MULTIPLEX HOMOLOGY-DIRECTED REPAIR

Abstract

Disclosed is a method for introducing a plurality of programmed nucleotide modifications into a single locus of a desired genomic DNA sequence in a single experiment. The method entails synthesizing a homology-directed repair (HDR) library comprising a plurality of oligonucleotides, wherein each oligonucleotide comprises a programmed nucleotide modification in the locus of the desired genome, and co-transfecting a population of cells with (i) an expression system capable of expressing Cas9 and a single guide RNA (sgRNA) and (ii) introducing a plurality of programmed nucleotide modifications to the locus of the desired genomic DNA sequence in one or more cells of the population. Also disclosed are methods for analyzing the functional consequence of a genomic mutation and for genomic screening.

Description

BACKGROUND

Saturation mutagenesis [1, 2]—coupled to an appropriate biological assay—represents a fundamental means of achieving a high-resolution understanding of regulatory [3] and protein-coding [4] nucleic acid sequences of interest. However, mutagenized sequences introduced in trans on episomes or via random or “safe-harbour” integration fail to capture the native context of the endogenous chromosomal locus [5]. This shortcoming markedly limits the interpretability of the resulting measurements of mutational impact.

Functional consequences of genetic variants are studied by manipulating the endogenous locus, which provides the native chromosomal context with respect to DNA sequence and epigenetic milieu, and for proteins, endogenous levels and patterns of expression [6]. Programmable endonucleases, e.g. zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) or clustered regularly interspaced short palindromic repeat (CRISPR)/Cas-based RNA-guided DNA endonucleases, enable direct genome editing with increasing practicality [7]. However, genome editing has primarily been applied to introduce single changes to one or a few genomic loci [8], rather than many programmed changes to a single genomic locus. There remains a need for a genomic editing method for introducing multiple programmed changes into a single genomic locus in a single experiment.

SUMMARY

In one aspect, this application relates to a method for introducing a plurality of programmed nucleotide modifications into a single locus of a desired genomic DNA sequence. The method entails the steps of: (a) synthesizing a homology-directed repair (HDR) library comprising a plurality of oligonucleotides, and (b) co-transfecting a population of cells with (i) an expression system capable of expressing Cas9 and a single guide RNA (sgRNA) and (ii) the HDR library, wherein the expression system is capable of introducing the plurality of oligonucleotides having the programmed nucleotide modifications to the locus of the desired genomic DNA sequence in one or more cells of the population. This method is carried out in a single experiment, i.e., in a single culture dish during a series of reactions carried out at the same time or within a single experimental protocol. In step (a), each oligonucleotide includes a programmed nucleotide modification in the locus of the desired genome.

In some embodiments, each programmed nucleotide modification is a single nucleotide variant. In some embodiments, the HDR library is constructed using an oligonucleotide including a degenerate sequence and optionally, a selective PCR site. For example, the degenerate sequence is between 1 and 100 nucleotides in length. In some embodiments, the HDR library contains a set of oligonucleotides having at least 100 unique programmed nucleotide modifications, at least 200 unique programmed nucleotide modifications, at least 300 unique programmed nucleotide modifications, at least 400 unique programmed nucleotide modifications, at least 500 unique programmed nucleotide modifications, at least 600 unique programmed nucleotide modifications, at least 700 unique programmed nucleotide modifications, at least 800 unique programmed nucleotide modifications, at least 900 unique programmed nucleotide modifications, at least 1,000 unique programmed nucleotide modifications, at least 3,000 unique programmed nucleotide modifications, at least 4,000 unique programmed nucleotide modifications, at least 5,000 unique programmed nucleotide modifications, at least 6,000 unique programmed nucleotide modifications, at least 7,000 unique programmed nucleotide modifications, at least 8,000 unique programmed nucleotide modifications, at least 9,000 unique programmed nucleotide modifications, at least 10,000 unique programmed nucleotide modifications, at least 12,000 unique programmed nucleotide modifications, at least 14,000 unique programmed nucleotide modifications, at least 16,000 unique programmed nucleotide modifications, at least 18,000 unique programmed nucleotide modifications, at least 20,000 unique programmed nucleotide modifications, at least 25,000 unique programmed nucleotide modifications, at least 30,000 unique programmed nucleotide modifications, at least 40,000 unique programmed nucleotide modifications, or at least 50,000 unique programmed nucleotide modifications.

In some embodiments, the plurality of programmed nucleotide modifications that are introduced to the locus of the desired genomic DNA sequence results in a saturating set of programmed nucleotide modifications. In some embodiments, the plurality of oligonucleotides are synthesized on a microarray. In other embodiments, the plurality of oligonucleotides are synthesized in column-based synthesis.

In some embodiments, the plurality of oligonucleotides that are synthesized as described above are used directly without any additional amplification or cloning steps. Alternatively, the plurality of oligonucleotides are amplified or cloned cloned to an HDR library before being used to introduce programmed nucleotide modifications.

In some embodiments, the expression system includes a Cas9 expression cassette that includes a nucleotide sequence which encodes a Cas9 nuclease, an sgRNA expression cassette, and a species-specific promoter that is specific to the population of cells.

In certain embodiments, each oligonucleotide of the HDR library includes a pair of homology arms.

In some embodiments, the method for introducing a plurality of programmed nucleotide modifications into a single locus of a desired genomic DNA sequence further entails the steps of: (c) harvesting the population of cells, (d) selectively amplifying a genomic DNA and RNA sample, wherein the edited sequences are amplified and the non-edited sequence are not amplified, and (e) sequencing the genomic DNA and RNA sample that has been selectively amplified, resulting in a set of genomic transcripts which include the plurality of programmed nucleotide modifications. Optionally, the method further entails functionally analyzing the set of genomic transcripts using a functional assay. For example, the functional assay is selected from the group consisting of targeted RNA sequencing to measure transcript abundance, targeted DNA sequencing to measure reduced cellular fitness, targeted chromatin immunoprecipitation-sequencing (CHiP-seq) of co-activators to assay enhancers, increased cellular growth rate to assay cancer drivers or drug resistance, and FACS-based phenotypic sorting for cellular assays.

In another aspect, this application relates to a method for analyzing the functional consequence of a genomic mutation. The method entails the steps of: (a) synthesizing a homology-directed repair (HDR) library including a plurality of oligonucleotides, wherein each oligonucleotide contains a programmed nucleotide modification in the locus of the desired genome, (b) co-transfecting a population of cells with (i) an expression system capable of expressing Cas9 and a single guide RNA (sgRNA) and (ii) the HDR library, wherein the expression system is capable of introducing the plurality of oligonucleotides having the programmed nucleotide modifications to the locus of the desired genomic DNA sequence in one or more cells of the population, (c) harvesting the population of cells, (d) selectively amplifying a genomic DNA and RNA sample, wherein the edited sequences are amplified and the non-edited sequence are not amplified, (e) sequencing the genomic DNA and RNA sample that has been selectively amplified, resulting in a set of genomic transcripts which include the plurality of programmed nucleotide modifications, and (f) functionally analyzing the set of genomic transcripts using a functional assay. This method is carried out in a single experiment, i.e., during a series of reactions carried out at the same time or within a single experimental protocol.

In some embodiments, the HDR library is constructed using an oligonucleotide containing a degenerate sequence and optionally, a selective PCR site. The degenerate sequence is between 1 and 100 nucleotides in length. In some embodiments, the plurality of oligonucleotides are synthesized on a microarray. In other embodiments, the plurality of oligonucleotides are synthesized in column-based synthesis. In some embodiments, the plurality of oligonucleotides are used directly without any cloning step to introduce programmed nucleotide modifications. Alternatively, the plurality of oligonucleotides are cloned to an HDR library before being used to introduce programmed nucleotide modifications.

In some embodiments, the expression system includes a Cas9 expression cassette having a nucleotide sequence which encodes a Cas9 nuclease, an sgRNA expression cassette, and a species promoter that is specific to the population of cells

In some embodiments, each oligonucleotide of the HDR library comprises a pair of homology arms.

In some embodiments, the functional assay is selected from the group consisting of targeted RNA sequencing to measure transcript abundance, targeted DNA sequencing to measure reduced cellular fitness, targeted chromatin immunoprecipitation-sequencing (CHiP-seq) of co-activators to assay enhancers, increased cellular growth rate to assay cancer drivers or drug resistance, and FACS-based phenotypic sorting for cellular assays.

In another aspect, this application relates to a method for genomic screening. The method entails the steps of: (a) introducing a plurality of programmed nucleotide modifications to a single genomic locus, wherein the plurality of programmed nucleotide modifications are introduced in a single experiment, i.e., during a series of reactions carried out at the same time or within a single experimental protocol, (b) sequencing the genomic DNA or cDNA of the edited locus, and (c) quantifying the transcript abundance of each mutation.

In some embodiments, step (a) includes (1) synthesizing a homology-directed repair (HDR) library comprising a plurality of oligonucleotides, wherein each oligonucleotide includes a programmed nucleotide modification in the locus of the desired genome, and (2) co-transfecting a population of cells with (i) an expression system capable of expressing Cas9 and a guide RNA (sgRNA) and (ii) the HDR library, wherein the expression system is capable of introducing the plurality of oligonucleotides having the programmed nucleotide modifications to the locus of the desired genomic DNA sequence in one or more cells of the population. This step is carried out in a single experiment, i.e., during a series of reactions carried out at the same time or within a single experimental protocol. In some embodiments, step (c) includes calculating an enrichment score for each mutation.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1 a-1c show saturation genome editing and multiplex functional analysis of a hexamer region influencing BRCA1 splicing. FIG. 1a is an experimental schematic. Cultured cells were co-transfected with a single Cas9-sgRNA construct (CRISPR) and a complex homology-directed repair (HDR) library containing an edited exon that harbors a random hexamer (blue, green, orange) and a fixed selective PCR site (red). CRISPR-induced cutting stimulated homologous recombination with the HDR library, inserting mutant exons into the genomes of many cells. At five days post-transfection, cells were harvested for gDNA and RNA. After reverse transcription, selective PCR was performed followed by sequencing of gDNA and cDNA derived amplicons. Hexamer enrichment scores were calculated by dividing cDNA counts normalized by gDNA counts. FIG. 1b shows correlation of enrichment scores between biological replicates for hexamers observed in each experiment with positions of previously identified [9] exonic splicing enhancers (ESEs), exonic splicing silencers (ESSs) and stop codons indicated. FIG. 1c shows rank-ordered plot of enrichment scores with positions of ESEs, ESSs, and stop codons indicated.

FIGS. 2 a-2c show that multiplex homology-directed repair reveals effects of single nucleotide variants on transcript abundance. Three separate HDR libraries (R, R2, and L) containing a 3% mutation rate (97% wt, 1% each non-wt base) in either half of BRCA1 exon 18 were introduced to the genome via co-transfection with pCas9-sgBRCA1x18. Enrichment scores were calculated for each haplotype observed at least 10 times in the gDNA, and effect sizes of SNVs were determined by weighted linear regression modeling. ‘Sense’ includes both missense and synonymous SNVs. FIG. 2a shows effect sizes calculated from replicate transfections of HDR library R, consisting of a 3% per-nucleotide mutation rate in the 3′-most 39 bases and the same selective PCR site used in FIG. 1, were highly correlated (R=0.846). FIG. 2b shows that Library R2 harbored a selective PCR site composed of 5 synonymous changes, none of which are present in Library R. When effect sizes derived from experiments with library R2 were plotted against those from library R, there was a strong correlation (R=0.847), indicating reproducibility and demonstrating that differences between selective PCR sites did not strongly influence scores. FIG. 2c shows effect sizes for SNVs across the exon are displayed. Datasets from libraries R and L were combined to span the entire exon. Dashed lines represent SNVs that introduce nonsense codons.

FIGS. 3 a-3c show saturation genome editing and multiplex functional analysis at an essential gene, DBR1, in Hap1 cells. An HDR library targeting a highly conserved region of DBR1 exon 2 was used with pCas9-EGFP-sgDbr1x2 to introduce point mutations across 75 base pair (bp) and all possible codon substitutions at three residues believed to participate at the enzyme's active site. FIG. 3a shows that sequencing of gDNA from the HDR library and populations of edited cells at D5, D8, and D11 reveals selection for synonymous mutations, and depletion of frameshift, nonsense, and missense variants. FIG. 3b shows that mean D11 enrichment scores are plotted as line segments for SNVs in the 3′-most 73 bases of exon 2 and two bases of intron 2. Above the enrichment scores in ascending order are the wt nucleotide at each position, each one by genome edit, the wild-type amino acid (AA), and the AA derived from each genome edit (asterisk indicates a stop codon). Segment color indicates mutation type, faded segments indicate discordant effects between replicates, and AAs are colored according to the Lesk color scheme (small nonpolar—orange, hydrophobic—green, polar—magenta, negatively-charged—red, and positively charged—blue). The first nine bases shown correspond to the active site residues. FIG. 3c shows that D8 and D11 amino acid level enrichment scores were calculated for active site residues N84, H85, E86 after excluding discordant observations between replicates (FIG. 13c). On both D8 and D11 strong selective effects and tolerance of only synonymous (green boxes) and a few missense variants were observed.

FIGS. 4 a-4d show the distribution and pair-wise correlations of hexamer abundances. FIG. 4a shows the relative abundance of hexamers within the HDR library (top), gDNA (middle), cDNA data (bottom) are shown for a single experiment. The vertical black line represents our threshold of 10 gDNA reads. FIG. 4b-4d demonstrate that scatterplots from a single replicate show pair-wise correlations between sequencing counts for the HDR library, gDNA, and cDNA for hexamers with at least 10 observations in the gDNA library, excluding wild type and control hexamers (n=3,633). The HDR library and the gDNA data are most highly correlated (R 95% confidence interval (CI): 0.596-0.636), followed by the gDNA and cDNA (R 95% CI: 0.419-0.471) and the HDR library and cDNA (R 95% CI: 0.341-0.394).

FIGS. 5 a-5d show correlations for hexamer genome editing efficiency and enrichment scores between replicates. FIG. 5a shows that gDNA counts for all hexamers with at least ten reads in each of two gDNA preps from separate transfections with the same HDR library (n=2,980) exhibited moderate correlation (R 95% CI: 0.355-0.416). FIG. 5b shows that hexamer editing rates, defined as gDNA counts normalized to HDR library counts, were substantially less correlated (R 95% CI: 0.084-0.155), consistent with a hexamer's HDR library abundance contributing more to its gDNA abundance than systematic differences in HDR efficiency secondary to the hexamer sequence itself. FIG. 5c shows that hexamer enrichment scores for two pools of cells from a single transfection split on D3 were well-correlated (R 95% CI: 0.643-0.681). FIG. 5d shows that pooling data from cells split on D3 replicates from a single transfection yielded an improved correlation between biological replicates (that is, independent transfections; R 95% CI: 0.690-0.722.

FIGS. 6 a-6b show comparison of genome-based hexamer enrichment scores to plasmid-based hexamer scores. FIG. 6a shows that there was a modest correlation between ESS and ESE hexamers defined by a previous study [9] (x-axis) and the enrichment scores calculated here (y-axis; Spearman p=0.524). The previous study also interrogated hexamers positioned +5 to +10 nucleotides relative to a splice junction, but was plasmid-based rather than genome-based and in the context of different exons. FIG. 6B shows that to reveal effects of GC content on hexamer abundance, histograms display the distribution of enrichment scores for each possible G+C level (0-6). Hexamers containing two or fewer G+C base pairs exhibited broadly lower enrichment scores than hexamers containing three or more G+C base pairs.

FIG. 7 shows experimental schematic for genome editing and functional analysis of BRCA1 exon 18. Cultured cells were co-transfected with a single Cas9-sgRNA construct (CRISPR) and an HDR library. Each HDR library was generated from cloning of an oligonucleotide synthesized with 3% nucleotide degeneracy (97WT:1:1:1) for approximately half of the exon and a selective PCR site introduced to the other (fixed) half of the exon (red). CRISPR-induced HDR integrates mutant exons into the genome. Cells were cultured for five days post-transfection, and then harvested for gDNA and total RNA. After reverse transcription, selective PCR was performed before sequencing the edited pools of gDNA and cDNA. Each exon haplotype's enrichment score was measured by dividing cDNA reads by gDNA reads, and effect sizes for each SNV were calculated via weighted linear regression.

FIGS. 8 a-8c show positional SNV editing rates and replication of effect sizes. FIG. 8a shows that editing rates for each SNV in BRCA1 exon 18 were calculated by dividing each SNV's gDNA sequencing abundance by its HDR library abundance. Editing rates were then plotted across the exon for each library (red=L, blue=R, green=R2) with locations of their selective PCR sites and the CRISPR-targeted PAM illustrated below. For HDR libraries R and R2, there was a subtle decrease in editing rate with increasing distance from the Cas9 cleavage site (rho^R=−0.264, p^R=4.1×10⁻³; rho^R2=−0.361, p^R2=4.8×10⁻⁵). For library L, which allowed re-cutting by not destroying the PAM, there was a sharp peak of editing centered on the Cas9 cleavage site, and a rapid decline in efficiencies in the 5′ direction (further from the 3′ selective PCR handle). FIGS. 8b-8c shows that SNV effect sizes were concordant across biological replicates for libraries R2 (FIG. 8b) and L (FIG. 8c) (library R shown in FIG. 2). Variants of high effect size scored similarly across independent transfections.

FIG. 9 shows biological replicate effect size reproducibility for all libraries. Three separate HDR libraries (R, R2, and L) containing 3% nucleotide degeneracy in either half of BRCA1 exon 18 were introduced to the genome via co-transfection with pCas9-sgBRCA1x18. Enrichment scores were calculated for each haplotype observed at least ten times in the gDNA, and effect sizes of SNVs were determined by weighted linear regression. Effect sizes of individual variants for libraries R2 (left), R (middle), and L (right) were well correlated between biological replicates. Dashed lines represent SNVs that introduce nonsense codons.

FIGS. 10 a-10c show correlation between effect sizes and predicted disruption of splicing motifs and indel effects. FIG. 10a shows that MutPred Splice [18] was used to predict the functional impact of all 234 single nucleotide substitutions on splicing in BRCA1 exon 18 (x-axis), and these scores were compared to absolute values of the empirically measured effect sizes (y-axis; p=0.322). Although nonsense variants contributed to this trend, the sense variants with the largest effect sizes generally had high MutPred Splice scores. FIG. 10b shows that for indels observed in gDNA from library 2 (virtually all of which occur at the Cas9 cleavage site), size frequencies are plotted. Indel size=0 includes all haplotypes with wild type length. FIG. 10c shows that for each indel size, enrichment scores were calculated and normalized to that of the average full length exon. As predicted by nonsense-mediated decay, indels that shift the coding frame were associated with low transcript abundance.

FIG. 11 shows experimental schematic for saturation genome editing and multiplex functional analysis of DBR1 exon 2. Hap1 cells were co-transfected with a single Cas9-2A-EGFP-sgRNA construct (CRISPR) and an HDR library cloned from array-synthesized oligonucleotides containing programmed SNVs (orange, blue) and active site codon substitutions (green). The HDR library exon haplotypes also included two synonymous mutations (red) to disrupt PAM and protospacer sequences to prevent Cas9 re-cutting, and a 6 bp selective PCR site (light blue) substituted in the downstream intron. Successfully transfected cells (EGFP+) were selected on D2 by FACS, and cultured. On D5, D8, and D11, samples of cells were taken and selective PCR was performed before targeted sequencing of gDNA. Each haplotype's enrichment score, a measure of the haplotype's fitness in cell culture, was calculated by dividing D8 or D11 abundance by D5 abundance.

FIGS. 12 a-12b show DBR1 editing rates by position and comparison of haplotype abundances between D5 and the HDR library, D8, and D11. FIG. 12a shows that editing rates for programmed SNVs represented in the DBR1 gDNA library above threshold (n=216) were calculated by normalizing each SNV's gDNA abundance by its HDR library abundance. Rates are plotted by position, with the locations of the targeted PAM (orange) and selective PCR site (purple) indicated below. The editing rate did not significantly change with position (P>0.05), consistent with positional effects being negated by eliminating re-cutting and performing selective PCR from a distal site. FIG. 12b shows that scatterplots display the frequencies at which each haplotype was observed in the D5 sample vs the HDR library, D8, and D11 samples. To account for bottlenecking from editing of a limited number of cells in this representative experiment, analysis of individual haplotypes was restricted to those present at frequencies above 5×10⁻⁵ in the D5 sample (n=377; represented by the vertical line). Selection was evident by the depletion of many haplotypes in D8 and D11 samples.

FIGS. 13 a-13c show performance of computational predictions of deleterious DBR1 mutations and reproducibility between biological replicates. FIG. 13a shows that D11 enrichment scores from a single experiment were used to empirically define deleterious mutations as those with scores fourfold below wild type (vertical line). FIG. 13b shows that three in silico metrics of functional impairment were tested for their ability to anticipate the deleteriousness of these mutations as indicated by the area under the receiver operating characteristic curve (AUC): BLOSUM62 [20] (AUC=0.672, 214 SNVs), PolyPhen-2 [21] (AUC=0.671, 155 non-synonymous SNVs), and CADD [22] (AUC=0.701, 214 SNVs). Despite the different approaches of these algorithms, all three exhibited comparably moderate predictive power. FIG. 13c shows that a biological replicate of the DBR1 experiment was performed and D11 enrichment scores for amino acid substitutions were well correlated (grey lines on scatterplot indicate the ‘deleteriousness’ threshold of fourfold depletion). The distribution of amino acid level enrichment scores for each experiment is displayed along each axis, reflecting bimodality. Unexpected effects (that is, nonsense mutations scoring as tolerated) were among the relatively small percentage of effects not consistent between replicates.

DETAILED DESCRIPTION

Methods for introducing multiple programmed nucleotide modifications into a single locus of a desired genomic DNA sequence are provided herein. The methods described herein are carried out in a single experiment, i.e., during a series of reactions carried out concurrently within a single experimental protocol in a single culture dish. Such methods may be used to analyze the functional consequence of a genomic mutation or for genomic screening.

To overcome the limitations of previously used methods, a method was developed to generate and functionally analyze hundreds to thousands of programmed genome edits at a single locus in a single experiment. The method allows a more accurate and scalable measurement of the functional consequences of genetic variations. Measurement of the functional consequences of large numbers of mutations with saturation genome editing potentially facilitates high-resolution functional dissection of both cis-regulatory elements and trans-acting factors, as well as the interpretation of variants of uncertain significance observed in clinical sequencing.

According to the embodiments described herein, this application relates to a method for introducing a plurality of programmed nucleotide modifications into a single locus of a desired genomic DNA sequence. Saturation editing of genomic regions may be achieved by coupling CRISPR/Cas9 RNA-guided cleavage [10] with multiplex homology-directed repair (HDR) using a complex library of donor templates. “Saturation editing” as used herein means that for a particular sequence, each nucleotide position of that sequence is systematically modified with each of all four traditional bases, A, T, G and C. For example, a hexamer substituted at each position would have 4,096 possible single nucleotide variants (four possible substitutions at each of the six nucleotide positions of the hexamer, or 4⁶=4,096).

The multiple programmed nucleotide modifications may be introduced during a single experiment. The phrase “a single experiment” means that multiple programmed edits are introduced to a region of a particular size within a single culture dish, during the course of one experiment or a series of reactions within a single experimental protocol. In other words, the programmed edits are introduced concurrently in a single culture dish. In certain embodiments, the single experimental protocol includes one or more concurrent reactions, i.e., the multiple programmed edits are introduced at approximately the same time. This is in contrast to programmed edits being introduced one-by-one or several at a time in physically separated reactions or experiments carried out using one or more multi-well or otherwise separated culture dishes. The region to be introduced with the programmed edits may have an optimal size that allows efficient multiplex editing in one experiment, for example, the region is about between 1 and 100 base pairs in size. The window associated with HDR mechanisms in mammalian cells [11] may affect the size of the region that can be subjected to multiple editing in one experiment. Therefore, it is within the purview of one skilled in the art to determine the size of the region for multiplex editing. By the same token, saturation genome editing of a full gene—e.g. to measure functional consequences of all possible variants of uncertain significance—will likely require multiple experiments tiling along its exons.

The terms “programmed modifications,” “programmed gene edits,” and “programmed edits” as used herein are interchangeable, meaning that for a particular oligonucleotide, one or more nucleotides at a particular position is changed, for example, from A to T, G, or C. In some embodiments, each programmed nucleotide modification or edit is a single nucleotide variant (SNV). The programmed changes may result in a deletion, substitution, insertion, or other type of mutation to the gene.

The method includes a step of synthesizing a homology-directed repair (HDR) library comprising a plurality of oligonucleotides, each of which includes a programmed nucleotide modification. The plurality of oligonucleotides may be synthesized on a microarray or in column-based synthesis. In some embodiments, the HDR library is constructed using an oligonucleotide having a degenerate sequence and optionally, a selective PCR site.

The degenerate sequence may be between 1 and 100 nucleotides in length, and the constructed library using the degenerate sequence may have a set of oligonucleotides having at least 100 unique programmed nucleotide modifications, at least 200 unique programmed nucleotide modifications, at least 300 unique programmed nucleotide modifications, at least 400 unique programmed nucleotide modifications, at least 500 unique programmed nucleotide modifications, at least 600 unique programmed nucleotide modifications, at least 700 unique programmed nucleotide modifications, at least 800 unique programmed nucleotide modifications, at least 900 unique programmed nucleotide modifications, at least 1,000 unique programmed nucleotide modifications, at least 3,000 unique programmed nucleotide modifications, at least 4,000 unique programmed nucleotide modifications, at least 5,000 unique programmed nucleotide modifications, at least 6,000 unique programmed nucleotide modifications, at least 7,000 unique programmed nucleotide modifications, at least 8,000 unique programmed nucleotide modifications, at least 9,000 unique programmed nucleotide modifications, at least 10,000 unique programmed nucleotide modifications, at least 12,000 unique programmed nucleotide modifications, at least 14,000 unique programmed nucleotide modifications, at least 16,000 unique programmed nucleotide modifications, at least 18,000 unique programmed nucleotide modifications, at least 20,000 unique programmed nucleotide modifications, at least 25,000 unique programmed nucleotide modifications, at least 30,000 unique programmed nucleotide modifications, at least 40,000 unique programmed nucleotide modifications, or at least 50,000 unique programmed nucleotide modifications.

The method further includes a step of co-transfecting a population of cells with (i) an expression system capable of expressing Cas9 and a guide RNA (sgRNA) and (ii) the HDR library. In such embodiments, the expression system acts to introduce a plurality of oligonucleotides (each of which includes a programmed nucleotide modification) to the locus of the desired genomic DNA sequence in one or more cells of the population. In certain embodiments, the expression system includes a plasmid which includes a Cas9 expression cassette that includes a nucleotide sequence which encodes a Cas9 nuclease, an sgRNA expression cassette, and a species-specific promoter that is specific to the population of cells. In certain aspects, each oligonucleotide member of the HDR library includes a pair of homology arms in order to target the desired genomic DNA sequence.

The method described herein may further include one or more steps of harvesting the population of cells after culturing the transfected cells, selectively amplifying a genomic DNA and RNA sample wherein the edited sequences are amplified and the non-edited sequence are not amplified, and sequencing the genomic DNA and RNA sample that has been selectively amplified, resulting in a set of genomic transcripts which include the plurality of programmed nucleotide modifications. In some embodiments, the method includes functionally analyzing the set of genomic transcripts using a functional assay, such as targeted RNA sequencing to measure transcript abundance, targeted DNA sequencing to measure reduced cellular fitness, targeted chromatin immunoprecipitation-sequencing (CHiP-seq) of co-activators to assay enhancers, increased cellular growth rate to assay cancer drivers or drug resistance, and FACS-based phenotypic sorting for cellular assays.

In one aspect, this application also relates to analyzing the functional consequence of a genomic mutation by carrying out the above steps, including: (a) synthesizing a homology-directed repair (HDR) library comprising a plurality of oligonucleotides, wherein each oligonucleotide comprises a programmed nucleotide modification in the locus of the desired genome; (b) co-transfecting a population of cells with (i) an expression system capable of expressing Cas9 and a guide RNA (sgRNA) and (ii) the HDR library, wherein the expression system is capable of introducing the plurality of oligonucleotides having the programmed nucleotide modifications to the locus of the desired genomic DNA sequence in one or more cells of the population; (c) harvesting the population of cells; (d) selectively amplifying a genomic DNA and RNA sample, wherein the edited sequences are amplified and the non-edited sequence are not amplified; (e) sequencing the genomic DNA and RNA sample that has been selectively amplified, resulting in a set of genomic transcripts which include the plurality of programmed nucleotide modifications; and (f) functionally analyzing the set of genomic transcripts using a functional assay.

In some embodiments, the functional assay is biologically relevant and technically viable. In some embodiments, the functional assay directly links genotype to phenotype. For example, the functional assay is a targeted RNA sequencing to measure transcript abundance or targeted DNA sequencing to measure reduced cellular fitness. In other embodiments, the functional assay is targeted ChIP-seq of co-activators to assay enhancers, increased cellular growth rate to assay cancer drivers or drug resistance [31], or FACS-based phenotypic sorting for cellular assays [32].

Also described herein is a method for genomic screening. The method includes a first step of introducing a plurality of programmed nucleotide modifications to a single genomic locus, for example, as described above. The genomic screening method further includes sequencing the genomic DNA or cDNA of the edited locus, and quantifying the transcript abundance of each mutation, e.g., by calculating an enrichment score for each mutation.

For illustration purposes, the saturation genome edits were introduced to exon 18 of BRCA1 and to a well-conserved coding region of an essential gene, DBR1, respectively. By no means the scope of this application is limited to these particular genes. It is within the purview of one skilled in the art to introduce genome edits including saturation genome edits to any gene of interest by carrying out the methods disclosed herein.

In exon 18 of BRCA1, a six base-pair (bp) genomic region was replaced with all possible hexamers, or the full exon was replaced with all possible single nucleotide variants (SNVs), and the effects on transcript abundance attributable to nonsense-mediated decay and exonic splicing elements were measured. Saturation genome edits were introduced to DBR1 in a similar fashion and the relative effects on growth that correlate with functional impact were measured.

In one embodiment, the methods described herein are exemplified by leveraging CRISPR/Cas9 [10, 12, 13] to introduce saturating sets of programmed edits to a specific locus via multiplex HDR. As illustrated in FIG. 1a, six bases of a BRCA1 exon are targeted [14] by cloning an HDR library containing random hexamers substituted at positions +5 to +10 of BRCA1 exon 18 and fixing nonsynonymous changes at positions +17 to +23 (as a ‘handle’ for selective PCR and to prevent re-cutting [15] by destroying the protospacer adjacent motif (PAM)). The oligonucleotide sequences used are shown in Table 1.

pCas9-sgBRCA1x18 and the HDR library were co-transfected into ˜800,000 HEK293T cells, achieving 3.33% HDR efficiency. Two independent transfections were performed with the same HDR library (biological replicates' 1, 2), and cells were split on day 3 (‘D3 replicates’ a, b).

Genomic DNA (gDNA) and cDNA from bulk cells on D5 were prepared. PCR reactions were primed on the ‘handle’ uniquely present within successfully edited genomes. Amplification was observed in HDR library/pCas9-sgBRCA1x18 transfected samples, but not in HDR library-only controls. Amplicons derived from gDNA and cDNA were deeply sequenced (FIG. 1a). The relative abundances of hexamers within replicates and the correlation between the HDR library and edited gDNA were consistent with limited ‘bottlenecking’ during transfection and minimal influence of hexamer identity on HDR efficiency (FIG. 4 and FIG. 5).

The effect of introducing each hexamer to these genomic coordinates on transcript abundance was estimated by calculating enrichment scores (cDNA divided by gDNA counts, calibrated to wild-type). These enrichment scores were well correlated between biological replicates (FIG. 1b, 1a vs. 2a: R=0.659) and between D3 replicates (FIG. 5c; 1a vs. 1b: R=0.662). Correlation between biological replicates improved when read counts were pooled from D3 replicates (FIG. 5d; 1 vs. 2: R=0.706).

To maximize precision, data across all four replicates for 4,048 hexamers were merged (FIG. 1c; Table 2). Several results support the biological validity of the resulting enrichment scores. First, as predicated by nonsense-mediated decay (NMD), hexamers introducing stop codons were associated with markedly reduced mRNA levels (FIG. 1c; Wilcoxon rank sum test (WRST) P=9.7×10-84; median for nonsense hexamers 12-fold below overall median). Second, previous studies measured hexamer influence on splicing at analogous coordinates of different exons via a plasmid minigene assay [9]. Despite these contextual differences, the strongest exonic splicing silencers (ESSs) (bottom 2% in ref [9]) scored 9-fold below median (FIG. 1c; WRST P=2.0×10-24), the strongest exonic splicing enhancers (ESEs) (top 2% in ref 14) scored 1.5-fold above median (FIG. 1c; WRST P=2.4×10-11), and the complete datasets correlated reasonably well (FIG. 6a; p=0.524). Correlation between GC content and enrichment scores was also observed (FIG. 6b), strongest for bases most proximal to the splice junction, consistent with a posited role for GC content in the stability of splicing structures [16] (although reverse transcription bias is a potential confounder).

In some embodiments, FIG. 7 illustrates the assay of the effects of SNVs across the full 78 bp BRCA1 exon 18. Three HDR libraries were cloned with selective PCR sites in either the 5′ or 3′ region and 3% doping [17] (97 (wt):1:1:1) in the other half of the exon (L: 5′ degeneracy, 3′ nonsynonymous selective PCR site; R: 3′ degeneracy, 5′ nonsynonymous selective PCR site; R2: 3′ degeneracy, 5′ synonymous selective PCR site) (Table 1). Five days post-transfection with pCas9-sgBRCA1x18 (1.02-1.29% HDR efficiency), gDNA and cDNA were selectively amplified and deeply sequenced.

Using data from all edited exons with ≧1 mutation and ≧10 gDNA counts, effect sizes (beta values) of all possible SNVs were estimated using a weighted linear model. Estimated effect sizes were reproducible (R=0.846 (R), 0.853 (R2), and 0.686 (L); FIG. 2a, FIGS. 8-9, Table 3). Effect sizes for the same SNVs interrogated with different selective PCR strategies (R vs. R2) were also well correlated (R=0.847; FIG. 2b).

The estimated effect sizes reflect empirically measured changes in transcript abundance resulting from programmed edits (FIG. 2c). As predicted with NMD, nonsense mutations reduced transcript abundance (WRST P=1.4×10−203; 5.6−fold below median). Additionally, several missense and synonymous SNVs reproducibly resulted in large reductions in transcript abundance, and SNV effect sizes correlated with a predictive model for exonic variants that disrupt splicing [18] (p=0.322; FIG. 10a). Because library L does not destroy the PAM, enrichment scores for indels were calculated from non-homologous end-joining (NHEJ). As predicted with NMD, only frameshifting indels were associated with large depletions (FIGS. 10b, 10c).

In another embodiment, FIG. 11 illustrates targeting a well-conserved region of DBR1, the RNA lariat debranching enzyme, which scored highly in a genome-wide screen for essentiality [19]. Array-synthesized oligonucleotides were used to program a DBR1 HDR library to include the wild-type sequence and every possible SNV across 75 bp (73 3′-most bases of exon 2 and first two bases of intron 2), and also all 63 possible codon substitutions at three residues (388 genome edits were programmed; single base deletions were abundant from synthesis errors). The HDR library also introduced two fixed synonymous changes (to disrupt the PAM and prevent re-cutting [15]) and a selective PCR site in intron 2.

An optimized single guide RNA (sgRNA) sequence [23, 24] was cloned into a bicistronic sgRNA/Cas9-2A-EGFP vector (pCas9-EGFP-sgDbr1x2). Five million haploid human cells [25] (Hap1) were co-transfected with the DBR1 HDR library and pCas9-EGFP-sgDbr1x2. On D2, ˜250,000 EGFP+ cells were FACS sorted and further cultured, taking samples on D5, D8 and D11 (1.14% HDR efficiency, estimated on D8). Following gDNA isolation and selective PCR, deep sequencing was performed to quantify the relative abundance of edited haplotypes in each sample.

The relative proportions of mutation classes at each time point were first examined (FIG. 3a). The strong enrichment of synonymous mutations and depletion of nonsense and frameshifting mutations over time indicated that selection was acting on edited cells in culture, consistent with DBR1 essentiality. The enrichment scores (D8 or D11 counts divided by D5 counts) for 365 of the 388 (94%) programmed edits and 12 single base deletions (the subset with relative abundance >5×10-5 on D5) were calculated (FIG. 3b; FIG. 12; Table 4). Enrichment scores strongly correlated with functional consequence. The median enrichment score for synonymous edits was nearly identical to wild-type (1.006-fold lower), but 73-fold lower for missense edits (P=1.7×10-8; WRST against synonymous edits), 207-fold lower for nonsense edits (P=1.9×10-9), and 211-fold lower for frameshifting single base deletion edits (P=1.5×10-8). Furthermore, enrichment scores for SNVs were inversely correlated with metrics of predicted deleteriousness like CADD [22] (p=−0.295; P=1.2×10-5; FIGS. 13a, 13b). Residues N84, H85 and E86 of DBR1 were edited to all 63 possible non-wild-type codons. Consistent with their predicted role in the active site of an essential enzyme [26], only synonymous mutations and a few missense substitutions were tolerated (FIG. 3c).

Amino-acid level enrichment scores were well correlated between D11 biological replicates (R=0.752; P=2.6×10-40; FIG. 13c), and were bimodally distributed in each replicate, allowing broad classification of changes as tolerated or deleterious. The small proportion of discordantly classified variants might be explained by Hap1 reversion to diploidy or off-target effects, highlighting the importance of biological replicates for this experimental design. There were no reproducibly tolerated nonsense or frameshifting edits. These data indicate that the empirically derived enrichment scores reflect true biological effects of specific genomic point mutations within DBR1.

Genome editing efficiency may be affected by factors such as bottlenecking complexity, limiting reproducibility and in some cases, necessitating the optional selective PCR sites. However, selective PCR sites are not necessarily required in all cases. In some embodiments, a variety of techniques, e.g. transient hypothermia [27] or oligonucleotide-based HDR [28], can be used to improve editing efficiency. In some embodiments, ZFNs and TALENs may improve efficiencies up to 50% [29, 30].

In some embodiments, haploid cells for DBR1 mutagenesis can be used to improve editing efficiency. In other embodiments, mutagenesis can be performed in diploid cells by knocking out one allele via NHEJ and then knocking in the HDR library to the other allele.

The following examples are intended to illustrate various embodiments of the invention. As such, the specific embodiments discussed are not to be construed as limitations on the scope of the invention. It will be apparent to one skilled in the art that various equivalents, changes, and modifications may be made without departing from the scope of invention, and it is understood that such equivalent embodiments are to be included herein. Further, all references cited in the disclosure are hereby incorporated by reference in their entireties, as if fully set forth herein.

Examples

BRCA1 Experimental Design

An exon in a clinically relevant gene in which known mutations cause aberrant splicing was chosen to be targeted. Previous molecular studies of a G to T nonsense mutation occurring naturally in cancer patients at chr17:41,215,963 suggested exon skipping [14] was secondary to the creation of an exonic splicing silencer site [33]. It is hypothesized that saturation genome editing of this exon could result in a wide range of splicing outcomes.

When performing parallel functional analysis of complex allelic series, how to associate each of many mutations with the biological effects they produce should be considered. It is more difficult when attempting such approaches at the endogenous genomic locus, and with limited editing efficiencies. By performing these experiments in an exon and focusing on the effects of mutations on transcript abundance, genotype and phenotype are directly linked by observing the frequency of each genome edit in the transcript pool, relative to its frequency in genomic DNA. This design is advantageous because it requires no specialized (i.e. gene-specific) functional assay, thus making it amenable to interrogation of transcribed variants' effects on splicing/transcript abundance in any gene.

Inclusion of Selective PCR Sites

Given the modest proportion of HDR-edited loci in a given experiment and the high number of variants to be interrogated (i.e. hundreds to thousands), it would require a large amount of sequencing to sufficiently sample every variant in gDNA and cDNA pools from a population of cells that are predominantly unedited or harboring products of NHEJ. Furthermore, at such efficiencies, the rate of error in high-throughput sequencing is high enough to obscure signal from single nucleotide variants (SNVs) (unpublished observations). Therefore, in certain embodiments, until better methods are developed, techniques to selectively sequence molecules derived from edited cells are likely to be advantageous to isolate populations of cells that have been successfully edited with HDR techniques. In some embodiments, selective PCR sites are present regardless how the HDR libraries are generated, for example, by degenerate oligonucleotide or by programmed edits via microarray-based synthesis. In other embodiments, selective PCR sites are not used.

The HDR libraries were designed to include short, fixed edits to serve as unique priming sites in genomes that successfully undergo HDR. PCR reactions primed at this site, therefore, should only amplify material from edited cells, thus reducing both the noise associated with error from sequencing unedited material and the cost of sequencing in each experiment. Additionally, selective PCR sites that mutate the PAM and protospacer sequences could prevent Cas9 from re-cutting HDR-edited genomes. This should have the effect of increasing the proportion of cells bearing experimentally informative edits, and given the bottleneck imposed by limitations on how many successfully edited cells can be sampled, should result in more robust experimental signal.

DBR1 Experimental Design

To demonstrate that saturation genome editing can be used to explore effects of mutations on protein function and cellular fitness, DBR1, a well-conserved gene that scored highly in a human haploid cell genome-wide loss-of-function screen for essentiality [19] was targeted. Using haploid cells prevents gene compensation from an unedited copy [25]. Without knowing how sensitive the cells would be to mutations, it was chosen to target a region of exon 2 that was highly conserved, included in all transcript annotations on the UCSC Genome Browser, and coded for at least 2 residues (N84, H85) predicted to participate at the enzyme's active site [26]. Selection against edited cells in culture allows phenotype to be linked to genotype from sequencing of the gDNA pool over a series of time points. During HDR library construction, a selective PCR site in a downstream intron was designed to minimize any effect on gene function, and two synonymous mutations to abrogate Cas9 re-cutting were used.

Given the lower transfection efficiency of Hap1 cells (˜4% for the plasmids used here), a DBR1-targeting CRISPR construct that expressed EGFP with Cas9 was cloned and FACS was used to sort a population of successfully transfected cells. The sgRNA was designed using the Zhang Lab tool [described at http://crispr.mit.edu/], and selected to minimize off-target effects that could potentially impair cellular fitness [23].

HDR Library and Cas9-sgRNA Cloning

A homology-directed repair (HDR) library containing all possible 4,096 DNA hexamers substituted at positions +5 to +10 of BRCA1 exon 18 (chr17:41,215,962-41,215,967; CCDS11453.1) was constructed using a partially degenerate oligonucleotide (IDT DNA; “BRCA1ex18NNNNNN5_—10 selPCR”) containing a 7 bp selective PCR site/EcoRV restriction digest site at position +17 to +23 (FIG. 1a, Table 1). The oligonucleotide was PCR amplified and cloned via the In-Fusion reaction (Clontech) into a PCR-linearized pUC19-BRCA1ex18 vector containing a pre-inserted 1,573 bp fragment amplified from the surrounding BRCA1ex18 locus in HEK293T cells (chr17:41,215,127-41,216,699) to serve as homologous arms. Additional libraries from a second degenerate oligonucleotide that was synthesized with a 3% mutation rate (97% wt, 1% each non-wt base) across the 78 bp exon were cloned similarly, such that one end of the exon would be fixed and contain either missense (as above) or synonymous mutations for selective PCR. Complete oligonucleotide and HDR library exon sequences are listed in Table 1. All PCR reactions were performed with the KAPA HiFi HotStart ReadyMix PCR Kit.

