGTGTGCAC
|
|
13283-L5-3
1p36.11
GGGCACGGGGGTTGGGTGTGCAAAGGGTGGCAGCAAGGAAGGCAGGGGTCCTAAGGTGTGTCCTCCTGCCCTC
2500
|
CTTGCTGTAGACTTTGGCCTGAGCAAAGAGGCC
|
|
13285-L5-3
1p36.32
CTGGGGGTGACCCCGTGCAGGGGCTGAGCTGGGCGGCTGGGTGCATAGCCCATCTGTAGCCTAAGCAATGGTG
2501
|
CAAAGCCCCCACGCCTTGGTTTCCTCTCCTGAACGCGGGCACACAGAG
|
|
13289-L5-3
1p35.1
TGCTTGGAGTGGCAGAGGGCAGAGGGGCCATGGGAGGCAAACTTTGAGCGTGTCTCAGGAGCCTAAAACATGA
2502
|
GAAGCCTCAGTTTCCCTCTCCTAGACCATCTGCTTATCCTCTCCAGGC
|
|
13291-L5-2
1p34.3
CGGGAGGGAAGGAGGGAGGAAGGGGCGCTTGGGCAGAACCAAGGGTGGCAGATTATCCTAGGGACTCTTGGGG
2503
|
CAGAACCAGACGCCTCTGCGTCCTCCCCTCTCCCC
|
|
13312-L5-2
15q24.1
GTGAGTGGGGCTGGGCTGTGGGGGAGGGGTGGGGTGGCAGGGAACAGGCAGACCATCCCTTCTACCCACAGGA
2504
|
TCCTGCTGCTGCAGACAG
|
|
13325-R5-1,
16q24.3
ACTCAGGCACTGCCTCTGACGATGCTCTCCCAGATCTGGTACGCTCATGGGGAAGAGCCCAGCGCCAGGCAGT
2505
|
13325-R5-2
GTTGGA
|
|
13326-L5-1,
17p12
TGCCATCGAAGGGCGGGTGGGGGGAAGCCGGAATCTCTGTCCACATGCTCCAGGCACCTAGCTGCTCTGAGGG
2506
|
13326-L5-2
GCAGAGAGCAGAGGTGGTGCTCCCCCCCATCAGCATTTTGAGTTGGCT
|
|
13343-L5-1
17q25.3
TGAGGGGGAGGGGCGCTGCGGGAGGGGTGGAGGGCCCAGGGAAGGGTGAGGGGCCGGGAGCCACTCTGCCCGG
2507
|
CACTCTCCGCCCAGAAACAGCCCAACGCCCCTTTCTTTCCCCTTT
|
|
13349-L5-1,
18q23
AGAGGAAGGAGGCGGCTGGGATAGCCCACACAGGTGGTGGGAGTCTGTCCTCTCCCTGCCAGGGTGCAGGACA
2508
|
13349-L5-2
GCAGGTCTCAATCTCGCCCAGTGGGACTCAGTGGTCCCTCATTCA
|
|
13365-L5-3
19p13.3
CCAAGCAGCTTATCGAGGAAAAGATCGAGGTGGGTTGGGGCGGGCTCTGGGGATTTGGTCTCACAGCCCGGAT
2509
|
CCCAGCCCACTTACCTTGGTTACTCTCCTTCCTTCTAGGG
|
|
13365-L5-3
19p13.3
GAGGAAAAGATCGAGGTGGGTTGGGGCGGGCTCTGGGGATTTGGTCTCACAGCCCGGATCCCAGCCCACTTAC
2510
|
CTTGGTTACTCTCCTT
|
|
13374-R5-1,
20q13.33
TGGCGCTGCTCTGCTGTTCCTCTGTCTCCCAGACTCTGGGTGGATGGAGCAGGTCGGGGGCCAGGGGACAGGA
2511
|
13374-R5-2
AGGCTAGGGCC
|
|
13374-R5-1,
20q13.33
CCAGACTCTGGGTGGATGGAGCAGGTCGGGGGCCAGGGGACAGGAAGGCTAGGGCCCCAGAGACCTGTCCTGG
2512
|
13374-R5-2
GCCCCATGTCCAGCTCTGCCCTTAGTGCTTGG
|
|
13375-L5-3
20q13.33
ACCCTCTCAGGACCCCTCCTAAGGGGTAGGCAGGGGCTGGGGTTTCAGGTTCTCAGTCAGAACCTTGGCCCCT
2513
|
CTCCCCAGACCCCCAGGCTGTGGTGAGGGTCTGAGAGCTGGTAC
|
|
13396-L5-2
22q11.21
GGGACAGCGGTAAGGAGCCCGAGTGGGGCGGGGCAGGTCCCTGCAGGGACTGTGACACTGAAGGACCTGCACC
2514
|
TTCGCCCACAGAAAGACTCCTAGCCAGGAGGGCCTGC
|
|
13431-L5-3
3p21.31
GCCTCTTCCTGTCTCTGCTGTGAGTGCGGCAGCGGCAGTGAGTGGGTGTCGACGCGGCGGAATGCCCGTCGCT
2515
|
GCTGCTGCTGCTGCCCGACGGGCCTGGGG
|
|
13432-R5-4
3p14.2
TGCTTTCTGCATTCTTCTCCCTCCCCGGTCTCTTGTGACAAGCCATACTGTTAAATATCAGAATAGTAGGTGA
2516
|
TTACGTGGAGTTTGGGGAGGTGGTAGGAAGTGCCAGAAACTGTAAA
|
|
13456-R5-2
4q12
CCAGGAGCTACCAAGCAGAGGTTTATTCAGTCTCCAGAAGGCTATGCAGGTTGGAAAAGATTTCATAGCGGGG