The DBR1 HDR library was cloned as above except with the following differences. HDR library variants were derived from 388 oligonucleotides synthesized on a microarray (CustomArray) to include all possible single base pair changes in a 75 bp region comprising part of DBR1 exon 2 (chr3:137,892,342-137,892,416), all codon variants at the first three residues of the 75 bp region (chr3:137,892,408-137,892,416), and the reference 75 bp sequence. All DBR1 HDR library sequences also included two synonymous mutations designed to prevent re-cutting of edited genomes by disrupting PAM and protospacer sequences (chr3:137,892,424 and chr3:137,892,421), and a 6 bp selective PCR site in intron 2 of DBR1 (chr3:137,892,331-137,892,336). The library was cloned into a pUC19-DBR1ex2 backbone, a vector containing the surrounding DBR1 sequence cloned from Hap1 gDNA (chr3:137,891,573-137,893,293).

A bicistronic Cas9-sgRNA vector designed to cleave within BRCA1 exon 18 (“pCas9-sgBRCA1x18”) was cloned according to a published protocol[24] by ligating annealed oligonucleotides into a human codon-optimized S. pyogenous Cas9-sgRNA vector from the lab of Feng Zhang (pX330-U6-Chimeric_BB-CBh-hSpCas9; Addgene plasmid #42230). The same protocol was followed to create pCas9-EGFP-sgDbr1x2 from a similar Zhang lab vector that allows for fluorescent identification of Cas9-expressing cells (pSpCas9(BB)-2A-GFP (pX458); Addgene plasmid #48138).

Cell Culture and Transfection

For BRCA1 experiments, HEK293T cells were cultured in Dulbecco's Modified Eagle Medium (Life Technologies) supplemented with 10% FBS (AATC) and 100 U/ml penicillin+100 ug/ml streptomycin (Life Technologies). One day prior to transfection, cells were split to ˜40% confluency in 12-well plates with antibiotic-free media. The next day, 0.5-1.0 ug of each library was co-transfected (Lipofectamine 2000, Invitrogen) with an equivalent amount of pCas9-sgBRCA1x18. Cells were expanded to 6-well plates, then split 1:4 on day 3 into two pools, and DNA and RNA were harvested on D5 (AllPrep DNA/RNA Mini Kit, Qiagen). Biological replicates of each transfection and negative control transfections of each library without pCas9-sgBRCA1x18 were also performed.

For the DBR1 experiment, Hap1 cells (Haplogen) were cultured in Iscove's Modified Dulbecco's Medium supplemented with 10% FBS and 100 U/ml penicillin+100 ug/ml streptomycin. ˜3×10⁶ Hap1 cells were passaged to a 60 mm dish in antibiotic-free media one day prior to co-transfection with 3 ug each of pCas9-EGFP-sgDbr1x2 and the DBR1 HDR library via Turbofectin 8.0 (OriGene) according to protocol. On D2, FACS was performed (BD FACSAria III) to isolate ˜250,000 EGFP+ cells, which were then expanded in culture with samples taken of ˜1×10⁶ cells on D5, and 4-8×10⁶ on D8 and D11. gDNA was isolated according to protocol with the QiaAmp Kit (Qiagen). A biological replicate was performed, as well as negative controls in which the HDR library was transfected with the empty pSpCas9(BB)-2A-GFP construct (to enable FACS of transfected cells without editing).

RT, Selective PCR and Sequencing

For BRCA1 experiments, reverse transcription (RT) was performed using SuperScriptIII (Invitrogen) with a gene-specific primer located in either BRCA1 exon 19 (hexamer experiments) or exon 21 (whole exon experiments). Initial rounds of PCR were performed on large quantities of sample gDNA (8-12 ug gDNA, 100-150 ng/reaction) and cDNA (25 ug total RNA reverse transcribed and split into 45-47 reactions) using the KAPA HiFi HotStart ReadyMix PCR kit. In the first gDNA PCR, a primer external to the HDR library was used to prevent amplification of plasmid DNA. cDNA reactions were either primed from exons 16 and 18 (hexamer experiment; Library L) or exons 18 and 20 (Libraries R, R2). After the initial gDNA and cDNA reactions, all PCR products from a single sample were pooled and purified using the QIAquick PCR Purification Kit (Qiagen).

For both cDNA and gDNA reactions, a primer designed to selectively amplify edited molecules bearing the selective PCR site was used either in the first or second reaction. Optimal annealing temperatures for each primer pair were determined via gradient PCR, and negative control reactions were performed using input from HDR library-only transfections to ensure products were derived from edited genomes as opposed to the HDR library. Negative controls failed to amplify for all experiments. Two subsequent PCRs were performed to add sequencing adaptors (“PU1L” and “PU1R”), sample indices, and flow cell adaptors.

For the DBR1 experiment, 30 cycles of selective PCR were performed on gDNA (300 ng per reaction) from D5 (3 ug), D8 and D11 (27 ug each). Wells from each sample were pooled, PCR purified, and then re-amplified for 15 additional cycles. The 1,055 bp product was gel-purified (QIAquick Gel Extraction Kit, Qiagen), and two subsequent PCRs were performed to incorporate sequencing and flow cell adaptors prior to sequencing as above.

After final reactions were purified (AMPure XP beads, Agencourt), paired-end sequencing was performed on all samples with the Illumina MiSeq to quantify gDNA and/or cDNA abundances for each edited haplotype. All primer sequences for RT, selective PCR, and sequencing library preparation are provided in Table 1.

HDR efficiencies were estimated for all experiments via deep sequencing of target loci by performing PCR on 150-300 ng of gDNA using primers external to the region of editing and the selective PCR site. Reported HDR efficiencies were conservatively calculated as the fraction of sequencing reads containing the selective PCR site and bearing at least one variant represented in the HDR library.

Analysis of Sequencing Data

For quality control, fully overlapping paired-end reads were merged with PEAR [34] (Paired-End reAd mergeR) and discordant pairs were eliminated. By design, the mutagenized region is covered by both the forward and reverse reads on the Illumina platform, resulting in high-confidence calls per site.

For BRCA1 hexamer reads to be included, the six bases on either side of the hexamer were required to match the reference sequence, and every base call in the hexamer required a quality score of at least Q30. For BRCA1 whole-exon mutagenesis, the full read was required to be the correct length and match the library consensus sequence outside of the mutagenized region, every base quality score inside the mutagenized region was required to be at least Q30, and no indels were tolerated in alignment with BWA-MEM [35]. cDNA reads not matching any gDNA haplotype with at least 10 reads were eliminated. After normalizing for sequencing coverage, enrichment scores were calculated as cDNA read counts incremented by one pseudocount divided by gDNA reads, calibrated to the wild-type hexamer.

For DBR1 mutagenesis, reads were subjected to the same requirements of the sequence outside the mutagenized bases matching the consensus and every quality score in the mutagenized region exceeding Q30. Only reads matching programmed haplotypes were analyzed, and haplotypes below a D5 relative abundance of 5E-5 were excluded from analysis. After incrementing all read counts by one pseudocount and dividing by the total number of reads, the abundance of each haplotype on D8 or D11 was divided by the corresponding abundance on D5, and the fold change relative to the wild type sequence was taken to calculate an enrichment score. Based on the bimodal distribution observed in each replicate, mutations with log₂-transformed enrichment scores less than −2 were considered “deleterious”; otherwise, mutations were considered “tolerated”. Discordant effects between replicates were defined as mutations “tolerated” in one replicate but “deleterious” in the other. Amino acid level enrichment scores were calculated as the median of SNV enrichment scores for programmed edits resulting in the same change (or lack of change, for synonymous edits).

SNV Effect Size Linear Modeling and Replicate Pooling

To determine effects of SNVs in the BRCA1 whole-exon experiments, cDNA and gDNA read counts were converted into percentages (number of reads for a given haplotype divided by the total number of reads for a given replicate) after discarding haplotypes with fewer than 10 gDNA reads. Because we had variance in the number of reads for each haplotype, the null expectation of equal variance (σ2) for each cDNA/gDNA ratio was violated. Because each effect size (yij) was the average of nij observations (reads), then var(yij)=var εij=σ2/nij, suggesting that the weight for each variable should be nij. To predict single nucleotide effect size across exon 18 of BRCA1, we then fit the weighted linear model:

y _ij=β₀+w_ijβ_ijX_ij

where y_ij is the log₂ enrichment score for a given haplotype, is the number of gDNA reads for a given haplotype, β_ij is the effect of nucleotide i at position j relative to the wild-type allele, and X_ij is a dummy variable indicating the presence or absence of a particular nucleotide change i at position j relative to the wild type allele. Regression analyses were performed in R 3.0.0 using the lm( ) function. The resulting coefficients of the model adjusted for the model intercepts (β₀+β_ij) were taken as effect sizes of the individual SNVs on exon splicing/stability. To merge data across replicates, effect sizes were averaged (including across overlapping bases between libraries L and R in BRCA1 exon).

Comparisons to Other Metrics of Functional Impact

For comparison to plasmid studies, ESR-seq scores were taken from Ke et al. (2011) [9]. Hexamers with positive ESR-seq scores are deemed exonic splicing enhancers, whereas negative ESR-seq scores denote exonic splicing silencers. For comparison of BRCA1 exon 18's SNV effect sizes to an in silico method, all SNVs were queried on MutPredSplice's web server (http://mutdb.org/mutpredsplice/submit.htm). MutPredSplice reports a single score estimating the likelihood that a variant will disrupt splicing at any genomic locus. Absolute values of BRCA1 exon 18 splicing effect sizes were then correlated with MutPredSplice scores to determine concordance between our data and predicted effects on splicing.

For DBR1, calculated enrichment scores were compared to BLOSUM62 substitution scores [20] (obtained from NCBI), PolyPhen-2 [21], and CADD [22] (PolyPhen-2 and CADD scores obtained from querying genomic coordinates from CADD's precomputed genomic annotations (http://cadd.gs.washington.edu/download). Whereas BLOSUM62 is derived from evolutionary conservation and PolyPhen-2 predicts changes in protein function, CADD is an integrated measure of deleteriousness that incorporates many functional annotations (including PolyPhen-2).

Discussion

Reproducibility of Saturation Genome Editing Experiments

The correlations between replicates for each of the experiments suggest that while this technique reproducibly measures effects of many concurrent programmed genome edits, there are also sources of noise.

The noise observed may relate to the fact that modest editing efficiencies lead to relatively few cells in each experiment harboring each specific edit. In the BRCA1 hexamer experiment and the DBR1 experiment, a bimodal distribution of gDNA read counts is observed (FIGS. 4a, 12b). This is consistent with a bottleneck resulting in not all HDR library edits being present in post-editing gDNA. If some edits are not present at all, some edits may be only made once or a few times, and may be represented by very few cells when measurements are made, possibly as few as one.

Consistent with lowly sampled edits being more prone to noise, hexamers that are more highly represented in gDNA counts are more reproducible. For example, whereas R=0.659 between two biological replicates overall, hexamers falling into the top third with respect to gDNA count correlated much more highly (R=0.857). Furthermore, considering the two BRCA1 experiments, because there were far fewer possible SNVs (n=234; experiment in FIG. 2) than hexamer substitutions (n=4,095; experiment in FIG. 1), each individual edit is expected to be created independently many more times during editing, given a generally similar experimental setup with respect to number of cells, functional assay, etc. This may give rise to the higher reproducibility of the SNV effect sizes as compared with the hexamer enrichment scores (i.e. FIG. 2a vs. FIG. 1b).

Whether the noise represents biological variability (for instance, two cells with the same edit producing transcripts at different rates) or technical variability (stochastic effects inherent to sample prep) it is reasoned that by pooling or averaging replicates, the number of successfully edited cells sampled is effectively increased, and therefore noise attributable to low sampling is reduced. Consistent with this, pooling read counts from D3 replicates in the BRCA1 hexamer experiment improved correlation between biological replicates.

For the DBR1 experiment, the overall reproducibility of D11 enrichment scores is reasonable (R=0.752; FIG. 13c). In each biological replicate, a bimodal distribution of enrichment scores (i.e. corresponding to tolerated vs. deleterious) is observed. While there are some observations, e.g. nonsense mutations that are tolerated in one replicate, not all of the observations replicated. While two synonymous changes score as reproducibly deleterious, there are no nonsense or frameshift mutations that are reproducibly tolerated.

This experiment, subject to bottlenecking at the editing step, generates clonal populations possibly expanded from a single edited cell. Falsely tolerated edits (i.e. nonsense mutations not selected against) in a given replicate could be explained by Hap1 cells' reversion to diploidy prior to editing occurring, as noted by Haplogen (the cell line's source). Falsely deleterious edits in a given replicate could be observed due to off-target CRISPR cutting in other essential regions, or random dropout when half the sample is split on D5.

These findings suggest that while the technique is sensitive enough to measure effects from very few edited cells, noise associated with sampling such small populations mandates the necessity of replicating data sets to improve confidence in the measurements associated with individual genome edits. The data also suggest that increased reproducibility may be achievable by a) transfecting and analyzing a higher number of cells, b) limiting complexity of HDR libraries, or c) improving HDR efficiency to allow for sampling of more edited cells.

Potential Applications of Saturation Genome Editing

In the experiments disclosed herein, genotype is directly linked to phenotype to assay pools of multiplex HDR-derived variants. Targeted RNA and DNA sequencing of the edits themselves via selective PCR are well suited to catalog variants' effects on splicing and cellular fitness, respectively. However, with relatively simple adaptations of the method, complex pools of genome edits can be subjected to many additional assays that measure diverse aspects of biology.

First, the approach illustrated in the BRCA1 experiments is broadly applicable to study how genomic variation within virtually any transcribed element affects its own RNA abundance. Specifically, this approach could readily be adopted to study how other transcribed elements contribute to expression levels (e.g. the influence of 5′- and 3′ UTRs sequence on RNA stability, etc.). In this context, enhancers are transcribed at low levels (eRNA), suggesting an approach for studying enhancer activity, as well.

Additionally, assays such as targeted ChIP-Seq could be performed to characterize how libraries of genomic edits affect epigenetic states in coding or non-coding regions. By taking large quantities of DNA from expanded populations of edited cells and functionally separating edits based on biochemical interactions (i.e. transcription factor binding, associated histone modification, nucleosome positioning, etc.), genotype-phenotype associations would be preserved.

Apart from the molecular assays described above, the DBR1 experiment is just one example of a cell-based assay that can be read out with high-throughput sequencing. In addition to essentiality (in haploid cells or diploid cells made functionally haploid through previous gene disruption), gain-of-function (such as drug resistance or growth gain), haploid insufficiency and dominant negative effects could be measured with appropriate selection assays. In fact, any well-customized assay that allows functionally-based separation of cell populations (e.g., with FACS) is amenable to downstream sequencing of edited populations of assayed cells as a readout. For instance, reporter cell lines engineered to express fluorescently tagged genes of interest could be used to assay multiplex HDR-edited transcription factors or enhancers.

Given the relative ease of targeted nuclease production and mutagenesis library cloning, the methods disclosed herein are readily scalable. Exons could be tiled to functionally assess each coding SNV across entire genes. Therefore, the methods disclosed herein provide a valuable approach for determining functional effects of large numbers of programmed genomic mutations in many biological contexts.

REFERENCES

The references, patents and published patent applications listed below, and all references cited in the specification above are hereby incorporated by reference in their entirety, as if fully set forth herein.

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TABLE 1
List of all oligonucleotides used in saturation genome editing experiments
BRCA1 Library Cloning	SEQ ID NO
Template for random hexamer library
BRCA1ex18NNNNNN5_10selPCR (machine-mixing)	SEQ ID NO: 1	GAGTGTTTTTCATTCTGCAGATGCNNNNNNTGTGTGGATATCCCACACTGAAATATTTTCTAGGAATTGCGGGAGG
To PCR-amplify hexamer library inserts
BRCA1ex18_Hexamers_F	SEQ ID NO: 2	GAGTGTTTTTCATTCTGCAG
BRCA1ex18_Hexamers_R	SEQ ID NO: 3	CCTCCCGCAATTCCTAGAAA
To PCR-amplify homologous arms from gDNA with pUC19
adaptors
pUC_gBRCA1_INF_5′	SEQ ID NO: 4	CGGTACCCGGGGATCGAACTCCCGACATCAGGTGA
pUC_gBRCA1_INF_3′	SEQ ID NO: 5	CGACTCTAGAGGATCAAGGATTCTGTGAGGGAGCA
To PCR-linearize pUC19-BRCA1ex18 for random hexamer
insertion
Lin_pUC_BRCA1ex18_5′	SEQ ID NO: 6	CTGCAGAATGAAAAACACTC
Lin_pUC_BRCA1ex18_3′	SEQ ID NO: 7	TTTCTAGGAATTGCGGGAGG
BRCA1ex18_3%_mut Template (blue = 97 wt/1/1/1 bases;	SEQ ID NO: 8	ATTCTGCAGATGCTGAGTTTGTGTGTGAACGGACACTGAAATATTTTCTAGGAATTGCGGGAGGA
hand-mixing)		AAATGGGGAGGAAAATGGGTAGTTAGCTATTTCTGTAAGTATAATAC
To PCR-amplify BRCA1ex18 3% mutation inserts
BRCA1ex18_5′1_Amp	SEQ ID NO: 9	GAGTGTTTTTCATTCTGCAG
5′2_Syn_Amp	SEQ ID NO: 10	TTCTGCAGATGCTGAGTTTGTCTGCGAGAGAACACTGAAATATTTTC
5′2_Eco_Amp	SEQ ID NO: 11	TTCTGCAGATGCTGAGTTTGTGTGGATATCCACACTGAAATATTTTC
BRCA1ex18_3′1_Amp	SEQ ID NO: 12	GGAGAAATAGTATTATACTTAC
3′2_Syn_Amp	SEQ ID NO: 13	TTATACTTACAGAAATAGCTTACAACCCACTTACCACCTGCAATTCCTA
3′2_Eco_Amp	SEQ ID NO: 14	TTATACTTACAGAAATAGCTAAGGATATCTTTTCCTCCCGCAAT
To PCR-linearize pUC19_BRCA1ex18 for 3% mutation
inserts
In-Fusion_Lin_5′1	SEQ ID NO: 15	CTGCAGAATGAAAAACACTC
In-Fusion_Lin_3′1	SEQ ID NO: 16	GTAAGTATAATACTATTTCTCC
In-Fusion_Lin_5′2	SEQ ID NO: 17	CAAACTCAGCATCTGCAGAA
In-Fusion_Lin_3′2	SEQ ID NO: 18	AGCTATTTCTGTAAGTATAA
pCas9-sgBRCA1x18 cloning
sgRNA_BRCA1ex18_F	SEQ ID NO: 19	CACCGATGCTGAGTTTGTGTGTGAA
sgRNA_BRCA1ex18_R	SEQ ID NO: 20	AAACTTCACACACAAACTCAGCATC
BRCA1 Sample Processing for Sequencing
Reverse Transcription
BRCA1ex19_RT	SEQ ID NO: 21	TTTCTTTCTTTAATAGACTGGGTCA
BRCA1ex21_RT	SEQ ID NO: 22	GTGGGCATGTTGGTGAAG
Primer to PCR-amplify from gDNA external to HDR Library
external_BRCA1ex18_F	SEQ ID NO: 23	CGGCTTTTGTAGCAGTTAAACA
gDNA/cDNA hexamer selective PCR primer
BRCA1ex18SelPCR_Hex_R	24SEQ ID NO:	CCTAGAAAATATTTCAGTGTGGATATC
cDNA hexamer PCR primers
BRCA1ex16_cDNA1_F	SEQ ID NO: 25	GGAGAAGCCAGAATTGACA
Hexamer sequencing adaptor primers
PU1L_BRCA1intron17_F	SEQ ID NO: 26	CTAAATGGCTGTGAGAGAGCTCAGTGGTGTTTTCAGCCTCTGATT
PU1R_BRCA1ex18SelPCR_Hex_R	SEQ ID NO: 27	ACTTTATCAATCTCGCTCCAAACCCCTAGAAAATATTTCAGTGTGGATATC
PU1L_BRCA1ex16_cDNA2_F	SEQ ID NO: 28	CTAAATGGCTGTGAGAGAGCTCAGGCTTCAACAGAAAGGGTCA
PU1R_BRCA1ex18_3′1_Amp	SEQ ID NO: 29	ACTTTATCAATCTCGCTCCAAACCGGAGAAATAGTATTATACTTAC
MiSeq Flowcell and Indexing Primers
FC_PU1L	SEQ ID NO: 30	AATGATACGGCGACCACCGAGATCTACACACGTAGGCCTAAATGGCTGTGAGAGAGCTCAG
FC_index_PU1R_142	SEQ ID NO: 31	CAAGCAGAAGACGGCATACGAGATAAGCGTTCAGACCGTCGGCACTTTATCAATCTCGCTCCAAACC
FC_index_PU1R_143	SEQ ID NO: 32	CAAGCAGAAGACGGCATACGAGATCGCAAGCGTGACCGTCGGCACTTTATCAATCTCGCTCCAAACC
FC_index_PU1R_144	SEQ ID NO: 33	CAAGCAGAAGACGGCATACGAGATGCAGCGCGAGACCGTCGGCACTTTATCAATCTCGCTCCAAACC
FC_index_PU1R_145	SEQ ID NO: 34	CAAGCAGAAGACGGCATACGAGATCGCGCAGCTGACCGTCGGCACTTTATCAATCTCGCTCCAAACC
FC_index_PU1R_146	SEQ ID NO: 35	CAAGCAGAAGACGGCATACGAGATTCAAGCGCAGACCGTCGGCACTTTATCAATCTCGCTCCAAACC
FC_index_PU1R_147	SEQ ID NO: 36	CAAGCAGAAGACGGCATACGAGATCAGTCGCAGGACCGTCGGCACTTTATCAATCTCGCTCCAAACC
FC_index_PU1R_148	SEQ ID NO: 37	CAAGCAGAAGACGGCATACGAGATGCGTCAGTTGACCGTCGGCACTTTATCAATCTCGCTCCAAACC
FC_index_PU1R_149	SEQ ID NO: 38	CAAGCAGAAGACGGCATACGAGATAGTCGCGCAGACCGTCGGCACTTTATCAATCTCGCTCCAAACC
Selective PCR and seq prep for 3% mut experiments
BRCA1ex20_R	SEQ ID NO: 39	CTTTCTGTCCTGGGATTCTC
PU1R_BRCA1ex20	SEQ ID NO: 40	ACTTTATCAATCTCGCTCCAAACCCTTTCTGTCCTGGGATTCTC
BRCA1ex16_cDNA2_F	SEQ ID NO: 41	GCTTCAACAGAAAGGGTCA
PU1L_BRCA1ex16_cDNA2_F	SEQ ID NO: 42	CTAAATGGCTGTGAGAGAGCTCAGGCTTCAACAGAAAGGGTCA
PU1L_BRCA1intron17_2	SEQ ID NO: 43	CTAAATGGCTGTGAGAGAGCTCAGCCAGATTGATCTTGGGAGTG
PU1R_BRCA1intron18	SEQ ID NO: 44	ACTTTATCAATCTCGCTCCAAACCGGTAACTCAGACTCAGCATC
BRCA1ex18_sel5Syn_F	SEQ ID NO: 45	TGAGTTTGTCTGCGAGAGA
PU1L_BRCA1ex18_sel5syn	SEQ ID NO: 46	CTAAATGGCTGTGAGAGAGCTCAGTGAGTTTGTCTGCGAGAGA
BRCA1ex18_sel5Eco_F	SEQ ID NO: 47	GCTGAGTTTGTGTGGATATCC
PU1L_BRCA1ex18_sel5Eco	SEQ ID NO: 48	CTAAATGGCTGTGAGAGAGCTCAGGCTGAGTTTGTGTGGATATCC
BRCA1ex18_sel3Syn_R	SEQ ID NO: 49	TACAACCCACTTACCACCT
PU1R_BRCA1ex18_sel3Syn	SEQ ID NO: 50	ACTTTATCAATCTCGCTCCAAACCTACAACCCACTTACCACCT
BRCA1ex18_sel3Eco_R	SEQ ID NO: 51	ACTTACAGAAATAGCTAAGGATATC
PU1R_BRCA1ex18_sel3Eco	SEQ ID NO: 52	ACTTTATCAATCTCGCTCCAAACCACTTACAGAAATAGCTAAGGATATC
DBR1 HDR Library Cloning
CustomArray DBR1 oligonucleotide pool	SEQ ID NO: 53	CCAGTTCTCACGCTCTTCATCGGCGGAAACCATGAAGCCTCAATCATTTGCAAGAGTTACCCTATGGTGGGTGGCA
(63x codon mutations bold; 225 1bp mutations blue; non-		CCAAACATTTATTATTTAGgtatgtgtgatactttgtggatac
reference red; intron lower-case)
To PCR-amplify HDR library inserts (oligonucleotide pool)
Dbr1X2D_AMP_F	SEQ ID NO: 54	TCTCACGCTCTTCATCGGCG
Dbr1X2D_AMP_R	SEQ ID NO: 55	TCCACAAAGTATCACACAT
To PCR-amplify homologous arms from Hap1 gDNA with
pUC19 adaptors
pUC19_Dbr1_Inf_F	SEQ ID NO: 56	CGGTACCCGGGGATCGAGGCGGGAAATGTATTCAG
pUC19_Dbr1_Inf_R	SEQ ID NO: 57	CGACTCTAGAGGATCCAGGAAATGCTGCAAGACAA
To PCR-linearize pUC19-Dbr1ex2 for library insertion
Lin_pUC19-Dbr1X2_5	SEQ ID NO: 58	CGCCGATGAAGAGCGTGAGAACTGG
Lin_pUC19-Dbr1X2_3	SEQ ID NO: 59	ATGTGTGATACTTTGTGGATACTTTTTTTTCCTGGG
DBR1 Sample Processing for Sequencing
To amplify gDNA from outside plasmid homology
external_Dbr1_F	SEQ ID NO: 60	GCCTGTTTCCCTTAGATCCT
Selective PCR from edited gDNA
Dbr1Int2_selAMP_R	SEQ ID NO: 61	AGTATCCACAAAGTATCACAC
Non-selective PCR from edited gDNA
Dbr1_Int2_R2	SEQ ID NO: 62	CCTGATAAGCTCTTCCATCC
To add adaptors for sequencing
PU1L_Dbr1Int1_AMP	SEQ ID NO: 63	CTAAATGGCTGTGAGAGAGCTCAGGCCTAATTGTGGTAACTGAC
PU1R_Dbr1Int2_selAMP_R	SEQ ID NO: 64	ACTTTATCAATCTCGCTCCAAACCAGTATCCACAAAGTATCACAC
PU1R_Dbr1_Int2_R2	SEQ ID NO: 65	ACTTTATCAATCTCGCTCCAAACCCCTGATAAGCTCTTCCATCC
pCas9-EGFP-sgDbr1x2 Cloning
sgRNA_Dbr1X2_F	SEQ ID NO: 66	CACCGCAGTTCTCACGCTCTTCATT
sgRNA_Dbr1X2_R	SEQ ID NO: 67	AAACAATGAAGAGCGTGAGAACTGC
Exon sequences in this study	SEQ ID NO: 68	.GAGTGTTTTTCATTCTGCAGATGCTGAGTTTGTGTGTGAACGGACACTGAAATATTTTCTA
WT BRCA1ex18 (PAM, protospacer underlined; introns gray)		GGAATTGCGGGAGGAAAATGGGTAGTTAGCTATTTCTGTAAGTATAATACTATTTC
BRCA1 and DBR1 HDR library exons in pUC19
homology donor plasmids
HDRL Random Hexamer BRCA1ex18	SEQ ID NO: 69	...GAGTGTTTTTCATTCTGCAGATGCNNNNNNTGTGTGGATATCCACACTGAAATATTTTCT
		AGGAATTGCGGGAGGAAAATGGGTAGTTAGCTATTTCTGTAAGTATAATACTATTTC...
HDRL 3% mut 5′ SYN BRCA1ex18	SEQ ID NO: 70	.GAGTGTTTTTCATTCTGCAGATGCTGAGTTTGTCTGCGAGAGAACACTGAAATATTTTCTAGG
		AATTGCGGGAGGAAAATGGGTAGTTAGCTATTTCTGTAAGTATAATACTATTTC.
HDRL 3% mut 5′ NONSYN BRCA1ex18	SEQ ID NO: 71	...GAGTGTTTTTCATTCTGCAGATGCTGAGTTTGTGTGGATATCCACACTGAAATATTTTCT
		AGGAATTGCGGGAGGAAAATGGGTAGTTAGCTATTTCTGTAAGTATAATACTATTTC ..
HDRL 3% mut 3′ NONSYN BRCA1ex18	SEQ ID NO: 72	...GAGTGTTTTTCATTCTGCAGATGCTGAGTTTGTGTGTGAACGGACACTGAAATATTTTC
(selective PCR sites red; mutated region blue)		TAGGAATTGCGGGAGGAAAAGATATCCTTAGCTATTTCTGTAAGTATAATACTATTTC
WT DBR1ex2	SEQ ID NO: 73	...CCAGTTCTCACGCTCTTCATTGGGGGAAACCATGAAGCCTCAAATCATTTGCAAGA
		GTTACCCTATGGTGGCTGGGTGGCACCAAACATTTATTATTTAGGTATGTGATTGTGTTTGTGGATAC
DBR1ex2 HDRL	SEQ ID NO: 74	...CCAGTTCTCACGCTCTTCATCGGCGGAAACCATGAAGCCTCAAATCATTTGCAAG
		AGTTACCCTATGGTGGCTGGGTGGCACCAAACATTATTATTTAGGTATGTGTGATACTTTGTGGATAC
(63x codon substitutions bold, PAM/protospacer mutations green)

TABLE 2
Empirical measurement of impact of introducing 4048
hexamers as genome edits to BRCA1 exon 18 (+5 to +10) on
abundance of exon 18 containing transcripts
				hamming	Log2
	% in input	Ke et al. 2011	nonsense	distance to	enrichment
Hexamer	library	ESRseq score	hexamer?	WT	score
TGAGTT	1.197%	NA	no	0	0.000
AGAGTT	0.049%	NA	no	1	−2.087
CGAGTT	0.014%	NA	no	1	−0.095
GGAGTT	0.040%	NA	no	1	−0.135
TAAGTT	0.024%	−0.493	no	1	−0.744
TCAGTT	0.019%	−0.311	no	1	−2.260
TGAATT	0.031%	NA	no	1	0.444
TGACTT	0.017%	NA	no	1	0.436
TGAGAT	0.033%	NA	no	1	−0.034
TGAGCT	0.019%	NA	no	1	0.674
TGAGGT	0.034%	NA	no	1	−0.310
TGAGTA	0.037%	NA	no	1	0.478
TGAGTC	0.016%	NA	no	1	−0.153
TGAGTG	0.023%	NA	no	1	−0.227
TGATTT	0.019%	NA	no	1	−0.051
TGCGTT	0.016%	NA	no	1	0.309
TGGGTT	0.021%	−0.521	no	1	−0.685
TGTGTT	0.022%	−0.198	no	1	−0.440
TTAGTT	0.017%	−0.831	yes	1	−4.278
AAAGTT	0.050%	NA	no	2	−2.917
ACAGTT	0.036%	NA	no	2	−3.111
AGAATT	0.037%	NA	no	2	−5.548
AGACTT	0.032%	NA	no	2	−3.599
AGAGAT	0.053%	0.367	no	2	−2.453
AGAGCT	0.033%	NA	no	2	−0.866
AGAGGT	0.054%	NA	no	2	−2.970
AGAGTA	0.062%	NA	no	2	−4.019
AGAGTC	0.039%	0.300	no	2	−3.721
AGAGTG	0.059%	NA	no	2	−3.279
AGATTT	0.032%	NA	no	2	−3.706
AGCGTT	0.028%	NA	no	2	−0.376
AGGGTT	0.051%	−0.470	no	2	−5.913
AGTGTT	0.035%	NA	no	2	−0.708
ATAGTT	0.030%	−0.554	yes	2	−5.399
CAAGTT	0.020%	NA	no	2	−1.781
CGAATT	0.023%	NA	no	2	0.094
CGACTT	0.010%	NA	no	2	−0.889
CGAGAT	0.023%	0.348	no	2	0.637
CGAGCT	0.015%	NA	no	2	1.281
CGAGGT	0.019%	NA	no	2	−0.099
CGAGTA	0.022%	NA	no	2	−1.055
CGAGTC	0.011%	0.399	no	2	−1.001
CGAGTG	0.018%	0.165	no	2	−0.742
CGATTT	0.008%	NA	no	2	−1.125
CGCGTT	0.008%	0.316	no	2	0.643
CGGGTT	0.017%	NA	no	2	0.523
CGTGTT	0.008%	NA	no	2	−0.268
CTAGTT	0.007%	−0.555	yes	2	−3.727
GAAGTT	0.040%	0.468	no	2	−1.915
GCAGTT	0.027%	NA	no	2	−1.427
GGAATT	0.044%	0.242	no	2	−1.710
GGACTT	0.028%	0.338	no	2	0.237
GGAGAT	0.058%	0.336	no	2	−0.559
GGAGCT	0.034%	NA	no	2	−0.362
GGAGGT	0.043%	NA	no	2	−0.966
GGAGTA	0.053%	NA	no	2	−0.989
GGAGTC	0.031%	0.516	no	2	1.196
GGAGTG	0.051%	NA	no	2	0.448
GGATTT	0.037%	NA	no	2	0.511
GGCGTT	0.014%	0.278	no	2	0.622
GGGGTT	0.038%	−0.543	no	2	−1.880
GGTGTT	0.023%	NA	no	2	0.407
GTAGTT	0.020%	−0.658	yes	2	−5.724
TAAATT	0.026%	−0.632	no	2	−3.111
TAACTT	0.021%	−0.457	no	2	−3.257
TAAGAT	0.035%	NA	no	2	−4.842
TAAGCT	0.023%	−0.368	no	2	−3.123
TAAGGT	0.041%	−0.468	no	2	−5.926
TAAGTA	0.037%	−0.667	no	2	−5.980
TAAGTC	0.018%	NA	no	2	−4.899
TAAGTG	0.029%	−0.461	no	2	−2.670
TAATTT	0.019%	−0.389	no	2	−2.975
TACGTT	0.016%	NA	no	2	−0.949
TAGGTT	0.020%	−0.796	no	2	−4.864
TATGTT	0.022%	−0.301	no	2	0.809
TCAATT	0.018%	NA	no	2	−1.685
TCACTT	0.020%	NA	no	2	−2.880
TCAGAT	0.030%	NA	no	2	−2.559
TCAGCT	0.018%	NA	no	2	−1.810
TCAGGT	0.034%	−0.438	no	2	−3.941
TCAGTA	0.027%	−0.407	no	2	−4.288
TCAGTC	0.019%	NA	no	2	−3.280
TCAGTG	0.019%	−0.267	no	2	−1.379
TCATTT	0.021%	NA	no	2	−1.268
TCCGTT	0.010%	NA	no	2	−1.495
TCGGTT	0.009%	NA	no	2	0.288
TCTGTT	0.009%	NA	no	2	−3.347
TGAAAT	0.044%	0.190	no	2	0.723
TGAACT	0.025%	0.339	no	2	0.102
TGAAGT	0.040%	0.384	no	2	0.269
TGAATA	0.039%	NA	no	2	−0.574
TGAATC	0.023%	0.426	no	2	0.250
TGAATG	0.033%	0.131	no	2	−0.509
TGACAT	0.028%	0.198	no	2	−0.058
TGACCT	0.016%	0.459	no	2	0.587
TGACGT	0.020%	0.482	no	2	−0.401
TGACTA	0.020%	NA	no	2	−0.011
TGACTC	0.014%	0.281	no	2	0.808
TGACTG	0.025%	0.319	no	2	0.017
TGAGAA	0.042%	0.338	no	2	−0.485
TGAGAC	0.023%	0.379	no	2	0.426
TGAGAG	0.039%	NA	no	2	0.032
TGAGCA	0.032%	NA	no	2	0.825
TGAGCC	0.013%	NA	no	2	−0.385
TGAGCG	0.028%	0.298	no	2	−0.504
TGAGGA	0.045%	0.459	no	2	−0.578
TGAGGC	0.026%	NA	no	2	−0.340
TGAGGG	0.036%	−0.255	no	2	−0.259
TGATAT	0.020%	NA	no	2	0.376
TGATCT	0.014%	0.250	no	2	−0.824
TGATGT	0.023%	0.187	no	2	−0.087
TGATTA	0.025%	−0.400	no	2	−1.266
TGATTC	0.015%	NA	no	2	0.431
TGATTG	0.023%	NA	no	2	−0.434
TGCATT	0.015%	−0.326	no	2	0.675
TGCCTT	0.012%	−0.306	no	2	−0.259
TGCGAT	0.021%	NA	no	2	−0.172
TGCGCT	0.014%	NA	no	2	0.218
TGCGGT	0.025%	NA	no	2	0.378
TGCGTA	0.027%	−0.382	no	2	−0.825
TGCGTC	0.013%	0.277	no	2	0.398
TGCGTG	0.018%	NA	no	2	−0.198
TGCTTT	0.016%	−0.394	no	2	−0.653
TGGATT	0.017%	0.323	no	2	1.166
TGGCTT	0.019%	NA	no	2	0.058
TGGGAT	0.029%	NA	no	2	−0.353
TGGGCT	0.017%	−0.259	no	2	0.128
TGGGGT	0.023%	−0.511	no	2	−0.953
TGGGTA	0.039%	−0.617	no	2	−0.059
TGGGTC	0.013%	−0.279	no	2	0.302
TGGGTG	0.024%	−0.379	no	2	0.271
TGGTTT	0.020%	−0.337	no	2	0.517
TGTATT	0.019%	−0.319	no	2	0.378
TGTCTT	0.017%	NA	no	2	−0.008
TGTGAT	0.027%	0.111	no	2	0.512
TGTGCT	0.018%	−0.251	no	2	0.576
TGTGGT	0.020%	NA	no	2	0.449
TGTGTA	0.021%	−0.320	no	2	0.571
TGTGTC	0.016%	−0.091	no	2	−0.114
TGTGTG	0.018%	−0.073	no	2	−0.106
TGTTTT	0.017%	−0.323	no	2	−1.622
TTAATT	0.021%	−0.507	yes	2	−5.963
TTACTT	0.010%	NA	no	2	−1.858
TTAGAT	0.029%	−0.578	yes	2	−6.001
TTAGCT	0.011%	−0.539	yes	2	−6.151
TTAGGT	0.020%	−0.783	yes	2	−5.014
TTAGTA	0.022%	−0.852	yes	2	−7.070
TTAGTC	0.013%	−0.539	yes	2	−3.757
TTAGTG	0.018%	−0.572	yes	2	−4.719
TTATTT	0.018%	−0.387	no	2	−4.650
TTCGTT	0.010%	0.263	no	2	0.414
TTGGTT	0.016%	−0.279	no	2	−2.771
TTTGTT	0.014%	−0.219	no	2	−4.474
AAAATT	0.041%	−0.420	no	3	−3.370
AAACTT	0.036%	NA	no	3	−3.803
AAAGAT	0.060%	NA	no	3	−2.175
AAAGCT	0.045%	NA	no	3	−1.456
AAAGGT	0.067%	NA	no	3	−3.660
AAAGTA	0.068%	NA	no	3	−3.718
AAAGTC	0.045%	NA	no	3	−3.758
AAAGTG	0.066%	NA	no	3	−0.446
AAATTT	0.032%	−0.321	no	3	−5.043
AACGTT	0.027%	0.344	no	3	−1.254
AAGGTT	0.039%	NA	no	3	−3.706
AATGTT	0.032%	NA	no	3	−3.322
ACAATT	0.039%	NA	no	3	−2.812
ACACTT	0.024%	NA	no	3	−0.816
ACAGAT	0.043%	0.254	no	3	−1.121
ACAGCT	0.032%	NA	no	3	−1.664
ACAGGT	0.047%	−0.315	no	3	−3.492
ACAGTA	0.045%	NA	no	3	−3.203
ACAGTC	0.029%	NA	no	3	−2.148
ACAGTG	0.044%	−0.161	no	3	−1.459
ACATTT	0.033%	NA	no	3	−3.087
ACCGTT	0.017%	NA	no	3	−0.727
ACGGTT	0.033%	NA	no	3	−1.170
ACTGTT	0.023%	NA	no	3	−2.396
AGAAAT	0.069%	NA	no	3	−5.660
AGAACT	0.037%	0.370	no	3	−6.371
AGAAGT	0.057%	0.423	no	3	−5.238
AGAATA	0.052%	NA	no	3	−6.123
AGAATC	0.036%	0.368	no	3	−7.624
AGAATG	0.032%	0.157	no	3	−3.970
AGACAT	0.048%	NA	no	3	−2.164
AGACCT	0.024%	0.540	no	3	−0.409
AGACGT	0.032%	0.542	no	3	−0.938
AGACTA	0.037%	NA	no	3	−3.628
AGACTC	0.030%	NA	no	3	−2.106
AGACTG	0.027%	0.372	no	3	−0.327
AGAGAA	0.078%	0.392	no	3	−3.001
AGAGAC	0.048%	0.535	no	3	−1.922
AGAGAG	0.062%	NA	no	3	−0.588
AGAGCA	0.049%	NA	no	3	−2.611
AGAGCC	0.034%	NA	no	3	−1.864
AGAGCG	0.046%	NA	no	3	−0.458
AGAGGA	0.072%	0.526	no	3	−2.083
AGAGGC	0.053%	NA	no	3	−2.144
AGAGGG	0.067%	−0.155	no	3	−1.469
AGATAT	0.044%	NA	no	3	−3.245
AGATCT	0.026%	0.293	no	3	−4.228
AGATGT	0.032%	NA	no	3	−2.907
AGATTA	0.048%	NA	no	3	−3.769
AGATTC	0.034%	NA	no	3	−3.977
AGATTG	0.039%	NA	no	3	−1.023
AGCATT	0.030%	NA	no	3	−0.977
AGCCTT	0.020%	−0.300	no	3	−0.676
AGCGAT	0.034%	NA	no	3	0.558
AGCGGT	0.034%	NA	no	3	−0.746
AGCGTA	0.039%	NA	no	3	0.056
AGCGTC	0.024%	0.515	no	3	0.682
AGCGTG	0.031%	NA	no	3	−0.212
AGCTTT	0.016%	−0.353	no	3	0.785
AGGATT	0.044%	NA	no	3	−4.617
AGGCTT	0.027%	NA	no	3	−3.483
AGGGAT	0.059%	NA	no	3	−4.510
AGGGCT	0.038%	NA	no	3	−4.903
AGGGGT	0.059%	−0.340	no	3	−5.948
AGGGTA	0.063%	−0.535	no	3	−8.531
AGGGTC	0.040%	NA	no	3	−8.002
AGGGTG	0.054%	−0.480	no	3	−1.698
AGGTTT	0.033%	−0.434	no	3	−4.722
AGTATT	0.038%	−0.387	no	3	−1.655
AGTCTT	0.024%	NA	no	3	−1.285
AGTGAT	0.043%	NA	no	3	−0.797
AGTGCT	0.028%	−0.116	no	3	−1.139
AGTGGT	0.037%	NA	no	3	−0.459
AGTGTA	0.049%	−0.354	no	3	−1.193
AGTGTC	0.030%	NA	no	3	−1.323
AGTGTG	0.039%	−0.255	no	3	−0.577
AGTTTT	0.022%	−0.106	no	3	−1.689
ATAATT	0.042%	−0.326	yes	3	−4.629
ATACTT	0.029%	−0.253	no	3	−3.405
ATAGAT	0.041%	NA	yes	3	−7.247
ATAGCT	0.021%	−0.266	yes	3	−3.911
ATAGGT	0.031%	−0.528	yes	3	−6.841
ATAGTA	0.038%	−0.504	yes	3	−8.063
ATAGTC	0.023%	NA	yes	3	−8.443
ATAGTG	0.041%	−0.337	yes	3	−4.360
ATATTT	0.031%	−0.534	no	3	−3.525
ATCGTT	0.022%	NA	no	3	0.820
ATGGTT	0.032%	−0.289	no	3	−5.190
ATTGTT	0.030%	NA	no	3	−3.539
CAAATT	0.021%	−0.223	no	3	−1.563
CAACTT	0.017%	NA	no	3	0.004
CAAGAT	0.035%	0.638	no	3	0.017
CAAGCT	0.018%	0.212	no	3	−2.428
CAAGGT	0.026%	NA	no	3	−2.327
CAAGTA	0.028%	NA	no	3	−2.177
CAAGTC	0.016%	0.334	no	3	−1.227
CAAGTG	0.025%	NA	no	3	−0.641
CAATTT	0.014%	NA	no	3	−3.535
CACGTT	0.015%	NA	no	3	−1.326
CAGGTT	0.023%	−0.433	no	3	−3.256
CATGTT	0.016%	NA	no	3	−1.058
CCAATT	0.010%	−0.476	no	3	−2.859
CCACTT	0.013%	−0.386	no	3	−2.052
CCAGAT	0.024%	NA	no	3	0.033
CCAGCT	0.016%	−0.365	no	3	0.244
CCAGGT	0.017%	−0.325	no	3	−0.936
CCAGTA	0.018%	−0.671	no	3	−1.440
CCAGTC	0.012%	−0.219	no	3	−0.429
CCAGTG	0.015%	−0.143	no	3	−1.218
CCATTT	0.009%	−0.590	no	3	−0.899
CCCGTT	0.007%	NA	no	3	−0.463
CCGGTT	0.011%	NA	no	3	0.340
CCTGTT	0.009%	NA	no	3	1.394
CGAAAT	0.026%	NA	no	3	−0.612
CGAACT	0.016%	0.321	no	3	−0.873
CGAAGT	0.020%	0.353	no	3	0.893
CGAATA	0.027%	NA	no	3	−0.691
CGAATC	0.015%	0.352	no	3	0.276
CGAATG	0.027%	0.207	no	3	−1.068
CGACAT	0.020%	0.286	no	3	−0.265
CGACCT	0.009%	0.288	no	3	−0.156
CGACGT	0.017%	0.644	no	3	1.045
CGACTA	0.012%	NA	no	3	−1.372
CGACTC	0.010%	NA	no	3	2.608
CGACTG	0.014%	0.515	no	3	−0.431
CGAGAA	0.025%	NA	no	3	1.080
CGAGAC	0.013%	NA	no	3	1.099
CGAGAG	0.020%	0.390	no	3	−1.104
CGAGCA	0.019%	NA	no	3	0.394
CGAGCC	0.009%	0.281	no	3	−0.259
CGAGCG	0.015%	0.531	no	3	−0.071
CGAGGA	0.021%	0.471	no	3	0.149
CGAGGC	0.016%	0.427	no	3	0.046
CGAGGG	0.026%	0.233	no	3	0.945
CGATAT	0.016%	NA	no	3	−1.021
CGATCT	0.008%	NA	no	3	−1.982
CGATGT	0.015%	NA	no	3	0.447
CGATTA	0.013%	−0.393	no	3	0.253
CGATTC	0.010%	NA	no	3	3.144
CGATTG	0.013%	0.149	no	3	1.897
CGCATT	0.012%	NA	no	3	−0.884
CGCCTT	0.007%	NA	no	3	0.871
CGCGAT	0.015%	0.491	no	3	−0.672
CGCGCT	0.006%	0.393	no	3	3.124
CGCGGT	0.011%	0.296	no	3	0.299
CGCGTA	0.014%	NA	no	3	−1.456
CGCGTC	0.009%	0.675	no	3	1.729
CGCGTG	0.008%	0.357	no	3	1.836
CGCTTT	0.009%	NA	no	3	0.506
CGGATT	0.016%	0.372	no	3	−0.897
CGGCTT	0.007%	NA	no	3	0.312
CGGGAT	0.026%	0.420	no	3	0.223
CGGGCT	0.015%	NA	no	3	0.553
CGGGGT	0.018%	NA	no	3	−1.640
CGGGTA	0.025%	NA	no	3	0.462
CGGGTC	0.014%	NA	no	3	0.464
CGGGTG	0.013%	NA	no	3	−0.247
CGGTTT	0.014%	NA	no	3	−1.467
CGTATT	0.009%	NA	no	3	1.250
CGTCTT	0.010%	NA	no	3	−2.684
CGTGAT	0.015%	0.311	no	3	−1.066
CGTGGT	0.009%	0.292	no	3	−1.389
CGTGTC	0.010%	0.418	no	3	−0.261
CGTGTG	0.013%	NA	no	3	−0.237
CGTTTT	0.007%	NA	no	3	1.457
CTAATT	0.011%	−0.682	yes	3	−5.037
CTACTT	0.006%	NA	no	3	−0.406
CTAGCT	0.008%	−0.441	yes	3	−8.166
CTAGGT	0.010%	−0.665	yes	3	−2.775
CTAGTA	0.011%	−0.925	yes	3	−5.226
CTAGTC	0.008%	−0.378	yes	3	−5.593
CTAGTG	0.010%	−0.387	yes	3	−6.779
CTCGTT	0.005%	NA	no	3	0.338
CTGGTT	0.010%	NA	no	3	−0.543
CTTGTT	0.011%	−0.302	no	3	−2.109
GAAATT	0.041%	NA	no	3	−2.356
GAACTT	0.029%	0.297	no	3	−2.602
GAAGAT	0.051%	0.992	no	3	0.259
GAAGCT	0.034%	0.476	no	3	−0.995
GAAGGT	0.044%	NA	no	3	−0.347
GAAGTA	0.057%	NA	no	3	−1.588
GAAGTC	0.034%	0.614	no	3	−0.335
GAAGTG	0.044%	0.247	no	3	−0.013
GAATTT	0.036%	NA	no	3	−2.861
GACGTT	0.021%	0.592	no	3	0.041
GAGGTT	0.032%	−0.250	no	3	−3.208
GATGTT	0.025%	0.289	no	3	−1.072
GCAATT	0.020%	NA	no	3	−2.914
GCACTT	0.020%	−0.392	no	3	−0.899
GCAGAT	0.035%	NA	no	3	−3.309
GCAGCT	0.023%	−0.113	no	3	−1.761
GCAGGT	0.032%	−0.475	no	3	−3.457
GCAGTA	0.036%	−0.297	no	3	−0.890
GCAGTC	0.019%	NA	no	3	−2.739
GCAGTG	0.039%	NA	no	3	−1.098
GCATTT	0.017%	−0.179	no	3	−0.876
GCCGTT	0.019%	NA	no	3	−0.043
GCGGTT	0.019%	NA	no	3	−2.216
GCTGTT	0.017%	NA	no	3	0.130
GGAAAT	0.066%	0.176	no	3	−0.475
GGAACT	0.046%	0.428	no	3	0.155
GGAAGT	0.057%	0.249	no	3	0.112
GGAATA	0.066%	NA	no	3	−1.106
GGAATC	0.043%	0.485	no	3	0.551
GGAATG	0.062%	0.208	no	3	−1.925
GGACAT	0.042%	0.452	no	3	0.202
GGACCT	0.029%	0.675	no	3	−0.141
GGACGT	0.034%	0.642	no	3	0.326
GGACTA	0.040%	0.212	no	3	0.117
GGACTC	0.021%	0.357	no	3	0.563
GGACTG	0.038%	0.479	no	3	−0.061
GGAGAA	0.075%	0.346	no	3	0.683
GGAGAC	0.041%	0.555	no	3	0.194
GGAGAG	0.057%	NA	no	3	−0.267
GGAGCA	0.056%	0.193	no	3	−0.902
GGAGCC	0.026%	0.507	no	3	0.546
GGAGCG	0.039%	0.339	no	3	0.798
GGAGGA	0.060%	0.409	no	3	0.328
GGAGGC	0.033%	0.361	no	3	0.855
GGAGGG	0.058%	−0.143	no	3	−0.684
GGATAT	0.041%	NA	no	3	−0.148
GGATCT	0.032%	NA	no	3	0.188
GGATGT	0.040%	0.229	no	3	−0.189
GGATTA	0.048%	NA	no	3	−0.693
GGATTC	0.030%	0.464	no	3	0.476
GGATTG	0.036%	0.244	no	3	0.652
GGCATT	0.022%	−0.082	no	3	−0.580
GGCCTT	0.013%	NA	no	3	−2.576
GGCGAT	0.023%	0.316	no	3	−0.263
GGCGCT	0.014%	0.188	no	3	1.147
GGCGGT	0.025%	NA	no	3	1.035
GGCGTA	0.027%	NA	no	3	−0.527
GGCGTC	0.019%	0.613	no	3	0.207
GGCGTG	0.018%	0.188	no	3	−0.668
GGCTTT	0.013%	−0.234	no	3	−1.419
GGGATT	0.033%	NA	no	3	0.234
GGGCTT	0.021%	−0.350	no	3	−0.716
GGGGAT	0.049%	−0.238	no	3	−0.226
GGGGCT	0.032%	−0.400	no	3	−0.763
GGGGGT	0.040%	−0.654	no	3	−1.990
GGGGTA	0.050%	−0.594	no	3	−0.603
GGGGTC	0.027%	−0.349	no	3	−1.000
GGGGTG	0.038%	−0.457	no	3	0.388
GGGTTT	0.028%	−0.581	no	3	−1.389
GGTATT	0.025%	−0.474	no	3	−0.435
GGTCTT	0.016%	−0.179	no	3	−0.127
GGTGAT	0.035%	NA	no	3	0.495
GGTGCT	0.019%	−0.189	no	3	1.239
GGTGGT	0.026%	−0.454	no	3	0.208
GGTGTA	0.035%	−0.244	no	3	0.050
GGTGTC	0.021%	NA	no	3	0.167
GGTGTG	0.031%	−0.217	no	3	−0.378
GGTTTT	0.022%	−0.371	no	3	0.528
GTAATT	0.024%	−0.589	yes	3	−2.628
GTACTT	0.020%	−0.338	no	3	−3.345
GTAGAT	0.042%	−0.455	yes	3	−6.967
GTAGCT	0.021%	−0.471	yes	3	−6.518
GTAGGT	0.033%	−0.709	yes	3	−6.858
GTAGTA	0.034%	−0.666	yes	3	−5.616
GTAGTC	0.019%	−0.348	yes	3	−6.261
GTAGTG	0.026%	−0.390	yes	3	−3.622
GTATTT	0.026%	−0.477	no	3	−5.037
GTCGTT	0.017%	NA	no	3	−0.515
GTGGTT	0.020%	−0.158	no	3	−1.517
GTTGTT	0.012%	NA	no	3	−2.903
TAAAAT	0.038%	−0.616	no	3	−5.006
TAAACT	0.028%	−0.351	no	3	−3.662
TAAAGT	0.043%	−0.299	no	3	−4.139
TAAATA	0.030%	−0.601	no	3	−3.979
TAAATC	0.022%	−0.298	no	3	−7.739
TAAATG	0.031%	−0.486	no	3	−1.724
TAACAT	0.035%	NA	no	3	−5.569
TAACCT	0.016%	NA	no	3	−4.175
TAACGT	0.027%	NA	no	3	−2.501
TAACTA	0.025%	−0.440	no	3	−4.034
TAACTC	0.017%	NA	no	3	−3.670
TAACTG	0.022%	−0.235	no	3	−0.752
TAAGAA	0.055%	NA	no	3	−3.674
TAAGAC	0.028%	NA	no	3	−4.744
TAAGAG	0.038%	−0.362	no	3	−1.026
TAAGCA	0.037%	−0.402	no	3	−5.206
TAAGCC	0.018%	−0.286	no	3	−4.348
TAAGCG	0.030%	NA	no	3	−1.758
TAAGGA	0.036%	NA	no	3	−5.836
TAAGGC	0.023%	−0.372	no	3	−5.147
TAAGGG	0.045%	−0.466	no	3	−4.923
TAATAT	0.022%	−0.539	no	3	−4.854
TAATCT	0.017%	NA	no	3	−6.017
TAATGT	0.022%	−0.340	no	3	−5.765
TAATTA	0.031%	−0.642	no	3	−5.341
TAATTC	0.020%	−0.483	no	3	−7.396
TAATTG	0.023%	−0.563	no	3	−1.442
TACATT	0.017%	−0.302	no	3	−2.043
TACCTT	0.007%	NA	no	3	−2.904
TACGAT	0.018%	NA	no	3	0.187
TACGCT	0.011%	NA	no	3	−1.509
TACGGT	0.018%	NA	no	3	−1.481
TACGTA	0.020%	NA	no	3	−0.495
TACGTC	0.013%	0.501	no	3	3.451
TACGTG	0.014%	NA	no	3	0.538
TACTTT	0.010%	−0.357	no	3	−3.068
TAGATT	0.019%	−0.550	no	3	−6.172
TAGCTT	0.013%	−0.691	no	3	−6.108
TAGGAT	0.025%	−0.343	no	3	−4.815
TAGGCT	0.014%	−0.609	no	3	−8.651
TAGGGT	0.028%	−0.822	no	3	−8.320
TAGGTA	0.031%	−0.997	no	3	−8.642
TAGGTC	0.010%	−0.723	no	3	−7.192
TAGGTG	0.028%	−0.594	no	3	−4.297
TAGTTT	0.015%	−0.678	no	3	−6.430
TATATT	0.029%	−0.716	no	3	−5.131
TATCTT	0.011%	−0.287	no	3	−6.037
TATGAT	0.028%	NA	no	3	−3.092
TATGCT	0.015%	−0.210	no	3	−3.754
TATGGT	0.025%	−0.271	no	3	−3.190
TATGTA	0.028%	−0.546	no	3	−3.796
TATGTC	0.024%	NA	no	3	−4.029
TATGTG	0.025%	−0.253	no	3	−2.263
TATTTT	0.019%	−0.564	no	3	−6.436
TCAAAT	0.029%	NA	no	3	−2.787
TCAACT	0.016%	0.275	no	3	−0.972
TCAAGT	0.031%	NA	no	3	−0.725
TCAATA	0.027%	NA	no	3	−1.793
TCAATC	0.018%	NA	no	3	−4.515
TCAATG	0.023%	NA	no	3	−0.014
TCACAT	0.021%	NA	no	3	−2.039
TCACCT	0.012%	0.270	no	3	−1.313
TCACGT	0.014%	NA	no	3	−0.998
TCACTA	0.018%	NA	no	3	−0.889
TCACTC	0.014%	NA	no	3	−1.772
TCACTG	0.016%	NA	no	3	−0.806
TCAGAA	0.047%	NA	no	3	−4.515
TCAGAC	0.021%	NA	no	3	−2.038
TCAGAG	0.035%	NA	no	3	−0.865
TCAGCA	0.025%	NA	no	3	−3.365
TCAGCC	0.012%	−0.241	no	3	−2.827
TCAGCG	0.022%	0.343	no	3	0.375
TCAGGA	0.034%	NA	no	3	−0.819
TCAGGC	0.016%	NA	no	3	−3.842
TCAGGG	0.033%	−0.370	no	3	−3.648
TCATAT	0.017%	NA	no	3	−2.724
TCATCT	0.014%	0.329	no	3	−0.379
TCATGT	0.021%	NA	no	3	−1.760
TCATTA	0.025%	NA	no	3	−4.234
TCATTC	0.017%	NA	no	3	−2.387
TCATTG	0.016%	NA	no	3	−0.997
TCCATT	0.009%	−0.265	no	3	−2.492
TCCCTT	0.009%	−0.278	no	3	−0.816
TCCGAT	0.011%	NA	no	3	−1.785
TCCGCT	0.010%	NA	no	3	−0.905
TCCGGT	0.010%	NA	no	3	0.209
TCCGTA	0.012%	NA	no	3	0.018
TCCGTC	0.008%	0.514	no	3	−0.799
TCCGTG	0.008%	0.274	no	3	0.624
TCGATT	0.014%	NA	no	3	−2.198
TCGCTT	0.010%	NA	no	3	−5.211
TCGGAT	0.022%	0.495	no	3	−0.641
TCGGCT	0.016%	0.287	no	3	−1.098
TCGGGT	0.019%	NA	no	3	−0.018
TCGGTA	0.020%	NA	no	3	−1.295
TCGGTC	0.012%	0.427	no	3	−0.464
TCGGTG	0.020%	NA	no	3	−0.376
TCGTTT	0.010%	NA	no	3	−0.219
TCTCTT	0.010%	NA	no	3	−3.415
TCTGAT	0.015%	NA	no	3	−1.266
TCTGCT	0.011%	0.232	no	3	−1.122
TCTGGT	0.014%	NA	no	3	−2.332
TCTGTA	0.016%	NA	no	3	−1.150
TCTGTC	0.015%	NA	no	3	−3.655
TCTGTG	0.015%	NA	no	3	−1.585
TCTTTT	0.015%	−0.284	no	3	−7.775
TGAAAA	0.045%	NA	no	3	−0.600
TGAAAC	0.028%	0.263	no	3	−0.135
TGAAAG	0.049%	NA	no	3	−0.400
TGAACA	0.036%	0.267	no	3	−0.244
TGAACC	0.022%	0.252	no	3	−1.184
TGAACG	0.036%	0.515	no	3	0.040
TGAAGA	0.045%	0.943	no	3	0.059
TGAAGC	0.029%	0.521	no	3	−0.184
TGAAGG	0.050%	0.166	no	3	−0.633
TGACAA	0.037%	0.229	no	3	−0.700
TGACAC	0.018%	NA	no	3	−0.663
TGACAG	0.035%	NA	no	3	−0.803
TGACCA	0.023%	0.293	no	3	−1.279
TGACCC	0.013%	NA	no	3	0.342
TGACCG	0.018%	0.547	no	3	1.260
TGACGA	0.025%	0.717	no	3	−0.063
TGACGC	0.015%	0.539	no	3	−0.065
TGACGG	0.032%	0.511	no	3	−0.330
TGATAA	0.034%	−0.373	no	3	−1.068
TGATAC	0.021%	NA	no	3	0.083
TGATAG	0.039%	−0.446	no	3	−0.368
TGATCA	0.024%	NA	no	3	−0.254
TGATCC	0.010%	0.172	no	3	−0.561
TGATCG	0.021%	0.536	no	3	−0.187
TGATGA	0.024%	0.451	no	3	0.825
TGATGC	0.019%	0.140	no	3	−0.150
TGATGG	0.033%	0.215	no	3	−0.654
TGCAAT	0.026%	−0.466	no	3	−0.898
TGCACT	0.016%	−0.272	no	3	0.361
TGCAGT	0.020%	−0.227	no	3	−1.736
TGCATA	0.022%	−0.622	no	3	0.019
TGCATC	0.016%	NA	no	3	−0.201
TGCATG	0.019%	NA	no	3	1.544
TGCCAT	0.018%	−0.287	no	3	0.349
TGCCCT	0.010%	−0.267	no	3	−0.272
TGCCGT	0.013%	NA	no	3	−1.273
TGCCTA	0.011%	−0.641	no	3	−0.768
TGCCTC	0.012%	NA	no	3	−0.002
TGCCTG	0.010%	0.154	no	3	0.076
TGCGAA	0.031%	NA	no	3	−0.027
TGCGAC	0.021%	0.357	no	3	0.251
TGCGAG	0.022%	NA	no	3	−0.411
TGCGCA	0.018%	NA	no	3	−0.683
TGCGCC	0.015%	0.309	no	3	0.544
TGCGCG	0.017%	0.311	no	3	0.159
TGCGGA	0.029%	0.458	no	3	0.733
TGCGGC	0.020%	NA	no	3	−0.896
TGCGGG	0.024%	0.298	no	3	0.135
TGCTAT	0.015%	−0.323	no	3	0.629
TGCTCT	0.014%	−0.181	no	3	−0.038
TGCTGT	0.018%	NA	no	3	0.114
TGCTTA	0.019%	−0.584	no	3	−0.135
TGCTTC	0.010%	NA	no	3	0.307
TGCTTG	0.013%	−0.181	no	3	−1.193
TGGAAT	0.039%	0.326	no	3	0.467
TGGACT	0.017%	0.449	no	3	1.333
TGGAGT	0.030%	0.275	no	3	−0.605
TGGATA	0.034%	0.123	no	3	−0.884
TGGATC	0.014%	0.359	no	3	1.283
TGGATG	0.034%	0.414	no	3	0.515
TGGCAT	0.029%	NA	no	3	0.327
TGGCCT	0.013%	NA	no	3	−0.865
TGGCGT	0.018%	0.321	no	3	0.781
TGGCTA	0.019%	−0.156	no	3	−0.691
TGGCTC	0.009%	NA	no	3	−1.112
TGGCTG	0.022%	0.169	no	3	−0.952
TGGGAA	0.044%	NA	no	3	−0.213
TGGGAC	0.025%	0.286	no	3	−0.590
TGGGAG	0.032%	0.077	no	3	−0.855
TGGGCA	0.029%	−0.105	no	3	0.600
TGGGCC	0.014%	NA	no	3	−0.785
TGGGCG	0.018%	NA	no	3	0.933
TGGGGA	0.037%	−0.113	no	3	0.433
TGGGGC	0.021%	−0.149	no	3	−0.473
TGGGGG	0.032%	−0.413	no	3	−0.787
TGGTAT	0.023%	−0.363	no	3	−0.380
TGGTCT	0.016%	NA	no	3	−0.378
TGGTGT	0.023%	NA	no	3	−0.162
TGGTTA	0.021%	−0.457	no	3	−0.466
TGGTTC	0.013%	NA	no	3	0.216
TGGTTG	0.022%	−0.211	no	3	−1.223
TGTAAT	0.029%	−0.389	no	3	−0.246
TGTACT	0.014%	NA	no	3	−1.112
TGTAGT	0.024%	−0.492	no	3	0.273
TGTATA	0.034%	−0.526	no	3	−0.677
TGTATC	0.018%	NA	no	3	0.045
TGTATG	0.030%	−0.152	no	3	0.022
TGTCAT	0.015%	NA	no	3	0.044
TGTCCT	0.011%	NA	no	3	1.450
TGTCGT	0.013%	0.280	no	3	−0.371
TGTCTA	0.012%	−0.259	no	3	−0.468
TGTCTC	0.015%	NA	no	3	0.228
TGTCTG	0.017%	NA	no	3	−0.289
TGTGAA	0.036%	0.381	no	3	−0.270
TGTGAC	0.019%	0.329	no	3	−0.279
TGTGAG	0.028%	0.171	no	3	0.107
TGTGCA	0.021%	−0.247	no	3	−0.470
TGTGCG	0.019%	−0.081	no	3	−0.277
TGTGGA	0.021%	0.595	no	3	−1.476
TGTGGC	0.019%	0.063	no	3	−0.805
TGTGGG	0.030%	−0.060	no	3	−0.614
TGTTAT	0.023%	−0.263	no	3	−0.909
TGTTCT	0.011%	NA	no	3	0.257
TGTTGT	0.018%	NA	no	3	0.259
TGTTTA	0.021%	−0.532	no	3	0.716
TGTTTC	0.012%	NA	no	3	−0.515
TGTTTG	0.015%	−0.161	no	3	−0.273
TTAAAT	0.028%	−0.558	yes	3	−5.460
TTAACT	0.025%	−0.216	yes	3	−3.918
TTAAGT	0.028%	−0.496	yes	3	−6.742
TTAATA	0.023%	−0.424	yes	3	−6.554
TTAATC	0.025%	NA	yes	3	−8.686
TTAATG	0.029%	−0.404	yes	3	−4.133
TTACAT	0.020%	NA	no	3	−3.758
TTACCT	0.010%	0.221	no	3	−1.043
TTACGT	0.010%	NA	no	3	−0.727
TTACTA	0.013%	NA	no	3	−2.319
TTACTC	0.016%	NA	no	3	−5.081
TTACTG	0.017%	NA	no	3	−0.218
TTAGAA	0.034%	−0.513	yes	3	−8.530
TTAGAC	0.016%	−0.392	yes	3	−6.524
TTAGAG	0.029%	−0.545	yes	3	−4.639
TTAGCA	0.023%	−0.523	yes	3	−7.346
TTAGCC	0.009%	−0.575	yes	3	−6.467
TTAGCG	0.021%	−0.326	yes	3	−5.679
TTAGGA	0.025%	−0.627	yes	3	−5.762
TTAGGC	0.011%	−0.712	yes	3	−5.624
TTAGGG	0.027%	−0.827	yes	3	−7.215
TTATAT	0.021%	−0.461	no	3	−2.689
TTATCT	0.009%	NA	no	3	−3.800
TTATGT	0.018%	−0.272	no	3	−4.521
TTATTA	0.022%	−0.478	no	3	−4.891
TTATTC	0.016%	NA	no	3	−5.148
TTATTG	0.023%	−0.343	no	3	−0.759
TTCATT	0.014%	NA	no	3	−1.816
TTCGAT	0.016%	0.344	no	3	0.678
TTCGCT	0.011%	0.308	no	3	−1.573
TTCGGT	0.014%	NA	no	3	0.331
TTCGTA	0.013%	NA	no	3	−1.039
TTCGTC	0.010%	0.789	no	3	−0.765
TTCGTG	0.012%	0.334	no	3	−0.550
TTCTTT	0.010%	−0.207	no	3	−3.591
TTGATT	0.017%	NA	yes	3	−2.576
TTGCTT	0.009%	NA	no	3	−2.608
TTGGAT	0.027%	0.261	no	3	−0.211
TTGGCT	0.015%	NA	no	3	−0.851
TTGGGT	0.025%	−0.453	no	3	−5.418
TTGGTA	0.023%	−0.369	no	3	−3.830
TTGGTC	0.011%	NA	no	3	−2.246
TTGGTG	0.015%	−0.173	no	3	0.241
TTGTTT	0.016%	−0.196	no	3	−2.805
TTTATT	0.013%	−0.491	no	3	−4.281
TTTCTT	0.011%	−0.214	no	3	−6.475
TTTGAT	0.015%	NA	no	3	−3.027
TTTGCT	0.011%	−0.219	no	3	−1.789
TTTGGT	0.021%	−0.323	no	3	−4.850
TTTGTA	0.018%	−0.291	no	3	−3.348
TTTGTC	0.015%	NA	no	3	−2.165
TTTGTG	0.019%	−0.222	no	3	−0.369
TTTTTT	0.011%	−0.381	no	3	−4.402
AAAAAT	0.088%	−0.343	no	4	−3.516
AAAACT	0.051%	NA	no	4	−2.594
AAAAGT	0.074%	NA	no	4	−3.958
AAAATA	0.054%	NA	no	4	−3.325
AAAATC	0.048%	NA	no	4	−4.381
AAAATG	0.069%	−0.216	no	4	−1.247
AAACAT	0.056%	NA	no	4	−3.092
AAACCT	0.029%	0.310	no	4	−2.728
AAACGT	0.047%	0.294	no	4	−1.513
AAACTA	0.047%	NA	no	4	−3.020
AAACTC	0.034%	NA	no	4	−2.516
AAACTG	0.046%	NA	no	4	−0.916
AAAGAA	0.103%	0.355	no	4	−1.592
AAAGAC	0.054%	0.390	no	4	−1.483
AAAGAG	0.080%	NA	no	4	0.060
AAAGCA	0.066%	NA	no	4	−3.346
AAAGCC	0.036%	NA	no	4	−0.725
AAAGCG	0.049%	0.309	no	4	−0.741
AAAGGA	0.084%	0.418	no	4	−1.714
AAAGGC	0.054%	NA	no	4	−0.894
AAAGGG	0.082%	−0.263	no	4	−2.890
AAATAT	0.036%	−0.413	no	4	−4.350
AAATCT	0.032%	NA	no	4	−3.355
AAATGT	0.048%	NA	no	4	−3.537
AAATTA	0.045%	NA	no	4	−5.631
AAATTC	0.024%	NA	no	4	−5.160
AAATTG	0.045%	−0.228	no	4	−1.111
AACATT	0.036%	NA	no	4	−1.558
AACCTT	0.022%	NA	no	4	−2.150
AACGAT	0.042%	0.386	no	4	0.296
AACGCT	0.026%	0.361	no	4	−0.309
AACGGT	0.039%	NA	no	4	−0.159
AACGTA	0.040%	NA	no	4	−0.906
AACGTC	0.032%	0.684	no	4	−0.611
AACGTG	0.037%	0.265	no	4	−0.098
AACTTT	0.022%	NA	no	4	−1.717
AAGATT	0.044%	0.448	no	4	−0.536
AAGCTT	0.031%	NA	no	4	−1.965
AAGGAT	0.053%	0.567	no	4	−0.813
AAGGCT	0.029%	NA	no	4	−3.067
AAGGGT	0.049%	NA	no	4	−7.986
AAGGTA	0.057%	NA	no	4	−5.594
AAGGTC	0.026%	NA	no	4	−2.533
AAGGTG	0.054%	−0.162	no	4	−0.085
AAGTTT	0.032%	NA	no	4	−2.517
AATATT	0.036%	−0.315	no	4	−4.895
AATCTT	0.021%	NA	no	4	−3.098
AATGAT	0.046%	NA	no	4	−2.293
AATGCT	0.024%	NA	no	4	−1.456
AATGGT	0.034%	−0.241	no	4	−2.975
AATGTA	0.037%	NA	no	4	−4.311
AATGTC	0.019%	NA	no	4	−5.201
AATGTG	0.036%	NA	no	4	−0.676
AATTTT	0.018%	NA	no	4	−5.472
ACAAAT	0.060%	NA	no	4	−2.498
ACAACT	0.034%	NA	no	4	−1.343
ACAAGT	0.043%	NA	no	4	−1.335
ACAATA	0.051%	NA	no	4	−2.992
ACAATC	0.035%	NA	no	4	−2.196
ACAATG	0.044%	NA	no	4	−0.777
ACACAT	0.039%	NA	no	4	−2.724
ACACCT	0.027%	0.299	no	4	−0.778
ACACGT	0.032%	NA	no	4	−1.097
ACACTA	0.025%	−0.421	no	4	−1.741
ACACTC	0.024%	0.299	no	4	−2.868
ACACTG	0.034%	0.160	no	4	−0.472
ACAGAA	0.065%	NA	no	4	−1.632
ACAGAC	0.040%	0.393	no	4	−0.419
ACAGAG	0.050%	NA	no	4	−0.040
ACAGCA	0.040%	NA	no	4	−0.830
ACAGCC	0.029%	NA	no	4	−0.837
ACAGCG	0.039%	0.332	no	4	0.693
ACAGGA	0.059%	NA	no	4	−0.977
ACAGGC	0.039%	NA	no	4	−2.302
ACAGGG	0.053%	−0.305	no	4	−3.989
ACATAT	0.038%	−0.375	no	4	−3.134
ACATCT	0.026%	0.265	no	4	−0.972
ACATGT	0.028%	NA	no	4	−1.629
ACATTA	0.038%	NA	no	4	−3.513
ACATTC	0.024%	NA	no	4	−3.662
ACATTG	0.029%	NA	no	4	−1.130
ACCATT	0.020%	NA	no	4	−0.629
ACCCTT	0.011%	−0.246	no	4	0.422
ACCGAT	0.022%	NA	no	4	−0.135
ACCGCT	0.016%	NA	no	4	−1.150
ACCGGT	0.021%	NA	no	4	−0.674
ACCGTA	0.024%	NA	no	4	−0.726
ACCGTC	0.016%	NA	no	4	−0.451
ACCGTG	0.023%	0.196	no	4	0.271
ACCTTT	0.014%	NA	no	4	−2.132
ACGATT	0.031%	NA	no	4	−1.041
ACGCTT	0.020%	NA	no	4	−1.397
ACGGAT	0.042%	0.588	no	4	0.238
ACGGCT	0.019%	NA	no	4	−0.593
ACGGGT	0.038%	NA	no	4	−0.240
ACGGTA	0.043%	NA	no	4	−1.121
ACGGTC	0.028%	0.541	no	4	−0.430
ACGGTG	0.022%	NA	no	4	−0.185
ACGTTT	0.025%	NA	no	4	−1.488
ACTATT	0.023%	−0.296	no	4	−5.484
ACTCTT	0.017%	NA	no	4	−3.181
ACTGAT	0.025%	0.268	no	4	−1.437
ACTGCT	0.020%	0.258	no	4	−2.009
ACTGGT	0.025%	NA	no	4	−2.074
ACTGTA	0.032%	NA	no	4	−2.334
ACTGTC	0.018%	0.305	no	4	−1.646
ACTGTG	0.030%	NA	no	4	−0.724
ACTTTT	0.018%	−0.426	no	4	−6.098
AGAAAA	0.098%	NA	no	4	−5.216
AGAAAC	0.053%	0.315	no	4	−5.765
AGAAAG	0.090%	NA	no	4	−1.012
AGAACA	0.065%	NA	no	4	−5.222
AGAACC	0.041%	NA	no	4	−4.164
AGAACG	0.045%	0.447	no	4	−2.160
AGAAGA	0.067%	1.034	no	4	−3.548
AGAAGC	0.040%	0.505	no	4	−4.989
AGAAGG	0.072%	NA	no	4	−3.572
AGACAA	0.067%	NA	no	4	−2.772
AGACAC	0.034%	NA	no	4	−1.755
AGACAG	0.048%	NA	no	4	−1.138
AGACCA	0.035%	NA	no	4	−1.356
AGACCC	0.020%	NA	no	4	−2.073
AGACCG	0.032%	0.453	no	4	0.067
AGACGA	0.037%	0.601	no	4	−1.130
AGACGC	0.032%	0.526	no	4	−0.923
AGACGG	0.045%	0.309	no	4	−0.496
AGATAA	0.054%	NA	no	4	−3.790
AGATAC	0.035%	NA	no	4	−2.669
AGATAG	0.049%	−0.630	no	4	−2.242
AGATCA	0.040%	NA	no	4	−3.429
AGATCC	0.023%	0.192	no	4	−2.733
AGATCG	0.034%	0.331	no	4	−0.645
AGATGA	0.041%	NA	no	4	−4.270
AGATGC	0.037%	0.194	no	4	−1.573
AGATGG	0.042%	NA	no	4	−0.703
AGCAAT	0.044%	NA	no	4	−0.655
AGCACT	0.026%	NA	no	4	0.946
AGCAGT	0.037%	NA	no	4	−0.523
AGCATA	0.048%	NA	no	4	−1.072
AGCATC	0.034%	NA	no	4	−0.139
AGCATG	0.033%	NA	no	4	0.113
AGCCAT	0.024%	NA	no	4	0.515
AGCCCT	0.015%	NA	no	4	0.461
AGCCGT	0.021%	NA	no	4	−0.579
AGCCTA	0.022%	−0.677	no	4	0.105
AGCCTC	0.019%	NA	no	4	−0.799
AGCCTG	0.020%	NA	no	4	0.459
AGCGAA	0.042%	NA	no	4	−0.480
AGCGAC	0.033%	0.462	no	4	−0.260
AGCGAG	0.039%	NA	no	4	0.894
AGCGCA	0.032%	NA	no	4	−0.334
AGCGCC	0.016%	NA	no	4	0.702
AGCGCG	0.037%	0.413	no	4	−0.188
AGCGGA	0.047%	0.440	no	4	0.284
AGCGGC	0.031%	NA	no	4	0.786
AGCGGG	0.038%	0.181	no	4	−0.245
AGCTAT	0.029%	−0.338	no	4	−0.014
AGCTCT	0.017%	NA	no	4	−0.602
AGCTGT	0.022%	NA	no	4	−0.424
AGCTTA	0.024%	−0.405	no	4	−1.115
AGCTTC	0.018%	NA	no	4	0.101
AGCTTG	0.026%	−0.330	no	4	−0.058
AGGAAT	0.067%	NA	no	4	−2.991
AGGACT	0.035%	0.392	no	4	−3.459
AGGAGT	0.039%	NA	no	4	−1.870
AGGATA	0.062%	NA	no	4	−7.902
AGGATC	0.035%	0.379	no	4	−4.373
AGGATG	0.052%	0.187	no	4	−5.328
AGGCAT	0.044%	NA	no	4	−1.828
AGGCCT	0.023%	NA	no	4	−0.382
AGGCGT	0.034%	NA	no	4	−0.397
AGGCTA	0.049%	−0.404	no	4	−3.324
AGGCTC	0.030%	NA	no	4	−1.454
AGGCTG	0.030%	NA	no	4	0.107
AGGGAA	0.077%	NA	no	4	−5.306
AGGGAC	0.043%	NA	no	4	−6.309
AGGGAG	0.059%	−0.373	no	4	−2.135
AGGGCA	0.057%	−0.267	no	4	−6.921
AGGGCC	0.032%	−0.371	no	4	−4.173
AGGGCG	0.043%	−0.249	no	4	−1.496
AGGGGA	0.080%	−0.275	no	4	−3.922
AGGGGC	0.038%	−0.225	no	4	−5.261
AGGGGG	0.065%	−0.464	no	4	−3.875
AGGTAT	0.042%	−0.401	no	4	−4.452
AGGTCT	0.029%	NA	no	4	−4.472
AGGTGT	0.037%	−0.286	no	4	−2.006
AGGTTA	0.047%	−0.602	no	4	−3.642
AGGTTC	0.028%	NA	no	4	−4.493
AGGTTG	0.041%	−0.476	no	4	−1.140
AGTAAT	0.049%	−0.394	no	4	−1.198
AGTACT	0.034%	NA	no	4	−0.954
AGTAGT	0.035%	−0.373	no	4	−3.359
AGTATA	0.055%	−0.425	no	4	−1.458
AGTATC	0.031%	NA	no	4	−1.182
AGTATG	0.041%	−0.251	no	4	−0.309
AGTCAT	0.039%	NA	no	4	−1.017
AGTCCT	0.017%	NA	no	4	−0.880
AGTCGT	0.024%	0.257	no	4	0.145
AGTCTA	0.035%	−0.467	no	4	−0.810
AGTCTC	0.020%	NA	no	4	1.087
AGTCTG	0.025%	NA	no	4	−0.660
AGTGAA	0.053%	NA	no	4	−0.256
AGTGAC	0.025%	0.323	no	4	−0.127
AGTGAG	0.045%	−0.374	no	4	−0.022
AGTGCA	0.043%	−0.169	no	4	−0.841
AGTGCC	0.017%	NA	no	4	0.818
AGTGCG	0.038%	NA	no	4	0.561
AGTGGA	0.060%	NA	no	4	−0.600
AGTGGC	0.030%	NA	no	4	0.516
AGTGGG	0.047%	−0.246	no	4	−0.432
AGTTAT	0.033%	−0.091	no	4	−1.026
AGTTCT	0.018%	0.158	no	4	−0.424
AGTTGT	0.024%	NA	no	4	0.336
AGTTTA	0.040%	−0.216	no	4	−2.315
AGTTTC	0.022%	0.254	no	4	−1.797
AGTTTG	0.026%	NA	no	4	0.155
ATAAAT	0.052%	−0.446	yes	4	−6.581
ATAACT	0.029%	−0.316	yes	4	−3.848
ATAAGT	0.052%	NA	yes	4	−7.114
ATAATA	0.054%	−0.503	yes	4	−5.864
ATAATC	0.032%	NA	yes	4	−5.629
ATAATG	0.049%	−0.335	yes	4	−4.245
ATACAT	0.033%	NA	no	4	−3.054
ATACCT	0.018%	NA	no	4	−1.447
ATACGT	0.032%	NA	no	4	−0.910
ATACTA	0.037%	NA	no	4	−5.216
ATACTC	0.020%	NA	no	4	−1.292
ATACTG	0.033%	NA	no	4	−0.298
ATAGAA	0.053%	NA	yes	4	−8.271
ATAGAC	0.031%	NA	yes	4	−8.524
ATAGAG	0.049%	−0.265	yes	4	−3.258
ATAGCA	0.040%	−0.383	yes	4	−7.504
ATAGCC	0.018%	−0.279	yes	4	−5.802
ATAGCG	0.040%	NA	yes	4	−4.412
ATAGGA	0.047%	NA	yes	4	−6.413
ATAGGC	0.021%	NA	yes	4	−5.793
ATAGGG	0.044%	−0.698	yes	4	−8.103
ATATAT	0.034%	−0.374	no	4	−3.377
ATATCT	0.027%	NA	no	4	−3.044
ATATGT	0.034%	NA	no	4	−3.775
ATATTA	0.045%	−0.360	no	4	−3.798
ATATTC	0.024%	NA	no	4	−5.407
ATATTG	0.041%	−0.328	no	4	−1.972
ATCATT	0.028%	NA	no	4	0.861
ATCCTT	0.019%	NA	no	4	0.264
ATCGAT	0.034%	0.312	no	4	−0.464
ATCGCT	0.021%	NA	no	4	0.221
ATCGGT	0.032%	NA	no	4	0.601
ATCGTA	0.032%	NA	no	4	0.152
ATCGTC	0.020%	0.652	no	4	−0.624
ATCGTG	0.032%	0.214	no	4	−0.159
ATCTTT	0.018%	NA	no	4	−0.768
ATGATT	0.040%	NA	yes	4	−4.782
ATGCTT	0.025%	NA	no	4	−2.106
ATGGAT	0.042%	0.299	no	4	−0.973
ATGGCT	0.027%	NA	no	4	−0.920
ATGGGT	0.042%	−0.494	no	4	−4.650
ATGGTA	0.043%	−0.484	no	4	−3.345
ATGGTC	0.035%	NA	no	4	−3.585
ATGGTG	0.038%	−0.148	no	4	−0.300
ATGTTT	0.030%	NA	no	4	−3.404
ATTATT	0.025%	−0.286	no	4	−4.186
ATTCTT	0.018%	−0.283	no	4	−3.950
ATTGAT	0.039%	NA	no	4	−2.368
ATTGCT	0.018%	−0.110	no	4	−3.597
ATTGGT	0.033%	NA	no	4	−1.753
ATTGTA	0.037%	−0.367	no	4	−3.645
ATTGTC	0.019%	NA	no	4	−4.034
ATTGTG	0.030%	−0.157	no	4	−0.111
ATTTTT	0.020%	−0.599	no	4	−6.439
CAAAAT	0.035%	−0.265	no	4	−1.870
CAAACT	0.026%	NA	no	4	−1.080
CAAAGT	0.031%	NA	no	4	−1.396
CAAATA	0.026%	−0.390	no	4	−2.759
CAAATC	0.020%	NA	no	4	−1.123
CAAATG	0.032%	NA	no	4	0.408
CAACAT	0.027%	0.196	no	4	−1.648
CAACCT	0.013%	0.189	no	4	−0.682
CAACGT	0.017%	0.414	no	4	−0.326
CAACTA	0.018%	NA	no	4	−0.869
CAACTC	0.012%	0.284	no	4	−1.207
CAACTG	0.022%	0.270	no	4	1.389
CAAGAA	0.041%	0.922	no	4	−0.995
CAAGAC	0.020%	0.705	no	4	−0.250
CAAGAG	0.031%	0.411	no	4	0.703
CAAGCA	0.026%	NA	no	4	−1.164
CAAGCC	0.016%	NA	no	4	−0.329
CAAGCG	0.021%	0.353	no	4	1.237
CAAGGA	0.038%	0.620	no	4	−0.511
CAAGGC	0.021%	0.209	no	4	−1.030
CAAGGG	0.034%	NA	no	4	−0.664
CAATAT	0.020%	−0.268	no	4	−2.422
CAATCT	0.014%	NA	no	4	1.219
CAATGT	0.019%	NA	no	4	−0.901
CAATTA	0.024%	−0.483	no	4	−1.901
CAATTG	0.015%	NA	no	4	0.420
CACATT	0.014%	NA	no	4	3.185
CACCTT	0.009%	−0.286	no	4	−1.341
CACGAT	0.023%	NA	no	4	−0.362
CACGCT	0.010%	NA	no	4	−0.082
CACGGT	0.019%	NA	no	4	−0.840
CACGTA	0.021%	−0.253	no	4	−0.043
CACGTC	0.010%	0.302	no	4	0.755
CACGTG	0.014%	NA	no	4	0.005
CACTTT	0.013%	−0.551	no	4	0.538
CAGATT	0.024%	NA	no	4	−2.078
CAGCTT	0.017%	−0.379	no	4	−0.713
CAGGAT	0.029%	NA	no	4	−0.515
CAGGCT	0.020%	−0.217	no	4	−3.261
CAGGGT	0.031%	−0.438	no	4	−5.036
CAGGTA	0.030%	−0.604	no	4	−4.058
CAGGTC	0.016%	−0.283	no	4	−3.073
CAGGTG	0.028%	−0.405	no	4	−1.431
CAGTTT	0.017%	−0.231	no	4	−1.048
CATATT	0.013%	−0.298	no	4	−3.047
CATCTT	0.009%	−0.255	no	4	−0.392
CATGAT	0.021%	NA	no	4	−1.500
CATGCT	0.015%	NA	no	4	1.442
CATGGT	0.018%	NA	no	4	−1.403
CATGTA	0.021%	−0.228	no	4	−1.773
CATGTC	0.011%	NA	no	4	−3.145