2517
|
CATCTG
|
|
13461-L5-4
5p15.33
TCCGGGAATCTGGAGGTTTCTAGCACTTTCACTTTCTCTAGGGGGTGGGGACGGGGCTGGGGAGAGAATCCCC
2518
|
CAGCCCTGTTCCCTCCATCCTGGCTCCAAATCCCAGTTACTCCCCGGA
|
|
13497-L5-1
7q22.1
GCGGTCCCCTGGGGGCTGGGAGCGAGGGGGGCACAGATCTGATGTGCCCCCCACCCTCTCACAGGACTGG
2519
|
|
227-L5-1
3q27.2
TGAGGGGCGGAAGCACTGGGGAGAGACAGGTGTGAGCTTCCCACGTGGTGATCAGCTCACACCTGTCTTGTGT
2520
|
TCTTGGTATTCACAGACTCTCA
|
|
266-R4-1,
12q14.3
GTTGCTATTTCCCTCAGTTGAGGGCGAAGTTAGCAAATCCGTAGCTGCAAGTCTCAACTTGGGGGAGGGGGCGAC
2521
|
266-R5-1
|
|
2819-R5-4
15q22.2
AATGCCAGTGAGTTTGAAAGGCACTTTGTCCAATTAGAAGTGTGGAGAAATATTCATCCTGTCCATGACAAAG
2522
|
ATGAAGTGCTTCTTTCAAAAGCGGCGGTGGCAGGCTG
|
|
3009-L5-1,
8q24.3
GAGAGTTTAAAGTCTGGTGGAGGAGACCGAGGTATCACTGGTTATTACAATACAGTGAGCCCCACATTGGAAA
2523
|
3009-L5-2,
GACCAGCCACGCTCTTGGTCTCCGTCCCCATAACTCTC
|
3009-L5-3
|
|
3249-L4-1,
1q22
GGCGGCGGCGGCGGCGGCTCCGGGGATGGCGGCGGCTCCGCTGCTGCTGCTGCTGCTGCTCGTGCCCGTGCCG
2524
|
3249-L5-2
CTGCTGCCGCTGCT
|
|
3799-R5-1
11q13.1
GAATTTGCCCTACGGTGTGACCCCAGCCTCTCCCTCTGGCCACAGCCAGGGCCGGCGGGGGGCCTCTGGGAGC
2525
|
ATCTTCAGCAAGTTC
|
|
3897-R5-2
9q12,9p
CGGAGCCGCCCGCGCCAGCCTCTCCATCTCGCAAGTTTTAATTAACGCTGAGGGGGAGGCGGCTGACGGGCGG
2526
|
11.2
GTCGG
|
|
3953-R3-2
9q33.3
GCTCCTGCTCCGCCGCGGGAGCTGCTCCGGCGGCCGCAGGGCTCGCTCGGGAAGCTGAGGCGGCGGAGGCTG
2527
|
GAGT
|
|
3966-L5-1
3q27.2
GGCGAAGGCGGCAGCGGCGGCGACAGCTCTGGGGTTTGCGTCTCGGGGTGTGTCGGCCGCCGCTGCTGCTTG
2528
|
GGCC
|
|
4303-R1-1
22q11.21
GGCTGGCCAGGCTCCGCCCCCGGCCCTCCCTGCGCCCGGCCGGTGCGCAGGGAGGTCGGAGGAGCGGGCACT
2529
|
GCCCACCC
|
|
4315_C-L4-1
1q22
GGGGAGGGGACCGGGAGGGCCGGGCGGCCGCGACCCCCAACCTCTCGGAGGAGGGGCTGCCGCTCGCCGCTC
2530
|
CGCTCTTTGTTGTTTGGGGCTCCGCGCCTCCCCCTCTCTCCCTCCTC
|
|
4315_D-R4-1
1q22
GGGGACGTGGCCCCTCCCCCCCGGAGCGGGACTCCAAGAACTCCGGGGGGCGCTGGGGGCTGACTTTCC
2531
|
|
4315_E-R4-1
1q22
TCCCCGCCACCCTTGGAGCACCTCAGCGTTCTTAGGGGAAGCCAGAGCCGGGGAGGATGCGGGAATAGGTTT
2532
|
GGTGGGGG
|
|
4315_F-R4-1
1q22
GATCAGGTTCCCCTCCCCCGCATACACCTGGGCGCAGGTGAAAGCTCAGGGAGCGGGTGGGGGAGCCCGGGTT
2533
|
|
4315_1-L4-1
1q22
CTGGGACGGGCGGGGCGCCGAGGCCCAGGGCGCCTGAGGGGCGCAGAGGTGTCAGCGTGCAACCGCCGCCCC
2534
|
CCAGCGTTCCCGCCACCACCGCCACCACCCTCAAAGCCCGG
|
|
4315_K-L4-1
1q22
CCGGGGCTGGGGGTGGAGGATGGCGAGGATTTGACAAGTTCAGGGCCCCCTGGGATCCTTTCCCTACTCCCT
2535
|
GGTCTTGTTGGACACCCTGTTTACCTGCCCTAATTGCCCCGG
|
|
4440-R3-1
7q11.22
GTGATGTGATTTCTGCCCAGTGCTCTGAATGTCAAACTGAAGAAATTCAGTGAAATGCGGGTAAACGGCGGG
2536
|
AGTAACTATGAC
|
|
4479-R3-1
1p32.3
CCCAAGCTCCTTCCTGGAGGACTTAACACTGTGTTGAGCAGTTGTTTTGAATTTCCGGGCAGGGGGCTGCAA
2537
|
AAGGG
|
|
4593-R5-1
15q23