CATGTG	0.017%	NA	no	4	1.066
CATTTT	0.013%	−0.488	no	4	−5.269
CCAAAT	0.018%	−0.435	no	4	−2.137
CCAACT	0.017%	NA	no	4	−1.663
CCAAGT	0.020%	NA	no	4	−1.211
CCAATA	0.020%	−0.660	no	4	−2.066
CCAATC	0.016%	−0.206	no	4	−2.827
CCAATG	0.019%	NA	no	4	−0.077
CCACAT	0.018%	NA	no	4	−1.707
CCACCT	0.013%	−0.247	no	4	−1.130
CCACGT	0.013%	0.193	no	4	−0.068
CCACTA	0.015%	−0.448	no	4	−1.820
CCACTC	0.011%	NA	no	4	−1.964
CCACTG	0.013%	NA	no	4	−0.784
CCAGAA	0.031%	NA	no	4	−1.968
CCAGAC	0.018%	−0.293	no	4	0.897
CCAGAG	0.023%	NA	no	4	−0.694
CCAGCA	0.020%	−0.894	no	4	0.249
CCAGCC	0.010%	−0.361	no	4	−0.074
CCAGCG	0.016%	NA	no	4	0.296
CCAGGA	0.023%	NA	no	4	−0.226
CCAGGC	0.014%	NA	no	4	0.094
CCAGGG	0.023%	−0.081	no	4	−0.517
CCATAT	0.014%	−0.454	no	4	−4.374
CCATCT	0.011%	NA	no	4	−1.363
CCATGT	0.011%	NA	no	4	−0.157
CCATTA	0.017%	−0.770	no	4	−1.677
CCATTC	0.009%	NA	no	4	−0.177
CCATTG	0.011%	NA	no	4	−1.246
CCCATT	0.007%	−0.354	no	4	−1.982
CCCCTT	0.005%	−0.393	no	4	−3.756
CCCGAT	0.013%	NA	no	4	−0.672
CCCGCT	0.012%	0.270	no	4	−1.878
CCCGGT	0.007%	0.115	no	4	−0.464
CCCGTA	0.010%	−0.151	no	4	0.711
CCCGTC	0.006%	0.533	no	4	−0.470
CCCGTG	0.009%	0.323	no	4	2.700
CCCTTT	0.007%	−0.551	no	4	−1.067
CCGATT	0.016%	NA	no	4	0.036
CCGCTT	0.007%	NA	no	4	1.319
CCGGAT	0.018%	0.357	no	4	−0.103
CCGGCT	0.012%	NA	no	4	0.454
CCGGGT	0.015%	NA	no	4	−0.140
CCGGTA	0.015%	NA	no	4	−1.501
CCGGTC	0.008%	0.221	no	4	0.045
CCGGTG	0.012%	0.134	no	4	−0.901
CCGTTT	0.008%	NA	no	4	−0.313
CCTATT	0.006%	−0.520	no	4	−0.699
CCTCTT	0.007%	−0.371	no	4	−1.879
CCTGAT	0.015%	NA	no	4	−0.602
CCTGCT	0.013%	0.416	no	4	−0.136
CCTGGT	0.011%	NA	no	4	0.693
CCTGTA	0.007%	−0.279	no	4	−0.935
CCTGTC	0.011%	NA	no	4	−0.597
CCTGTG	0.012%	0.149	no	4	−0.177
CCTTTT	0.005%	−0.777	no	4	−3.580
CGAAAA	0.031%	NA	no	4	−0.325
CGAAAC	0.019%	0.331	no	4	2.952
CGAAAG	0.030%	NA	no	4	−0.310
CGAACA	0.028%	NA	no	4	−0.344
CGAACC	0.018%	0.405	no	4	−0.518
CGAACG	0.028%	0.614	no	4	0.655
CGAAGA	0.026%	0.750	no	4	−0.446
CGAAGC	0.016%	0.640	no	4	−1.093
CGAAGG	0.042%	0.274	no	4	−0.938
CGACAA	0.018%	NA	no	4	1.181
CGACAC	0.020%	NA	no	4	−0.391
CGACAG	0.021%	NA	no	4	0.596
CGACCA	0.018%	0.529	no	4	0.429
CGACCC	0.011%	0.219	no	4	−2.014
CGACCG	0.016%	0.578	no	4	0.463
CGACGA	0.015%	0.805	no	4	−0.028
CGACGC	0.011%	0.740	no	4	−0.538
CGACGG	0.013%	0.825	no	4	−0.848
CGATAA	0.020%	NA	no	4	0.330
CGATAC	0.018%	NA	no	4	−1.775
CGATAG	0.018%	−0.372	no	4	0.689
CGATCA	0.018%	NA	no	4	−0.304
CGATCC	0.009%	0.447	no	4	0.031
CGATCG	0.014%	0.517	no	4	0.830
CGATGA	0.017%	0.512	no	4	−0.894
CGATGC	0.014%	0.283	no	4	−0.550
CGATGG	0.018%	0.422	no	4	0.218
CGCAAT	0.007%	NA	no	4	−0.769
CGCACT	0.014%	NA	no	4	−0.908
CGCAGT	0.013%	NA	no	4	0.009
CGCATA	0.013%	NA	no	4	0.526
CGCATC	0.012%	0.410	no	4	−0.491
CGCATG	0.015%	NA	no	4	−0.422
CGCCAT	0.013%	NA	no	4	0.443
CGCCCT	0.007%	0.299	no	4	0.095
CGCCGT	0.010%	0.479	no	4	−1.365
CGCCTA	0.012%	NA	no	4	0.513
CGCCTC	0.005%	NA	no	4	−1.467
CGCCTG	0.007%	0.445	no	4	−1.598
CGCGAA	0.021%	0.542	no	4	0.075
CGCGAC	0.009%	0.747	no	4	2.830
CGCGAG	0.014%	0.503	no	4	−0.598
CGCGCA	0.016%	0.350	no	4	−1.400
CGCGCC	0.006%	0.622	no	4	0.969
CGCGCG	0.013%	0.725	no	4	−0.929
CGCGGA	0.017%	0.784	no	4	0.208
CGCGGC	0.009%	NA	no	4	1.168
CGCGGG	0.016%	0.640	no	4	0.489
CGCTAT	0.010%	NA	no	4	0.803
CGCTCT	0.009%	NA	no	4	−0.502
CGCTGT	0.008%	0.248	no	4	0.701
CGCTTA	0.013%	NA	no	4	−0.500
CGCTTC	0.006%	0.397	no	4	−0.684
CGCTTG	0.010%	NA	no	4	0.365
CGGAAT	0.022%	0.487	no	4	0.037
CGGACT	0.018%	0.444	no	4	1.943
CGGAGT	0.022%	0.430	no	4	−0.112
CGGATA	0.024%	NA	no	4	0.093
CGGATC	0.010%	0.439	no	4	−0.003
CGGATG	0.023%	0.573	no	4	0.003
CGGCAT	0.016%	NA	no	4	−0.147
CGGCCT	0.007%	NA	no	4	0.935
CGGCGT	0.013%	0.570	no	4	−1.007
CGGCTA	0.014%	NA	no	4	0.336
CGGCTC	0.012%	NA	no	4	1.684
CGGCTG	0.013%	0.249	no	4	−0.227
CGGGAA	0.029%	0.392	no	4	0.280
CGGGAC	0.020%	0.486	no	4	−0.590
CGGGAG	0.029%	0.496	no	4	−0.051
CGGGCA	0.025%	0.387	no	4	−0.248
CGGGCC	0.011%	0.242	no	4	0.006
CGGGCG	0.021%	0.335	no	4	−1.589
CGGGGA	0.032%	0.320	no	4	−0.896
CGGGGC	0.015%	0.291	no	4	0.341
CGGGGG	0.026%	0.102	no	4	0.833
CGGTAT	0.015%	NA	no	4	1.168
CGGTCT	0.009%	0.261	no	4	0.198
CGGTTA	0.017%	NA	no	4	−0.187
CGGTTC	0.007%	0.358	no	4	−1.306
CGGTTG	0.013%	NA	no	4	−0.579
CGTAAT	0.017%	NA	no	4	0.298
CGTACT	0.009%	NA	no	4	−1.035
CGTAGT	0.011%	NA	no	4	1.330
CGTATA	0.017%	NA	no	4	−0.144
CGTATC	0.011%	NA	no	4	0.476
CGTATG	0.011%	NA	no	4	1.448
CGTCAT	0.008%	0.367	no	4	0.543
CGTCCT	0.005%	0.477	no	4	−0.983
CGTCGT	0.006%	0.685	no	4	0.655
CGTCTA	0.010%	NA	no	4	−0.340
CGTCTC	0.006%	0.353	no	4	−1.327
CGTCTG	0.012%	0.574	no	4	0.286
CGTGAA	0.022%	0.406	no	4	−1.418
CGTGAC	0.011%	0.488	no	4	2.362
CGTGAG	0.015%	NA	no	4	−0.829
CGTGCA	0.018%	0.186	no	4	0.425
CGTGCC	0.011%	0.437	no	4	0.169
CGTGCG	0.015%	0.538	no	4	−0.486
CGTGGA	0.014%	0.693	no	4	−1.367
CGTGGC	0.010%	0.436	no	4	4.292
CGTGGG	0.018%	0.366	no	4	−0.381
CGTTAT	0.012%	NA	no	4	−2.301
CGTTGT	0.007%	NA	no	4	1.554
CGTTTA	0.010%	NA	no	4	−0.902
CGTTTC	0.008%	NA	no	4	−1.057
CGTTTG	0.007%	NA	no	4	−0.386
CTAAAT	0.016%	−0.493	yes	4	−4.226
CTAACT	0.011%	−0.371	yes	4	−3.767
CTAAGT	0.015%	−0.515	yes	4	−5.028
CTAATA	0.012%	−0.705	yes	4	−5.432
CTAATC	0.010%	NA	yes	4	−3.637
CTAATG	0.015%	−0.382	yes	4	−2.958
CTACAT	0.007%	NA	no	4	1.999
CTACCT	0.004%	NA	no	4	−0.421
CTACGT	0.010%	0.348	no	4	0.615
CTACTA	0.008%	NA	no	4	−1.895
CTACTC	0.009%	NA	no	4	−0.966
CTACTG	0.005%	0.182	no	4	−0.861
CTAGAA	0.015%	NA	yes	4	−5.617
CTAGAC	0.011%	−0.350	yes	4	−4.679
CTAGAG	0.011%	−0.315	yes	4	−3.370
CTAGCA	0.012%	−0.848	yes	4	−6.462
CTAGCC	0.005%	−0.415	yes	4	−2.428
CTAGCG	0.008%	NA	yes	4	−3.916
CTAGGA	0.015%	NA	yes	4	−3.358
CTAGGC	0.010%	−0.457	yes	4	−5.406
CTAGGG	0.015%	−0.600	yes	4	−7.655
CTATAT	0.008%	−0.636	no	4	−2.937
CTATCT	0.005%	NA	no	4	−4.321
CTATGT	0.009%	−0.307	no	4	−2.655
CTATTA	0.010%	−0.634	no	4	−2.367
CTATTC	0.009%	−0.292	no	4	−3.078
CTATTG	0.009%	−0.357	no	4	−1.023
CTCCTT	0.006%	NA	no	4	0.943
CTCGAT	0.008%	0.285	no	4	0.153
CTCGCT	0.008%	NA	no	4	1.062
CTCGTA	0.013%	NA	no	4	−1.622
CTCGTC	0.008%	0.486	no	4	0.350
CTCGTG	0.009%	0.250	no	4	−0.417
CTCTTT	0.007%	−0.352	no	4	0.105
CTGATT	0.011%	NA	yes	4	−4.011
CTGCTT	0.010%	NA	no	4	1.029
CTGGAT	0.013%	0.434	no	4	1.593
CTGGCT	0.010%	NA	no	4	1.129
CTGGGT	0.011%	NA	no	4	0.004
CTGGTA	0.014%	−0.388	no	4	0.522
CTGGTC	0.007%	NA	no	4	1.659
CTGGTG	0.009%	NA	no	4	−0.709
CTGTTT	0.008%	NA	no	4	−0.953
CTTCTT	0.006%	−0.279	no	4	−1.950
CTTGAT	0.012%	NA	no	4	1.198
CTTGGT	0.010%	NA	no	4	−0.218
CTTGTA	0.010%	−0.365	no	4	−2.510
CTTGTC	0.005%	NA	no	4	−2.410
CTTGTG	0.008%	NA	no	4	0.217
CTTTTT	0.006%	−0.780	no	4	−5.717
GAAAAT	0.049%	NA	no	4	−1.270
GAAACT	0.048%	0.383	no	4	−1.006
GAAAGT	0.053%	NA	no	4	−2.007
GAAATA	0.036%	NA	no	4	−1.518
GAAATC	0.033%	0.426	no	4	−2.935
GAAATG	0.053%	NA	no	4	−0.642
GAACAT	0.044%	0.361	no	4	−1.180
GAACCT	0.024%	0.566	no	4	−0.178
GAACGT	0.038%	0.508	no	4	−0.118
GAACTA	0.038%	NA	no	4	−0.585
GAACTC	0.021%	0.348	no	4	−0.898
GAACTG	0.038%	0.477	no	4	0.027
GAAGAA	0.068%	0.845	no	4	−0.634
GAAGAC	0.038%	0.964	no	4	−0.261
GAAGAG	0.073%	0.490	no	4	−0.123
GAAGCA	0.058%	0.357	no	4	−0.302
GAAGCC	0.032%	0.598	no	4	−0.252
GAAGCG	0.045%	0.556	no	4	−0.199
GAAGGA	0.066%	0.565	no	4	0.084
GAAGGC	0.046%	0.553	no	4	−0.739
GAAGGG	0.069%	NA	no	4	−1.285
GAATAT	0.033%	NA	no	4	−2.215
GAATCT	0.027%	0.354	no	4	−1.541
GAATGT	0.045%	NA	no	4	−1.735
GAATTA	0.044%	NA	no	4	−1.820
GAATTC	0.020%	0.350	no	4	−2.628
GAATTG	0.039%	0.142	no	4	−0.239
GACATT	0.026%	0.245	no	4	−1.062
GACCTT	0.017%	0.438	no	4	−2.298
GACGAT	0.036%	0.760	no	4	−0.060
GACGCT	0.022%	0.544	no	4	−0.296
GACGGT	0.024%	0.405	no	4	1.144
GACGTA	0.030%	0.372	no	4	−0.589
GACGTC	0.019%	0.984	no	4	1.098
GACGTG	0.035%	0.487	no	4	0.160
GACTTT	0.018%	NA	no	4	−0.754
GAGATT	0.031%	0.237	no	4	−1.633
GAGCTT	0.023%	NA	no	4	0.449
GAGGAT	0.049%	0.531	no	4	−0.571
GAGGCT	0.031%	NA	no	4	0.152
GAGGGT	0.032%	−0.340	no	4	−6.092
GAGGTA	0.047%	−0.287	no	4	−3.978
GAGGTC	0.022%	0.262	no	4	−1.787
GAGGTG	0.041%	NA	no	4	−0.762
GAGTTT	0.031%	NA	no	4	−1.716
GATATT	0.031%	NA	no	4	−2.944
GATCTT	0.015%	NA	no	4	−0.802
GATGAT	0.035%	0.456	no	4	−1.235
GATGCT	0.013%	0.262	no	4	−0.287
GATGGT	0.026%	NA	no	4	−1.077
GATGTA	0.028%	NA	no	4	−1.822
GATGTC	0.023%	0.521	no	4	−0.002
GATGTG	0.026%	NA	no	4	−0.720
GATTTT	0.023%	NA	no	4	−3.296
GCAAAT	0.035%	NA	no	4	−1.702
GCAACT	0.023%	0.248	no	4	−0.187
GCAAGT	0.036%	0.245	no	4	−0.425
GCAATA	0.032%	−0.178	no	4	−1.745
GCAATC	0.019%	0.247	no	4	−1.903
GCAATG	0.036%	0.107	no	4	−0.278
GCACAT	0.026%	−0.166	no	4	−1.646
GCACCT	0.020%	−0.246	no	4	−0.666
GCACGT	0.027%	NA	no	4	−0.048
GCACTA	0.027%	−0.331	no	4	−2.294
GCACTC	0.018%	−0.183	no	4	−1.563
GCACTG	0.019%	NA	no	4	−0.601
GCAGAA	0.038%	0.343	no	4	−6.925
GCAGAC	0.035%	0.271	no	4	−2.639
GCAGAG	0.036%	NA	no	4	−1.011
GCAGCA	0.039%	0.120	no	4	−0.720
GCAGCC	0.018%	−0.320	no	4	−1.494
GCAGCG	0.030%	0.204	no	4	−1.455
GCAGGA	0.044%	0.120	no	4	−2.136
GCAGGC	0.029%	NA	no	4	−1.642
GCAGGG	0.045%	−0.272	no	4	−3.944
GCATAT	0.025%	NA	no	4	−1.368
GCATCT	0.015%	−0.139	no	4	−0.114
GCATGT	0.026%	NA	no	4	−1.883
GCATTA	0.028%	−0.261	no	4	−2.675
GCATTC	0.017%	NA	no	4	−2.250
GCATTG	0.022%	NA	no	4	−0.636
GCCATT	0.014%	−0.318	no	4	−0.142
GCCCTT	0.011%	−0.247	no	4	4.529
GCCGAT	0.019%	NA	no	4	0.211
GCCGCT	0.011%	NA	no	4	−0.760
GCCGGT	0.019%	NA	no	4	0.710
GCCGTA	0.018%	NA	no	4	−1.313
GCCGTC	0.013%	0.485	no	4	0.306
GCCGTG	0.017%	0.215	no	4	−0.949
GCCTTT	0.012%	−0.405	no	4	0.054
GCGATT	0.020%	NA	no	4	0.051
GCGCTT	0.015%	NA	no	4	−0.932
GCGGAT	0.033%	0.541	no	4	−0.771
GCGGCT	0.022%	NA	no	4	0.004
GCGGGT	0.022%	NA	no	4	−2.285
GCGGTA	0.029%	NA	no	4	−0.965
GCGGTC	0.016%	0.359	no	4	1.092
GCGGTG	0.021%	NA	no	4	0.297
GCGTTT	0.013%	NA	no	4	1.112
GCTATT	0.009%	−0.350	no	4	−0.895
GCTCTT	0.011%	−0.258	no	4	−0.708
GCTGAT	0.018%	NA	no	4	−0.478
GCTGCT	0.011%	0.337	no	4	1.276
GCTGGT	0.017%	NA	no	4	−0.001
GCTGTA	0.021%	NA	no	4	−0.812
GCTGTC	0.012%	0.466	no	4	0.824
GCTGTG	0.022%	NA	no	4	−0.104
GCTTTT	0.019%	−0.329	no	4	−3.786
GGAAAA	0.078%	NA	no	4	−0.519
GGAAAC	0.058%	0.455	no	4	−0.299
GGAAAG	0.073%	NA	no	4	−0.182
GGAACA	0.056%	0.415	no	4	−0.135
GGAACC	0.031%	0.593	no	4	0.121
GGAACG	0.058%	0.522	no	4	0.398
GGAAGA	0.070%	0.651	no	4	0.217
GGAAGC	0.041%	0.486	no	4	0.471
GGAAGG	0.063%	NA	no	4	−0.272
GGACAA	0.065%	0.466	no	4	−0.825
GGACAC	0.039%	0.516	no	4	0.198
GGACAG	0.052%	NA	no	4	−0.415
GGACCA	0.034%	0.364	no	4	−0.509
GGACCC	0.022%	0.372	no	4	0.013
GGACCG	0.029%	0.636	no	4	0.962
GGACGA	0.041%	0.697	no	4	0.739
GGACGC	0.034%	0.761	no	4	−0.271
GGACGG	0.034%	0.396	no	4	0.562
GGATAA	0.063%	NA	no	4	0.416
GGATAC	0.039%	0.426	no	4	0.494
GGATAG	0.052%	−0.376	no	4	−0.358
GGATCA	0.037%	0.194	no	4	0.022
GGATCC	0.020%	0.445	no	4	−0.093
GGATCG	0.031%	0.388	no	4	1.722
GGATGA	0.049%	0.391	no	4	−0.001
GGATGC	0.029%	0.417	no	4	0.427
GGATGG	0.047%	NA	no	4	−0.240
GGCAAT	0.028%	0.112	no	4	−0.483
GGCACT	0.020%	−0.251	no	4	0.601
GGCAGT	0.050%	−0.107	no	4	−0.032
GGCATA	0.027%	NA	no	4	−0.266
GGCATC	0.016%	NA	no	4	0.824
GGCATG	0.020%	0.074	no	4	−0.492
GGCCAT	0.019%	NA	no	4	−0.309
GGCCCT	0.012%	NA	no	4	2.149
GGCCGT	0.015%	NA	no	4	−0.527
GGCCTA	0.016%	−0.260	no	4	0.274
GGCCTC	0.011%	NA	no	4	0.063
GGCCTG	0.018%	0.128	no	4	−0.511
GGCGAA	0.038%	0.405	no	4	0.166
GGCGAC	0.024%	0.608	no	4	0.471
GGCGAG	0.030%	0.169	no	4	0.217
GGCGCA	0.027%	0.299	no	4	1.041
GGCGCC	0.011%	0.480	no	4	0.303
GGCGCG	0.023%	0.455	no	4	−0.923
GGCGGA	0.034%	0.499	no	4	−0.059
GGCGGC	0.021%	0.302	no	4	−1.131
GGCGGG	0.033%	0.148	no	4	0.621
GGCTAT	0.021%	−0.223	no	4	0.232
GGCTCT	0.016%	−0.222	no	4	0.361
GGCTGT	0.021%	0.169	no	4	1.237
GGCTTA	0.021%	−0.295	no	4	0.226
GGCTTC	0.009%	0.251	no	4	−0.796
GGCTTG	0.016%	−0.193	no	4	0.210
GGGAAT	0.063%	NA	no	4	−0.739
GGGACT	0.038%	NA	no	4	0.251
GGGAGT	0.043%	NA	no	4	0.533
GGGATA	0.049%	NA	no	4	−0.751
GGGATC	0.024%	NA	no	4	1.275
GGGATG	0.052%	NA	no	4	−0.042
GGGCAT	0.041%	−0.190	no	4	−0.624
GGGCCT	0.018%	NA	no	4	−0.153
GGGCGT	0.024%	NA	no	4	0.901
GGGCTA	0.033%	−0.444	no	4	0.594
GGGCTC	0.018%	−0.236	no	4	0.395
GGGCTG	0.029%	NA	no	4	0.530
GGGGAA	0.067%	−0.337	no	4	−0.749
GGGGAC	0.034%	NA	no	4	0.050
GGGGAG	0.053%	−0.073	no	4	0.293
GGGGCA	0.048%	−0.080	no	4	−0.674
GGGGCC	0.019%	−0.206	no	4	−1.051
GGGGCG	0.029%	−0.237	no	4	−0.037
GGGGGA	0.059%	−0.232	no	4	−1.399
GGGGGC	0.032%	−0.277	no	4	−0.109
GGGGGG	0.043%	−0.358	no	4	−4.336
GGGTAT	0.048%	−0.508	no	4	−0.700
GGGTCT	0.019%	−0.347	no	4	−0.111
GGGTGT	0.027%	−0.392	no	4	−0.589
GGGTTA	0.031%	−0.737	no	4	−1.798
GGGTTC	0.022%	NA	no	4	−0.140
GGGTTG	0.034%	−0.472	no	4	−0.592
GGTAAT	0.043%	−0.489	no	4	−0.439
GGTACT	0.023%	−0.215	no	4	0.632
GGTAGT	0.035%	−0.612	no	4	−0.599
GGTATA	0.040%	−0.540	no	4	0.227
GGTATC	0.023%	NA	no	4	0.044
GGTATG	0.036%	−0.317	no	4	0.528
GGTCAT	0.032%	NA	no	4	−0.896
GGTCCT	0.016%	NA	no	4	−1.892
GGTCGT	0.020%	NA	no	4	0.208
GGTCTA	0.020%	−0.305	no	4	−1.591
GGTCTC	0.015%	NA	no	4	0.749
GGTCTG	0.027%	NA	no	4	−0.024
GGTGAA	0.050%	NA	no	4	0.240
GGTGAC	0.027%	0.200	no	4	0.088
GGTGAG	0.033%	−0.416	no	4	−0.066
GGTGCA	0.030%	−0.150	no	4	0.432
GGTGCC	0.015%	NA	no	4	−1.141
GGTGCG	0.023%	NA	no	4	−0.078
GGTGGA	0.032%	NA	no	4	0.676
GGTGGC	0.025%	−0.350	no	4	−0.348
GGTGGG	0.033%	−0.359	no	4	0.100
GGTTAT	0.026%	−0.434	no	4	−0.053
GGTTGT	0.019%	−0.427	no	4	−0.566
GGTTTA	0.025%	−0.700	no	4	−1.313
GGTTTC	0.015%	NA	no	4	−0.270
GTAAAT	0.039%	−0.450	yes	4	−5.587
GTAACT	0.028%	−0.326	yes	4	−8.508
GTAAGT	0.036%	−0.569	yes	4	−8.380
GTAATA	0.034%	−0.538	yes	4	−4.998
GTAATC	0.021%	−0.264	yes	4	−4.319
GTAATG	0.041%	−0.313	yes	4	−3.064
GTACAT	0.027%	−0.249	no	4	−2.516
GTACCT	0.014%	NA	no	4	−1.269
GTACGT	0.025%	NA	no	4	−1.743
GTACTA	0.018%	−0.479	no	4	−2.948
GTACTC	0.013%	NA	no	4	−2.897
GTACTG	0.020%	NA	no	4	−1.301
GTAGAA	0.046%	−0.357	yes	4	−7.153
GTAGAC	0.020%	NA	yes	4	−7.542
GTAGAG	0.039%	−0.393	yes	4	−3.410
GTAGCA	0.037%	−0.466	yes	4	−4.915
GTAGCC	0.018%	−0.537	yes	4	−7.972
GTAGCG	0.031%	NA	yes	4	−4.069
GTAGGA	0.033%	−0.351	yes	4	−6.807
GTAGGC	0.022%	−0.566	yes	4	−6.937
GTAGGG	0.035%	−0.733	yes	4	−8.788
GTATAT	0.026%	−0.383	no	4	−3.147
GTATCT	0.013%	−0.249	no	4	−4.117
GTATGT	0.024%	−0.335	no	4	−1.977
GTATTA	0.031%	−0.755	no	4	−3.084
GTATTC	0.018%	NA	no	4	−4.031
GTATTG	0.030%	−0.271	no	4	−0.604
GTCATT	0.014%	NA	no	4	−0.130
GTCCTT	0.008%	NA	no	4	−0.271
GTCGAT	0.018%	NA	no	4	1.936
GTCGCT	0.016%	NA	no	4	−0.815
GTCGGT	0.020%	NA	no	4	−1.066
GTCGTA	0.023%	NA	no	4	−0.555
GTCGTC	0.012%	0.774	no	4	−1.239
GTCGTG	0.022%	0.263	no	4	−0.507
GTCTTT	0.012%	−0.243	no	4	−0.916
GTGATT	0.025%	NA	yes	4	−3.033
GTGCTT	0.016%	−0.416	no	4	−1.320
GTGGAT	0.034%	0.389	no	4	−0.576
GTGGCT	0.024%	NA	no	4	0.805
GTGGGT	0.037%	−0.337	no	4	−2.621
GTGGTA	0.033%	−0.223	no	4	−0.949
GTGGTC	0.022%	NA	no	4	−0.247
GTGGTG	0.029%	NA	no	4	−1.036
GTGTTT	0.025%	−0.267	no	4	−1.785
GTTATT	0.023%	−0.254	no	4	−4.384
GTTCTT	0.011%	NA	no	4	−2.936
GTTGAT	0.031%	NA	no	4	−1.551
GTTGCT	0.013%	NA	no	4	−5.537
GTTGGT	0.019%	−0.158	no	4	−0.195
GTTGTA	0.026%	−0.157	no	4	−2.294
GTTGTC	0.010%	0.267	no	4	−0.361
GTTGTG	0.026%	−0.109	no	4	−1.123
GTTTTT	0.019%	−0.256	no	4	−4.352
TAAAAA	0.052%	−0.365	no	4	−4.607
TAAAAC	0.044%	−0.380	no	4	−5.540
TAAAAG	0.048%	−0.310	no	4	−0.877
TAAACA	0.051%	NA	no	4	−5.134
TAAACC	0.026%	−0.306	no	4	−3.324
TAAACG	0.038%	NA	no	4	−0.381
TAAAGA	0.048%	NA	no	4	−5.819
TAAAGC	0.031%	NA	no	4	−2.365
TAAAGG	0.048%	−0.407	no	4	−2.467
TAACAA	0.044%	NA	no	4	−4.893
TAACAC	0.025%	NA	no	4	−3.223
TAACAG	0.038%	−0.436	no	4	−2.106
TAACCA	0.022%	−0.233	no	4	−3.482
TAACCC	0.018%	−0.442	no	4	−5.544
TAACCG	0.026%	0.286	no	4	−0.202
TAACGA	0.030%	NA	no	4	−2.567
TAACGC	0.024%	NA	no	4	−2.384
TAACGG	0.032%	NA	no	4	−0.389
TAATAA	0.032%	−0.491	no	4	−4.881
TAATAC	0.021%	−0.299	no	4	−4.682
TAATAG	0.031%	−0.647	no	4	−4.229
TAATCA	0.026%	NA	no	4	−4.280
TAATCC	0.010%	−0.266	no	4	−2.751
TAATCG	0.027%	NA	no	4	−1.773
TAATGA	0.029%	NA	no	4	−4.909
TAATGC	0.025%	−0.398	no	4	−4.292
TAATGG	0.026%	−0.300	no	4	−2.506
TACAAT	0.022%	−0.257	no	4	−1.284
TACACT	0.020%	NA	no	4	−1.208
TACAGT	0.022%	−0.265	no	4	−0.749
TACATA	0.018%	NA	no	4	−1.980
TACATC	0.015%	0.314	no	4	−1.724
TACATG	0.014%	−0.190	no	4	1.238
TACCAT	0.014%	NA	no	4	−0.613
TACCGT	0.014%	NA	no	4	0.179
TACCTA	0.007%	NA	no	4	−0.056
TACCTC	0.006%	NA	no	4	−1.598
TACCTG	0.010%	0.337	no	4	−2.466
TACGAA	0.028%	NA	no	4	−0.365
TACGAC	0.016%	0.542	no	4	−0.568
TACGAG	0.021%	NA	no	4	−0.315
TACGCA	0.021%	NA	no	4	0.237
TACGCC	0.010%	0.354	no	4	1.754
TACGCG	0.016%	0.546	no	4	−0.239
TACGGA	0.021%	0.425	no	4	−0.398
TACGGC	0.016%	0.391	no	4	1.082
TACGGG	0.028%	0.230	no	4	−0.753
TACTAT	0.013%	−0.249	no	4	−1.412
TACTCT	0.008%	NA	no	4	−2.017
TACTGT	0.013%	NA	no	4	−1.244
TACTTA	0.012%	−0.475	no	4	−3.824
TACTTC	0.014%	NA	no	4	−1.406
TACTTG	0.008%	−0.255	no	4	−1.427
TAGAAT	0.029%	−0.419	no	4	−4.933
TAGACT	0.016%	NA	no	4	−2.457
TAGAGT	0.027%	−0.406	no	4	−5.672
TAGATA	0.028%	−0.861	no	4	−7.189
TAGATC	0.010%	NA	no	4	−7.528
TAGATG	0.030%	−0.328	no	4	−3.495
TAGCAT	0.021%	−0.499	no	4	−6.178
TAGCCT	0.010%	−0.266	no	4	−5.320
TAGCGT	0.019%	−0.344	no	4	−2.887
TAGCTA	0.016%	−0.812	no	4	−7.930
TAGCTC	0.008%	−0.436	no	4	−5.048
TAGCTG	0.016%	−0.306	no	4	−2.301
TAGGAA	0.034%	−0.600	no	4	−6.755
TAGGAC	0.021%	NA	no	4	−7.387
TAGGAG	0.028%	−0.464	no	4	−3.571
TAGGCA	0.018%	−0.835	no	4	−7.713
TAGGCC	0.011%	−0.517	no	4	−5.906
TAGGCG	0.019%	−0.387	no	4	−3.855
TAGGGA	0.031%	−0.838	no	4	−9.429
TAGGGC	0.021%	−0.635	no	4	−9.433
TAGGGG	0.030%	−0.659	no	4	−6.441
TAGTAT	0.021%	−0.723	no	4	−6.245
TAGTCT	0.013%	−0.369	no	4	−7.485
TAGTGT	0.021%	−0.579	no	4	−5.277
TAGTTA	0.019%	−0.893	no	4	−7.370
TAGTTC	0.013%	−0.509	no	4	−6.180
TAGTTG	0.016%	−0.692	no	4	−5.193
TATAAT	0.033%	−0.595	no	4	−5.470
TATACT	0.019%	NA	no	4	−2.988
TATAGT	0.023%	−0.551	no	4	−5.083
TATATA	0.027%	−0.586	no	4	−5.232
TATATC	0.019%	NA	no	4	−8.641
TATATG	0.021%	−0.443	no	4	−1.371
TATCAT	0.021%	NA	no	4	−6.799
TATCCT	0.008%	NA	no	4	−1.638
TATCGT	0.015%	NA	no	4	−0.464
TATCTA	0.016%	NA	no	4	−2.487
TATCTC	0.013%	NA	no	4	−3.535
TATCTG	0.015%	NA	no	4	−0.043
TATGAA	0.035%	NA	no	4	−3.180
TATGAC	0.019%	NA	no	4	−3.071
TATGAG	0.033%	−0.294	no	4	−0.513
TATGCA	0.027%	−0.299	no	4	−3.824
TATGCC	0.010%	NA	no	4	−2.631
TATGCG	0.022%	NA	no	4	−0.008
TATGGA	0.032%	NA	no	4	−0.571
TATGGC	0.027%	NA	no	4	−2.052
TATGGG	0.017%	−0.217	no	4	−2.241
TATTAT	0.024%	−0.434	no	4	−5.274
TATTCT	0.010%	NA	no	4	−3.611
TATTGT	0.024%	−0.361	no	4	−2.956
TATTTA	0.022%	−0.674	no	4	−7.627
TATTTC	0.011%	−0.407	no	4	−3.981
TATTTG	0.020%	−0.421	no	4	−2.248
TCAAAA	0.040%	NA	no	4	−3.057
TCAAAC	0.027%	NA	no	4	−1.499
TCAAAG	0.041%	NA	no	4	−0.991
TCAACA	0.034%	NA	no	4	−1.340
TCAACC	0.017%	0.222	no	4	−0.613
TCAACG	0.021%	0.643	no	4	−0.347
TCAAGA	0.038%	0.464	no	4	−0.818
TCAAGC	0.027%	0.356	no	4	−1.126
TCAAGG	0.036%	NA	no	4	−1.564
TCACAA	0.028%	NA	no	4	−2.351
TCACAC	0.019%	NA	no	4	−1.523
TCACAG	0.024%	−0.253	no	4	−1.167
TCACCA	0.017%	−0.146	no	4	0.899
TCACCC	0.012%	NA	no	4	0.396
TCACCG	0.011%	0.651	no	4	1.213
TCACGA	0.024%	NA	no	4	−1.241
TCACGC	0.013%	0.449	no	4	−0.583
TCACGG	0.021%	0.253	no	4	−0.521
TCATAA	0.024%	NA	no	4	−2.852
TCATAC	0.019%	NA	no	4	−2.260
TCATAG	0.018%	−0.517	no	4	−1.141
TCATCA	0.022%	NA	no	4	−1.249
TCATCC	0.012%	0.274	no	4	−0.772
TCATCG	0.020%	0.752	no	4	−1.097
TCATGA	0.024%	NA	no	4	−2.227
TCATGC	0.018%	NA	no	4	−0.559
TCATGG	0.023%	NA	no	4	−0.187
TCCAAT	0.016%	NA	no	4	−1.686
TCCACT	0.012%	NA	no	4	−2.259
TCCAGT	0.013%	NA	no	4	−0.435
TCCATA	0.011%	NA	no	4	−1.884
TCCATC	0.013%	NA	no	4	−2.238
TCCATG	0.014%	NA	no	4	−0.464
TCCCCT	0.006%	NA	no	4	−2.834
TCCCGT	0.010%	NA	no	4	−1.561
TCCCTA	0.010%	−0.566	no	4	−1.649
TCCCTC	0.007%	NA	no	4	−1.868
TCCCTG	0.011%	0.247	no	4	−1.229
TCCGAA	0.018%	NA	no	4	−0.603
TCCGAC	0.013%	0.526	no	4	−0.994
TCCGAG	0.014%	0.308	no	4	0.708
TCCGCA	0.017%	NA	no	4	3.924
TCCGCC	0.006%	0.192	no	4	−0.356
TCCGCG	0.014%	0.675	no	4	−0.386
TCCGGA	0.014%	0.636	no	4	0.382
TCCGGC	0.008%	0.480	no	4	0.198
TCCGGG	0.011%	0.514	no	4	−0.296
TCCTAT	0.008%	−0.293	no	4	−1.800
TCCTCT	0.006%	NA	no	4	1.476
TCCTGT	0.008%	NA	no	4	−0.731
TCCTTA	0.008%	−0.527	no	4	−1.399
TCCTTC	0.006%	NA	no	4	−2.387
TCCTTG	0.009%	NA	no	4	−0.389
TCGAAT	0.023%	NA	no	4	−0.659
TCGACT	0.016%	0.542	no	4	−0.567
TCGAGT	0.024%	NA	no	4	−0.308
TCGATA	0.017%	NA	no	4	−1.960
TCGATC	0.014%	0.582	no	4	−1.568
TCGATG	0.023%	0.337	no	4	0.044
TCGCAT	0.016%	NA	no	4	−0.904
TCGCCT	0.009%	0.492	no	4	−2.184
TCGCGT	0.011%	0.436	no	4	−0.065
TCGCTA	0.016%	NA	no	4	−1.448
TCGCTC	0.008%	0.356	no	4	−1.002
TCGCTG	0.013%	0.311	no	4	−1.082
TCGGAA	0.035%	0.447	no	4	−0.690
TCGGAC	0.018%	0.559	no	4	−0.018
TCGGAG	0.021%	0.315	no	4	−0.928
TCGGCA	0.023%	NA	no	4	−0.004
TCGGCC	0.009%	0.441	no	4	−0.727
TCGGCG	0.018%	0.863	no	4	−0.307
TCGGGA	0.025%	0.421	no	4	0.414
TCGGGC	0.008%	0.350	no	4	3.317
TCGGGG	0.024%	0.237	no	4	0.171
TCGTAT	0.011%	NA	no	4	−0.103
TCGTGT	0.015%	0.255	no	4	1.091
TCGTTA	0.018%	NA	no	4	−1.875
TCGTTC	0.010%	0.473	no	4	0.488
TCGTTG	0.017%	0.189	no	4	0.022
TCTAAT	0.016%	−0.402	no	4	−1.638
TCTACT	0.012%	NA	no	4	−1.419
TCTAGT	0.008%	−0.450	no	4	−6.596
TCTATA	0.012%	−0.491	no	4	−5.035
TCTATC	0.008%	NA	no	4	−2.815
TCTATG	0.014%	−0.240	no	4	−0.022
TCTCAT	0.009%	NA	no	4	−1.436
TCTCCT	0.007%	0.362	no	4	−2.722
TCTCGT	0.008%	NA	no	4	2.443
TCTCTA	0.012%	NA	no	4	−2.895
TCTCTC	0.009%	NA	no	4	−1.950
TCTCTG	0.010%	0.164	no	4	−0.454
TCTGAA	0.025%	NA	no	4	−1.857
TCTGAC	0.014%	0.417	no	4	−0.726
TCTGAG	0.019%	NA	no	4	−0.435
TCTGCA	0.013%	0.322	no	4	−6.092
TCTGCC	0.011%	0.248	no	4	−2.157
TCTGCG	0.015%	0.698	no	4	−0.979
TCTGGA	0.021%	NA	no	4	−0.788
TCTGGC	0.014%	NA	no	4	0.062
TCTGGG	0.020%	NA	no	4	−0.821
TCTTAT	0.010%	−0.317	no	4	−4.585
TCTTGT	0.008%	NA	no	4	−3.419
TCTTTA	0.013%	−0.477	no	4	−5.750
TCTTTC	0.011%	NA	no	4	−4.034
TCTTTG	0.016%	−0.218	no	4	−0.563
TGCAAA	0.037%	−0.487	no	4	0.628
TGCAAC	0.021%	NA	no	4	−0.765
TGCAAG	0.033%	NA	no	4	−0.646
TGCACA	0.023%	−0.335	no	4	−0.123
TGCACC	0.012%	NA	no	4	1.585
TGCACG	0.025%	NA	no	4	−0.571
TGCAGA	0.021%	NA	no	4	−2.629
TGCAGC	0.015%	−0.365	no	4	−0.747
TGCAGG	0.020%	−0.190	no	4	−0.828
TGCCAA	0.023%	−0.257	no	4	−0.822
TGCCAC	0.014%	−0.258	no	4	0.707
TGCCAG	0.018%	NA	no	4	−0.233
TGCCCC	0.010%	−0.255	no	4	1.354
TGCCCG	0.013%	NA	no	4	0.875
TGCCGA	0.016%	NA	no	4	−0.401
TGCCGC	0.015%	NA	no	4	−0.379
TGCCGG	0.018%	0.357	no	4	−0.880
TGCTAA	0.030%	−0.319	no	4	0.980
TGCTAC	0.010%	NA	no	4	0.541
TGCTAG	0.021%	−0.680	no	4	−1.668
TGCTCA	0.013%	−0.284	no	4	1.841
TGCTCC	0.007%	NA	no	4	0.367
TGCTCG	0.013%	NA	no	4	−0.775
TGCTGA	0.017%	NA	no	4	−0.005
TGCTGC	0.009%	0.229	no	4	−0.943
TGCTGG	0.017%	−0.210	no	4	1.781
TGGAAA	0.037%	0.333	no	4	−0.668
TGGAAC	0.022%	0.612	no	4	−0.753
TGGAAG	0.036%	0.395	no	4	−0.299
TGGACA	0.029%	0.482	no	4	−0.524
TGGACC	0.014%	0.608	no	4	−1.530
TGGACG	0.026%	0.686	no	4	−0.755
TGGAGA	0.041%	0.427	no	4	−1.040
TGGAGC	0.022%	0.299	no	4	−0.481
TGGAGG	0.034%	0.101	no	4	0.826
TGGCAA	0.029%	0.259	no	4	−0.639
TGGCAC	0.022%	−0.133	no	4	−0.046
TGGCAG	0.032%	NA	no	4	−0.242
TGGCCA	0.018%	NA	no	4	−0.328
TGGCCC	0.012%	NA	no	4	0.218
TGGCCG	0.011%	0.195	no	4	−0.952
TGGCGA	0.023%	0.443	no	4	−0.868
TGGCGC	0.008%	0.422	no	4	−0.003
TGGCGG	0.021%	0.301	no	4	0.063
TGGTAA	0.030%	−0.538	no	4	−0.010
TGGTAC	0.019%	−0.144	no	4	0.413
TGGTAG	0.023%	−0.626	no	4	−0.138
TGGTCA	0.017%	NA	no	4	−0.950
TGGTCC	0.009%	0.136	no	4	−0.215
TGGTCG	0.013%	0.156	no	4	1.450
TGGTGA	0.023%	NA	no	4	−0.493
TGGTGC	0.018%	NA	no	4	−0.289
TGGTGG	0.025%	−0.308	no	4	0.415
TGTAAA	0.043%	−0.304	no	4	−0.358
TGTAAC	0.026%	NA	no	4	−0.018
TGTAAG	0.035%	−0.362	no	4	0.147
TGTACA	0.024%	−0.205	no	4	−0.191
TGTACC	0.013%	NA	no	4	−0.029
TGTACG	0.021%	0.188	no	4	−0.778
TGTAGA	0.037%	−0.303	no	4	−1.079
TGTAGC	0.020%	−0.359	no	4	−0.526
TGTAGG	0.030%	−0.688	no	4	−0.622
TGTCAA	0.027%	NA	no	4	0.482
TGTCAC	0.013%	NA	no	4	−0.717
TGTCAG	0.021%	−0.433	no	4	0.164
TGTCCA	0.015%	NA	no	4	−0.235
TGTCCC	0.007%	NA	no	4	1.386
TGTCCG	0.007%	0.234	no	4	0.057
TGTCGA	0.021%	0.362	no	4	−0.882
TGTCGC	0.014%	0.219	no	4	−0.680
TGTCGG	0.015%	0.312	no	4	−0.819
TGTTAA	0.028%	−0.439	no	4	−0.240
TGTTAC	0.016%	NA	no	4	0.656
TGTTAG	0.017%	−0.758	no	4	−1.458
TGTTCA	0.019%	NA	no	4	0.643
TGTTCG	0.013%	0.424	no	4	1.367
TGTTGA	0.019%	NA	no	4	0.146
TGTTGC	0.012%	NA	no	4	0.101
TGTTGG	0.022%	NA	no	4	0.046
TTAAAA	0.041%	−0.349	yes	4	−6.257
TTAAAC	0.019%	NA	yes	4	−5.625
TTAAAG	0.037%	−0.242	yes	4	−3.276
TTAACA	0.035%	NA	yes	4	−4.812
TTAACC	0.023%	NA	yes	4	−4.758
TTAACG	0.029%	NA	yes	4	−3.931
TTAAGA	0.033%	−0.217	yes	4	−7.483
TTAAGC	0.029%	−0.260	yes	4	−5.977
TTAAGG	0.035%	−0.489	yes	4	−5.448
TTACAA	0.027%	NA	no	4	−4.111
TTACAC	0.023%	NA	no	4	−4.213
TTACAG	0.018%	−0.207	no	4	−2.331
TTACCA	0.014%	NA	no	4	−4.483
TTACCC	0.010%	NA	no	4	−2.309
TTACCG	0.011%	0.416	no	4	−1.287
TTACGA	0.014%	0.307	no	4	−1.468
TTACGC	0.014%	0.331	no	4	−1.441
TTACGG	0.018%	NA	no	4	−1.053
TTATAA	0.029%	−0.441	no	4	−4.000
TTATAC	0.019%	NA	no	4	−5.871
TTATAG	0.026%	−0.594	no	4	−3.787
TTATCA	0.026%	NA	no	4	−3.704
TTATCC	0.008%	NA	no	4	−2.232
TTATCG	0.019%	0.238	no	4	−0.251
TTATGA	0.026%	NA	no	4	−5.339
TTATGC	0.018%	−0.300	no	4	−0.623
TTATGG	0.022%	−0.263	no	4	−0.347
TTCAAT	0.018%	NA	no	4	−2.208
TTCACT	0.010%	NA	no	4	−1.187
TTCAGT	0.019%	−0.197	no	4	−0.135
TTCATA	0.016%	NA	no	4	−2.081
TTCATC	0.015%	0.597	no	4	−0.541
TTCATG	0.016%	NA	no	4	−0.760
TTCCAT	0.008%	NA	no	4	1.476
TTCCGT	0.007%	NA	no	4	−0.918
TTCCTC	0.006%	NA	no	4	−0.978
TTCCTG	0.011%	0.388	no	4	−0.489
TTCGAA	0.022%	0.421	no	4	−0.274
TTCGAC	0.013%	0.749	no	4	1.026
TTCGAG	0.015%	0.397	no	4	0.701
TTCGCA	0.016%	0.460	no	4	−0.065
TTCGCC	0.010%	0.637	no	4	−0.549
TTCGCG	0.013%	0.720	no	4	−0.507
TTCGGA	0.017%	0.487	no	4	−0.120
TTCGGC	0.012%	0.615	no	4	−0.684
TTCGGG	0.022%	0.326	no	4	−0.467
TTCTAT	0.009%	−0.185	no	4	−3.859
TTCTCT	0.010%	NA	no	4	0.032
TTCTGT	0.013%	NA	no	4	−0.825
TTCTTA	0.012%	−0.207	no	4	−4.174
TTCTTC	0.009%	0.446	no	4	−2.850
TTCTTG	0.012%	−0.217	no	4	−0.295
TTGAAT	0.029%	NA	yes	4	−3.343
TTGACT	0.018%	NA	yes	4	−3.981
TTGAGT	0.021%	−0.224	yes	4	−3.268
TTGATA	0.026%	−0.226	yes	4	−3.154
TTGATC	0.014%	0.330	yes	4	−3.707
TTGATG	0.024%	NA	yes	4	−2.991
TTGCAT	0.020%	NA	no	4	−1.414
TTGCCT	0.009%	0.262	no	4	0.493
TTGCGT	0.014%	0.240	no	4	−1.217
TTGCTA	0.010%	NA	no	4	−0.981
TTGCTC	0.011%	−0.151	no	4	−1.593
TTGCTG	0.010%	0.184	no	4	−1.199
TTGGAA	0.032%	0.206	no	4	−0.962
TTGGAC	0.021%	0.315	no	4	0.463
TTGGAG	0.031%	NA	no	4	−0.221
TTGGCA	0.021%	NA	no	4	−1.925
TTGGCC	0.008%	NA	no	4	−1.264
TTGGCG	0.018%	0.355	no	4	−0.284
TTGGGA	0.024%	NA	no	4	−2.123
TTGGGC	0.011%	−0.138	no	4	−2.203
TTGGGG	0.023%	−0.218	no	4	−2.416
TTGTAT	0.017%	NA	no	4	−2.518
TTGTCT	0.014%	NA	no	4	−2.588
TTGTGT	0.013%	NA	no	4	−2.719
TTGTTA	0.025%	−0.337	no	4	−4.186
TTGTTC	0.011%	0.230	no	4	−3.284
TTGTTG	0.014%	−0.150	no	4	−1.180
TTTAAT	0.020%	−0.494	no	4	−6.052
TTTACT	0.015%	NA	no	4	−5.274
TTTAGT	0.018%	−0.635	no	4	−9.622
TTTATA	0.019%	−0.421	no	4	−5.136
TTTATC	0.014%	NA	no	4	−5.023
TTTATG	0.015%	−0.370	no	4	−1.536
TTTCAT	0.014%	NA	no	4	−2.833
TTTCCT	0.008%	NA	no	4	−3.520
TTTCGT	0.013%	0.291	no	4	−1.753
TTTCTA	0.019%	NA	no	4	−3.406
TTTCTC	0.014%	NA	no	4	−5.454
TTTCTG	0.012%	NA	no	4	−3.087
TTTGAA	0.031%	NA	no	4	−2.719
TTTGAC	0.017%	NA	no	4	−2.842
TTTGAG	0.021%	−0.225	no	4	0.059
TTTGCA	0.018%	−0.243	no	4	−3.287
TTTGCC	0.013%	NA	no	4	−1.957
TTTGCG	0.016%	0.274	no	4	1.190
TTTGGA	0.031%	NA	no	4	−0.740
TTTGGC	0.018%	NA	no	4	−1.142
TTTGGG	0.021%	−0.200	no	4	−2.438
TTTTAT	0.016%	−0.433	no	4	−3.129
TTTTCT	0.012%	NA	no	4	−5.242
TTTTGT	0.015%	−0.281	no	4	−3.951
TTTTTA	0.017%	−0.436	no	4	−5.801
TTTTTC	0.009%	NA	no	4	−4.067
TTTTTG	0.015%	−0.451	no	4	−4.376
AAAAAA	0.116%	NA	no	5	−4.298
AAAAAC	0.083%	NA	no	5	−3.426
AAAAAG	0.096%	NA	no	5	−0.607
AAAACA	0.070%	NA	no	5	−2.840
AAAACC	0.036%	NA	no	5	−2.847
AAAACG	0.066%	NA	no	5	−0.718
AAAAGA	0.099%	NA	no	5	−3.161
AAAAGC	0.070%	NA	no	5	−2.806
AAAAGG	0.101%	−0.210	no	5	−2.186
AAACAA	0.076%	NA	no	5	−2.675
AAACAC	0.040%	NA	no	5	−4.391
AAACAG	0.063%	NA	no	5	−1.710
AAACCA	0.044%	NA	no	5	−1.597
AAACCC	0.023%	−0.292	no	5	−2.155
AAACCG	0.040%	0.295	no	5	0.265
AAACGA	0.061%	0.408	no	5	−1.551
AAACGC	0.035%	0.399	no	5	−1.063
AAACGG	0.056%	0.177	no	5	−0.487
AAATAA	0.064%	NA	no	5	−4.264
AAATAC	0.038%	NA	no	5	−3.313
AAATAG	0.047%	−0.518	no	5	−2.333
AAATCA	0.044%	NA	no	5	−3.412
AAATCC	0.014%	NA	no	5	−3.685
AAATCG	0.035%	0.271	no	5	−0.576
AAATGA	0.058%	NA	no	5	−2.896
AAATGC	0.042%	−0.223	no	5	−2.509
AAATGG	0.055%	NA	no	5	−1.576
AACAAT	0.046%	NA	no	5	−1.641
AACACT	0.031%	0.256	no	5	−1.171
AACAGT	0.044%	NA	no	5	−0.666
AACATA	0.049%	NA	no	5	−1.138
AACATC	0.033%	0.351	no	5	−0.742
AACATG	0.042%	NA	no	5	−0.489
AACCAT	0.029%	NA	no	5	−0.757
AACCCT	0.018%	0.324	no	5	−1.525
AACCGT	0.021%	NA	no	5	0.533
AACCTA	0.023%	NA	no	5	−0.741
AACCTC	0.019%	0.286	no	5	−1.607
AACCTG	0.022%	0.458	no	5	0.184
AACGAA	0.059%	NA	no	5	−0.009
AACGAC	0.036%	0.481	no	5	−0.297
AACGAG	0.051%	NA	no	5	−0.840
AACGCA	0.041%	NA	no	5	−1.264
AACGCC	0.022%	0.516	no	5	0.729
AACGCG	0.042%	0.692	no	5	0.372
AACGGA	0.061%	0.780	no	5	−0.270
AACGGC	0.034%	0.523	no	5	0.480
AACGGG	0.048%	0.288	no	5	−0.238
AACTAT	0.019%	NA	no	5	−1.804
AACTCT	0.017%	NA	no	5	−0.369
AACTGT	0.021%	NA	no	5	0.684
AACTTA	0.024%	NA	no	5	−2.119
AACTTC	0.015%	0.414	no	5	−0.767
AACTTG	0.032%	NA	no	5	0.526
AAGAAT	0.068%	0.613	no	5	−1.100
AAGACT	0.032%	0.778	no	5	−0.590
AAGAGT	0.058%	0.316	no	5	−1.370
AAGATA	0.063%	0.391	no	5	−1.436
AAGATC	0.036%	0.637	no	5	−1.025
AAGATG	0.058%	0.465	no	5	−0.342
AAGCAT	0.041%	NA	no	5	−1.973
AAGCCT	0.024%	NA	no	5	−1.669
AAGCGT	0.027%	NA	no	5	−1.179
AAGCTA	0.035%	NA	no	5	−1.865
AAGCTC	0.020%	NA	no	5	−0.488
AAGCTG	0.040%	0.235	no	5	0.107
AAGGAA	0.083%	0.545	no	5	−2.097
AAGGAC	0.047%	0.571	no	5	−1.555
AAGGAG	0.058%	NA	no	5	−0.136
AAGGCA	0.053%	NA	no	5	−2.465
AAGGCC	0.023%	NA	no	5	−1.155
AAGGCG	0.035%	0.306	no	5	−0.214
AAGGGA	0.074%	−0.207	no	5	−3.974
AAGGGC	0.038%	−0.146	no	5	−4.913
AAGGGG	0.069%	−0.193	no	5	−2.523
AAGTAT	0.039%	NA	no	5	−2.379
AAGTCT	0.024%	0.381	no	5	−1.489
AAGTGT	0.046%	NA	no	5	−1.648
AAGTTA	0.043%	NA	no	5	−2.458
AAGTTC	0.026%	0.292	no	5	−3.454
AAGTTG	0.034%	NA	no	5	−1.179
AATAAT	0.040%	−0.289	no	5	−3.529
AATACT	0.022%	NA	no	5	−3.995
AATAGT	0.035%	−0.463	no	5	−7.162
AATATA	0.042%	−0.477	no	5	−3.683
AATATC	0.021%	NA	no	5	−2.339
AATATG	0.040%	−0.245	no	5	−0.688
AATCAT	0.033%	NA	no	5	−2.366
AATCCT	0.018%	0.417	no	5	−1.551
AATCGT	0.027%	0.314	no	5	−1.588
AATCTA	0.024%	NA	no	5	−3.222
AATCTC	0.010%	NA	no	5	−2.828
AATCTG	0.030%	0.228	no	5	−0.659
AATGAA	0.056%	NA	no	5	−2.047
AATGAC	0.018%	0.349	no	5	−1.261
AATGAG	0.029%	NA	no	5	−0.549
AATGCA	0.035%	−0.225	no	5	−3.043
AATGCC	0.009%	NA	no	5	−1.035
AATGCG	0.025%	0.295	no	5	−0.655
AATGGA	0.043%	0.386	no	5	−0.864
AATGGC	0.024%	0.119	no	5	−0.700
AATGGG	0.040%	−0.266	no	5	−2.138
AATTAT	0.024%	−0.392	no	5	−4.140
AATTCT	0.006%	NA	no	5	−3.905
AATTGT	0.020%	NA	no	5	−3.972
AATTTA	0.026%	NA	no	5	−3.956
AATTTC	0.013%	NA	no	5	−5.056
AATTTG	0.021%	−0.175	no	5	−2.374
ACAAAA	0.082%	NA	no	5	−2.854
ACAAAC	0.049%	NA	no	5	−2.644
ACAAAG	0.070%	NA	no	5	−0.187
ACAACA	0.053%	NA	no	5	−1.154
ACAACC	0.027%	NA	no	5	−0.819
ACAACG	0.043%	0.587	no	5	0.377
ACAAGA	0.065%	0.488	no	5	−0.926
ACAAGC	0.048%	0.353	no	5	−1.421
ACAAGG	0.065%	NA	no	5	−0.420
ACACAA	0.048%	NA	no	5	−2.059
ACACAC	0.028%	NA	no	5	−3.690
ACACAG	0.048%	NA	no	5	−0.472
ACACCA	0.030%	−0.127	no	5	−1.609
ACACCC	0.017%	NA	no	5	−1.031
ACACCG	0.025%	0.536	no	5	−0.067
ACACGA	0.044%	NA	no	5	−0.517
ACACGC	0.027%	0.497	no	5	−1.236
ACACGG	0.044%	0.350	no	5	−0.332
ACATAA	0.047%	NA	no	5	−3.398
ACATAC	0.032%	NA	no	5	−3.445
ACATAG	0.045%	−0.435	no	5	−1.259
ACATCA	0.034%	NA	no	5	−2.158
ACATCC	0.015%	0.231	no	5	−0.653
ACATCG	0.030%	0.571	no	5	−0.659
ACATGA	0.037%	NA	no	5	−2.797
ACATGC	0.026%	NA	no	5	−0.300
ACATGG	0.049%	NA	no	5	−0.971
ACCAAT	0.029%	NA	no	5	0.074
ACCACT	0.015%	NA	no	5	−0.829
ACCAGT	0.030%	NA	no	5	−0.548
ACCATA	0.028%	−0.569	no	5	−1.492
ACCATC	0.017%	NA	no	5	0.452
ACCATG	0.029%	NA	no	5	−0.179
ACCCAT	0.019%	−0.188	no	5	−0.502
ACCCCT	0.013%	−0.152	no	5	−1.971
ACCCGT	0.016%	0.279	no	5	−0.472
ACCCTA	0.012%	−0.298	no	5	−3.091
ACCCTC	0.010%	0.137	no	5	−1.155
ACCCTG	0.016%	0.155	no	5	0.953
ACCGAA	0.035%	NA	no	5	−0.100
ACCGAC	0.025%	NA	no	5	0.296
ACCGAG	0.032%	NA	no	5	0.018
ACCGCA	0.021%	NA	no	5	−0.489
ACCGCC	0.017%	NA	no	5	1.759
ACCGCG	0.022%	0.487	no	5	−0.743
ACCGGA	0.034%	NA	no	5	−0.278
ACCGGC	0.019%	NA	no	5	0.949
ACCGGG	0.030%	0.550	no	5	−0.455
ACCTAT	0.016%	−0.268	no	5	−1.735
ACCTCT	0.012%	NA	no	5	−1.503
ACCTGT	0.020%	NA	no	5	0.204
ACCTTA	0.021%	NA	no	5	−1.504
ACCTTC	0.012%	NA	no	5	−1.703
ACCTTG	0.016%	NA	no	5	−0.361
ACGAAT	0.047%	NA	no	5	−0.211
ACGACT	0.021%	0.496	no	5	−0.097
ACGAGT	0.037%	NA	no	5	−0.119
ACGATA	0.033%	NA	no	5	−0.708
ACGATC	0.025%	0.631	no	5	−0.942
ACGATG	0.035%	0.361	no	5	0.446
ACGCAT	0.025%	NA	no	5	−1.115
ACGCCT	0.020%	0.525	no	5	−0.441
ACGCGT	0.022%	0.363	no	5	−0.420
ACGCTA	0.023%	NA	no	5	−0.307
ACGCTC	0.017%	0.387	no	5	0.271
ACGCTG	0.023%	0.380	no	5	−0.317
ACGGAA	0.061%	0.504	no	5	−0.653
ACGGAC	0.036%	0.676	no	5	−0.672
ACGGAG	0.041%	0.381	no	5	−0.388
ACGGCA	0.031%	NA	no	5	−0.083
ACGGCC	0.021%	0.363	no	5	0.717
ACGGCG	0.024%	0.709	no	5	0.796
ACGGGA	0.044%	0.425	no	5	0.084
ACGGGC	0.035%	0.359	no	5	0.315
ACGGGG	0.043%	0.204	no	5	−0.443
ACGTAT	0.030%	NA	no	5	−1.543
ACGTCT	0.021%	0.513	no	5	−0.717
ACGTGT	0.028%	NA	no	5	−0.255
ACGTTA	0.033%	NA	no	5	−1.795
ACGTTC	0.018%	0.520	no	5	−0.743
ACGTTG	0.032%	0.252	no	5	−0.021
ACTAAT	0.033%	−0.334	no	5	−3.642
ACTACT	0.016%	0.308	no	5	−2.192
ACTAGT	0.025%	−0.409	no	5	−7.390
ACTATA	0.024%	−0.391	no	5	−4.008
ACTATC	0.021%	NA	no	5	−3.883
ACTATG	0.021%	NA	no	5	−0.814
ACTCAT	0.023%	NA	no	5	−3.471
ACTCCT	0.017%	0.416	no	5	−2.373
ACTCGT	0.018%	0.266	no	5	−1.264
ACTCTA	0.022%	−0.394	no	5	−3.332
ACTCTC	0.014%	NA	no	5	−2.268
ACTCTG	0.021%	0.194	no	5	−0.477
ACTGAA	0.040%	NA	no	5	−0.118
ACTGAC	0.023%	0.335	no	5	−1.737
ACTGAG	0.025%	NA	no	5	0.822
ACTGCA	0.025%	0.203	no	5	−2.160
ACTGCC	0.018%	NA	no	5	0.120
ACTGCG	0.024%	0.510	no	5	0.118
ACTGGA	0.037%	NA	no	5	−0.286
ACTGGC	0.025%	NA	no	5	−0.588
ACTGGG	0.037%	NA	no	5	−1.048
ACTTAT	0.023%	NA	no	5	−3.348
ACTTCT	0.012%	0.263	no	5	−2.599
ACTTGT	0.018%	NA	no	5	−2.260
ACTTTA	0.025%	−0.551	no	5	−6.474
ACTTTC	0.012%	NA	no	5	−2.527
ACTTTG	0.018%	−0.155	no	5	−0.536
AGCAAA	0.066%	NA	no	5	−0.231
AGCAAC	0.040%	NA	no	5	−0.478
AGCAAG	0.052%	NA	no	5	−0.850
AGCACA	0.035%	NA	no	5	−0.568
AGCACC	0.020%	−0.302	no	5	−1.046
AGCACG	0.038%	NA	no	5	−0.230
AGCAGA	0.048%	NA	no	5	−0.701
AGCAGC	0.027%	−0.295	no	5	0.466
AGCAGG	0.039%	−0.304	no	5	−0.610
AGCCAA	0.033%	NA	no	5	0.048
AGCCAC	0.021%	NA	no	5	−0.708
AGCCAG	0.035%	−0.193	no	5	−0.625
AGCCCA	0.024%	−0.292	no	5	−1.079
AGCCCC	0.018%	−0.233	no	5	0.248
AGCCCG	0.022%	NA	no	5	0.030
AGCCGA	0.031%	NA	no	5	0.240
AGCCGC	0.018%	NA	no	5	−0.319
AGCCGG	0.029%	0.257	no	5	−0.016
AGCTAA	0.033%	−0.436	no	5	−0.386
AGCTAC	0.025%	NA	no	5	−0.221
AGCTAG	0.041%	−0.772	no	5	−0.344
AGCTCA	0.034%	NA	no	5	−0.220
AGCTCC	0.018%	NA	no	5	−0.968
AGCTCG	0.023%	NA	no	5	1.106
AGCTGA	0.032%	NA	no	5	−0.143
AGCTGC	0.017%	0.152	no	5	−0.427
AGCTGG	0.029%	−0.227	no	5	−0.206
AGGAAA	0.092%	NA	no	5	−3.561
AGGAAC	0.064%	0.338	no	5	−2.293
AGGAAG	0.066%	NA	no	5	−1.064
AGGACA	0.066%	NA	no	5	−3.251
AGGACC	0.034%	0.246	no	5	−1.549
AGGACG	0.047%	0.394	no	5	−0.096
AGGAGA	0.078%	NA	no	5	−1.908
AGGAGC	0.040%	0.336	no	5	−1.938
AGGAGG	0.065%	−0.147	no	5	−1.028
AGGCAA	0.055%	NA	no	5	−2.114
AGGCAC	0.039%	NA	no	5	−3.296
AGGCAG	0.052%	−0.490	no	5	−1.343
AGGCCA	0.035%	NA	no	5	−1.280
AGGCCC	0.029%	NA	no	5	−0.420
AGGCCG	0.031%	NA	no	5	−0.324
AGGCGA	0.040%	NA	no	5	−0.846
AGGCGC	0.025%	NA	no	5	1.091
AGGCGG	0.035%	NA	no	5	−0.488
AGGTAA	0.065%	−0.555	no	5	−5.154
AGGTAC	0.038%	NA	no	5	−4.296
AGGTAG	0.042%	−0.871	no	5	−3.122
AGGTCA	0.043%	NA	no	5	−2.539
AGGTCC	0.025%	−0.226	no	5	−1.406
AGGTCG	0.032%	NA	no	5	−0.550
AGGTGA	0.039%	−0.429	no	5	−2.689
AGGTGC	0.033%	−0.262	no	5	−1.279
AGGTGG	0.044%	−0.423	no	5	−0.072
AGTAAA	0.063%	NA	no	5	−1.632
AGTAAC	0.050%	NA	no	5	−0.695
AGTAAG	0.062%	−0.505	no	5	−0.778
AGTACA	0.044%	NA	no	5	−1.271
AGTACC	0.029%	NA	no	5	−1.082
AGTACG	0.046%	NA	no	5	0.024
AGTAGA	0.052%	NA	no	5	−3.087
AGTAGC	0.032%	−0.483	no	5	−2.096
AGTAGG	0.052%	−0.703	no	5	−2.394
AGTCAA	0.049%	NA	no	5	−0.576
AGTCAC	0.024%	NA	no	5	−0.941
AGTCAG	0.039%	−0.684	no	5	−1.114
AGTCCA	0.024%	NA	no	5	−0.521
AGTCCC	0.015%	−0.237	no	5	−0.021
AGTCCG	0.018%	0.277	no	5	0.367
AGTCGA	0.034%	NA	no	5	0.016
AGTCGC	0.023%	0.365	no	5	−0.564
AGTCGG	0.031%	0.160	no	5	−0.096
AGTTAA	0.054%	−0.172	no	5	−1.972
AGTTAC	0.020%	0.192	no	5	−0.533
AGTTAG	0.040%	−0.645	no	5	−0.840
AGTTCA	0.031%	0.204	no	5	−1.079
AGTTCC	0.013%	−0.098	no	5	1.774
AGTTCG	0.021%	0.505	no	5	2.317
AGTTGA	0.039%	0.119	no	5	0.377
AGTTGC	0.021%	0.176	no	5	1.008
AGTTGG	0.034%	NA	no	5	−0.493
ATAAAA	0.080%	−0.542	yes	5	−5.299
ATAAAC	0.059%	NA	yes	5	−4.890
ATAAAG	0.058%	−0.271	yes	5	−3.286
ATAACA	0.058%	−0.364	yes	5	−6.056
ATAACC	0.031%	−0.274	yes	5	−3.913
ATAACG	0.047%	NA	yes	5	−3.211
ATAAGA	0.056%	NA	yes	5	−5.331
ATAAGC	0.040%	NA	yes	5	−5.799
ATAAGG	0.061%	−0.365	yes	5	−5.184
ATACAA	0.047%	NA	no	5	−2.992
ATACAC	0.032%	NA	no	5	−3.030
ATACAG	0.040%	NA	no	5	−1.862
ATACCA	0.029%	NA	no	5	−1.355
ATACCC	0.017%	−0.229	no	5	−1.258
ATACCG	0.019%	0.319	no	5	−0.173
ATACGA	0.043%	NA	no	5	−2.295
ATACGC	0.022%	0.358	no	5	−1.628
ATACGG	0.038%	0.193	no	5	−0.746
ATATAA	0.056%	−0.361	no	5	−5.270
ATATAC	0.037%	NA	no	5	−4.232
ATATAG	0.041%	−0.674	no	5	−2.537
ATATCA	0.036%	NA	no	5	−4.023
ATATCC	0.016%	NA	no	5	−0.528
ATATCG	0.032%	NA	no	5	0.356
ATATGA	0.043%	NA	no	5	−1.698
ATATGC	0.030%	−0.243	no	5	−2.881
ATATGG	0.043%	NA	no	5	−0.719
ATCAAT	0.036%	NA	no	5	−0.510
ATCACT	0.021%	NA	no	5	0.192
ATCAGT	0.029%	−0.409	no	5	−1.810
ATCATA	0.034%	NA	no	5	−0.557
ATCATC	0.021%	NA	no	5	0.534
ATCATG	0.028%	NA	no	5	−0.848
ATCCAT	0.026%	NA	no	5	−0.850
ATCCCT	0.014%	NA	no	5	−1.684
ATCCGT	0.015%	NA	no	5	−1.359
ATCCTA	0.017%	NA	no	5	−0.827
ATCCTC	0.014%	NA	no	5	−0.712
ATCCTG	0.016%	0.447	no	5	0.126
ATCGAA	0.041%	NA	no	5	−0.076
ATCGAC	0.020%	0.539	no	5	−0.078
ATCGAG	0.037%	NA	no	5	−0.805
ATCGCA	0.030%	NA	no	5	0.443
ATCGCC	0.022%	0.290	no	5	0.958
ATCGCG	0.025%	0.541	no	5	−0.167
ATCGGA	0.039%	0.342	no	5	−0.115
ATCGGC	0.025%	0.334	no	5	0.218
ATCGGG	0.035%	0.390	no	5	−0.354
ATCTAT	0.021%	−0.315	no	5	−0.895
ATCTCT	0.015%	NA	no	5	−1.080
ATCTGT	0.023%	NA	no	5	0.256
ATCTTA	0.022%	−0.350	no	5	−0.819
ATCTTC	0.016%	NA	no	5	−1.648
ATCTTG	0.017%	−0.191	no	5	−0.218
ATGAAT	0.047%	0.279	yes	5	−3.010
ATGACT	0.032%	0.367	yes	5	−1.853
ATGAGT	0.043%	NA	yes	5	−4.072
ATGATA	0.041%	NA	yes	5	−5.173
ATGATC	0.029%	0.442	yes	5	−4.543
ATGATG	0.035%	0.187	yes	5	−2.675
ATGCAT	0.031%	NA	no	5	−2.752
ATGCCT	0.012%	0.331	no	5	0.031
ATGCGT	0.024%	NA	no	5	−1.629
ATGCTA	0.030%	NA	no	5	−2.856
ATGCTC	0.020%	NA	no	5	−4.102
ATGCTG	0.021%	0.208	no	5	0.015
ATGGAA	0.052%	0.393	no	5	−0.996
ATGGAC	0.039%	0.589	no	5	−0.534
ATGGAG	0.047%	0.229	no	5	−0.418
ATGGCA	0.044%	NA	no	5	−1.948
ATGGCC	0.022%	NA	no	5	0.689
ATGGCG	0.034%	0.388	no	5	−0.119
ATGGGA	0.064%	0.054	no	5	−2.200
ATGGGC	0.028%	−0.106	no	5	−2.348
ATGGGG	0.052%	−0.331	no	5	−2.867
ATGTAT	0.034%	NA	no	5	−3.231
ATGTCT	0.019%	NA	no	5	−3.313
ATGTGT	0.030%	NA	no	5	−2.322
ATGTTA	0.041%	NA	no	5	−3.521
ATGTTC	0.024%	0.354	no	5	−4.463
ATGTTG	0.030%	NA	no	5	−1.595
ATTAAT	0.042%	−0.360	no	5	−4.518
ATTACT	0.016%	NA	no	5	−1.163
ATTAGT	0.034%	−0.437	no	5	−9.337
ATTATA	0.038%	−0.813	no	5	−4.559
ATTATC	0.025%	NA	no	5	−5.888
ATTATG	0.030%	−0.355	no	5	−2.309
ATTCAT	0.019%	NA	no	5	−1.547
ATTCCT	0.007%	NA	no	5	−0.611
ATTCGT	0.017%	NA	no	5	1.588
ATTCTA	0.020%	NA	no	5	−3.930
ATTCTC	0.015%	NA	no	5	−2.827
ATTCTG	0.020%	0.188	no	5	−1.028
ATTGAA	0.049%	NA	no	5	−2.491
ATTGAC	0.029%	NA	no	5	−2.342
ATTGAG	0.034%	NA	no	5	−0.692
ATTGCA	0.027%	−0.178	no	5	−3.833
ATTGCC	0.015%	NA	no	5	−2.134
ATTGCG	0.026%	0.287	no	5	−0.600
ATTGGA	0.042%	0.347	no	5	−0.875
ATTGGC	0.028%	NA	no	5	−1.255
ATTGGG	0.040%	−0.103	no	5	−2.010
ATTTAT	0.023%	−0.260	no	5	−3.982
ATTTCT	0.017%	NA	no	5	−6.887
ATTTGT	0.023%	NA	no	5	−4.055
ATTTTA	0.027%	−0.725	no	5	−5.043
ATTTTC	0.017%	NA	no	5	−3.757
ATTTTG	0.029%	−0.257	no	5	−2.146
CAAAAA	0.047%	−0.255	no	5	−2.163
CAAAAC	0.042%	NA	no	5	−2.136
CAAAAG	0.037%	NA	no	5	−0.198
CAAACA	0.040%	NA	no	5	−1.402
CAAACC	0.025%	NA	no	5	−1.664
CAAACG	0.035%	0.292	no	5	0.022
CAAAGA	0.034%	0.230	no	5	−0.798
CAAAGC	0.025%	NA	no	5	−1.331
CAAAGG	0.043%	NA	no	5	−0.013
CAACAA	0.035%	0.269	no	5	−0.491
CAACAC	0.019%	0.282	no	5	−1.086
CAACAG	0.026%	NA	no	5	−0.336
CAACCA	0.021%	NA	no	5	−0.273
CAACCC	0.012%	NA	no	5	−0.916
CAACCG	0.021%	NA	no	5	−0.342
CAACGA	0.027%	0.224	no	5	−0.189
CAACGC	0.020%	0.542	no	5	−0.395
CAACGG	0.031%	0.503	no	5	−0.182
CAATAA	0.032%	−0.286	no	5	−2.882
CAATAC	0.018%	NA	no	5	−0.569
CAATAG	0.029%	−0.465	no	5	−1.951
CAATCA	0.026%	NA	no	5	−1.283
CAATCC	0.014%	NA	no	5	0.622
CAATCG	0.020%	0.297	no	5	−0.238
CAATGA	0.024%	0.266	no	5	−1.142
CAATGC	0.017%	NA	no	5	−0.317
CAATGG	0.028%	NA	no	5	−0.403
CACAAT	0.029%	−0.217	no	5	−0.731
CACACT	0.017%	NA	no	5	−1.344
CACAGT	0.019%	−0.197	no	5	−1.502
CACATA	0.023%	−0.538	no	5	−1.630
CACATC	0.012%	NA	no	5	0.617
CACATG	0.019%	NA	no	5	0.305
CACCAT	0.016%	−0.373	no	5	−0.703
CACCCT	0.012%	NA	no	5	−3.190
CACCGT	0.012%	NA	no	5	0.124
CACCTA	0.015%	−0.737	no	5	0.587
CACCTC	0.011%	NA	no	5	−1.006
CACCTG	0.010%	0.154	no	5	−0.859
CACGAA	0.034%	NA	no	5	−1.082
CACGAC	0.016%	NA	no	5	0.161
CACGAG	0.027%	NA	no	5	0.053
CACGCA	0.017%	NA	no	5	0.202
CACGCC	0.014%	0.268	no	5	−0.845
CACGCG	0.020%	0.289	no	5	−0.662
CACGGA	0.021%	0.304	no	5	−0.142
CACGGC	0.019%	NA	no	5	−0.459
CACGGG	0.024%	0.344	no	5	0.662
CACTAT	0.013%	−0.324	no	5	−1.230
CACTCT	0.016%	−0.268	no	5	−2.049
CACTGT	0.011%	NA	no	5	−1.174
CACTTA	0.015%	−0.562	no	5	−1.130
CACTTC	0.011%	NA	no	5	−1.667
CACTTG	0.015%	−0.275	no	5	−1.849
CAGAAT	0.029%	0.207	no	5	−1.732
CAGACT	0.027%	NA	no	5	−1.070
CAGAGT	0.031%	NA	no	5	−0.940
CAGATA	0.032%	−0.309	no	5	−1.291
CAGATC	0.014%	NA	no	5	−0.205
CAGATG	0.031%	0.190	no	5	0.162
CAGCAT	0.025%	−0.194	no	5	0.369
CAGCCT	0.016%	−0.303	no	5	−0.481
CAGCGT	0.015%	NA	no	5	0.330
CAGCTA	0.018%	−0.349	no	5	−1.378
CAGCTC	0.010%	NA	no	5	−0.268
CAGCTG	0.015%	NA	no	5	0.199
CAGGAA	0.039%	NA	no	5	−0.800
CAGGAC	0.025%	0.250	no	5	−0.298
CAGGAG	0.033%	NA	no	5	0.020
CAGGCA	0.029%	−0.223	no	5	−3.182
CAGGCC	0.019%	NA	no	5	−0.707
CAGGCG	0.023%	NA	no	5	−0.949
CAGGGA	0.045%	−0.328	no	5	−4.328
CAGGGC	0.016%	−0.181	no	5	−3.990
CAGGGG	0.033%	−0.227	no	5	−2.819
CAGTAT	0.024%	−0.363	no	5	−0.732
CAGTCT	0.013%	NA	no	5	−1.272
CAGTGT	0.020%	−0.196	no	5	−0.107
CAGTTA	0.023%	−0.341	no	5	−1.461
CAGTTC	0.011%	NA	no	5	−1.817
CAGTTG	0.016%	NA	no	5	−0.664
CATAAT	0.025%	−0.348	no	5	−1.706
CATACT	0.012%	NA	no	5	−2.389
CATAGT	0.016%	−0.342	no	5	−4.310
CATATA	0.015%	−0.414	no	5	−1.444
CATATC	0.013%	NA	no	5	−1.787
CATATG	0.020%	−0.169	no	5	0.027
CATCAT	0.019%	NA	no	5	−0.887
CATCCT	0.008%	NA	no	5	−0.945
CATCGT	0.014%	NA	no	5	0.552
CATCTA	0.016%	−0.335	no	5	−0.187
CATCTC	0.009%	NA	no	5	−0.670
CATCTG	0.020%	0.215	no	5	0.405
CATGAA	0.033%	0.373	no	5	−1.218
CATGAC	0.009%	0.274	no	5	0.391
CATGAG	0.016%	NA	no	5	0.562
CATGCA	0.026%	−0.095	no	5	−1.129
CATGCC	0.009%	NA	no	5	0.172
CATGCG	0.020%	NA	no	5	−0.372
CATGGA	0.027%	0.524	no	5	0.007
CATGGC	0.016%	NA	no	5	−0.052
CATGGG	0.026%	0.101	no	5	−0.444
CATTAT	0.015%	−0.435	no	5	−4.230
CATTCT	0.009%	NA	no	5	−1.799
CATTGT	0.011%	NA	no	5	−2.348
CATTTA	0.014%	−0.404	no	5	−1.953
CATTTC	0.008%	NA	no	5	−3.017
CATTTG	0.017%	−0.160	no	5	−2.055
CCAAAA	0.027%	−0.592	no	5	−2.109
CCAAAC	0.022%	−0.360	no	5	−1.518
CCAAAG	0.025%	−0.218	no	5	−0.565
CCAACA	0.019%	NA	no	5	−0.150
CCAACC	0.011%	NA	no	5	−0.488
CCAACG	0.020%	0.408	no	5	0.002
CCAAGA	0.019%	NA	no	5	−0.890
CCAAGC	0.016%	NA	no	5	−0.437
CCAAGG	0.022%	NA	no	5	−0.256
CCACAA	0.027%	NA	no	5	−1.804
CCACAC	0.015%	NA	no	5	−1.872
CCACAG	0.015%	−0.283	no	5	−0.639
CCACCA	0.014%	−0.597	no	5	−1.636
CCACCC	0.010%	−0.303	no	5	1.119
CCACCG	0.012%	NA	no	5	−0.229
CCACGA	0.018%	0.317	no	5	−0.224
CCACGC	0.011%	NA	no	5	−0.187
CCACGG	0.018%	0.426	no	5	−0.510
CCATAA	0.018%	−0.566	no	5	−2.321
CCATAC	0.013%	−0.342	no	5	−1.822
CCATAG	0.015%	−0.497	no	5	−1.244
CCATCA	0.014%	−0.216	no	5	−1.072
CCATCC	0.009%	NA	no	5	0.526
CCATCG	0.013%	0.391	no	5	−0.053
CCATGA	0.014%	NA	no	5	−0.894
CCATGC	0.011%	NA	no	5	−0.891
CCATGG	0.014%	0.183	no	5	−1.268
CCCAAT	0.014%	−0.365	no	5	−1.469
CCCACT	0.011%	−0.255	no	5	−1.277
CCCAGT	0.010%	−0.388	no	5	−2.238
CCCATA	0.012%	−0.475	no	5	−3.772
CCCATC	0.010%	NA	no	5	−1.096
CCCATG	0.012%	NA	no	5	0.331
CCCCCT	0.006%	−0.217	no	5	−3.983
CCCCGT	0.010%	NA	no	5	−1.571
CCCCTA	0.007%	−0.434	no	5	−4.929
CCCCTG	0.007%	0.114	no	5	0.211
CCCGAA	0.015%	0.281	no	5	−0.873
CCCGAC	0.014%	0.264	no	5	0.265
CCCGAG	0.016%	0.320	no	5	0.805
CCCGCA	0.014%	NA	no	5	−1.168
CCCGCC	0.008%	NA	no	5	0.112
CCCGCG	0.008%	0.571	no	5	−0.368
CCCGGA	0.013%	0.454	no	5	0.068
CCCGGC	0.010%	NA	no	5	−0.045
CCCGGG	0.010%	0.386	no	5	0.233
CCCTAT	0.006%	−0.386	no	5	−4.151
CCCTCT	0.006%	NA	no	5	−0.306
CCCTGT	0.007%	NA	no	5	−0.619
CCCTTA	0.013%	−0.622	no	5	−5.544
CCCTTC	0.006%	NA	no	5	0.005
CCCTTG	0.006%	−0.092	no	5	−1.191
CCGAAT	0.017%	NA	no	5	−0.405
CCGACT	0.009%	NA	no	5	−0.619
CCGAGT	0.018%	0.211	no	5	−0.240
CCGATA	0.016%	NA	no	5	−0.167
CCGATC	0.008%	NA	no	5	0.961
CCGATG	0.018%	0.275	no	5	0.722
CCGCAT	0.014%	NA	no	5	−0.323
CCGCCT	0.010%	NA	no	5	−0.453
CCGCGT	0.007%	0.411	no	5	0.802
CCGCTA	0.017%	NA	no	5	−0.641
CCGCTC	0.008%	0.224	no	5	−1.731
CCGCTG	0.006%	0.337	no	5	1.427
CCGGAA	0.028%	0.524	no	5	0.192
CCGGAC	0.012%	0.288	no	5	−0.652
CCGGAG	0.020%	0.622	no	5	−0.362
CCGGCA	0.017%	−0.276	no	5	1.306
CCGGCC	0.010%	NA	no	5	0.175
CCGGCG	0.017%	0.621	no	5	−1.036
CCGGGA	0.020%	0.590	no	5	0.206
CCGGGC	0.012%	0.454	no	5	−0.736
CCGGGG	0.019%	0.358	no	5	−0.436
CCGTAT	0.009%	NA	no	5	0.872
CCGTCT	0.006%	0.337	no	5	−0.172
CCGTTA	0.013%	−0.283	no	5	−3.315
CCGTTC	0.009%	0.196	no	5	0.261
CCGTTG	0.010%	0.241	no	5	−0.661
CCTAAT	0.010%	−0.628	no	5	−3.190
CCTACT	0.008%	NA	no	5	0.297
CCTAGT	0.006%	−0.517	no	5	−5.949
CCTATA	0.010%	−0.599	no	5	−2.207
CCTATC	0.007%	−0.285	no	5	−6.011
CCTATG	0.008%	−0.201	no	5	−1.218
CCTCAT	0.009%	NA	no	5	−0.277
CCTCCT	0.006%	NA	no	5	−1.459
CCTCGT	0.009%	0.284	no	5	−0.414
CCTCTA	0.011%	−0.215	no	5	−2.105
CCTCTC	0.005%	NA	no	5	1.159
CCTCTG	0.008%	0.206	no	5	0.809
CCTGAA	0.021%	NA	no	5	−0.274
CCTGAC	0.010%	NA	no	5	−0.072
CCTGAG	0.011%	NA	no	5	0.683
CCTGCA	0.013%	0.332	no	5	−1.474
CCTGCC	0.007%	0.151	no	5	−0.210
CCTGCG	0.015%	0.584	no	5	1.012
CCTGGA	0.011%	0.407	no	5	0.176
CCTGGC	0.012%	NA	no	5	−0.365
CCTGGG	0.013%	0.277	no	5	0.803
CCTTAT	0.007%	−0.537	no	5	−1.326
CCTTCT	0.005%	NA	no	5	−2.992
CCTTGT	0.009%	−0.207	no	5	−1.603
CCTTTA	0.005%	−0.881	no	5	−4.138
CCTTTG	0.006%	−0.241	no	5	−1.149
CGCAAA	0.026%	NA	no	5	0.561
CGCAAC	0.021%	0.386	no	5	0.278
CGCAAG	0.020%	NA	no	5	0.669
CGCACA	0.020%	NA	no	5	−2.160
CGCACC	0.009%	0.280	no	5	1.388
CGCACG	0.013%	0.604	no	5	0.400
CGCAGA	0.023%	NA	no	5	−0.597
CGCAGC	0.012%	−0.402	no	5	−0.575
CGCAGG	0.022%	NA	no	5	0.050
CGCCAA	0.014%	NA	no	5	0.443
CGCCAC	0.011%	NA	no	5	0.179
CGCCAG	0.010%	0.298	no	5	−1.002
CGCCCA	0.007%	0.225	no	5	−0.574
CGCCCC	0.008%	NA	no	5	−1.953
CGCCCG	0.005%	0.636	no	5	0.220
CGCCGA	0.009%	0.450	no	5	−1.108
CGCCGC	0.006%	0.353	no	5	2.704
CGCCGG	0.010%	0.746	no	5	0.998
CGCTAA	0.014%	NA	no	5	0.149
CGCTAC	0.008%	0.302	no	5	0.629
CGCTAG	0.012%	−0.399	no	5	−0.124
CGCTCA	0.009%	NA	no	5	0.549
CGCTCC	0.008%	0.260	no	5	0.173
CGCTCG	0.009%	0.487	no	5	−0.835
CGCTGA	0.013%	0.545	no	5	−1.332
CGCTGC	0.009%	0.418	no	5	−1.093
CGCTGG	0.011%	NA	no	5	−0.925
CGGAAA	0.035%	NA	no	5	0.338
CGGAAC	0.023%	0.618	no	5	0.258
CGGAAG	0.026%	0.528	no	5	0.224
CGGACA	0.026%	NA	no	5	−0.284
CGGACC	0.016%	0.447	no	5	0.568
CGGACG	0.026%	0.841	no	5	0.639
CGGAGA	0.026%	0.599	no	5	−1.101
CGGAGC	0.017%	0.618	no	5	0.538
CGGAGG	0.029%	0.385	no	5	−0.032
CGGCAA	0.025%	NA	no	5	−0.210
CGGCAC	0.015%	NA	no	5	0.170
CGGCAG	0.021%	NA	no	5	0.374
CGGCCA	0.012%	0.142	no	5	−0.568
CGGCCC	0.011%	NA	no	5	0.288
CGGCCG	0.009%	0.460	no	5	2.910
CGGCGA	0.018%	0.686	no	5	1.084
CGGCGC	0.009%	0.595	no	5	−0.606
CGGCGG	0.018%	0.721	no	5	−0.511
CGGTAA	0.024%	NA	no	5	−0.222
CGGTAC	0.015%	0.364	no	5	0.310
CGGTAG	0.015%	−0.530	no	5	−0.516
CGGTCA	0.014%	NA	no	5	−0.746
CGGTCC	0.007%	0.431	no	5	−0.815
CGGTCG	0.013%	0.483	no	5	0.514
CGGTGA	0.018%	NA	no	5	0.579
CGGTGC	0.011%	NA	no	5	−0.800
CGGTGG	0.015%	NA	no	5	1.378
CGTAAA	0.026%	NA	no	5	0.878
CGTAAC	0.016%	NA	no	5	0.417
CGTAAG	0.018%	NA	no	5	0.358
CGTACA	0.016%	NA	no	5	0.019
CGTACC	0.010%	0.277	no	5	0.658
CGTACG	0.016%	0.408	no	5	1.020
CGTAGA	0.020%	NA	no	5	−0.415
CGTAGC	0.011%	−0.294	no	5	0.979
CGTAGG	0.015%	−0.484	no	5	−0.882
CGTCAA	0.019%	0.515	no	5	0.678
CGTCAC	0.011%	0.401	no	5	0.156
CGTCAG	0.014%	NA	no	5	0.073
CGTCCA	0.008%	0.640	no	5	0.170
CGTCCC	0.007%	0.218	no	5	0.041
CGTCCG	0.010%	0.753	no	5	−0.220
CGTCGA	0.015%	0.885	no	5	0.287
CGTCGC	0.010%	0.885	no	5	−0.034
CGTCGG	0.006%	0.844	no	5	−0.670
CGTTAA	0.021%	NA	no	5	0.155
CGTTAC	0.009%	NA	no	5	−1.673
CGTTAG	0.012%	−0.626	no	5	−2.079
CGTTCA	0.012%	NA	no	5	0.168
CGTTCC	0.006%	0.395	no	5	1.633
CGTTCG	0.010%	0.601	no	5	0.885
CGTTGA	0.013%	NA	no	5	−1.480
CGTTGC	0.010%	0.191	no	5	−0.171
CGTTGG	0.012%	0.290	no	5	−0.722
CTAAAA	0.020%	−0.424	yes	5	−5.083
CTAAAC	0.012%	−0.456	yes	5	−3.039
CTAAAG	0.020%	−0.364	yes	5	−3.512
CTAACA	0.013%	NA	yes	5	−4.892
CTAACC	0.007%	−0.217	yes	5	−2.610
CTAACG	0.008%	NA	yes	5	−2.195
CTAAGA	0.019%	NA	yes	5	−4.433
CTAAGC	0.012%	−0.283	yes	5	−4.345
CTAAGG	0.018%	−0.377	yes	5	−4.084
CTACAA	0.013%	NA	no	5	0.791
CTACAC	0.007%	NA	no	5	−0.163
CTACAG	0.012%	NA	no	5	−0.758
CTACCA	0.006%	−0.188	no	5	0.181
CTACCC	0.004%	−0.211	no	5	−0.343
CTACCG	0.010%	0.356	no	5	−0.436
CTACGA	0.012%	0.366	no	5	−0.213
CTACGC	0.006%	0.446	no	5	0.518
CTACGG	0.010%	0.503	no	5	0.285
CTATAA	0.019%	−0.566	no	5	−3.209
CTATAC	0.006%	NA	no	5	−2.641
CTATAG	0.015%	−0.604	no	5	−0.860
CTATCA	0.009%	−0.456	no	5	−4.031
CTATCC	0.005%	NA	no	5	−5.014
CTATCG	0.010%	NA	no	5	0.587
CTATGA	0.011%	NA	no	5	−2.579
CTATGC	0.006%	−0.228	no	5	−1.462
CTATGG	0.011%	NA	no	5	−1.357
CTCAAT	0.016%	NA	no	5	−2.638
CTCACT	0.007%	NA	no	5	−3.336
CTCAGT	0.014%	NA	no	5	−2.816
CTCATA	0.011%	−0.431	no	5	−1.054
CTCATC	0.011%	NA	no	5	−0.961
CTCATG	0.010%	NA	no	5	0.531
CTCCAT	0.009%	NA	no	5	0.155
CTCCGT	0.007%	0.481	no	5	−1.212
CTCCTA	0.005%	NA	no	5	−3.446
CTCCTC	0.005%	NA	no	5	−1.099
CTCCTG	0.007%	0.444	no	5	0.418
CTCGAA	0.015%	NA	no	5	−0.108
CTCGAC	0.010%	0.491	no	5	−1.782
CTCGAG	0.012%	0.308	no	5	1.826
CTCGCA	0.008%	NA	no	5	−1.403
CTCGCG	0.015%	0.536	no	5	−0.761
CTCGGA	0.013%	0.520	no	5	0.278
CTCGGC	0.009%	0.432	no	5	1.334
CTCGGG	0.012%	0.323	no	5	1.920
CTCTAT	0.009%	−0.374	no	5	−4.034
CTCTCT	0.007%	NA	no	5	−0.997
CTCTGT	0.006%	NA	no	5	−3.627
CTCTTA	0.012%	−0.642	no	5	−2.883
CTCTTC	0.004%	NA	no	5	0.471
CTCTTG	0.008%	−0.257	no	5	−0.439
CTGAAT	0.023%	NA	yes	5	−1.424
CTGACT	0.012%	NA	yes	5	−2.077
CTGAGT	0.015%	NA	yes	5	−3.901
CTGATA	0.014%	NA	yes	5	−5.101
CTGATC	0.012%	NA	yes	5	−2.539
CTGATG	0.016%	0.235	yes	5	−2.001
CTGCAT	0.019%	NA	no	5	−1.930
CTGCCT	0.008%	0.310	no	5	−1.990
CTGCGT	0.011%	0.423	no	5	−0.420
CTGCTA	0.010%	NA	no	5	−1.068
CTGCTC	0.008%	0.334	no	5	−0.467
CTGCTG	0.013%	0.333	no	5	−1.002
CTGGAA	0.016%	NA	no	5	1.036
CTGGAC	0.009%	NA	no	5	−0.724
CTGGAG	0.017%	NA	no	5	−0.675
CTGGCA	0.016%	NA	no	5	0.172
CTGGCC	0.007%	NA	no	5	0.854
CTGGCG	0.013%	0.317	no	5	−0.298
CTGGGA	0.015%	0.115	no	5	−0.526
CTGGGC	0.010%	NA	no	5	−0.027
CTGGGG	0.015%	NA	no	5	0.165
CTGTAT	0.012%	NA	no	5	−0.148
CTGTCT	0.008%	NA	no	5	0.684
CTGTGT	0.013%	−0.177	no	5	2.444
CTGTTA	0.011%	NA	no	5	1.526
CTGTTC	0.008%	NA	no	5	−0.152
CTGTTG	0.013%	NA	no	5	0.424
CTTAAT	0.011%	−0.598	no	5	−1.921
CTTACT	0.010%	NA	no	5	−3.914
CTTAGT	0.010%	−0.774	no	5	−7.156
CTTATA	0.011%	−0.791	no	5	−1.113
CTTATC	0.009%	NA	no	5	−3.039
CTTATG	0.012%	−0.307	no	5	−1.075
CTTCAT	0.008%	NA	no	5	0.389
CTTCCT	0.005%	0.298	no	5	1.368
CTTCGT	0.007%	0.413	no	5	1.632
CTTCTA	0.008%	−0.363	no	5	−0.565
CTTCTC	0.006%	NA	no	5	−0.968
CTTCTG	0.006%	0.309	no	5	−0.153
CTTGAA	0.013%	NA	no	5	0.006
CTTGAC	0.008%	NA	no	5	2.668
CTTGAG	0.012%	NA	no	5	−0.635
CTTGCA	0.011%	−0.191	no	5	−0.758
CTTGCG	0.013%	NA	no	5	−1.131
CTTGGA	0.019%	NA	no	5	−0.476
CTTGGC	0.011%	NA	no	5	−0.152
CTTGGG	0.013%	NA	no	5	−0.037
CTTTAT	0.008%	−0.753	no	5	−1.800
CTTTCT	0.004%	NA	no	5	−3.554
CTTTGT	0.010%	−0.303	no	5	−0.930
CTTTTA	0.011%	−1.061	no	5	−2.689
CTTTTG	0.007%	−0.322	no	5	1.020
GAAAAA	0.073%	NA	no	5	−1.912
GAAAAC	0.063%	0.303	no	5	−0.762
GAAAAG	0.070%	NA	no	5	−0.456
GAAACA	0.067%	NA	no	5	−1.225
GAAACC	0.039%	0.340	no	5	−0.658
GAAACG	0.049%	0.468	no	5	−0.535
GAAAGA	0.067%	0.346	no	5	−1.562
GAAAGC	0.048%	0.298	no	5	−0.957
GAAAGG	0.074%	−0.141	no	5	−0.732
GAACAA	0.071%	0.467	no	5	−1.161
GAACAC	0.043%	0.417	no	5	−0.564
GAACAG	0.054%	NA	no	5	−1.772
GAACCA	0.036%	0.363	no	5	−0.524
GAACCC	0.022%	NA	no	5	−0.257
GAACCG	0.032%	0.585	no	5	0.157
GAACGA	0.046%	0.642	no	5	−0.098
GAACGC	0.032%	0.703	no	5	−0.930
GAACGG	0.056%	0.441	no	5	−0.213
GAATAA	0.067%	NA	no	5	−2.770
GAATAC	0.037%	0.406	no	5	−1.138
GAATAG	0.066%	−0.335	no	5	−1.653
GAATCA	0.043%	NA	no	5	−0.566
GAATCC	0.023%	0.470	no	5	−0.292
GAATCG	0.041%	0.586	no	5	0.067
GAATGA	0.061%	NA	no	5	−2.111
GAATGC	0.039%	0.197	no	5	−0.256
GAATGG	0.060%	NA	no	5	−0.599
GACAAT	0.030%	NA	no	5	0.539
GACACT	0.021%	0.281	no	5	−0.605
GACAGT	0.040%	NA	no	5	−1.244
GACATA	0.032%	NA	no	5	−0.663
GACATC	0.023%	0.682	no	5	0.415
GACATG	0.029%	0.262	no	5	0.258
GACCAT	0.024%	0.380	no	5	−0.090
GACCCT	0.018%	0.545	no	5	−0.032
GACCGT	0.017%	0.536	no	5	0.344
GACCTA	0.020%	NA	no	5	1.043
GACCTC	0.014%	0.384	no	5	−0.229
GACCTG	0.016%	0.664	no	5	0.902
GACGAA	0.034%	0.718	no	5	0.028
GACGAC	0.027%	0.846	no	5	−0.223
GACGAG	0.038%	0.529	no	5	−0.271
GACGCA	0.032%	0.514	no	5	−1.035
GACGCC	0.011%	0.663	no	5	−0.620
GACGCG	0.024%	0.821	no	5	0.142
GACGGA	0.041%	0.873	no	5	−0.316
GACGGC	0.021%	0.724	no	5	0.421
GACGGG	0.032%	0.470	no	5	0.153
GACTAT	0.022%	NA	no	5	−0.196
GACTCT	0.014%	0.397	no	5	−1.331
GACTGT	0.021%	0.323	no	5	0.052
GACTTA	0.027%	NA	no	5	−0.558
GACTTC	0.016%	0.445	no	5	−0.267
GACTTG	0.021%	0.168	no	5	0.013
GAGAAT	0.062%	0.309	no	5	−1.153
GAGACT	0.033%	0.490	no	5	−0.030
GAGAGT	0.050%	0.247	no	5	−1.343
GAGATA	0.052%	NA	no	5	−0.848
GAGATC	0.023%	0.477	no	5	−1.372
GAGATG	0.050%	0.327	no	5	−0.289
GAGCAT	0.034%	NA	no	5	−0.396
GAGCCT	0.014%	NA	no	5	−0.557
GAGCGT	0.028%	0.305	no	5	−0.085
GAGCTA	0.031%	−0.294	no	5	−0.698
GAGCTC	0.016%	NA	no	5	−0.583
GAGCTG	0.024%	0.270	no	5	0.367
GAGGAA	0.070%	0.410	no	5	−0.457
GAGGAC	0.032%	0.626	no	5	−0.912
GAGGAG	0.056%	0.247	no	5	−0.609
GAGGCA	0.043%	NA	no	5	−1.224
GAGGCC	0.025%	0.380	no	5	−0.061
GAGGCG	0.031%	0.332	no	5	−0.424
GAGGGA	0.058%	NA	no	5	−4.266
GAGGGC	0.029%	−0.084	no	5	−2.555
GAGGGG	0.053%	−0.144	no	5	−3.081
GAGTAT	0.039%	NA	no	5	−1.700
GAGTCT	0.019%	0.271	no	5	−0.853
GAGTGT	0.030%	NA	no	5	−0.801
GAGTTA	0.033%	−0.179	no	5	−2.132
GAGTTC	0.023%	0.210	no	5	−0.912
GAGTTG	0.028%	0.132	no	5	0.633
GATAAT	0.036%	NA	no	5	−2.443
GATACT	0.018%	0.225	no	5	−1.391
GATAGT	0.026%	−0.235	no	5	−6.217
GATATA	0.037%	NA	no	5	−2.538
GATATC	0.030%	NA	no	5	−2.461
GATATG	0.035%	NA	no	5	−0.826
GATCAT	0.020%	0.298	no	5	−1.305
GATCCT	0.013%	0.275	no	5	−0.810
GATCGT	0.019%	0.458	no	5	−0.584
GATCTA	0.021%	NA	no	5	−1.813
GATCTC	0.012%	NA	no	5	−1.894
GATCTG	0.025%	0.385	no	5	0.068
GATGAA	0.052%	0.510	no	5	−0.891
GATGAC	0.018%	0.643	no	5	0.550
GATGAG	0.024%	NA	no	5	−0.869
GATGCA	0.036%	0.205	no	5	−1.369
GATGCC	0.013%	0.546	no	5	0.690
GATGCG	0.021%	0.540	no	5	−0.126
GATGGA	0.033%	0.664	no	5	0.483
GATGGC	0.018%	0.576	no	5	0.448
GATGGG	0.034%	0.131	no	5	−0.136
GATTAT	0.020%	NA	no	5	−3.377
GATTCT	0.013%	0.273	no	5	−4.732
GATTGT	0.022%	NA	no	5	−2.355
GATTTA	0.033%	NA	no	5	−3.989
GATTTC	0.021%	NA	no	5	−3.935
GATTTG	0.023%	NA	no	5	−0.041
GCAAAA	0.051%	NA	no	5	−1.794
GCAAAC	0.033%	0.251	no	5	−1.201
GCAAAG	0.054%	NA	no	5	−0.704
GCAACA	0.042%	0.306	no	5	−0.302
GCAACC	0.019%	0.106	no	5	−0.899
GCAACG	0.035%	0.392	no	5	0.324
GCAAGA	0.047%	0.891	no	5	−0.150
GCAAGC	0.038%	0.195	no	5	−0.964
GCAAGG	0.039%	NA	no	5	−1.281
GCACAA	0.033%	NA	no	5	−1.175
GCACAC	0.027%	NA	no	5	−0.308
GCACAG	0.028%	NA	no	5	−0.687
GCACCA	0.029%	−0.116	no	5	−0.412
GCACCC	0.012%	−0.117	no	5	−1.725
GCACCG	0.020%	NA	no	5	0.718
GCACGA	0.033%	NA	no	5	−0.733
GCACGC	0.022%	NA	no	5	−0.224
GCACGG	0.028%	0.164	no	5	−0.404
GCATAA	0.037%	−0.153	no	5	−1.497
GCATAC	0.022%	NA	no	5	−1.032
GCATAG	0.036%	−0.161	no	5	−0.258
GCATCA	0.021%	NA	no	5	0.441
GCATCC	0.012%	NA	no	5	0.670
GCATCG	0.022%	NA	no	5	−0.098
GCATGA	0.035%	0.253	no	5	−0.535
GCATGC	0.018%	NA	no	5	−0.325
GCATGG	0.035%	0.097	no	5	−0.014
GCCAAT	0.023%	NA	no	5	−0.619
GCCACT	0.017%	NA	no	5	−0.735
GCCAGT	0.022%	−0.227	no	5	1.500
GCCATA	0.019%	−0.395	no	5	−1.324
GCCATC	0.015%	NA	no	5	−0.140
GCCATG	0.021%	NA	no	5	0.377
GCCCAT	0.017%	NA	no	5	−0.072
GCCCGT	0.012%	NA	no	5	−0.015
GCCCTA	0.009%	−0.425	no	5	−0.434
GCCCTC	0.009%	NA	no	5	−0.362
GCCCTG	0.011%	NA	no	5	0.271
GCCGAA	0.027%	NA	no	5	−0.995
GCCGAC	0.014%	0.435	no	5	−0.378
GCCGAG	0.022%	NA	no	5	0.343
GCCGCA	0.018%	NA	no	5	−0.175
GCCGCC	0.016%	NA	no	5	−1.112
GCCGCG	0.017%	0.487	no	5	1.475
GCCGGA	0.023%	0.428	no	5	0.006
GCCGGC	0.013%	NA	no	5	−0.237
GCCGGG	0.022%	0.409	no	5	0.540
GCCTAT	0.016%	−0.310	no	5	−0.958
GCCTCT	0.009%	NA	no	5	−0.415
GCCTGT	0.014%	NA	no	5	0.090
GCCTTA	0.016%	−0.481	no	5	−1.227
GCCTTC	0.010%	NA	no	5	−0.560
GCCTTG	0.015%	NA	no	5	0.114
GCGAAT	0.037%	NA	no	5	0.140
GCGACT	0.023%	0.434	no	5	0.664
GCGAGT	0.026%	NA	no	5	0.903
GCGATA	0.032%	NA	no	5	−0.079
GCGATC	0.015%	0.474	no	5	−0.188
GCGATG	0.023%	0.320	no	5	0.666
GCGCAT	0.020%	NA	no	5	0.153
GCGCCT	0.011%	0.298	no	5	−0.807
GCGCGT	0.016%	0.285	no	5	−1.638
GCGCTA	0.019%	NA	no	5	−0.341
GCGCTC	0.014%	NA	no	5	0.385
GCGCTG	0.020%	0.251	no	5	−0.476
GCGGAA	0.040%	0.461	no	5	−0.051
GCGGAC	0.021%	0.725	no	5	−0.390
GCGGAG	0.036%	0.346	no	5	−0.355
GCGGCA	0.025%	NA	no	5	0.120
GCGGCC	0.015%	NA	no	5	0.790
GCGGCG	0.027%	0.555	no	5	1.289
GCGGGA	0.042%	0.461	no	5	−0.986
GCGGGC	0.020%	0.289	no	5	−1.162
GCGGGG	0.030%	0.178	no	5	−0.662
GCGTAT	0.019%	NA	no	5	−1.712
GCGTCT	0.011%	0.302	no	5	−1.378
GCGTGT	0.017%	NA	no	5	−1.271
GCGTTA	0.016%	NA	no	5	−0.524
GCGTTC	0.012%	0.447	no	5	−0.686
GCGTTG	0.014%	0.149	no	5	−0.045
GCTAAT	0.019%	−0.321	no	5	−4.088
GCTACT	0.013%	NA	no	5	−1.692
GCTAGT	0.017%	−0.474	no	5	−7.760
GCTATA	0.024%	−0.534	no	5	−1.898
GCTATC	0.011%	NA	no	5	−2.675
GCTATG	0.015%	−0.251	no	5	1.611
GCTCAT	0.017%	NA	no	5	−1.340
GCTCCT	0.011%	NA	no	5	−0.085
GCTCGT	0.014%	NA	no	5	0.090
GCTCTA	0.020%	−0.349	no	5	−3.023
GCTCTC	0.013%	NA	no	5	−0.873
GCTCTG	0.016%	NA	no	5	0.288
GCTGAA	0.034%	NA	no	5	0.186
GCTGAC	0.017%	0.488	no	5	0.663
GCTGAG	0.024%	NA	no	5	−0.329
GCTGCA	0.021%	0.115	no	5	−0.911
GCTGCC	0.008%	0.179	no	5	2.076
GCTGCG	0.021%	0.446	no	5	−0.124
GCTGGA	0.028%	NA	no	5	−0.633
GCTGGC	0.013%	NA	no	5	0.510
GCTGGG	0.025%	−0.216	no	5	0.086
GCTTAT	0.018%	−0.369	no	5	−2.526
GCTTCT	0.008%	NA	no	5	−1.708
GCTTGT	0.022%	NA	no	5	0.587
GCTTTA	0.017%	−0.795	no	5	−2.826
GCTTTC	0.011%	NA	no	5	−1.505
GCTTTG	0.016%	−0.241	no	5	−0.412
GGCAAA	0.047%	0.128	no	5	−0.459
GGCAAC	0.026%	0.283	no	5	−0.188
GGCAAG	0.036%	0.398	no	5	0.412
GGCACA	0.030%	−0.086	no	5	−0.271
GGCACC	0.015%	−0.171	no	5	0.260
GGCACG	0.024%	NA	no	5	−0.495
GGCAGA	0.041%	0.210	no	5	0.887
GGCAGC	0.029%	NA	no	5	−0.243
GGCAGG	0.043%	−0.229	no	5	0.010
GGCCAA	0.028%	NA	no	5	0.253
GGCCAC	0.019%	NA	no	5	0.005
GGCCAG	0.025%	NA	no	5	−0.011
GGCCCA	0.015%	NA	no	5	−0.133
GGCCCC	0.012%	NA	no	5	−0.295
GGCCCG	0.014%	NA	no	5	0.293
GGCCGA	0.026%	0.204	no	5	0.231
GGCCGC	0.009%	0.202	no	5	2.060
GGCCGG	0.019%	0.129	no	5	−0.641
GGCTAA	0.027%	−0.257	no	5	0.240
GGCTAC	0.019%	NA	no	5	−0.109
GGCTAG	0.022%	−0.519	no	5	0.275
GGCTCA	0.016%	−0.282	no	5	0.232
GGCTCC	0.009%	NA	no	5	3.465
GGCTCG	0.019%	NA	no	5	1.424
GGCTGA	0.022%	0.192	no	5	0.203
GGCTGC	0.015%	0.151	no	5	0.186
GGCTGG	0.028%	−0.221	no	5	0.177
GGGAAA	0.073%	−0.218	no	5	−0.163
GGGAAC	0.046%	0.211	no	5	0.186
GGGAAG	0.065%	NA	no	5	−0.359
GGGACA	0.050%	NA	no	5	0.256
GGGACC	0.027%	0.292	no	5	0.047
GGGACG	0.039%	0.266	no	5	−0.327
GGGAGA	0.053%	NA	no	5	0.171
GGGAGC	0.030%	0.194	no	5	0.400
GGGAGG	0.045%	−0.461	no	5	−0.705
GGGCAA	0.044%	−0.271	no	5	−0.283
GGGCAC	0.031%	NA	no	5	0.330
GGGCAG	0.037%	−0.367	no	5	−0.572
GGGCCA	0.028%	NA	no	5	0.059
GGGCCC	0.016%	NA	no	5	0.440
GGGCCG	0.023%	NA	no	5	−0.113
GGGCGA	0.036%	NA	no	5	−0.193
GGGCGC	0.023%	0.189	no	5	−0.169
GGGCGG	0.028%	−0.213	no	5	0.023
GGGTAA	0.063%	−0.710	no	5	−1.042
GGGTAC	0.031%	−0.297	no	5	−0.338
GGGTAG	0.042%	−0.786	no	5	0.223
GGGTCA	0.031%	−0.432	no	5	0.385
GGGTCC	0.019%	NA	no	5	0.232
GGGTCG	0.024%	NA	no	5	−0.370
GGGTGA	0.031%	−0.361	no	5	0.084
GGGTGC	0.027%	−0.248	no	5	−0.622
GGGTGG	0.039%	−0.643	no	5	−0.238
GGTAAA	0.067%	−0.588	no	5	0.380
GGTAAC	0.035%	−0.330	no	5	0.469
GGTAAG	0.047%	−0.770	no	5	−1.643
GGTACA	0.041%	−0.359	no	5	0.125
GGTACG	0.029%	NA	no	5	−0.411
GGTAGA	0.040%	−0.530	no	5	−0.432
GGTAGC	0.028%	−0.532	no	5	−0.268
GGTAGG	0.039%	−0.818	no	5	−3.067
GGTCAA	0.038%	NA	no	5	0.106
GGTCAC	0.026%	NA	no	5	0.375
GGTCAG	0.032%	−0.351	no	5	−0.019
GGTCCA	0.017%	NA	no	5	−0.107
GGTCCC	0.009%	NA	no	5	0.610
GGTCCG	0.010%	NA	no	5	−0.116
GGTCGA	0.031%	NA	no	5	0.781
GGTCGC	0.017%	0.211	no	5	−0.479
GGTCGG	0.021%	NA	no	5	−0.400
GGTTAA	0.042%	−0.569	no	5	0.857
GGTTAC	0.021%	−0.225	no	5	0.462
GGTTAG	0.038%	−0.781	no	5	−0.483
GGTTCA	0.025%	−0.261	no	5	0.137
GGTTCC	0.006%	NA	no	5	−1.212
GGTTCG	0.019%	NA	no	5	−1.113
GGTTGA	0.031%	−0.204	no	5	0.084
GGTTGC	0.016%	−0.236	no	5	0.246
GGTTGG	0.027%	−0.324	no	5	−0.233
GTAAAA	0.060%	−0.504	yes	5	−5.354
GTAAAC	0.044%	−0.319	yes	5	−4.406
GTAAAG	0.047%	−0.374	yes	5	−3.346
GTAACA	0.040%	−0.466	yes	5	−4.312
GTAACC	0.027%	NA	yes	5	−3.350
GTAACG	0.040%	NA	yes	5	−2.749
GTAAGA	0.047%	−0.374	yes	5	−4.868
GTAAGC	0.033%	−0.425	yes	5	−5.240
GTAAGG	0.046%	−0.549	yes	5	−5.149
GTACAA	0.033%	−0.338	no	5	−2.376
GTACAC	0.027%	NA	no	5	−1.926
GTACAG	0.028%	−0.323	no	5	−0.605
GTACCA	0.022%	NA	no	5	−0.815
GTACCC	0.011%	NA	no	5	−0.631
GTACCG	0.018%	0.241	no	5	−0.081
GTACGA	0.023%	NA	no	5	−0.940
GTACGC	0.017%	NA	no	5	0.275
GTACGG	0.026%	0.162	no	5	−0.333
GTATAA	0.040%	−0.642	no	5	−4.297
GTATAC	0.025%	NA	no	5	−2.689
GTATAG	0.026%	−0.715	no	5	−1.271
GTATCA	0.029%	−0.292	no	5	−1.926
GTATCC	0.017%	NA	no	5	0.022
GTATCG	0.021%	NA	no	5	−0.770
GTATGA	0.037%	NA	no	5	−2.042
GTATGC	0.025%	−0.144	no	5	−0.688
GTATGG	0.030%	−0.214	no	5	−0.812
GTCAAT	0.025%	NA	no	5	−1.344
GTCACT	0.018%	NA	no	5	0.785
GTCAGT	0.032%	−0.308	no	5	−1.632
GTCATA	0.028%	NA	no	5	−0.727
GTCATC	0.018%	0.352	no	5	−0.151
GTCATG	0.025%	NA	no	5	−0.051
GTCCAT	0.018%	NA	no	5	−0.880
GTCCCT	0.008%	NA	no	5	−0.675
GTCCTA	0.013%	NA	no	5	−1.202
GTCCTC	0.007%	NA	no	5	−5.098
GTCCTG	0.010%	0.400	no	5	−2.620
GTCGAA	0.039%	NA	no	5	−1.055
GTCGAC	0.020%	0.686	no	5	0.900
GTCGAG	0.026%	NA	no	5	−0.778
GTCGCA	0.019%	NA	no	5	−1.538
GTCGCC	0.010%	0.441	no	5	−0.453
GTCGCG	0.022%	0.497	no	5	−0.592
GTCGGA	0.024%	0.394	no	5	−0.690
GTCGGC	0.020%	0.440	no	5	1.670
GTCGGG	0.025%	0.312	no	5	0.431
GTCTAT	0.020%	NA	no	5	−0.762
GTCTCT	0.011%	NA	no	5	−0.765
GTCTGT	0.016%	NA	no	5	−1.155
GTCTTA	0.013%	−0.386	no	5	−1.347
GTCTTC	0.008%	0.325	no	5	−2.003
GTCTTG	0.019%	NA	no	5	−0.336
GTGAAT	0.040%	0.199	yes	5	−2.115
GTGACT	0.020%	0.221	yes	5	−2.125
GTGAGT	0.039%	NA	yes	5	−3.111
GTGATA	0.035%	−0.165	yes	5	−2.428