CAATCAATTAGCACATGAGTAATACCAAGCCCATTAGGACAAACTGATGCCGGGGGAGTTATGTCATCTGCT
2538
|
ATAGAAATGATTG
|
|
4829-R2-1
1q21.3
GGTGTGTCTGCCTCTCTTTCTGCCCCCCTATACCCCTTGACCCCAGGGGGAAGGCACTCGGGCAGCACAAAG
2539
|
GGAGCAGATGCCC
|
|
4855-R5-2
12q13.11
GGGTCCGGGTCTCTACCGCGCCCTCATGCAGGAGGCCCTTGGAGCAGGAGGGGGAAGCGGGAGACCCGGCAG
2540
|
CCC
|
|
4884-R5-1
17q11.2
TCCACAGCTCCATAAATGTTTAATGCCACCGGCTGGGCAGGAATGAGGCAGGTGCTGAAACAGGGAGACTGG
2541
|
GGA
|
|
4988-R4-1,
14q24.3
CTTTTTCTCTCTGCTGGGAAACCTTGCTTGACTTCATGTCCAGTGTTTGGTATCCAAAGACGGGGAGGAGGAG
2542
|
4988-R5-2
|
|
5071-R5-1,
17q12
GATTCCTGCTCCCAGAGCCATAAAGTGGGAGCCCCCATTTATTAATTGGGCTGGGACTGGGGCGGGGGTC
2543
|
5071-R5-2
|
|
5640-L3-1
1p34.1
TCTCGAGAGGGGCAGGCACGGTGTTCCATGGCAAGACGGCGGTTGATGTATAGGCGTGGCATGAAGCTGGGCT
2544
|
TGCTGCTCTCAGA
|
|
5707-L5-2
9q34.3
GCTCCTCGTGCTGTGTGAAGACCACCGGGGCCGCATGGTGAAGCACCAGTGCTGTCCTGGCTGTGGCTACTTC
2545
|
TGCACAGCGGTAAGAGC
|
|
6198-R5-2
1q25.3
GCCGCCAGCACCCGCGGTGCCGCGGGGCCGCTCCGAGGAGCCTGAGAGACCCACGGAGGCTTCGCGGGAAGAC
2546
|
GCGGCGGCGGCGGC
|
|
6216-R5-2
11q14.1
CATGTGATTTCTGCCCAGTGCTCTGAATGTCAAAGTGAAGAAATTCAATGAAGCACGGGTAAACGGCGGGAGT
2547
|
AACTATG
|
|
6825-R5-1
9q31.3
CAAATTACATCTGTTTATGCTTCTATTTGTTAGACAATCTGGCACCGGGAACAGCTGAGCAGAAGGATTTG
2548
|
|
6880-L3-2
1q42.13
GGCTTGCAGAATGTGGATGTCTTCGCGGGGGAGGTGGCCACGTTCTCCTGTGAGGTGTCTCACGCGGGTGGGCC
2549
|
|
7061-R5-2
1p13.3
TCATGGCAGCGACCCACCTCCAGTCCCCTGGACAATCGGGTACAAGAGACTTAAGGTTGGGCATGGGAAGGGT
2550
|
GGGGTTTCCATGA
|
|
7126-L3-1
5q31.1
CAGGGGCGCGGGCCGGAGAGCGGGTGTGCAAAGTGGGCGCAGGGCCCTGGGGCCGCGCCCCTTGCTCTGCCGGC
2551
|
TCGACTCTTG
|
|
7356_A-R4-1
8q24.3
CGGAGGTCGCTCGCTCGCTCGCTCGGCTCGCTGACTCGCCGGAGCGCTCTGTGGCGGTCGGCGGCAGGTCGGTC
2552
|
GCGAGAGCGGGCTCTG
|
|
7702-L2-1
10q21.2
GGGGCGGGGAGGAATTCCGGTTCTCTGGGACTTTCCAAAAAAGGCGAAGATCCGGTGCCGGCGGCTCCGCCTCC
2553
|
CTAGCCCT
|
|
7824-R5-1
6q16.2
CCTGGATGCTGTTTCATTATGTAGAGTCAGGCAAAAGACAGACGGATGTGTGTGTGAGGCGGCGATGAAGCTGG
2554
|
CACCAGG
|
|
7949-R5-1
5q31.3
GGTGCGCGCGGTGGACGCCGATTCGGGCTACAATGCGTGGCTTTCGTATGAATTGCAGCTGGCGGCGGTCGGCG
2555
|
CGCGCATC
|
|
8016-L3-1
12q21.1
AGAGGGGTGACTGCGGGGCTTGTTGCGCTGAAGATTTACAATGTACTTCTTGCAGGCGGCTCAGCAACCCCCTCT
2556
|
|
8250-R5-2
9p11.2
CGGAGCCGCCCGCGCCAGCCTCTCCATCTCGCAAGTTTTAATTAACGCTGAGGGAGAGGCGGCTGACGGGCGGGT
2557
|
CGG
|
|
8394-L5-1
7p13
GGGGCCAGGGATAGTCGGAGATGGGCAGGGCGGGGGCCCCACTGGCGAGGGGCCCTCGGCTTCTGGGGTCCCTGA
2558
|
GCCCC
|
|
8898-R5-1
17p13.3
GGCGCTGTCGGCCGGGGCGGCCGCCGGCAACTCGTCCGTCTTGATAACCATGGTGGCGGGAGCGGGCGTCCGCCT
2559
|
CGGCTGTCCGCGCC
|
|
9053-R3-1
X827.3
GGAAGGGCACTGTCTCTCTGATTCCCAGGGCCTGTCATTTCCCGAGGGCTGGTGGAGCCCGGGGATTGGAGGGCA