GTGATC	0.023%	0.249	yes	5	−3.472
GTGATG	0.033%	0.235	yes	5	−3.399
GTGCAT	0.025%	−0.441	no	5	−0.232
GTGCCT	0.011%	−0.422	no	5	−0.446
GTGCGT	0.022%	−0.172	no	5	−0.824
GTGCTA	0.020%	−0.525	no	5	−0.885
GTGCTC	0.013%	−0.092	no	5	−0.179
GTGCTG	0.020%	NA	no	5	−1.182
GTGGAA	0.048%	0.587	no	5	−0.533
GTGGAC	0.031%	0.622	no	5	−0.439
GTGGAG	0.031%	0.512	no	5	0.284
GTGGCA	0.039%	NA	no	5	−0.129
GTGGCC	0.017%	NA	no	5	1.182
GTGGCG	0.024%	0.308	no	5	0.828
GTGGGA	0.043%	0.153	no	5	−1.383
GTGGGC	0.025%	−0.140	no	5	−0.349
GTGGGG	0.034%	−0.214	no	5	−0.841
GTGTAT	0.019%	−0.295	no	5	−0.725
GTGTCT	0.019%	NA	no	5	−1.105
GTGTGT	0.023%	−0.159	no	5	−0.949
GTGTTA	0.024%	−0.436	no	5	−0.211
GTGTTC	0.017%	NA	no	5	−0.341
GTGTTG	0.021%	−0.111	no	5	0.886
GTTAAT	0.026%	−0.287	no	5	−3.781
GTTACT	0.017%	NA	no	5	−2.622
GTTAGT	0.027%	−0.707	no	5	−8.956
GTTATA	0.021%	−0.314	no	5	−3.026
GTTATC	0.023%	0.149	no	5	−3.730
GTTATG	0.021%	−0.147	no	5	−1.779
GTTCAT	0.024%	0.162	no	5	−0.873
GTTCCT	0.005%	NA	no	5	0.484
GTTCGT	0.016%	0.428	no	5	−0.689
GTTCTA	0.017%	NA	no	5	−2.578
GTTCTC	0.011%	0.246	no	5	−2.189
GTTCTG	0.017%	0.165	no	5	0.789
GTTGAA	0.037%	0.175	no	5	−1.037
GTTGAC	0.014%	0.362	no	5	−1.330
GTTGAG	0.026%	−0.218	no	5	0.387
GTTGCA	0.025%	NA	no	5	−1.266
GTTGCC	0.014%	0.338	no	5	−0.182
GTTGCG	0.018%	0.366	no	5	0.269
GTTGGA	0.032%	0.175	no	5	0.049
GTTGGC	0.017%	0.180	no	5	−0.486
GTTGGG	0.024%	−0.182	no	5	−0.890
GTTTAT	0.017%	−0.244	no	5	−2.759
GTTTCT	0.015%	NA	no	5	−3.512
GTTTGT	0.022%	NA	no	5	−2.699
GTTTTA	0.020%	−0.312	no	5	−3.897
GTTTTC	0.012%	0.142	no	5	−6.195
GTTTTG	0.020%	−0.196	no	5	−0.776
TACAAA	0.034%	NA	no	5	−1.744
TACAAC	0.019%	NA	no	5	−0.751
TACAAG	0.035%	NA	no	5	−0.198
TACACA	0.026%	NA	no	5	−0.939
TACACC	0.014%	NA	no	5	−1.353
TACACG	0.023%	0.299	no	5	−0.284
TACAGA	0.029%	NA	no	5	−0.020
TACAGC	0.020%	NA	no	5	0.419
TACAGG	0.024%	−0.303	no	5	−0.484
TACCAA	0.020%	NA	no	5	−0.661
TACCAC	0.010%	NA	no	5	−1.428
TACCAG	0.018%	−0.081	no	5	−0.955
TACCCA	0.012%	−0.192	no	5	−0.595
TACCCC	0.010%	−0.148	no	5	−1.060
TACCCG	0.006%	0.302	no	5	−1.404
TACCGA	0.013%	0.439	no	5	−0.416
TACCGC	0.015%	NA	no	5	−0.105
TACCGG	0.014%	0.450	no	5	−0.806
TACTAA	0.014%	NA	no	5	−2.034
TACTAC	0.010%	NA	no	5	−1.549
TACTAG	0.017%	−0.521	no	5	−1.505
TACTCA	0.020%	NA	no	5	−2.617
TACTCC	0.007%	NA	no	5	−0.371
TACTCG	0.013%	0.268	no	5	−0.441
TACTGA	0.018%	NA	no	5	−1.449
TACTGC	0.015%	0.131	no	5	−0.786
TACTGG	0.015%	NA	no	5	−0.002
TAGAAA	0.039%	−0.457	no	5	−6.589
TAGAAC	0.016%	NA	no	5	−3.798
TAGAAG	0.041%	−0.334	no	5	−2.207
TAGACA	0.022%	−0.586	no	5	−5.210
TAGACC	0.014%	−0.252	no	5	−3.376
TAGACG	0.023%	NA	no	5	−2.794
TAGAGA	0.026%	−0.424	no	5	−4.534
TAGAGC	0.010%	NA	no	5	−3.536
TAGAGG	0.033%	−0.452	no	5	−4.480
TAGCAA	0.025%	−0.545	no	5	−6.255
TAGCAC	0.016%	−0.451	no	5	−7.027
TAGCAG	0.020%	−0.644	no	5	−1.294
TAGCCA	0.015%	−0.561	no	5	−5.679
TAGCCC	0.009%	−0.599	no	5	−4.306
TAGCCG	0.021%	NA	no	5	−0.532
TAGCGA	0.019%	NA	no	5	−4.953
TAGCGC	0.008%	NA	no	5	−2.377
TAGCGG	0.025%	−0.179	no	5	−0.275
TAGTAA	0.026%	−0.812	no	5	−8.863
TAGTAC	0.017%	−0.557	no	5	−7.798
TAGTAG	0.025%	−0.938	no	5	−4.603
TAGTCA	0.015%	−0.684	no	5	−4.130
TAGTCC	0.007%	−0.447	no	5	−4.568
TAGTCG	0.015%	NA	no	5	−5.048
TAGTGA	0.021%	−0.578	no	5	−8.614
TAGTGC	0.014%	−0.352	no	5	−4.905
TAGTGG	0.021%	−0.589	no	5	−4.232
TATAAA	0.035%	−0.504	no	5	−4.694
TATAAC	0.025%	−0.328	no	5	−4.439
TATAAG	0.037%	−0.518	no	5	−1.982
TATACA	0.024%	NA	no	5	−6.137
TATACC	0.010%	−0.224	no	5	−3.607
TATACG	0.020%	NA	no	5	−1.105
TATAGA	0.025%	−0.447	no	5	−5.487
TATAGC	0.023%	−0.401	no	5	−9.389
TATAGG	0.025%	−0.771	no	5	−3.740
TATCAA	0.019%	NA	no	5	−3.486
TATCAC	0.018%	NA	no	5	−3.211
TATCAG	0.020%	−0.379	no	5	−2.726
TATCCA	0.016%	NA	no	5	−2.892
TATCCC	0.008%	−0.329	no	5	−1.310
TATCCG	0.009%	0.426	no	5	−0.178
TATCGA	0.019%	NA	no	5	−0.977
TATCGC	0.017%	NA	no	5	−1.008
TATCGG	0.014%	0.215	no	5	−1.506
TATTAA	0.037%	−0.602	no	5	−5.478
TATTAC	0.023%	−0.356	no	5	−3.997
TATTAG	0.024%	−0.781	no	5	−3.825
TATTCA	0.025%	NA	no	5	−4.573
TATTCC	0.005%	−0.329	no	5	−5.515
TATTCG	0.011%	NA	no	5	−1.459
TATTGA	0.028%	NA	no	5	−4.403
TATTGC	0.021%	−0.358	no	5	−4.090
TATTGG	0.025%	−0.256	no	5	−1.227
TCCAAA	0.025%	NA	no	5	−0.289
TCCAAC	0.012%	NA	no	5	0.190
TCCAAG	0.021%	NA	no	5	−0.417
TCCACA	0.016%	NA	no	5	0.579
TCCACC	0.011%	−0.225	no	5	−0.574
TCCACG	0.013%	0.537	no	5	−0.677
TCCAGA	0.025%	0.053	no	5	0.050
TCCAGC	0.013%	NA	no	5	0.101
TCCAGG	0.017%	NA	no	5	−0.781
TCCCAA	0.013%	−0.444	no	5	−0.474
TCCCAC	0.010%	NA	no	5	−2.680
TCCCAG	0.014%	−0.292	no	5	−1.114
TCCCCA	0.012%	−0.476	no	5	0.763
TCCCCC	0.005%	−0.393	no	5	−0.635
TCCCCG	0.009%	0.350	no	5	0.046
TCCCGA	0.011%	NA	no	5	−0.342
TCCCGC	0.009%	NA	no	5	−0.775
TCCCGG	0.012%	0.401	no	5	1.328
TCCTAA	0.010%	NA	no	5	−1.571
TCCTAC	0.004%	NA	no	5	−1.401
TCCTAG	0.005%	−0.437	no	5	−0.513
TCCTCA	0.010%	NA	no	5	−0.458
TCCTCC	0.009%	NA	no	5	−0.145
TCCTCG	0.010%	0.623	no	5	0.593
TCCTGA	0.010%	NA	no	5	0.509
TCCTGC	0.010%	0.484	no	5	0.942
TCCTGG	0.010%	0.335	no	5	−0.442
TCGAAA	0.034%	NA	no	5	−0.872
TCGAAC	0.021%	0.477	no	5	−0.143
TCGAAG	0.035%	0.297	no	5	−0.951
TCGACA	0.018%	0.428	no	5	−1.033
TCGACC	0.013%	0.650	no	5	0.297
TCGACG	0.015%	0.875	no	5	−1.137
TCGAGA	0.025%	0.467	no	5	1.436
TCGAGC	0.022%	0.449	no	5	−0.432
TCGAGG	0.027%	0.256	no	5	−0.282
TCGCAA	0.026%	NA	no	5	0.831
TCGCAC	0.013%	0.502	no	5	−0.998
TCGCAG	0.016%	NA	no	5	−0.069
TCGCCA	0.016%	0.422	no	5	−0.507
TCGCCC	0.005%	0.352	no	5	−0.672
TCGCCG	0.007%	0.911	no	5	0.036
TCGCGA	0.014%	0.661	no	5	−0.336
TCGCGC	0.011%	0.674	no	5	−0.179
TCGCGG	0.022%	0.621	no	5	−0.504
TCGTAA	0.027%	NA	no	5	−2.058
TCGTAC	0.013%	0.472	no	5	0.648
TCGTAG	0.013%	−0.318	no	5	−1.878
TCGTCA	0.012%	0.502	no	5	−0.100
TCGTCC	0.008%	0.650	no	5	0.701
TCGTCG	0.012%	0.952	no	5	0.033
TCGTGA	0.018%	0.435	no	5	−0.519
TCGTGC	0.010%	0.216	no	5	−0.335
TCGTGG	0.017%	0.404	no	5	0.453
TCTAAA	0.022%	NA	no	5	−3.197
TCTAAC	0.015%	NA	no	5	−3.877
TCTAAG	0.017%	−0.346	no	5	−1.726
TCTACA	0.015%	NA	no	5	−1.131
TCTACC	0.006%	NA	no	5	−0.777
TCTACG	0.011%	0.646	no	5	0.472
TCTAGA	0.018%	NA	no	5	−4.489
TCTAGC	0.012%	NA	no	5	−4.016
TCTAGG	0.012%	−0.561	no	5	−4.521
TCTCAA	0.019%	NA	no	5	−2.451
TCTCAC	0.006%	NA	no	5	−0.333
TCTCAG	0.021%	NA	no	5	−1.602
TCTCCA	0.013%	−0.144	no	5	−0.625
TCTCCC	0.008%	NA	no	5	−1.035
TCTCCG	0.007%	0.647	no	5	0.334
TCTCGA	0.013%	0.385	no	5	−0.680
TCTCGC	0.015%	0.475	no	5	−0.125
TCTCGG	0.012%	0.283	no	5	1.031
TCTTAA	0.017%	NA	no	5	−4.390
TCTTAC	0.010%	NA	no	5	−2.830
TCTTAG	0.015%	−0.622	no	5	−2.510
TCTTCA	0.013%	0.348	no	5	−0.233
TCTTCC	0.004%	NA	no	5	−2.014
TCTTCG	0.008%	0.741	no	5	3.396
TCTTGA	0.018%	NA	no	5	−2.890
TCTTGC	0.007%	−0.251	no	5	−1.897
TCTTGG	0.017%	NA	no	5	0.655
TTCAAA	0.031%	NA	no	5	−0.805
TTCAAC	0.019%	0.504	no	5	−0.794
TTCAAG	0.024%	0.257	no	5	0.367
TTCACA	0.017%	NA	no	5	−1.522
TTCACC	0.010%	0.229	no	5	0.986
TTCACG	0.014%	0.388	no	5	−0.429
TTCAGA	0.028%	NA	no	5	−0.116
TTCAGC	0.013%	0.200	no	5	0.379
TTCAGG	0.022%	−0.322	no	5	−0.183
TTCCAA	0.016%	NA	no	5	−0.030
TTCCAG	0.013%	−0.066	no	5	−0.407
TTCCCA	0.011%	−0.468	no	5	−2.337
TTCCCG	0.007%	NA	no	5	−1.343
TTCCGA	0.011%	0.249	no	5	−0.972
TTCCGC	0.007%	0.275	no	5	−0.268
TTCCGG	0.005%	0.489	no	5	1.161
TTCTAA	0.014%	NA	no	5	−2.612
TTCTAC	0.011%	0.436	no	5	−0.142
TTCTAG	0.013%	−0.396	no	5	−1.354
TTCTCA	0.011%	NA	no	5	−2.262
TTCTCC	0.007%	0.170	no	5	0.765
TTCTCG	0.009%	0.383	no	5	−1.025
TTCTGA	0.015%	0.215	no	5	−0.870
TTCTGC	0.007%	0.286	no	5	−2.414
TTCTGG	0.013%	NA	no	5	0.018
TTGAAA	0.033%	NA	yes	5	−4.030
TTGAAC	0.018%	0.310	yes	5	−3.608
TTGAAG	0.025%	NA	yes	5	−1.958
TTGACA	0.025%	NA	yes	5	−2.711
TTGACC	0.015%	0.275	yes	5	−0.405
TTGACG	0.015%	0.454	yes	5	−2.523
TTGAGA	0.034%	NA	yes	5	−4.157
TTGAGC	0.018%	NA	yes	5	−4.963
TTGAGG	0.028%	−0.328	yes	5	−3.720
TTGCAA	0.022%	NA	no	5	−2.424
TTGCAC	0.015%	−0.183	no	5	−1.474
TTGCAG	0.021%	NA	no	5	−0.307
TTGCCA	0.017%	NA	no	5	−0.548
TTGCCC	0.009%	NA	no	5	0.299
TTGCCG	0.009%	0.568	no	5	1.067
TTGCGA	0.022%	0.421	no	5	−0.172
TTGCGC	0.013%	0.383	no	5	−1.171
TTGCGG	0.017%	0.281	no	5	−0.356
TTGTAA	0.030%	−0.266	no	5	−4.571
TTGTAC	0.018%	NA	no	5	−3.284
TTGTAG	0.024%	−0.529	no	5	−2.313
TTGTCA	0.019%	NA	no	5	−2.718
TTGTCC	0.008%	NA	no	5	−1.316
TTGTCG	0.011%	0.393	no	5	−2.406
TTGTGA	0.017%	NA	no	5	−1.559
TTGTGC	0.016%	−0.151	no	5	−1.858
TTGTGG	0.018%	−0.200	no	5	−1.023
TTTAAA	0.024%	−0.374	no	5	−5.352
TTTAAC	0.020%	−0.205	no	5	−4.093
TTTAAG	0.027%	−0.444	no	5	−1.160
TTTACA	0.019%	NA	no	5	−3.337
TTTACC	0.011%	NA	no	5	−1.276
TTTACG	0.015%	NA	no	5	−1.019
TTTAGA	0.022%	−0.485	no	5	−6.601
TTTAGC	0.017%	−0.551	no	5	−6.999
TTTAGG	0.024%	−0.785	no	5	−5.226
TTTCAA	0.021%	NA	no	5	−2.008
TTTCAC	0.012%	NA	no	5	−2.971
TTTCAG	0.018%	−0.189	no	5	−4.757
TTTCCA	0.018%	−0.218	no	5	−1.259
TTTCCC	0.005%	−0.179	no	5	−2.008
TTTCCG	0.009%	0.475	no	5	−0.553
TTTCGA	0.014%	0.442	no	5	−1.799
TTTCGC	0.012%	0.453	no	5	−1.907
TTTCGG	0.019%	0.214	no	5	−2.131
TTTTAA	0.021%	−0.387	no	5	−4.022
TTTTAC	0.015%	−0.193	no	5	−5.053
TTTTAG	0.025%	−0.648	no	5	−6.442
TTTTCA	0.017%	NA	no	5	−9.618
TTTTCC	0.005%	−0.165	no	5	−3.637
TTTTCG	0.012%	0.251	no	5	−2.527
TTTTGA	0.022%	NA	no	5	−5.532
TTTTGC	0.009%	−0.331	no	5	−3.122
TTTTGG	0.015%	−0.268	no	5	−1.089
AACAAA	0.079%	NA	no	6	−1.223
AACAAC	0.045%	0.551	no	6	−0.435
AACAAG	0.066%	NA	no	6	−0.152
AACACA	0.041%	NA	no	6	−0.450
AACACC	0.020%	NA	no	6	0.583
AACACG	0.039%	0.474	no	6	−0.449
AACAGA	0.064%	0.537	no	6	−0.863
AACAGC	0.038%	NA	no	6	−0.176
AACAGG	0.050%	−0.274	no	6	−0.552
AACCAA	0.044%	0.403	no	6	−0.664
AACCAC	0.025%	NA	no	6	−0.872
AACCAG	0.026%	NA	no	6	−0.484
AACCCA	0.027%	−0.352	no	6	−0.786
AACCCC	0.017%	−0.255	no	6	−0.008
AACCCG	0.020%	0.470	no	6	0.317
AACCGA	0.027%	NA	no	6	−0.091
AACCGC	0.022%	NA	no	6	0.099
AACCGG	0.027%	0.439	no	6	−0.504
AACTAA	0.032%	NA	no	6	−2.020
AACTAC	0.022%	0.312	no	6	−1.103
AACTAG	0.029%	−0.317	no	6	−0.749
AACTCA	0.028%	NA	no	6	−1.181
AACTCC	0.012%	NA	no	6	−1.754
AACTCG	0.027%	0.416	no	6	−0.043
AACTGA	0.038%	NA	no	6	−0.866
AACTGC	0.024%	0.209	no	6	−1.788
AACTGG	0.033%	NA	no	6	−0.353
AAGAAA	0.100%	0.795	no	6	−1.070
AAGAAC	0.051%	0.630	no	6	−0.752
AAGAAG	0.091%	0.591	no	6	−0.870
AAGACA	0.066%	0.424	no	6	−1.011
AAGACC	0.032%	0.397	no	6	−0.096
AAGACG	0.043%	0.725	no	6	−0.365
AAGAGA	0.071%	0.675	no	6	−2.059
AAGAGC	0.045%	0.394	no	6	−1.261
AAGAGG	0.074%	NA	no	6	−0.907
AAGCAA	0.051%	NA	no	6	−2.326
AAGCAC	0.040%	NA	no	6	−1.268
AAGCAG	0.045%	NA	no	6	−0.556
AAGCCA	0.031%	NA	no	6	−1.117
AAGCCC	0.015%	NA	no	6	−0.267
AAGCCG	0.022%	0.355	no	6	0.761
AAGCGA	0.039%	0.418	no	6	0.113
AAGCGC	0.028%	0.435	no	6	−0.954
AAGCGG	0.043%	0.286	no	6	−0.174
AAGTAA	0.070%	NA	no	6	−3.365
AAGTAC	0.030%	NA	no	6	−2.618
AAGTAG	0.058%	−0.478	no	6	−2.525
AAGTCA	0.033%	NA	no	6	−2.071
AAGTCC	0.009%	NA	no	6	−0.638
AAGTCG	0.026%	0.427	no	6	0.228
AAGTGA	0.053%	NA	no	6	−2.274
AAGTGC	0.029%	NA	no	6	−1.434
AAGTGG	0.049%	−0.168	no	6	−0.181
AATAAA	0.066%	−0.344	no	6	−3.830
AATAAC	0.026%	NA	no	6	−3.783
AATAAG	0.056%	−0.292	no	6	−1.313
AATACA	0.046%	NA	no	6	−4.253
AATACC	0.012%	NA	no	6	−2.592
AATACG	0.034%	NA	no	6	−0.468
AATAGA	0.048%	NA	no	6	−6.561
AATAGC	0.025%	NA	no	6	−4.772
AATAGG	0.047%	−0.629	no	6	−6.146
AATCAA	0.042%	NA	no	6	−2.974
AATCAC	0.033%	NA	no	6	−3.043
AATCAG	0.044%	NA	no	6	−2.719
AATCCA	0.027%	NA	no	6	−1.675
AATCCC	0.008%	−0.213	no	6	−3.348
AATCCG	0.018%	0.457	no	6	0.042
AATCGA	0.030%	0.468	no	6	−2.530
AATCGC	0.021%	0.396	no	6	0.006
AATCGG	0.034%	0.266	no	6	−0.083
AATTAA	0.031%	NA	no	6	−4.301
AATTAC	0.010%	NA	no	6	−3.265
AATTAG	0.026%	−0.609	no	6	−3.921
AATTCA	0.012%	NA	no	6	−6.142
AATTCC	0.002%	−0.220	no	6	−4.851
AATTCG	0.010%	0.321	no	6	−1.960
AATTGA	0.037%	NA	no	6	−3.507
AATTGC	0.012%	−0.205	no	6	−1.931
AATTGG	0.026%	NA	no	6	−0.842
ACCAAA	0.041%	NA	no	6	−1.640
ACCAAC	0.026%	NA	no	6	0.173
ACCAAG	0.039%	NA	no	6	−0.064
ACCACA	0.025%	NA	no	6	−1.649
ACCACC	0.015%	−0.424	no	6	−0.772
ACCACG	0.030%	0.371	no	6	−0.266
ACCAGA	0.032%	NA	no	6	0.760
ACCAGC	0.018%	NA	no	6	0.644
ACCAGG	0.038%	NA	no	6	0.447
ACCCAA	0.031%	−0.146	no	6	−1.064
ACCCAC	0.015%	−0.138	no	6	−1.499
ACCCAG	0.023%	−0.227	no	6	−0.827
ACCCCA	0.016%	−0.328	no	6	−1.261
ACCCCC	0.011%	−0.181	no	6	−1.060
ACCCCG	0.016%	0.122	no	6	0.043
ACCCGA	0.022%	0.318	no	6	0.129
ACCCGC	0.015%	0.273	no	6	−0.661
ACCCGG	0.022%	0.317	no	6	−0.080
ACCTAA	0.021%	−0.587	no	6	−1.676
ACCTAC	0.016%	NA	no	6	0.459
ACCTAG	0.020%	−0.327	no	6	−0.439
ACCTCA	0.018%	NA	no	6	−0.718
ACCTCC	0.011%	NA	no	6	0.266
ACCTCG	0.017%	0.548	no	6	−0.647
ACCTGA	0.027%	NA	no	6	−0.620
ACCTGC	0.016%	0.442	no	6	0.784
ACCTGG	0.022%	0.352	no	6	−0.530
ACGAAA	0.059%	NA	no	6	−0.509
ACGAAC	0.034%	0.473	no	6	−0.601
ACGAAG	0.054%	0.405	no	6	0.044
ACGACA	0.033%	NA	no	6	−0.435
ACGACC	0.019%	0.415	no	6	−0.709
ACGACG	0.035%	0.724	no	6	−0.168
ACGAGA	0.054%	NA	no	6	0.255
ACGAGC	0.032%	0.325	no	6	−1.146
ACGAGG	0.046%	0.215	no	6	−0.521
ACGCAA	0.033%	NA	no	6	−0.561
ACGCAC	0.021%	NA	no	6	−1.187
ACGCAG	0.028%	NA	no	6	0.578
ACGCCA	0.030%	0.372	no	6	−0.027
ACGCCC	0.014%	0.323	no	6	−0.528
ACGCCG	0.019%	0.809	no	6	0.736
ACGCGA	0.023%	0.485	no	6	0.189
ACGCGC	0.026%	0.608	no	6	−0.105
ACGCGG	0.029%	0.600	no	6	0.058
ACGTAA	0.033%	NA	no	6	−2.273
ACGTAC	0.021%	0.286	no	6	−1.357
ACGTAG	0.032%	−0.390	no	6	−0.423
ACGTCA	0.026%	NA	no	6	−0.306
ACGTCC	0.016%	0.553	no	6	−0.992
ACGTCG	0.019%	0.810	no	6	1.044
ACGTGA	0.031%	NA	no	6	0.058
ACGTGC	0.019%	0.195	no	6	0.168
ACGTGG	0.028%	0.352	no	6	−0.177
ACTAAA	0.040%	−0.583	no	6	−2.421
ACTAAC	0.028%	NA	no	6	−4.117
ACTAAG	0.040%	−0.359	no	6	−0.554
ACTACA	0.026%	NA	no	6	−1.668
ACTACC	0.016%	−0.209	no	6	−1.170
ACTACG	0.026%	0.510	no	6	−0.436
ACTAGA	0.031%	NA	no	6	−4.202
ACTAGC	0.016%	NA	no	6	−5.326
ACTAGG	0.027%	−0.542	no	6	−3.660
ACTCAA	0.033%	NA	no	6	−5.224
ACTCAC	0.020%	NA	no	6	−4.276
ACTCAG	0.030%	NA	no	6	−3.063
ACTCCA	0.021%	−0.139	no	6	−1.530
ACTCCC	0.013%	NA	no	6	−2.385
ACTCCG	0.017%	0.602	no	6	−0.524
ACTCGA	0.030%	NA	no	6	−2.188
ACTCGC	0.017%	0.389	no	6	−2.331
ACTCGG	0.025%	0.290	no	6	−0.663
ACTTAA	0.032%	−0.672	no	6	−2.935
ACTTAC	0.018%	NA	no	6	−2.808
ACTTAG	0.028%	−0.656	no	6	−2.578
ACTTCA	0.023%	NA	no	6	−2.397
ACTTCC	0.005%	NA	no	6	−1.028
ACTTCG	0.026%	0.621	no	6	0.417
ACTTGA	0.024%	NA	no	6	−1.997
ACTTGC	0.010%	−0.139	no	6	−1.414
ACTTGG	0.024%	NA	no	6	−0.685
ATCAAA	0.056%	NA	no	6	−0.835
ATCAAC	0.029%	NA	no	6	−0.314
ATCAAG	0.045%	NA	no	6	0.147
ATCACA	0.037%	NA	no	6	−0.680
ATCACC	0.019%	−0.206	no	6	−0.633
ATCACG	0.029%	0.259	no	6	0.279
ATCAGA	0.046%	NA	no	6	−0.826
ATCAGC	0.030%	NA	no	6	−2.575
ATCAGG	0.037%	−0.262	no	6	−0.642
ATCCAA	0.034%	NA	no	6	−0.925
ATCCAC	0.021%	NA	no	6	−0.263
ATCCAG	0.028%	0.145	no	6	0.100
ATCCCA	0.022%	−0.279	no	6	−0.105
ATCCCC	0.014%	−0.303	no	6	−1.336
ATCCCG	0.017%	0.506	no	6	0.680
ATCCGA	0.027%	NA	no	6	0.176
ATCCGC	0.014%	NA	no	6	0.323
ATCCGG	0.020%	0.511	no	6	−1.276
ATCTAA	0.034%	NA	no	6	−1.364
ATCTAC	0.021%	NA	no	6	−0.528
ATCTAG	0.021%	−0.547	no	6	−0.354
ATCTCA	0.023%	NA	no	6	−1.512
ATCTCC	0.010%	NA	no	6	0.658
ATCTCG	0.022%	0.322	no	6	0.927
ATCTGA	0.027%	NA	no	6	−0.341
ATCTGC	0.016%	0.286	no	6	−1.701
ATCTGG	0.031%	NA	no	6	−0.188
ATGAAA	0.066%	NA	yes	6	−3.745
ATGAAC	0.046%	0.449	yes	6	−3.231
ATGAAG	0.064%	0.338	yes	6	−2.507
ATGACA	0.041%	NA	yes	6	−5.400
ATGACC	0.022%	0.325	yes	6	−3.099
ATGACG	0.026%	0.544	yes	6	−2.841
ATGAGA	0.058%	NA	yes	6	−4.763
ATGAGC	0.032%	NA	yes	6	−4.554
ATGAGG	0.061%	−0.233	yes	6	−3.655
ATGCAA	0.043%	NA	no	6	−3.871
ATGCAC	0.028%	−0.109	no	6	−4.321
ATGCAG	0.032%	NA	no	6	−0.954
ATGCCA	0.029%	0.121	no	6	−2.194
ATGCCC	0.017%	NA	no	6	−1.692
ATGCCG	0.017%	0.422	no	6	−0.635
ATGCGA	0.040%	NA	no	6	−1.188
ATGCGC	0.024%	0.408	no	6	−1.314
ATGCGG	0.032%	0.291	no	6	−0.769
ATGTAA	0.050%	NA	no	6	−3.819
ATGTAC	0.028%	NA	no	6	−2.984
ATGTAG	0.044%	−0.544	no	6	−2.805
ATGTCA	0.032%	NA	no	6	−2.740
ATGTCC	0.014%	NA	no	6	−1.365
ATGTCG	0.024%	0.397	no	6	−0.366
ATGTGA	0.040%	NA	no	6	−2.236
ATGTGC	0.026%	NA	no	6	−2.607
ATGTGG	0.040%	NA	no	6	−0.587
ATTAAA	0.059%	−0.520	no	6	−3.838
ATTAAC	0.034%	NA	no	6	−3.640
ATTAAG	0.047%	−0.359	no	6	−1.145
ATTACA	0.046%	NA	no	6	−3.134
ATTACC	0.019%	−0.226	no	6	−0.545
ATTACG	0.020%	NA	no	6	−0.823
ATTAGA	0.045%	NA	no	6	−6.264
ATTAGC	0.025%	−0.441	no	6	−4.786
ATTAGG	0.036%	−0.727	no	6	−6.758
ATTCAA	0.035%	NA	no	6	−3.119
ATTCAC	0.021%	NA	no	6	−2.825
ATTCAG	0.031%	NA	no	6	−4.356
ATTCCA	0.016%	−0.152	no	6	−2.110
ATTCCG	0.009%	0.453	no	6	0.015
ATTCGA	0.026%	NA	no	6	−1.285
ATTCGC	0.017%	0.453	no	6	−0.274
ATTCGG	0.024%	0.274	no	6	−0.292
ATTTAA	0.035%	−0.490	no	6	−6.043
ATTTAC	0.021%	NA	no	6	−4.089
ATTTAG	0.034%	−0.668	no	6	−2.827
ATTTCA	0.030%	NA	no	6	−5.418
ATTTCC	0.009%	−0.330	no	6	−4.799
ATTTCG	0.024%	0.301	no	6	−1.362
ATTTGA	0.033%	NA	no	6	−3.536
ATTTGC	0.023%	−0.177	no	6	−3.379
ATTTGG	0.031%	NA	no	6	−1.002
CACAAA	0.030%	−0.211	no	6	−0.771
CACAAC	0.019%	NA	no	6	0.539
CACAAG	0.026%	NA	no	6	−0.359
CACACA	0.024%	NA	no	6	−2.081
CACACC	0.016%	NA	no	6	0.247
CACACG	0.020%	NA	no	6	0.003
CACAGA	0.022%	NA	no	6	−0.253
CACAGC	0.019%	−0.222	no	6	−0.260
CACAGG	0.026%	−0.235	no	6	−0.779
CACCAA	0.020%	−0.265	no	6	−0.763
CACCAC	0.013%	NA	no	6	−0.990
CACCAG	0.017%	−0.233	no	6	0.104
CACCCA	0.013%	−0.268	no	6	−1.539
CACCCC	0.012%	−0.179	no	6	−1.296
CACCCG	0.012%	0.193	no	6	0.915
CACCGA	0.022%	NA	no	6	−0.286
CACCGC	0.013%	NA	no	6	0.030
CACCGG	0.019%	0.390	no	6	−0.746
CACTAA	0.024%	−0.481	no	6	−2.068
CACTAC	0.011%	NA	no	6	−0.250
CACTAG	0.016%	−0.509	no	6	−0.299
CACTCA	0.019%	−0.208	no	6	−0.887
CACTCC	0.008%	NA	no	6	−1.706
CACTCG	0.014%	NA	no	6	−0.577
CACTGA	0.013%	NA	no	6	−1.397
CACTGC	0.010%	NA	no	6	0.823
CACTGG	0.019%	NA	no	6	0.426
CAGAAA	0.044%	NA	no	6	−1.080
CAGAAC	0.030%	0.200	no	6	−0.460
CAGAAG	0.044%	0.390	no	6	0.587
CAGACA	0.033%	NA	no	6	−1.182
CAGACC	0.014%	NA	no	6	−0.740
CAGACG	0.026%	0.466	no	6	−0.530
CAGAGA	0.038%	0.349	no	6	−0.391
CAGAGC	0.022%	NA	no	6	−0.552
CAGAGG	0.039%	NA	no	6	0.289
CAGCAA	0.026%	NA	no	6	−0.836
CAGCAC	0.016%	NA	no	6	−0.794
CAGCAG	0.022%	NA	no	6	−0.735
CAGCCA	0.018%	−0.445	no	6	−1.254
CAGCCC	0.011%	−0.242	no	6	3.943
CAGCCG	0.014%	NA	no	6	−0.381
CAGCGA	0.021%	NA	no	6	−0.777
CAGCGC	0.017%	NA	no	6	0.405
CAGCGG	0.025%	0.262	no	6	0.134
CAGTAA	0.036%	−0.456	no	6	−1.590
CAGTAC	0.019%	NA	no	6	1.194
CAGTAG	0.027%	−0.530	no	6	−0.331
CAGTCA	0.020%	−0.297	no	6	−0.655
CAGTCC	0.013%	NA	no	6	−0.147
CAGTCG	0.020%	0.213	no	6	−0.761
CAGTGA	0.025%	NA	no	6	−0.735
CAGTGC	0.012%	−0.163	no	6	−0.562
CAGTGG	0.029%	NA	no	6	−0.249
CATAAA	0.029%	−0.324	no	6	−2.097
CATAAC	0.021%	−0.238	no	6	−2.125
CATAAG	0.035%	NA	no	6	−0.479
CATACA	0.021%	NA	no	6	−1.533
CATACC	0.010%	NA	no	6	−1.021
CATACG	0.020%	NA	no	6	1.296
CATAGA	0.024%	NA	no	6	−2.030
CATAGC	0.015%	NA	no	6	−3.406
CATAGG	0.023%	−0.456	no	6	−2.964
CATCAA	0.021%	NA	no	6	0.271
CATCAC	0.018%	NA	no	6	−0.493
CATCAG	0.016%	NA	no	6	−0.703
CATCCA	0.012%	0.125	no	6	−0.239
CATCCC	0.008%	NA	no	6	−0.847
CATCCG	0.010%	0.184	no	6	0.198
CATCGA	0.023%	NA	no	6	−0.618
CATCGC	0.016%	0.232	no	6	0.067
CATCGG	0.020%	0.420	no	6	−0.054
CATTAA	0.018%	−0.355	no	6	−2.843
CATTAC	0.015%	NA	no	6	−2.805
CATTAG	0.017%	−0.514	no	6	−3.177
CATTCA	0.015%	NA	no	6	−2.604
CATTCC	0.006%	NA	no	6	−1.749
CATTCG	0.011%	0.186	no	6	1.072
CATTGA	0.016%	NA	no	6	−0.844
CATTGC	0.012%	NA	no	6	1.900
CATTGG	0.020%	NA	no	6	−1.491
CCCAAA	0.018%	−0.434	no	6	−2.557
CCCAAC	0.012%	NA	no	6	−0.519
CCCAAG	0.017%	NA	no	6	−0.776
CCCACA	0.012%	−0.150	no	6	−3.281
CCCACC	0.005%	−0.429	no	6	0.806
CCCACG	0.008%	0.302	no	6	−0.005
CCCAGA	0.010%	−0.243	no	6	0.265
CCCAGC	0.012%	−0.541	no	6	0.198
CCCAGG	0.010%	−0.091	no	6	−0.919
CCCCAA	0.010%	−0.359	no	6	−3.543
CCCCAC	0.005%	−0.155	no	6	−4.110
CCCCAG	0.011%	−0.423	no	6	−0.160
CCCCCA	0.010%	−0.396	no	6	−1.610
CCCCCC	0.004%	−0.137	no	6	−3.894
CCCCCG	0.004%	0.128	no	6	0.494
CCCCGA	0.010%	NA	no	6	−1.287
CCCCGC	0.008%	0.197	no	6	−0.294
CCCCGG	0.007%	0.192	no	6	−1.772
CCCTAA	0.012%	−0.467	no	6	−2.684
CCCTAC	0.003%	NA	no	6	−2.166
CCCTAG	0.005%	−0.531	no	6	−1.334
CCCTCA	0.010%	NA	no	6	−1.825
CCCTCC	0.005%	0.115	no	6	−1.343
CCCTCG	0.008%	0.365	no	6	−0.699
CCCTGA	0.012%	NA	no	6	0.587
CCCTGC	0.008%	0.317	no	6	0.904
CCCTGG	0.012%	0.134	no	6	0.020
CCGAAA	0.022%	NA	no	6	0.254
CCGAAC	0.016%	0.309	no	6	−0.653
CCGAAG	0.017%	0.455	no	6	−1.615
CCGACA	0.016%	NA	no	6	−0.232
CCGACC	0.008%	0.193	no	6	0.208
CCGACG	0.010%	0.786	no	6	−0.263
CCGAGA	0.020%	0.263	no	6	0.081
CCGAGC	0.012%	0.216	no	6	−0.027
CCGAGG	0.019%	0.358	no	6	0.033
CCGCAA	0.003%	NA	no	6	−2.683
CCGCAC	0.014%	NA	no	6	−1.423
CCGCAG	0.013%	−0.179	no	6	0.287
CCGCCA	0.011%	−0.119	no	6	−1.825
CCGCCC	0.006%	NA	no	6	−1.404
CCGCCG	0.007%	0.387	no	6	0.270
CCGCGA	0.014%	0.583	no	6	−0.361
CCGCGC	0.008%	0.485	no	6	−1.506
CCGCGG	0.008%	0.662	no	6	−0.293
CCGTAA	0.012%	NA	no	6	−0.303
CCGTAC	0.009%	NA	no	6	1.249
CCGTAG	0.011%	−0.348	no	6	−0.076
CCGTCA	0.010%	0.347	no	6	−0.858
CCGTCC	0.009%	0.395	no	6	0.551
CCGTCG	0.008%	0.857	no	6	−0.255
CCGTGA	0.015%	0.356	no	6	−0.091
CCGTGC	0.008%	0.205	no	6	0.378
CCGTGG	0.014%	0.447	no	6	0.216
CCTAAA	0.013%	−0.562	no	6	−2.307
CCTAAC	0.006%	−0.367	no	6	−1.831
CCTAAG	0.011%	−0.380	no	6	1.499
CCTACA	0.011%	NA	no	6	0.212
CCTACC	0.006%	NA	no	6	−0.373
CCTACG	0.012%	0.382	no	6	0.262
CCTAGA	0.010%	−0.469	no	6	−5.503
CCTAGC	0.007%	−0.608	no	6	−2.402
CCTAGG	0.010%	−0.465	no	6	−3.453
CCTCAA	0.010%	NA	no	6	−1.196
CCTCAC	0.008%	NA	no	6	−1.720
CCTCAG	0.012%	NA	no	6	−0.872
CCTCCA	0.011%	NA	no	6	−1.175
CCTCCC	0.005%	NA	no	6	−1.838
CCTCCG	0.007%	0.532	no	6	0.464
CCTCGA	0.009%	0.378	no	6	−0.270
CCTCGC	0.010%	0.374	no	6	−1.018
CCTCGG	0.011%	0.483	no	6	0.379
CCTTAA	0.013%	−0.629	no	6	−3.250
CCTTAC	0.005%	−0.322	no	6	−2.738
CCTTAG	0.008%	−0.773	no	6	−2.026
CCTTCA	0.008%	NA	no	6	−1.677
CCTTCC	0.006%	NA	no	6	−0.883
CCTTCG	0.006%	0.414	no	6	0.015
CCTTGA	0.008%	NA	no	6	−0.905
CCTTGC	0.005%	NA	no	6	0.222
CCTTGG	0.007%	0.141	no	6	−0.611
CTCAAA	0.023%	−0.488	no	6	0.380
CTCAAC	0.008%	NA	no	6	−1.472
CTCAAG	0.014%	NA	no	6	0.634
CTCACA	0.014%	NA	no	6	−0.348
CTCACC	0.008%	NA	no	6	0.519
CTCACG	0.009%	NA	no	6	−0.693
CTCAGA	0.022%	NA	no	6	−1.547
CTCAGC	0.008%	NA	no	6	−0.792
CTCAGG	0.016%	−0.316	no	6	−0.412
CTCCAA	0.012%	NA	no	6	0.477
CTCCAC	0.006%	NA	no	6	−0.726
CTCCAG	0.011%	−0.112	no	6	−0.419
CTCCCA	0.007%	−0.225	no	6	−3.150
CTCCCC	0.006%	−0.260	no	6	−3.218
CTCCGA	0.008%	0.507	no	6	−0.550
CTCCGC	0.007%	0.458	no	6	−2.501
CTCCGG	0.009%	0.532	no	6	−1.221
CTCTAA	0.012%	−0.382	no	6	−2.334
CTCTAC	0.009%	NA	no	6	−0.627
CTCTAG	0.009%	−0.387	no	6	−1.260
CTCTCA	0.006%	NA	no	6	−0.599
CTCTCG	0.009%	0.264	no	6	−1.408
CTCTGA	0.014%	NA	no	6	0.324
CTCTGC	0.013%	0.263	no	6	−1.298
CTCTGG	0.012%	NA	no	6	−0.087
CTGAAA	0.022%	NA	yes	6	−2.700
CTGAAC	0.011%	NA	yes	6	−4.087
CTGAAG	0.023%	0.266	yes	6	−1.983
CTGACA	0.013%	NA	yes	6	−2.374
CTGACC	0.009%	0.264	yes	6	−1.931
CTGACG	0.014%	0.522	yes	6	−2.443
CTGAGA	0.017%	NA	yes	6	−2.198
CTGAGG	0.014%	NA	yes	6	−3.700
CTGCAA	0.020%	NA	no	6	−0.143
CTGCAC	0.015%	0.260	no	6	0.900
CTGCAG	0.012%	NA	no	6	−0.984
CTGCCA	0.006%	NA	no	6	2.754
CTGCCC	0.010%	NA	no	6	−0.749
CTGCCG	0.011%	0.619	no	6	−0.021
CTGCGA	0.019%	0.659	no	6	0.152
CTGCGC	0.010%	0.585	no	6	1.570
CTGCGG	0.019%	0.581	no	6	0.797
CTGTAA	0.023%	NA	no	6	−0.148
CTGTAC	0.007%	NA	no	6	1.658
CTGTAG	0.013%	−0.556	no	6	1.942
CTGTCA	0.010%	NA	no	6	−0.657
CTGTCC	0.008%	0.214	no	6	1.759
CTGTCG	0.008%	0.540	no	6	1.654
CTGTGA	0.014%	0.272	no	6	−0.346
CTGTGC	0.008%	−0.312	no	6	−0.669
CTGTGG	0.014%	0.169	no	6	−0.424
CTTAAA	0.017%	−0.879	no	6	−1.900
CTTAAC	0.012%	−0.432	no	6	−1.462
CTTAAG	0.019%	−0.427	no	6	−0.539
CTTACA	0.012%	−0.564	no	6	−2.129
CTTACC	0.010%	NA	no	6	−1.288
CTTACG	0.009%	NA	no	6	−0.300
CTTAGA	0.014%	−0.503	no	6	−3.987
CTTAGG	0.017%	−0.727	no	6	−4.087
CTTCAA	0.014%	NA	no	6	−0.449
CTTCAC	0.007%	NA	no	6	−1.351
CTTCAG	0.009%	NA	no	6	−1.926
CTTCCA	0.008%	NA	no	6	1.026
CTTCCC	0.009%	−0.231	no	6	−1.730
CTTCGA	0.009%	0.509	no	6	−0.601
CTTCGC	0.009%	0.571	no	6	−0.222
CTTCGG	0.006%	0.540	no	6	−0.297
CTTTAA	0.014%	−1.050	no	6	−4.048
CTTTAC	0.006%	−0.372	no	6	−2.111
CTTTAG	0.011%	−0.855	no	6	−4.136
CTTTCA	0.009%	−0.561	no	6	−3.027
CTTTCC	0.005%	−0.238	no	6	−2.440
CTTTCG	0.007%	NA	no	6	−0.773
CTTTGA	0.010%	NA	no	6	−1.354
CTTTGC	0.005%	−0.256	no	6	−0.927
CTTTGG	0.011%	NA	no	6	0.375
GACAAA	0.048%	NA	no	6	−1.019
GACAAC	0.036%	0.513	no	6	0.299
GACAAG	0.047%	0.288	no	6	−0.317
GACACA	0.040%	NA	no	6	−0.164
GACACC	0.025%	NA	no	6	−0.184
GACACG	0.033%	0.493	no	6	−0.023
GACAGA	0.048%	0.414	no	6	−0.131
GACAGC	0.036%	NA	no	6	0.088
GACAGG	0.042%	−0.224	no	6	−0.521
GACCAA	0.033%	0.412	no	6	−0.634
GACCAC	0.020%	NA	no	6	−0.639
GACCAG	0.027%	0.338	no	6	−0.990
GACCCA	0.021%	NA	no	6	−0.026
GACCCC	0.014%	NA	no	6	0.042
GACCCG	0.015%	0.625	no	6	−0.042
GACCGA	0.022%	0.598	no	6	−0.695
GACCGC	0.017%	0.342	no	6	1.073
GACCGG	0.026%	0.647	no	6	0.166
GACTAA	0.030%	NA	no	6	−0.387
GACTAC	0.018%	0.414	no	6	−0.665
GACTAG	0.025%	−0.304	no	6	0.221
GACTCA	0.027%	NA	no	6	−1.031
GACTCC	0.012%	0.198	no	6	1.074
GACTCG	0.021%	0.502	no	6	0.492
GACTGA	0.025%	0.472	no	6	−0.563
GACTGC	0.018%	0.515	no	6	0.507
GACTGG	0.025%	0.199	no	6	−0.051
GAGAAA	0.075%	0.302	no	6	−0.608
GAGAAC	0.046%	0.504	no	6	−0.072
GAGAAG	0.064%	0.245	no	6	−0.118
GAGACA	0.042%	NA	no	6	−0.990
GAGACC	0.025%	0.480	no	6	−0.090
GAGACG	0.036%	0.528	no	6	0.029
GAGAGA	0.055%	0.355	no	6	−0.401
GAGAGC	0.035%	0.462	no	6	0.030
GAGAGG	0.056%	NA	no	6	−0.680
GAGCAA	0.050%	NA	no	6	−0.602
GAGCAC	0.021%	NA	no	6	−0.633
GAGCAG	0.030%	NA	no	6	−0.687
GAGCCA	0.028%	0.299	no	6	−0.128
GAGCCC	0.012%	NA	no	6	−0.182
GAGCCG	0.021%	0.367	no	6	0.563
GAGCGA	0.033%	0.483	no	6	−0.104
GAGCGC	0.023%	0.535	no	6	0.993
GAGCGG	0.025%	0.252	no	6	0.596
GAGTAA	0.059%	NA	no	6	−1.639
GAGTAC	0.030%	0.276	no	6	−0.956
GAGTAG	0.040%	−0.344	no	6	−0.575
GAGTCA	0.036%	NA	no	6	−1.241
GAGTCC	0.016%	0.454	no	6	2.359
GAGTCG	0.023%	0.400	no	6	−1.485
GAGTGA	0.049%	NA	no	6	−0.933
GAGTGC	0.023%	NA	no	6	−0.697
GAGTGG	0.046%	NA	no	6	0.097
GATAAA	0.046%	NA	no	6	−2.806
GATAAC	0.025%	NA	no	6	−2.792
GATAAG	0.039%	NA	no	6	−0.480
GATACA	0.037%	NA	no	6	−1.321
GATACC	0.015%	0.232	no	6	−0.654
GATACG	0.028%	0.389	no	6	0.151
GATAGA	0.036%	NA	no	6	−4.398
GATAGC	0.031%	NA	no	6	−4.817
GATAGG	0.033%	−0.688	no	6	−4.666
GATCAA	0.035%	NA	no	6	−1.017
GATCAC	0.018%	NA	no	6	−1.087
GATCAG	0.030%	−0.223	no	6	−0.915
GATCCA	0.021%	0.400	no	6	−0.191
GATCCC	0.010%	NA	no	6	−0.396
GATCCG	0.013%	0.488	no	6	−0.810
GATCGA	0.025%	0.518	no	6	0.807
GATCGC	0.018%	0.392	no	6	0.474
GATCGG	0.024%	0.443	no	6	−0.459
GATTAA	0.032%	−0.297	no	6	−2.387
GATTAC	0.016%	NA	no	6	−2.926
GATTAG	0.028%	−0.496	no	6	−2.360
GATTCA	0.017%	NA	no	6	−3.109
GATTCC	0.010%	0.223	no	6	−2.216
GATTCG	0.015%	0.518	no	6	−1.842
GATTGA	0.035%	0.284	no	6	−1.102
GATTGC	0.017%	0.123	no	6	0.027
GATTGG	0.031%	NA	no	6	0.014
GCCAAA	0.039%	−0.438	no	6	−0.555
GCCAAC	0.018%	NA	no	6	−1.562
GCCAAG	0.018%	NA	no	6	0.564
GCCACA	0.023%	NA	no	6	−1.006
GCCACC	0.012%	−0.311	no	6	0.422
GCCACG	0.023%	NA	no	6	−0.096
GCCAGA	0.032%	0.072	no	6	−0.378
GCCAGC	0.021%	−0.294	no	6	−0.658
GCCAGG	0.026%	−0.320	no	6	−0.140
GCCCAA	0.020%	−0.363	no	6	−0.822
GCCCAG	0.016%	NA	no	6	−0.433
GCCCCA	0.011%	−0.238	no	6	−1.599
GCCCCC	0.007%	−0.212	no	6	−1.362
GCCCCG	0.010%	NA	no	6	0.358
GCCCGA	0.016%	NA	no	6	0.050
GCCCGC	0.010%	NA	no	6	−0.827
GCCCGG	0.012%	0.337	no	6	−0.658
GCCTAA	0.021%	−0.647	no	6	−1.440
GCCTAC	0.012%	NA	no	6	−0.634
GCCTAG	0.014%	−0.583	no	6	−0.571
GCCTCA	0.017%	NA	no	6	−1.086
GCCTCC	0.009%	NA	no	6	−0.243
GCCTCG	0.015%	0.277	no	6	−0.446
GCCTGA	0.018%	NA	no	6	−0.038
GCCTGC	0.012%	0.260	no	6	−0.509
GCCTGG	0.017%	0.174	no	6	−0.392
GCGAAA	0.045%	NA	no	6	−0.470
GCGAAC	0.028%	0.478	no	6	−0.177
GCGAAG	0.043%	0.358	no	6	0.338
GCGACA	0.028%	NA	no	6	−0.690
GCGACC	0.016%	0.595	no	6	0.321
GCGACG	0.023%	0.718	no	6	0.170
GCGAGA	0.034%	0.353	no	6	−0.578
GCGAGC	0.023%	0.331	no	6	−0.297
GCGAGG	0.031%	NA	no	6	−0.506
GCGCAA	0.035%	NA	no	6	−0.479
GCGCAC	0.016%	0.375	no	6	−0.288
GCGCAG	0.021%	NA	no	6	−0.199
GCGCCA	0.022%	0.434	no	6	−0.253
GCGCCC	0.010%	0.289	no	6	−0.851
GCGCCG	0.010%	0.536	no	6	1.066
GCGCGA	0.029%	0.506	no	6	−0.952
GCGCGC	0.010%	0.556	no	6	−0.880
GCGCGG	0.017%	0.462	no	6	−0.572
GCGTAA	0.034%	NA	no	6	−0.710
GCGTAC	0.017%	NA	no	6	−0.423
GCGTAG	0.022%	−0.428	no	6	0.175
GCGTCA	0.020%	NA	no	6	−0.702
GCGTCC	0.012%	0.618	no	6	−1.056
GCGTCG	0.014%	0.676	no	6	0.218
GCGTGA	0.024%	NA	no	6	0.073
GCGTGC	0.021%	0.128	no	6	0.219
GCGTGG	0.023%	0.287	no	6	0.105
GCTAAA	0.032%	NA	no	6	−1.867
GCTAAC	0.017%	NA	no	6	−1.272
GCTAAG	0.027%	−0.416	no	6	0.145
GCTACA	0.019%	NA	no	6	−0.911
GCTACC	0.014%	NA	no	6	−0.258
GCTACG	0.023%	0.351	no	6	−0.409
GCTAGA	0.024%	NA	no	6	−3.703
GCTAGC	0.014%	−0.448	no	6	−4.537
GCTAGG	0.029%	−0.764	no	6	−5.587
GCTCAA	0.027%	NA	no	6	−0.588
GCTCAC	0.018%	NA	no	6	0.296
GCTCAG	0.021%	−0.343	no	6	−1.498
GCTCCA	0.021%	NA	no	6	−0.338
GCTCCC	0.010%	NA	no	6	0.651
GCTCCG	0.010%	0.283	no	6	0.669
GCTCGA	0.018%	NA	no	6	−1.157
GCTCGC	0.014%	NA	no	6	−0.417
GCTCGG	0.017%	0.150	no	6	−0.412
GCTTAA	0.026%	−0.508	no	6	−2.096
GCTTAC	0.014%	NA	no	6	−1.977
GCTTAG	0.019%	−0.606	no	6	−2.010
GCTTCA	0.014%	NA	no	6	−0.754
GCTTCG	0.014%	0.412	no	6	−0.136
GCTTGA	0.019%	NA	no	6	−1.411
GCTTGC	0.012%	−0.236	no	6	−0.179
GCTTGG	0.012%	NA	no	6	1.196
GTCAAA	0.045%	NA	no	6	−0.412
GTCAAC	0.020%	NA	no	6	0.672
GTCAAG	0.032%	NA	no	6	−0.189
GTCACA	0.030%	NA	no	6	−1.449
GTCACC	0.020%	NA	no	6	−0.815
GTCACG	0.024%	NA	no	6	−0.600
GTCAGA	0.039%	NA	no	6	−0.765
GTCAGC	0.020%	−0.251	no	6	−1.363
GTCAGG	0.044%	−0.467	no	6	−1.558
GTCCAA	0.023%	NA	no	6	−1.184
GTCCAC	0.015%	NA	no	6	−0.609
GTCCAG	0.023%	0.249	no	6	−0.943
GTCCCA	0.014%	−0.124	no	6	−1.573
GTCCCC	0.013%	−0.215	no	6	−0.382
GTCCCG	0.011%	0.260	no	6	0.504
GTCCGA	0.014%	NA	no	6	−0.097
GTCCGC	0.010%	NA	no	6	1.157
GTCCGG	0.015%	0.422	no	6	0.354
GTCTAA	0.020%	−0.418	no	6	0.162
GTCTAC	0.013%	NA	no	6	−1.077
GTCTAG	0.019%	−0.552	no	6	−0.533
GTCTCA	0.016%	NA	no	6	−1.110
GTCTCC	0.012%	NA	no	6	−0.588
GTCTCG	0.019%	0.226	no	6	0.787
GTCTGA	0.023%	NA	no	6	0.604
GTCTGC	0.018%	0.308	no	6	−4.146
GTCTGG	0.024%	NA	no	6	0.134
GTGAAA	0.050%	0.237	yes	6	−3.116
GTGAAC	0.035%	0.362	yes	6	−2.820
GTGAAG	0.047%	0.561	yes	6	−2.380
GTGACA	0.037%	0.119	yes	6	−2.181
GTGACC	0.017%	0.335	yes	6	−1.395
GTGACG	0.023%	0.584	yes	6	−3.743
GTGAGA	0.046%	0.363	yes	6	−3.601
GTGAGC	0.031%	NA	yes	6	−3.323
GTGAGG	0.047%	NA	yes	6	−1.848
GTGCAA	0.034%	−0.448	no	6	−1.188
GTGCAC	0.027%	−0.066	no	6	−0.335
GTGCAG	0.024%	−0.378	no	6	−0.583
GTGCCA	0.019%	−0.185	no	6	0.193
GTGCCC	0.013%	−0.378	no	6	1.213
GTGCCG	0.013%	NA	no	6	−0.739
GTGCGA	0.023%	NA	no	6	0.420
GTGCGC	0.013%	NA	no	6	−0.636
GTGCGG	0.030%	NA	no	6	0.075
GTGTAA	0.037%	−0.335	no	6	−1.019
GTGTAC	0.025%	NA	no	6	−0.619
GTGTAG	0.024%	−0.504	no	6	−0.551
GTGTCA	0.029%	−0.246	no	6	−1.512
GTGTCC	0.013%	NA	no	6	0.463
GTGTCG	0.020%	0.188	no	6	−0.356
GTGTGA	0.036%	0.125	no	6	−0.522
GTGTGC	0.022%	−0.174	no	6	0.097
GTGTGG	0.024%	NA	no	6	0.418
GTTAAA	0.041%	−0.232	no	6	−3.467
GTTAAC	0.024%	NA	no	6	−3.293
GTTAAG	0.036%	−0.390	no	6	−0.661
GTTACA	0.032%	NA	no	6	−3.654
GTTACC	0.016%	0.258	no	6	−2.418
GTTACG	0.017%	0.226	no	6	−0.631
GTTAGA	0.031%	−0.551	no	6	−6.895
GTTAGC	0.026%	−0.483	no	6	−3.657
GTTAGG	0.028%	−0.831	no	6	−9.046
GTTCAA	0.025%	0.224	no	6	−1.432
GTTCAC	0.015%	0.275	no	6	−0.576
GTTCAG	0.022%	NA	no	6	−3.395
GTTCCA	0.019%	0.146	no	6	−0.906
GTTCCC	0.009%	−0.385	no	6	−1.074
GTTCCG	0.008%	0.212	no	6	1.510
GTTCGA	0.026%	0.508	no	6	−1.121
GTTCGC	0.015%	0.589	no	6	−1.492
GTTCGG	0.016%	0.354	no	6	−0.379
GTTTAA	0.035%	−0.296	no	6	−3.228
GTTTAC	0.015%	NA	no	6	−2.741
GTTTAG	0.026%	−0.622	no	6	−2.072
GTTTCA	0.019%	NA	no	6	−4.684
GTTTCC	0.008%	0.180	no	6	−1.709
GTTTCG	0.015%	0.367	no	6	0.269
GTTTGA	0.025%	NA	no	6	−1.573
GTTTGC	0.015%	NA	no	6	−1.237
GTTTGG	0.019%	−0.200	no	6	0.065

TABLE 3
Effect sizes for the effects of each individual SNV in exon 18 of BRCA1 on exon splicing/stability
						Library	Library	Library	Library	Library	Library
		Average				R1	R1	R	R	L	L
		effect				Repli-	Repli-	Repli-	Repli-	Repli-	Repli-
		size (both				cate 1	cate 2	cate 1	cate 2	cate 1	cate 2
Exon		reps of	MutPredSplice		Mutation	effect	effect	effect	effect	effect	effect
Position	Variant	L and R)	score	MutPredSplice output	Type	size	size	size	size	size	size
1	C	−0.476	0.82	Splice Affecting Variant (SAV)	sense	NA	NA	NA	NA	−0.577	−0.376
				Loss of natural 3′ SS
				(P < 0.000001)
1	G	−0.493	0.9	Splice Affecting Variant (SAV)	sense	NA	NA	NA	NA	−0.839	−0.147
1	T	−0.661	0.85	Splice Affecting Variant (SAV)	sense	NA	NA	NA	NA	−1.048	−0.274
				Loss of natural 3′ SS
				(P < 0.000001)
2	A	−0.504	0.83	Splice Affecting Variant (SAV)	sense	NA	NA	NA	NA	−0.529	−0.478
				Loss of natural 3′ SS
				(P < 0.000001)
2	C	−0.630	0.85	Splice Affecting Variant (SAV)	sense	NA	NA	NA	NA	−0.746	−0.513
				Loss of natural 3′ SS
				(P < 0.000001)
2	G	−0.535	0.85	Splice Affecting Variant (SAV)	sense	NA	NA	NA	NA	−0.791	−0.278
				Loss of natural 3′ SS
				(P < 0.000001)
3	A	−0.494	0.77	Splice Affecting Variant (SAV)	sense	NA	NA	NA	NA	−0.528	−0.460
3	C	−0.300	0.65	Splice Affecting Variant (SAV)	sense	NA	NA	NA	NA	−0.022	−0.579
3	T	−0.466	0.8	Splice Affecting Variant (SAV)	sense	NA	NA	NA	NA	−0.563	−0.369
4	A	−0.119	0.52	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	−0.232	−0.007
4	G	−0.432	0.95	Splice Affecting Variant (SAV)	sense	NA	NA	NA	NA	−0.369	−0.495
				Cryptic 5′ SS (P = 0.001003)
4	T	−0.547	0.62	Splice Affecting Variant (SAV)	sense	NA	NA	NA	NA	−0.300	−0.794
5	A	−0.399	0.34	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	−0.599	−0.198
5	C	−0.841	0.39	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	−0.824	−0.859
5	G	−0.387	0.4	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	−0.437	−0.338
6	A	−0.436	0.79	Splice Affecting Variant (SAV)	sense	NA	NA	NA	NA	−0.330	−0.543
6	C	−0.192	0.53	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	−0.326	−0.058
6	T	−2.084	0.88	Splice Affecting Variant (SAV)	nonsense	NA	NA	NA	NA	−2.001	−2.167
				ESS Gain (P < 0.000001)
7	C	0.044	0.39	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	0.023	0.065
7	G	−0.192	0.74	Splice Affecting Variant (SAV)	sense	NA	NA	NA	NA	−0.293	−0.091
7	T	−0.246	0.53	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	−0.440	−0.052
8	A	−0.039	0.28	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	0.173	−0.251
8	C	−0.675	0.28	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	−1.104	−0.246
8	T	0.092	0.35	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	0.084	0.100
9	A	−0.342	0.3	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	−0.551	−0.134
9	C	−0.269	0.29	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	−0.063	−0.475
9	G	−0.294	0.48	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	−0.288	−0.301
10	A	−0.211	0.74	Splice Affecting Variant (SAV)	sense	NA	NA	NA	NA	−0.566	0.143
10	C	−0.027	0.35	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	−0.457	0.403
10	G	−0.138	0.39	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	−0.234	−0.043
11	A	−0.735	0.66	Splice Affecting Variant (SAV)	sense	NA	NA	NA	NA	−0.644	−0.827
11	C	−0.391	0.35	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	−0.277	−0.504
11	G	−0.171	0.72	Splice Affecting Variant (SAV)	sense	NA	NA	NA	NA	−0.169	−0.172
12	A	−0.191	0.56	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	−0.355	−0.027
12	C	−0.152	0.43	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	−0.301	−0.004
12	T	−0.321	0.53	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	−0.439	−0.203
13	A	−0.088	0.44	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	0.001	−0.178
13	C	−0.036	0.31	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	−0.073	0.002
13	G	−0.052	0.66	Splice Affecting Variant (SAV)	sense	NA	NA	NA	NA	−0.160	0.057
14	A	−0.074	0.76	Splice Affecting Variant (SAV)	sense	NA	NA	NA	NA	−0.009	−0.139
14	C	−0.034	0.36	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	−0.153	0.085
14	T	−0.068	0.55	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	−0.007	−0.130
15	A	0.195	0.77	Splice Affecting Variant (SAV)	sense	NA	NA	NA	NA	0.058	0.332
				Cryptic 5′ SS (P = 0.015766)
15	C	−0.047	0.34	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	−0.009	−0.084
15	G	−0.111	0.56	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	−0.185	−0.038
16	A	0.148	0.6	Splice Affecting Variant (SAV)	sense	NA	NA	NA	NA	0.103	0.192
16	C	−0.020	0.33	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	−0.081	0.040
16	T	−0.047	0.59	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	−0.123	0.028
17	A	−1.387	0.4	Splice Neutral Variant (SNV)	nonsense	NA	NA	NA	NA	−1.483	−1.292
17	C	−0.058	0.35	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	−0.038	−0.078
17	G	−0.074	0.36	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	−0.085	−0.063
18	A	−0.028	0.77	Splice Affecting Variant (SAV)	sense	NA	NA	NA	NA	0.101	−0.156
18	C	−0.194	0.36	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	−0.368	−0.021
18	T	−1.699	0.84	Splice Affecting Variant (SAV)	nonsense	NA	NA	NA	NA	−1.657	−1.740
				ESE Loss (P = 0.046524)
				ESS Gain (P = 0.000732)
19	C	−0.018	0.4	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	−0.034	−0.003
19	G	−0.069	0.39	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	−0.117	−0.021
19	T	0.226	0.77	Splice Affecting Variant (SAV)	sense	NA	NA	NA	NA	0.238	0.214
				ESE Loss (P = 0.004064)
20	C	0.054	0.33	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	0.047	0.060
20	G	0.049	0.49	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	−0.096	0.193
20	T	0.131	0.49	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	0.059	0.204
21	A	0.194	0.42	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	0.000	0.389
21	G	0.005	0.58	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	0.005	0.005
21	T	−0.529	0.53	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	−1.231	0.174
22	A	0.169	0.41	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	0.225	0.114
22	C	0.064	0.33	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	0.113	0.015
22	T	−0.232	0.37	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	−0.272	−0.193
23	A	0.134	0.39	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	0.047	0.221
23	C	0.270	0.58	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	0.419	0.121
23	T	0.164	0.58	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	0.254	0.075
24	C	0.187	0.59	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	0.040	0.335
24	G	0.161	0.54	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	0.132	0.190
24	T	0.071	0.67	Splice Affecting Variant (SAV)	sense	NA	NA	NA	NA	0.062	0.081
				ESE Loss (P = 0.000173)
25	A	0.098	0.35	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	0.241	−0.044
25	G	0.046	0.35	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	−0.041	0.133
25	T	−0.084	0.57	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	−0.145	−0.023
26	C	0.031	0.29	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	0.167	−0.105
26	G	−0.155	0.39	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	−0.177	−0.134
26	T	−0.088	0.34	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	−0.041	−0.134
27	A	−0.154	0.44	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	−0.216	−0.091
27	G	0.235	0.5	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	0.132	0.337
27	T	−0.144	0.36	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	−0.173	−0.116
28	A	−0.071	0.36	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	−0.017	−0.125
28	C	−0.334	0.34	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	−0.646	−0.022
28	G	−0.181	0.37	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	−0.363	0.002
29	A	0.000	0.76	Splice Affecting Variant (SAV)	sense	NA	NA	NA	NA	0.082	−0.081
				ESE Loss (P = 0.046524)
				ESS Gain (P = 0.034846)
29	C	0.010	0.48	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	0.073	−0.053
29	T	−0.537	0.8	Splice Affecting Variant (SAV)	sense	NA	NA	NA	NA	−0.637	−0.436
				ESE Loss (P = 0.046524)
				ESS Gain (P = 0.034846)
30	C	−0.039	0.43	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	−0.279	0.201
30	G	0.109	0.31	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	0.284	−0.065
30	T	−1.353	0.82	Splice Affecting Variant (SAV)	nonsense	NA	NA	NA	NA	−1.626	−1.081
				Cryptic 3′ SS (P = 0.03882)
31	C	−0.205	0.37	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	−0.211	−0.199
31	G	0.029	0.33	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	−0.102	0.160
31	T	−0.006	0.49	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	−0.074	0.062
32	C	0.228	0.28	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	0.367	0.088
32	G	−0.067	0.45	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	−0.015	−0.118
32	T	−0.097	0.38	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	−0.006	−0.188
33	A	0.189	0.28	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	0.023	0.355
33	C	−0.057	0.26	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	0.055	−0.169
33	G	−0.078	0.28	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	−0.683	0.527
34	C	0.085	0.31	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	0.066	0.104
34	G	0.207	0.45	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	0.163	0.252
34	T	−0.180	0.37	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	−0.300	−0.061
35	A	−1.130	0.36	Splice Neutral Variant (SNV)	nonsense	NA	NA	NA	NA	−0.842	−1.417
35	C	0.041	0.29	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	0.087	−0.004
35	G	−1.279	0.51	Splice Neutral Variant (SNV)	nonsense	NA	NA	NA	NA	−1.364	−1.195
36	A	−0.023	0.36	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	−0.065	0.018
36	C	0.039	0.32	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	0.243	−0.165
36	G	0.024	0.37	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	−0.028	0.077
37	A	0.111	0.37	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	0.170	0.052
37	C	−0.137	0.33	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	−0.455	0.180
37	G	−0.309	0.33	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	−0.270	−0.347
38	A	−0.010	0.42	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	−0.295	0.276
38	C	0.100	0.34	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	0.050	0.149
38	G	−0.146	0.36	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	−0.382	0.090
39	A	−0.034	0.44	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	−0.106	0.038
39	G	−0.073	0.47	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	−0.053	−0.093
39	T	−0.130	0.49	Splice Neutral Variant (SNV)	sense	NA	NA	NA	NA	0.055	−0.315
40	A	0.273	0.31	Splice Neutral Variant (SNV)	sense	0.857	−0.291	0.164	1.299	−0.084	−0.285
40	C	0.157	0.35	Splice Neutral Variant (SNV)	sense	1.050	0.107	0.496	0.146	−0.075	0.063
40	G	0.031	0.32	Splice Neutral Variant (SNV)	sense	1.239	0.694	−0.122	0.185	−0.102	0.164
41	C	−0.008	0.32	Splice Neutral Variant (SNV)	sense	0.475	0.340	0.578	−0.178	−0.212	−0.219
41	G	0.057	0.4	Splice Neutral Variant (SNV)	sense	0.042	0.078	0.515	0.253	−0.030	−0.509
41	T	0.094	0.32	Splice Neutral Variant (SNV)	nonsense	−0.027	0.287	0.170	0.267	−0.101	0.042
42	A	−0.166	0.42	Splice Neutral Variant (SNV)	sense	−0.084	0.671	−0.288	0.034	−0.413	0.004
42	C	0.102	0.36	Splice Neutral Variant (SNV)	sense	0.308	0.090	0.109	0.139	−0.154	0.312
42	T	−1.417	0.48	Splice Neutral Variant (SNV)	sense	−1.140	−0.760	−1.491	−1.723	−1.501	−0.952
43	A	0.117	0.34	Splice Neutral Variant (SNV)	sense	0.145	0.495	−0.119	0.195	0.065	0.326
43	C	0.151	0.42	Splice Neutral Variant (SNV)	sense	0.046	0.608	0.110	0.431	−0.057	0.119
43	T	−0.377	0.8	Splice Affecting Variant (SAV)	sense	−0.071	−0.219	−1.125	−0.950	0.162	0.404
44	C	−0.047	0.48	Splice Neutral Variant (SNV)	sense	0.044	0.120	−0.235	0.157	0.293	−0.402
44	G	−0.824	0.53	Splice Neutral Variant (SNV)	sense	0.041	0.049	−1.455	−0.786	−0.884	−0.171
44	T	−0.616	0.96	Splice Affecting Variant (SAV)	sense	−0.162	0.335	−1.208	−0.547	−0.569	−0.141
				ESS Gain (P = 0.000003)
				Cryptic 5′ SS (P = 0.018361)
45	C	0.114	0.37	Splice Neutral Variant (SNV)	sense	0.079	0.109	0.087	0.141	NA	NA
45	G	−0.257	0.42	Splice Neutral Variant (SNV)	sense	0.178	0.241	−0.316	−0.198	NA	NA
45	T	0.120	0.46	Splice Neutral Variant (SNV)	sense	0.046	−0.011	0.029	0.211	NA	NA
46	A	0.055	0.43	Splice Neutral Variant (SNV)	sense	0.352	0.488	−0.328	0.437	NA	NA
46	C	0.966	0.24	Splice Neutral Variant (SNV)	sense	0.244	0.316	0.550	1.382	NA	NA
46	G	0.071	0.36	Splice Neutral Variant (SNV)	sense	0.207	0.183	−0.030	0.173	NA	NA
47	A	0.149	0.46	Splice Neutral Variant (SNV)	sense	0.064	−0.220	0.395	−0.097	NA	NA
47	C	0.234	0.26	Splice Neutral Variant (SNV)	sense	0.252	0.660	−0.031	0.499	NA	NA
47	G	−0.494	0.35	Splice Neutral Variant (SNV)	sense	−0.272	0.232	−0.588	−0.400	NA	NA
48	A	0.211	0.42	Splice Neutral Variant (SNV)	sense	−0.183	0.321	0.127	0.294	NA	NA
48	C	0.222	0.3	Splice Neutral Variant (SNV)	sense	0.099	0.208	0.031	0.414	NA	NA
48	T	0.138	0.37	Splice Neutral Variant (SNV)	sense	0.072	0.146	0.153	0.124	NA	NA
49	A	−0.759	0.36	Splice Neutral Variant (SNV)	sense	−0.332	0.288	−0.610	−0.909	NA	NA
49	G	−2.574	0.61	Splice Affecting Variant (SAV)	sense	−1.447	−1.282	−2.905	−2.243	NA	NA
49	T	−0.784	0.48	Splice Neutral Variant (SNV)	sense	−0.264	−0.202	−0.877	−0.692	NA	NA
50	A	0.450	0.36	Splice Neutral Variant (SNV)	sense	0.532	0.158	0.310	0.590	NA	NA
50	C	0.106	0.25	Splice Neutral Variant (SNV)	sense	0.158	0.629	0.075	0.137	NA	NA
50	T	0.255	0.25	Splice Neutral Variant (SNV)	sense	0.152	0.198	0.382	0.127	NA	NA
51	A	0.408	0.29	Splice Neutral Variant (SNV)	sense	0.194	−0.245	0.265	0.551	NA	NA
51	C	0.567	0.33	Splice Neutral Variant (SNV)	sense	0.337	−0.034	0.767	0.367	NA	NA
51	T	−1.076	0.54	Splice Neutral Variant (SNV)	nonsense	−1.157	−0.704	−0.905	−1.248	NA	NA
52	A	0.039	0.34	Splice Neutral Variant (SNV)	sense	−0.027	0.076	0.100	−0.022	NA	NA
52	C	0.476	0.43	Splice Neutral Variant (SNV)	sense	0.079	−0.061	0.484	0.468	NA	NA
52	T	−0.334	0.92	Splice Affecting Variant (SAV)	sense	−0.340	−0.502	−0.268	−0.400	NA	NA
				Cryptic 5′ SS (P = 0.009018)
53	C	−0.048	0.4	Splice Neutral Variant (SNV)	sense	0.298	0.836	−0.067	−0.028	NA	NA
53	G	−1.757	0.69	Splice Affecting Variant (SAV)	sense	−0.949	−0.312	−1.933	−1.580	NA	NA
				ESE Loss (P = 0.046524)
				ESS Gain (P = 0.034846)
53	T	−0.070	0.46	Splice Neutral Variant (SNV)	sense	0.303	0.246	−0.077	−0.062	NA	NA
54	A	0.470	0.43	Splice Neutral Variant (SNV)	sense	−0.303	−0.264	0.035	0.905	NA	NA
54	C	0.222	0.4	Splice Neutral Variant (SNV)	sense	0.186	0.551	0.448	−0.004	NA	NA
54	T	−0.673	0.47	Splice Neutral Variant (SNV)	nonsense	−1.089	−0.743	−0.796	−0.549	NA	NA
55	A	0.796	0.5	Splice Neutral Variant (SNV)	sense	0.193	0.075	0.508	1.083	NA	NA
55	C	0.140	0.43	Splice Neutral Variant (SNV)	sense	0.171	−0.046	−0.201	0.481	NA	NA
55	T	0.073	0.84	Splice Affecting Variant (SAV)	sense	0.062	0.357	0.219	−0.073	NA	NA
				ESE Loss (P = 0.004064)
				ESS Gain (P = 0.034846)
56	C	−0.464	0.57	Splice Neutral Variant (SNV)	sense	0.380	0.579	−0.466	−0.463	NA	NA
56	G	−1.586	0.75	Splice Affecting Variant (SAV)	sense	−1.392	−0.978	−1.516	−1.656	NA	NA
				ESE Loss (P = 0.004064)
56	T	−0.926	0.98	Splice Affecting Variant (SAV)	sense	−0.836	−1.042	−0.923	−0.930	NA	NA
				ESE Loss (P = 0.004064)
				Cryptic 5′ SS (P = 0.003403)
57	C	0.275	0.31	Splice Neutral Variant (SNV)	sense	0.617	0.091	0.063	0.488	NA	NA
57	G	−0.159	0.31	Splice Neutral Variant (SNV)	sense	0.028	0.147	−0.594	0.276	NA	NA
57	T	−1.998	0.62	Splice Affecting Variant (SAV)	nonsense	−1.675	−1.613	−1.949	−2.048	NA	NA
58	C	−0.181	0.29	Splice Neutral Variant (SNV)	sense	0.206	−0.031	−0.209	−0.154	NA	NA
58	G	−0.068	0.35	Splice Neutral Variant (SNV)	sense	0.657	0.338	0.009	−0.145	NA	NA
58	T	0.344	0.44	Splice Neutral Variant (SNV)	sense	0.149	0.321	0.246	0.441	NA	NA
59	C	−0.037	0.31	Splice Neutral Variant (SNV)	sense	−0.110	0.042	0.427	−0.500	NA	NA
59	G	−0.192	0.56	Splice Neutral Variant (SNV)	sense	−0.067	−0.130	−0.366	−0.017	NA	NA
59	T	0.137	0.41	Splice Neutral Variant (SNV)	sense	−0.332	−0.015	0.283	−0.010	NA	NA
60	A	0.046	0.58	Splice Neutral Variant (SNV)	sense	0.350	0.033	−0.102	0.193	NA	NA
60	C	0.325	0.58	Splice Neutral Variant (SNV)	sense	0.079	−0.308	0.517	0.133	NA	NA
60	G	−0.473	0.59	Splice Neutral Variant (SNV)	sense	−0.622	−0.343	−0.440	−0.505	NA	NA
61	A	−2.485	0.84	Splice Affecting Variant (SAV)	nonsense	−1.871	−1.798	−2.150	−2.820	NA	NA
61	C	0.504	0.6	Splice Affecting Variant (SAV)	sense	−0.015	0.149	0.396	0.612	NA	NA
				ESS Loss (P < 0.000001)
61	T	0.316	0.56	Splice Neutral Variant (SNV)	sense	0.278	0.295	0.448	0.184	NA	NA
62	A	−0.827	0.61	Splice Affecting Variant (SAV)	nonsense	−0.638	−0.412	−0.674	−0.980	NA	NA
				ESS Loss (P < 0.000001)
62	C	0.112	0.52	Splice Neutral Variant (SNV)	sense	0.367	0.571	0.120	0.105	NA	NA
62	T	0.737	0.55	Splice Neutral Variant (SNV)	sense	0.396	−0.456	0.824	0.651	NA	NA
63	A	0.133	0.39	Splice Neutral Variant (SNV)	sense	0.570	0.316	0.311	−0.045	NA	NA
63	C	−0.144	0.44	Splice Neutral Variant (SNV)	sense	0.897	0.597	0.087	−0.374	NA	NA
63	T	−2.229	0.82	Splice Affecting Variant (SAV)	sense	−2.707	−2.655	−2.037	−2.421	NA	NA
				Cryptic 5′ SS (P = 0.007933)
64	A	0.247	0.53	Splice Neutral Variant (SNV)	sense	0.153	−0.203	0.031	0.463	NA	NA
64	C	0.260	0.47	Splice Neutral Variant (SNV)	sense	0.505	1.164	−0.026	0.546	NA	NA
64	G	−0.056	0.55	Splice Neutral Variant (SNV)	sense	−0.095	0.672	−0.656	0.544	NA	NA
65	C	0.535	0.44	Splice Neutral Variant (SNV)	sense	0.917	0.447	0.258	0.813	NA	NA
65	G	0.291	0.54	Splice Neutral Variant (SNV)	sense	0.271	0.442	0.517	0.064	NA	NA
65	T	0.362	0.5	Splice Neutral Variant (SNV)	sense	0.152	0.415	0.377	0.348	NA	NA
66	A	−0.386	0.87	Splice Affecting Variant (SAV)	sense	−0.490	−0.570	−0.088	−0.684	NA	NA
				Cryptic 5′ SS (P = 0.013422)
66	C	0.301	0.7	Splice Affecting Variant (SAV)	sense	0.393	0.115	0.104	0.499	NA	NA
66	T	0.217	0.75	Splice Affecting Variant (SAV)	sense	0.202	0.131	0.149	0.285	NA	NA
67	A	−0.154	0.59	Splice Neutral Variant (SNV)	sense	0.125	0.081	−0.431	0.123	NA	NA
67	C	0.117	0.55	Splice Neutral Variant (SNV)	sense	0.012	0.052	0.138	0.096	NA	NA
67	G	−4.136	0.93	Splice Affecting Variant (SAV)	sense	−4.512	−3.529	−3.967	−4.306	NA	NA
				Cryptic 5′ SS (P = 0.009018)
68	A	−0.097	0.75	Splice Affecting Variant (SAV)	sense	0.011	0.173	0.289	−0.483	NA	NA
68	C	0.054	0.37	Splice Neutral Variant (SNV)	sense	0.367	0.025	0.248	−0.140	NA	NA
68	G	0.102	0.48	Splice Neutral Variant (SNV)	sense	0.211	0.111	0.297	−0.093	NA	NA
69	C	0.001	0.4	Splice Neutral Variant (SNV)	sense	0.300	−0.419	0.124	−0.122	NA	NA
69	G	−0.131	0.38	Splice Neutral Variant (SNV)	sense	0.061	0.140	−0.251	−0.011	NA	NA
69	T	−0.030	0.57	Splice Neutral Variant (SNV)	sense	−0.008	−0.170	−0.137	0.076	NA	NA
70	A	−0.212	0.58	Splice Neutral Variant (SNV)	sense	0.019	−0.386	−0.182	−0.242	NA	NA
70	C	−0.191	0.38	Splice Neutral Variant (SNV)	sense	−0.334	−0.909	−0.001	−0.381	NA	NA
70	T	−0.159	0.56	Splice Neutral Variant (SNV)	sense	−0.217	0.183	0.087	−0.405	NA	NA
71	A	−0.020	0.59	Splice Neutral Variant (SNV)	sense	0.433	0.021	−0.712	0.671	NA	NA
71	G	−0.547	0.97	Splice Affecting Variant (SAV)	sense	−0.203	−0.771	−0.761	−0.332	NA	NA
				ESS Gain (P < 0.000001)
				Cryptic 5′ SS (P = 0.021088)
71	T	−0.325	0.76	Splice Affecting Variant (SAV)	sense	0.060	0.257	−0.317	−0.332	NA	NA
				ESS Gain (P < 0.000001)
72	A	−0.320	0.32	Splice Neutral Variant (SNV)	sense	0.623	0.348	−0.168	−0.473	NA	NA
72	C	0.106	0.34	Splice Neutral Variant (SNV)	sense	−0.167	0.024	−0.017	0.229	NA	NA
72	G	−0.044	0.37	Splice Neutral Variant (SNV)	sense	0.627	0.199	−0.086	−0.002	NA	NA
73	C	0.234	0.35	Splice Neutral Variant (SNV)	sense	0.181	0.119	0.491	−0.024	NA	NA
73	G	0.089	0.34	Splice Neutral Variant (SNV)	sense	0.352	0.113	−0.248	0.427	NA	NA
73	T	−0.229	0.4	Splice Neutral Variant (SNV)	sense	0.103	0.196	0.013	−0.471	NA	NA
74	A	−1.758	0.45	Splice Neutral Variant (SNV)	nonsense	−0.942	−1.421	−1.427	−2.090	NA	NA
74	C	−0.153	0.37	Splice Neutral Variant (SNV)	sense	−0.153	−0.065	−0.100	−0.206	NA	NA
74	G	−2.168	0.59	Splice Neutral Variant (SNV)	nonsense	−1.380	−1.661	−2.321	−2.016	NA	NA
75	A	0.422	0.51	Splice Neutral Variant (SNV)	sense	0.847	0.405	0.340	0.504	NA	NA
75	C	0.019	0.45	Splice Neutral Variant (SNV)	sense	0.624	0.503	−0.035	0.073	NA	NA
75	G	0.415	0.54	Splice Neutral Variant (SNV)	sense	0.206	0.384	0.577	0.253	NA	NA
76	A	−0.002	0.69	Splice Affecting Variant (SAV)	sense	−0.103	0.311	−0.328	0.323	NA	NA
76	C	0.100	0.75	Splice Affecting Variant (SAV)	sense	−0.023	−0.306	−0.132	0.332	NA	NA
76	G	−0.031	0.68	Splice Affecting Variant (SAV)	sense	0.441	0.298	−0.362	0.301	NA	NA
77	A	−0.095	0.85	Splice Affecting Variant (SAV)	sense	−0.386	−0.936	0.220	−0.409	NA	NA
				Loss of natural 5′ SS
				(P < 0.000001)
77	G	−0.005	0.85	Splice Affecting Variant (SAV)	sense	0.318	0.769	−0.223	0.213	NA	NA
77	T	−0.564	0.85	Splice Affecting Variant (SAV)	sense	0.094	−0.340	−0.385	−0.743	NA	NA
78	A	−0.277	0.82	Splice Affecting Variant (SAV)	sense	−0.094	−0.418	0.054	−0.608	NA	NA
78	C	−0.024	0.82	Splice Affecting Variant (SAV)	sense	−0.269	0.327	0.170	−0.219	NA	NA
78	G	0.686	0.83	Splice Affecting Variant (SAV)	sense	−0.004	0.512	0.753	0.620	NA	NA