2560
|
AGAAGCCCAGCC
|
|
9387-R2-2
3p21.1
TCTCCATCCTCTGTCTCCCTTGATCCTCTGTTCTCCCTGATGGCTTTGAGATGAAGGCGACGGCAAGGATGGAGG
2561
|
|
9691-L5-1
14q24.3
GCAAGGGGCCAAGAGGGAGATGCGGATGAAATGGATGATTTAATGGGTCATCTCTCCTGTAGTTAATTTCTCTAG
2562
|
ATCTCTTGT
|
|
9774-R2-2
13q13.3
GCTTGTCCTAAAAGATCTTCCTTCTGTTTCCCTGGGTTTATCCACTTGGTTGGCCTGATGGGAGCAGGAGGCGGT
2563
|
GAGGGGGCGGGC
|
|
miR-1228*
12q13.3
GTGGGCGGGGGCAGGTGTGTGGTGGGTGGTGGCCTGCGGTGAGCAGGGCCCTCACACCTGCCTCGCCCCCCAG
2564
|
|
miR-1275
6p21.31
CCTCTGTGAGAAAGGGTGTGGGGGAGAGGCTGTCTTGTGTCTGTAAGTATGCCAAACTTATTTTCCCCAAGGCAG
2565
|
AGGGA
|
|
miR-1308
Xp22.11
CCCCGCATGGGTGGTTCAGTGGCAGAATTCTCAAATTGTAATCCCCATAATCCC
2566
|
|
miR-21
17q23.1
TGTCGGGTAGCTTATCAGACTGATGTTGACTGTTGAATCTCATGGCAACACCAGTCGATGGGCTGTCTGACA
2567
|
|
miR-373*
19q13.41
GGGATACTCAAAATGGGGGCGCTTTCCTTTTTGTCTGTACTGGGAAGTGCTTCGATTTTGGGGTGTCCC
2568
|
|
miR-423-5p
17q11.2
ATAAAGGAAGTTAGGCTGAGGGGCAGAGAGCGAGACTTTTCTATTTTCCAAAAGCTCGGTCTGAGGCCCCTCAGT
2569
|
CTTGCTTCCTAACCCGCGC
|
|
miR-486-3p
8p11.21
GCATCCTGTACTGAGCTGCCCCGAGGCCCTTCATGCTGCCCAGCTCGGGGCAGCTCAGTACAGGATAC
2570
|
|
miR-612
11q13.1
TCCCATCTGGACCCTGCTGGGCAGGGCTTCTGAGCTCCTTAGCACTAGCAGGAGGGGCTCCAGGGGCCCTCCCTC
2571
|
CATGGCAGCCAGGACAGGACTCTCA
|
|
miR-638
19p13.2
GTGAGCGGGCGCGGCAGGGATCGCGGGCGGGTGGCGGCCTAGGGCGCGGAGGGCGGACCGGGAATGGCGCGCCGT
2572
|
GCGCCGCCGGCGTAACTGCGGCGCT
|
|
miR-663
20p11.1
CCTTCCGGCGTCCCAGGCGGGGCGCCGCGGGACCGCCCTCGTGTCTGTGGCGGTGGGATCCCGCGGCCGTGTTTT
2573
|
CCTGGTGGCCCGGCCATG
|
|
miR-744
17p12
TTGGGCAAGGTGCGGGGCTAGGGCTAACAGCAGTCTTACTGAAGGTTTCCTGGAAACCACGCACATGCTGTTGCC
2574
|
ACTAACCTCAACCTTACTCGGTC
|
|
miR-923
17q12
TATTTGTCAGCGGAGGAAAAGAAACTAACCAGGATTCCCTCAGTAATGGCGAGTG
2575
|
|
5.6 Example 6
Target RNA Levels in Primary Tumors and Cell Lines
Data from Examples 4 and 5 were analyzed to identify target RNAs that were found to be up-expressed in both primary lung tumors and in lung cancer cell lines. Table 32 shows a list of the target RNAs from Table 27 (i.e., target RNAs that are present at increased levels in at least four lung cancer cell lines) that are also in Tables 18 to 21 (i.e., target RNAs that are present at increased levels in more than 50% of primary lung tumors tested, and target RNAs that are present at least 5-fold increased levels in fewer than 50% of primary lung tumors tested). Table 33 shows a list of the target RNAs from Table 28 (i.e., target RNAs that are present at least 5-fold increased levels in two or three cell lines) that are also in Tables 18 to 21.