TABLE 4
Emprical measurement of the effects of genome edits to exon 2 of DBR1 on cellular growth
Gray rows indicate missing data across both replicates

Claims

1. A method for introducing a plurality of programmed nucleotide modifications into a single locus of a desired genomic DNA sequence, comprising: (a) synthesizing a homology-directed repair (HDR) library comprising a plurality of oligonucleotides, wherein each oligonucleotide comprises a programmed nucleotide modification in the locus of the desired genome; and(b) co-transfecting a population of cells with (i) an expression system capable of expressing Cas9 and a single guide RNA (sgRNA), and (ii) the HDR library, wherein the expression system is capable of introducing the plurality of oligonucleotides having the programmed nucleotide modifications to the locus of the desired genomic DNA sequence in one or more cells of the population;wherein the method is carried out in a single experiment.

2. The method of claim 1, wherein each programmed nucleotide modification is a single nucleotide variant.

3. The method of claim 1, wherein the HDR library is constructed using an oligonucleotide comprising a degenerate sequence.

4. The method of claim 3, wherein the degenerate sequence is between 1 and 100 nucleotides in length.

5. The method of claim 4, wherein the HDR library comprises a set of oligonucleotides having at least 100 unique programmed nucleotide modifications, a least 200 unique programmed nucleotide modifications, at least 300 unique programmed nucleotide modifications, at least 400 unique programmed nucleotide modifications, at least 500 unique programmed nucleotide modifications, at least 600 unique programmed nucleotide modifications, at least 700 unique programmed nucleotide modifications, at least 800 unique programmed nucleotide modifications, at least 900 unique programmed nucleotide modifications, at least 1,000 unique programmed nucleotide modifications, at least 3,000 unique programmed nucleotide modifications, at least 4,000 unique programmed nucleotide modifications, at least 5,000 unique programmed nucleotide modifications, at least 6,000 unique programmed nucleotide modifications, at least 7,000 unique programmed nucleotide modifications, at least 8,000 unique programmed nucleotide modifications, at least 9,000 unique programmed nucleotide modifications, at least 10,000 unique programmed nucleotide modifications, at least 12,000 unique programmed nucleotide modifications, at least 14,000 unique programmed nucleotide modifications, at least 16,000 unique programmed nucleotide modifications, at least 18,000 unique programmed nucleotide modifications, at least 20,000 unique programmed nucleotide modifications, at least 25,000 unique programmed nucleotide modifications, at least 30,000 unique programmed nucleotide modifications, at least 40,000 unique programmed nucleotide modifications, or at least 50,000 unique programmed nucleotide modifications.

6. The method of claim 1, wherein the plurality of programmed nucleotide modifications that are introduced to the locus of the desired genomic DNA sequence results in a saturating set of programmed nucleotide modifications.

7. The method of claim 1, wherein the plurality of oligonucleotides are synthesized on a microarray or in column-based synthesis.

8. The method of claim 1, wherein the expression system comprises a plasmid which comprises (i) a Cas9 expression cassette that includes a nucleotide sequence which encodes a Cas9 nuclease, (ii) an sgRNA expression cassette, and (iii) a species-specific promoter that is specific to the population of cells.

9. The method of claim 1, further comprising cloning the HDR library prior to the step of co-transfecting the population of cells.

10. The method of claim 1, wherein each oligonucleotide of the HDR library further comprises a pair of homology arms.

11. The method of claim 1, further comprising (c) harvesting the population of cells,(d) selectively amplifying a genomic DNA and RNA sample, wherein the edited sequences are amplified and the non-edited sequence are not amplified, and(e) sequencing the genomic DNA and RNA sample that has been selectively amplified, resulting in a set of genomic transcripts which include the plurality of programmed nucleotide modifications.

12. The method of claim 11, further comprising functionally analyzing the set of genomic transcripts using a functional assay.

13. The method of claim 12, wherein the functional assay is selected from the group consisting of targeted RNA sequencing to measure transcript abundance, targeted DNA sequencing to measure reduced cellular fitness, targeted chromatin immunoprecipitation-sequencing (CHiP-seq) of co-activators to assay enhancers, increased cellular growth rate to assay cancer drivers or drug resistance, and FACS-based phenotypic sorting for cellular assays.

14. A method for analyzing the functional consequence of a genomic mutation comprising: (a) synthesizing a homology-directed repair (HDR) library comprising a plurality of oligonucleotides, wherein each oligonucleotide comprises a programmed nucleotide modification in the locus of the desired genome;(b) co-transfecting a population of cells with (i) an expression system capable of expressing Cas9 and a guide RNA (sgRNA) and (ii) the HDR library, wherein the expression system is capable of introducing the plurality of oligonucleotides having the programmed nucleotide modifications to the locus of the desired genomic DNA sequence in one or more cells of the population;(c) harvesting the population of cells;(d) selectively amplifying a genomic DNA and RNA sample, wherein the edited sequences are amplified and the non-edited sequence are not amplified;(e) sequencing the genomic DNA and RNA sample that has been selectively amplified, resulting in a set of genomic transcripts which include the plurality of programmed nucleotide modifications; and(f) functionally analyzing the set of genomic transcripts using a functional assay;wherein the method is carried out in a single experiment.

15. The method of claim 14, wherein the HDR library is constructed using an oligonucleotide comprising a degenerate sequence, wherein the degenerate sequence is between 1 and 100 nucleotides in length.

16. The method of claim 14, wherein the plurality of oligonucleotides are synthesized on a microarray or in column-based synthesis.

17. The method of claim 14, wherein the expression system comprises a plasmid which comprises (i) a Cas9 expression cassette that includes a nucleotide sequence which encodes a Cas9 nuclease, (ii) an sgRNA expression cassette, and (iii) a species-specific promoter that is specific to the population of cells.

18. The method of claim 14, wherein the functional assay is selected from the group consisting of targeted RNA sequencing to measure transcript abundance, targeted DNA sequencing to measure reduced cellular fitness, targeted chromatin immunoprecipitation-sequencing (CHiP-seq) of co-activators to assay enhancers, increased cellular growth rate to assay cancer drivers or drug resistance, and FACS-based phenotypic sorting for cellular assays.

19. A method for genomic screening, comprising: (a) introducing a plurality of programmed nucleotide modifications to a single genomic locus in a single experiment, wherein step (a) comprises the method of claim 1;(b) sequencing the genomic DNA or cDNA of the edited locus; and(c) quantifying the transcript abundance of each mutation.

20. The method of claim 19, wherein step (c) comprises calculating an enrichment score for each mutation.