TABLE 32
|
|
Target RNAs from Table 27 that are also in Tables 18 to 21
|
target RNA from
Present in Tables 20
|
Table 27 (increased
probe
pre-
Present in Tables 18
and 21 (increased at
|
in at least four cell
SEQ ID
microRNA
microRNA
and 19 (increased in at
least 5-fold in <50%
|
lines)
NO
SEQ ID NO
SEQ ID NO
least 50% tumors)?
tumors)?
|
|
10083-L5-1
1090
1211
Yes
|
13122-L5-1
1066
1242
2587
Yes
|
13185-L5-3
1118
1243
2603
Yes
|
13219-L5-1
1067
1245
Yes
|
3744-R5-1
1143
1271
2645, 2646
Yes
|
6235-R5-2
1075
1296
2661
Yes
|
6474-L5-1
1164
1299
Yes
|
6681-R2-1
1166
1301
Yes
|
8004-R3-2
97
492
Yes
|
836-R4-1
3
400
Yes
|
9594-R5-1
1081
1328
Yes
|
miR-103
361
754, 755
803
Yes
|
miR-200b
193
692
839
Yes
|
miR-200c
194
693
840
Yes
|
miR-20b
380
776
843
Yes
|
miR-298
1088
1351
858
Yes
|
|
TABLE 33
|
|
Target RNAs from Table 28 that are also in Tables 18 to 21
|
target RNA from
Present in Tables 20
|
Table 28 (increased
probe
pre-
Present in Tables 18
and 21 (increased at
|
5-fold in 2 or 3 cell
SEQ ID
microRNA
microRNA
and 19 (increased in at
least 5-fold in <50%
|
lines)
NO
SEQ ID NO
SEQ ID NO
least 50% tumors)?
tumors)?
|
|
10335-L5-2
1092
1213
Yes
|
12729-R5-1
1103
1186
Yes
|
12888-L5-2
1105
1188
Yes
|
12917-R5-2
1108
1230
Yes
|
12992-L5-1
1112
1235
Yes
|
13001-L5-1
1113
1236
Yes
|
13070-R5-3
1115
1238
Yes
|
13274-L5-3
1124
1251
2612
Yes
|
13357-L5-4
1128
1255
2621
Yes
|
13366-R5-3
1129
1256
2623
Yes
|
13467-L5-1
1069
1262
2630
Yes
|
13470-R5-1
1136
1264
Yes
|
3875-R5-2
1144
1272
Yes
|
3923-R5-1
1070
1273
2647
Yes
|
5108-R5-2
1153
1286
Yes
|
5723-R5-1
1156
1289
Yes
|
6752-R5-2
1168
1303
Yes
|
6803-R5-2
1169
1304
Yes
|
6930-R5-1
1173
1308
2667
Yes
|
8433_C-R4-1
1177
1317
Yes
|
8433-L3-1
1179
1318, 1319
Yes
|
8724-R5-2
1181
1320
Yes
|
8808-R5-1
1183
1322
Yes
|
8832-R5-1
1184
1323
Yes
|
9349-R5-2
1080
1325
2672
Yes
|
miR-198
1202
1343
834
Yes
|
miR-720
1089
1362
917
Yes
|
|
Finally, Table 34 shows target RNAs that are present at decreased levels in both primary tumors and cell lines relative to normal tissue or cell lines.
TABLE 34
|
|
Target RNAs present at decreased levels in
|
primary tumors and cell lines
|
pre-
|
probe SEQ
microRNA
microRNA
|
Gene
ID NO
SEQ ID NO
SEQ ID NO
|
|
10010_B-L4-1
157
551
|
10010_D-L4-1
158
552
|
10231-R3-1
1368
1713
|
10342-R2-2
1371
1716
|
11370-L5-5
1379
1724
|
12691-R5-1
1385
1730
|
12692-L5-1
1386
1731
|
12693-L5-1
1387
1732
|
12694-R5-1
1388
1733
|
12696-R5-2
1389
1734
|
12697-R5-1
1390
1735
|
12699-L5-1
1391
1736
2585
|
12701-L5-1
1392
1737
|
12703-L5-3
1393
1738
|
12704-L5-2
1394
1739
|
12713-R5-1
1395
1740
|
12722-L5-1
1396
1741
|
13004-R5-1
1411
1756
|
13047-R5-2
1412
1757
|
13052-L5-1
1414
1759
|
13093-L5-2
1419
1765
|
13097-L5-2
1422
1767
|
13119-R5-2
1425
1771
|
13129-L5-3
1427
1773, 1774
|
13130-L5-2
2352
2486
|
13137-L5-1
1431
1779
|
13138-R5-1
1432
1780
|
13209-R5-3
1444
1792
|
13211-L5-1
1445
1793
|
13229-L5-1
1447
1795
|
13239-L5-2
1451
1800
|
13240-L5-2
1452
1801
|
13267-L5-1
1456
1805
|
13281-L5-3
1457
1806
|
13283-L5-3
1458
1807
|
13285-L5-3
1459
1808
|
13291-L5-1
1461
1810
|
13312-L5-2
1467
1816
|
13326-L5-2
1470
1820
|
13343-L5-1
1477
1828
2619
|
13349-L5-2
1478
1829
|
13365-L5-3
1487
1838
|
13374-R5-1
1490
1842, 1843
|
13375-L5-3
1491
1844
2625
|
13396-L5-2
1495
1848
|
13431-L5-3
1501
1854
|
13432-R5-4
2387
2516
|
13456-R5-2
1503
1856
|
13461-L5-4
1505
1858
|
13497-L5-1
1508
1861
|
266-R5-2
1513
1866
|
2819-R5-4
1516
1869
|
3799-R5-1
1519
1872
|
3897-R5-2
1520
1873
|
3953-R3-2
1523
1876
|
3966-L5-1
1524
1877
|
4315_C-L4-1
1533
1886
|
4315_D-R4-1
1534
1887
|
4315_E-R4-1
1535
1888
|
4315_F-R4-1
1536
1889
|
4315_1-L4-1
1537
1890
|
4315_K-L4-1
1538
1891
|
4593-R5-1
1547
1900
|
5071-R5-2
1560
1913
|
5640-L3-1
1569
1922
|
6198-R5-2
1582
1935
|
6880-L3-2
1596
1949
|
7126-L3-1
1604
1857
|
7356_A-R4-1
1609
1962
|
7702-L2-1
1618
1971
|
7824-R5-1
1622
1975
|
7949-R5-1
1626
1979
|
8016-L3-1
1628
1981
|
8250-R5-2
1633
1986
|
8394-L5-2
1638
1991
|
8898-R5-1
1641
1994
|
9387-R2-2
1651
2004
|
9691-L5-1
1654
2007
|
9774-R2-2
1656
2009
|
miR-373*
1693
2049
|
miR-486-3p
1695
2051
|
miR-638
1699
2055
|
miR-663
1700
2056
|
miR-744
1702
2058
|
|
5.7 Example 7
Additional Target RNAs from Primary Tumors
In addition to the target RNAs identified in Example 4, certain additional target RNAs were identified in that experiment as being present at elevated levels in squamous cell carcinoma (SCC). Further, one additional target RNA (miR-320c) was identified as being elevated in at least three of the most aggressive tumors in Example 4. Those additional target RNAs, and miR-320c, are shown in Tables 35 and 36, along with the fold-change in each of the primary tumors. Data for six of the tumors are shown in Table 35 and data for the remaining 13 tumors are shown in Table 36. Table 35 also shows the probe sequences used to detect the target RNAs. Table 37 shows the pre-microRNA sequences and chromosomal location of the pre-microRNA gene for each of the target RNAs in Tables 36 and 37.
TABLE 35
|
|
Additional target RNAs more frequently present at elevated levels in squamous
|
cell carcinoma (SCC), and miR-320c
|
SEQ ID
|
Gene
Probes sequences
NO
ADK9
ADK10
Adk29
Adk15
Adk23
ADK48
|
|
13108-L5-2
CTGCTGCCTTCCTTGGTTGAGGGGCCTGAGCACG
2673
−5.44
−5.44
1.00
−1.07
−2.30
−1.55
|
|
13272-R5-2
TCACCGTGCCTCCCTTTGGAAGAGGTAGAAGTCA
2674
−2.63
−2.63
−2.63
−2.63
−1.60
5.15
|
|
13316-R5-2
CCACCACCTTGCTGCTGGCCCACAGCACCAGGCC
2675
−4.30
−4.30
−2.50
−2.88
−4.30
−1.25
|
|
13331-L5-2
CCCGAACCCACTCTGAGCACTCGGCACCAGCA
2676
1.69
−3.04
−1.84
1.35
−1.38
−3.04
|
|
13499-R5-1
ACAAGTTTCTCAGGAAGTCTGAACACTGGGTTT
2677
2.23
−2.83
1.29
1.39
−1.37
1.07
|
|
5971-R5-2
TGCCTGCTCAGCCTCCCACATCTGTTCCTGG
2678
1.36
−2.71
−5.23
−1.20
−2.32
2.33
|
|
7026-L3-1
GAAAACCTCACCCACCAGATCCGGGAACGA
2679
−4.57
−4.57
−4.57
−3.02
−2.20
−4.57
|
|
7471-L5-1
AAATGCAAATGCCCCCTAAGGAGAAGAACTTC
2680
−6.11
−6.11
−6.11
−1.41
−3.03
3.29
|
|
miR-320c
ACCCTCTCAACCCAGCTTTT
2689
−6.09
−6.09
−3.75
−1.52
1.03
−6.09
|
|
TABLE 36
|
|
Additional target RNAs more frequently present at elevated levels in squamous cell carcinoma (SCC), and miR-320c (con't)
|
Gene
Adk40
Adk41
Adk49
Epi42
Epi43
Ksarc19
Kmalp21
Kmalp25
EPI-4
Kmalp44
Scc27
Lcnec31
Car13
|
|
13108-L5-2
−5.44
−5.44
3.75
2.76
2.52
2.92
1.32
1.28
6.13
2.43
1.71
2.26
−5.44
|
13272-R5-2
−2.63
−2.63
−1.32
−2.63
3.89
2.75
2.27
1.53
10.30
3.13
2.20
2.16
−2.63
|
13316-R5-2
−4.30
−4.30
−2.20
2.94
2.28
1.96
3.07
−1.31
4.09
1.82
2.30
1.24
−4.30
|
13331-L5-2
−3.04
−3.04
4.06
−3.04
4.60
2.19
1.84
2.46
8.67
4.20
1.80
2.26
−3.04
|
13499-R5-1
−2.83
−2.83
5.02
4.08
4.17
1.08
2.12
1.95
−2.83
3.61
1.34
1.21
−2.83
|
5971-R5-2
−5.23
−5.23
−2.44
2.15
2.01
2.54
1.93
1.48
4.62
−5.23
1.20
1.38
−5.23
|
7026-L3-1
−4.57
1.04
2.37
−1.93
2.63
2.98
2.00
−1.19
4.29
2.31
1.36
1.10
−4.57
|
7471-L5-1
−6.11
−6.11
−1.05
6.18
3.37
2.29
3.21
−1.10
8.46
−6.11
−1.14
−1.42
−6.11
|
miR-320c
−6.09
−6.09
1.74
−2.76
2.05
11.65
2.58
1.15
5.22
1.76
2.06
−1.01
−6.09
|
|
TABLE 37
|
|
Chromosomal locations and pre-microRNA sequences for target
|
RNAs in Tables 36 and 37
|
Chromo-
SEQ
|
somal
ID
|
Gene
Location
precursor sequence
NO
|
|
13108-L5-2
2p23.1
TTCCCACACGTGCTCAGGCCCCTCAACCAAGGAAGGCAGCAGGCCCACTGGCCTCCTTATTCAGAGGGGCTGCACT
2681
|
GCACCCTAGGGAG
|
|
13272-R5-2
12q13.11
GTCACACAGTTATGTTAGGCCATCACAGCATTGGAATAGGGGATATCTCAGCATGTTGAGCCCTGTCTCTGGGGAGC
2682
|
TGACTTCTACCTCTTCCAAAGGGAGGCACGGTGATTGGAAGTGC
|
|
13316-R5-2
16p12.3,
GCTCAATGCCTCCAACGCAGTCAGCTGGGTCTCAGCCACGTACAACCTCACGGTGGAGGAGCCCATCGTGGGCCTG
2683
|
16p13.11
GTGCTGTGGGCCAGCAGCAAGGTGGTGGCGCCCGGGCA
|
|
13331-L5-2
17q21.2
TGCGGAGTGCTGGTGCCGAGTGCTCAGAGTGGGTTCGGGTTCAGTCCCTGAACCCAAGCATCCTCTGCACCCAGAT
2684
|
CCTGC
|
|
13499-R5-1
7q32.2
AACAGTCCAGGGAAATGACAGTTGAGTTGCACAAACCCAGTGTTCAGACTTCCTGAGAAACTTGT
2685
|
|
5971-R5-2
1q24.1
TGCCATCTGCTCTGAAGCCTCCCAAGCTGGGCCTCCCCTCCCACTTCTGGAGCCCAGGAACAGATGTGGGAGGCTG
2686
|
AGCAGGCA
|
|
7026-L3-1
15q15.3
TCGTTCCCGGATCTGGTGGGTGAGGTTTTCGATCAGGGCAAATACCTGATCACAGACCTTCACAGGATTCTGGATGA
2687
|
|
7471-L5-1
1q21.1
GAAGTTCTTCTCCTTAGGGGGCATTTGCATTTTAATGGGAATCTTAAAAACCCAAAGGAAATGTTCTCTAATGGTGGG
2688
|
ATTTC
|
|
miR-320c
18q11.2
TTTGCATTAAAAATGAGGCCTTCTCTTCCCAGTTCTTCCCAGAGTCAGGAAAAGCTGGGTTGAGAGGGTAGAAAAAAA
2690
|
ATGATGTAGGCTTCTCTTTCCAGTTCTTCCCAGAATTGGGAAAAGCTGGGTTGAGAGGGT
|
|
miR-320c
18q11.2
CTTCTCTTTCCAGTTCTTCCCAGAATTGGGAAAAGCTGGGTTGAGAGGGT
2691
|
|
5.8 Example 8
Bioinformatic Analysis to Identify microRNAs
In order to identify the microRNAs detected with the probes shown, e.g., in Tables 1, 2, 6 to 9, 18 to 21, 23, 27, 28, 30, and 32 to 34, small RNA sequencing (smRNASeq) datasets were analysed using the probe sequences to identify expressed microRNAs detected by those sequences. The analysis identified 97 sequences with precise ends. Those 97 candidate microRNA sequences are show in Table 38.
TABLE 38
|
|
microRNA candidate sequences corresponding to
|
probes
|
SEQ
|
Name
Candidate sequences 5′->3′
ID NO
|
|
10233-R
TCTACTGCCTGCTGCTC
2576
|
|
10333-L
GGAGGGGGTGGGCAGGG
2577
|
|
10455-L
AGAGGGATGTTTGGCGC
2578
|
|
10520-L
CAGAGAAGGCTGGAGGAGG
2579
|
|
10844-R
AACACATGTTTGAAAGT
2580
|
|
11358-R
CATGTCAGCCTAGTTTCCC
2581
|
|
11605-L
AAAGAAGGGAAGAGAAGA
2582
|
|
11688-R
GTCGGCGTCTCCATCCTG
2583
|
|
12223-L
AGAGGGAGAAGAAACAA
2584
|
|
12699-R
CCACCACCGCCACCACCC
2585
|
|
12707-L
AGTTGTTGGATTGCAGA
2586
|
|
12723-R
CAGGAAGGGGCTGGGGG
2587
|
|
12730-R
CCCGGAGAGCGGAGCACAACACA
2588
|
|
12730-R
CCGGAGAGCGGAGCACAAC
2589
|
|
12911-L
GAGGAAAAGGAAGGAGG
2590
|
|
12912-L
CTGTGGGTGGAAGGTGCCAGAA
2591
|
|
12974-R
AAGTTAAATAACTCTGAACCA
2592
|
|
13071-L
ATGTGCCGAGATGTGAGCAGTC
2593
|
|
13071-L
ATGTGCCGAGATGTGAGCAGTCAC
2594
|
|
13108-L
CCAAGGAAGGCAGCAGGC
2595
|
|
13115-L
TTGGGGTGGTCGGCCCTGGAGG
2596
|
|
13122-L
GATGGAATTTCCTAAAGG
2597
|
|
13124-L
GGAGGGGAGGAGACATG
2598
|
|
13124-L
GGAGGGGAGGAGACATG
2599
|
|
13163-R
GGGAGGGAGAGAAGGAG
2600
|
|
13163-R
GGGAGGGAGAGAAGGAGG
2601
|
|
13163-R
GGGAGGGAGAGAAGGAGGGG
2602
|
|
13185-L
AGAGGGAAGAAAAAAAA
2603
|
|
13225-L
AGTGGGCAGGAAGAACCAGGCT
2604
|
|
13235-R
AGAGCTGAGACTAGAAAGCCCA
2605
|
|
13237-L
TTGGGGTGGTCGGCCCTGGAGG
2606
|
|
13245-L
GGGAGTAGAAGGGAAAGACTAT
2607
|
|
13247-L
GAGGTCGGGAGGGGAAGGCGGCT
2608
|
|
13252-L
TCAAGGAGCTCACAGTC
2609
|
|
13254-R
GCATGAGTGGTTCAGTGGT
2610
|
|
13272-R
TGACTTCTACCTCTTCCAAAG
2611
|
|
13274-L
TGAGGGAGGGTGGGAGC
2612
|
|
13278-R
GTGGAGTCCTGGGGAATGGAGA
2613
|
|
13287-L
AGGGTGGGGTGGCTCCTCTGCAG
2614
|
|
13309-L
TCCCTGTCCTCCACAAGCT
2615
|
|
13316-R
CAGCAGCAAGGTGGTGG
2616
|
|
13331-L
TGGTGCCGAGTGCTCAGAGTG
2617
|
|
13334-L
AGTGGGAGGGGAGGGGAGTCCTGCCA
2618
|
|
13343-L
TGAGGGGCCGGGAGCCA
2619
|
|
13352-R
TAGCCCCATTTCACAGAT
2620
|
|
13357-L
GCTGCAGGGAGGTGTGGGGA
2621
|
|
13358-L
AGTGTGGAGGGGGTGGTGA
2622
|
|
13366-R
TGGGAATAGGAGAGGGCACTG
2623
|
|
13373-R
TGCCCCACCTGCTGACCACCCTC
2624
|
|
13375-R
AACCTTGGCCCCTCTCCCCAG
2625
|
|
13395-R
GTGGAGTCCTGGGGAATGGAGA
2626
|
|
13398-R
CAAAGTGAGTCTAGTCTGCA
2627
|
|
13403-L
TTGGGGGGACACGGGTGG
2628
|
|
13436-L
AGCTGTGGTCACCGGAGCTCAGAGGC
2629
|
|
13467-L
GAGGGTCTGACTGTCACTTGGA
2630
|
|
13468-L
GAGGGTCTGATGGCCACTTGGA
2631
|
|
13472-L
CAGGAGGACGTCACACACAGTG
2632
|
|
13473-L
TAGGTGGTAGAAGGGCAAACA
2633
|
|
13499-R
CCCAGTGTTCAGACTTCCTG
2634
|
|
13500-L
TGGAGAGAGAGGCCTGGAAGA
2635
|
|
13500-L
TGGAGAGAGAGGCCTGGAAGAT
2636
|
|
13508-L
TGTGAGGAAGCTAAGAGCAG
2637
|
|
13522-L
AGTGCAGTGGTGTGATC
2638
|
|
13523-R
GCAGGGGAAGAAGCCTT
2639
|
|
13530-L
GGGGGACCCAGGGGAAGGAGG
2640
|
|
13545-L
ACAGCCTCCCTTGCGCCACAG
2641
|
|
25-R
TTAGAAAAAGAGGGGGTGAGG
2642
|
|
3249-L
GCGGCGGCGGCGGCGGC
2643
|
|
3371-L
TGGGGTGTGGAGGGGAGG
2644
|
|
3744-R
AGGGGAGCAGGGAGGAA
2645
|
|
3744-R
GCAGGGAGGAAGGAGAA
2646
|
|
3923-R
TGGAGAGGGATGAAGGAGAT
2647
|
|
4440-L
TCTGCCCAGTGCTCTGAATGTCA
2648
|
|
4440-L
CCAGTGCTCTGAATGTCAAA
2649
|
|
5080-R
TGGAGAGGGATGAAGGAGA
2650
|
|
5192-L
GAGGAAGGAAGGGGAAA
2651
|
|
5192-L
AGGAAGGAAGGGGAAAAA
2652
|
|
5232-L
CCTTGATGTCCTGCAAATGA
2653
|
|
5392-R
ATGAGATACTGTCGGAGA
2654
|
|
5723-R
CTGCTGGAGAAAGGGGAGGAGG
2655
|
|
5842-R
TTCATTTCTCTTTCATAA
2656
|
|
5971-R
ACTTCTGGAGCCCAGGAACA
2657
|
|
6037-R
TAGTTGGAGGAAAATTGGAG
2658
|
|
6216-L
TGCCCAGTGCTCTGAATGTC
2659
|
|
6216-R
ACGGCGGGAGTAACTATG
2660
|
|
6235-R
AAATGGATTTTTGGAGCAG
2661
|
|
6496-R
AGGGGAAGTGGTGGGTG
2662
|
|
6496-R
GTGGGTGGGGGAGGGGG
2663
|
|
6681-R
GGAGGGGCAGAGAGAGAG
2664
|
|
6864-R
AGGTGGGCACTCTAAGG
2665
|
|
6906-L
TGGTTGGGGAGAAGACA
2666
|
|
6930-R
TGCAAGATCAGAGGGGAGA
2667
|
|
7726-R
TCCTCTTCTCCTCTTCT
2668
|
|
8433-L
CGGTGGAGGGAAAGGGGAAA
2669
|
|
8452-L
AACACCCCAGCCATGTA
2670
|
|
8832-R
CAAAGTGGGGGAAAAACAGGTG
2671
|
|
9349-R
TCCGAGACCTGGAGCAG
2672
|
|
All publications, patents, patent applications and other documents cited in this application are hereby incorporated by reference in their entireties for all purposes to the same extent as if each individual publication, patent, patent application or other document were individually indicated to be incorporated by reference for all purposes.
While various specific embodiments have been illustrated and described, it will be appreciated that changes can be made without departing from the spirit and scope of the invention(s).