ANALYSIS OF SALIVA PROTEOME FOR BIOMARKERS OF GINGIVITIS AND PERIODONTITIS USING FT-ICR-MS/MS

The present application pertains to the fields of proteomics and bioinformatics. More particularly, the present application relates to diagnosing a status of an oral disease, e.g. periodontitis, at varying levels of severity through the quantification of protein biomarkers.

Gingivitis is a non-destructive form of periodontal disease involving soft tissue inflammation of the gums. Gingivitis typically occurs as a bodily response to bacterial biofilms, or plaques, which have adhered to teeth. In the absence of proper treatment, gingivitis may progress to periodontitis, which represents a destructive form of periodontal disease. Periodontitis may begin with a milder of the disease, which later progresses into severe periodontitis. Periodontitis is always preceded by the onset of gingivitis.

Periodontal diseases are the leading cause of tooth loss in adults. Accordingly, diagnostic tests have been developed to identify the probability of whether an individual has developed periodontitis. Oral-fluid-based point-of-case (POC) diagnostics are commonly used for various diagnostic tests in medicine and more recently are being adapted for the determination of oral diseases (Tabak, 2007, Ann N Y Acad Sci 1098: 7-14). The use of oral fluids for POC diagnostics has been shown to be effective in detecting oral cancer (Li et al., 2004, Clin Cancer Res 10:8442-8450; Zimmerman et al., 2008, Oral Oncol. 44(5):425-9) or HIV infection (Delaney et al., 2006, Aids 20: 1655-1660).

Periodontal diseases are presently diagnosed by evaluating clinical parameters such as pocket depth, bleeding on probing, and radiographs. These parameters have limitations in that they lack the ability to predict future attachment loss, and provide information only on the existence of past disease activity. Furthermore, no clinical parameters have been shown to be predictive for periodontal disease activity (“Clinical risk indicators for periodontal attachment loss,” Journal of Clinical Periodontology 1991: v. 18:117-125”). Diagnostic methods in clinical practice today lack the ability to both detect the onset of inflammation, e.g. non-destructive gingivitis, and to identify the likelihood of developing destructive forms of periodontitis in the future.

Thus, there exists a need in the art for an efficient, accurate, and sensitive oral fluid diagnostic methods that can not only recognize the existence of past oral disease activity, but can also diagnose and assess earlier stages of oral diseases. In the case of periodontitis, oral fluid diagnostic methods should be able to distinguish at least between healthy patients and those that have developed gingivitis, milder forms of periodontitis, and/or more severe forms of periodontitis. This diagnostic method may advantageously include the quantification of particular protein biomarkers which are present in oral fluids. These oral fluids may be non-invasively acquired from a patient as gingival crevicular fluid (GCF) and/or saliva fluid.

BRIEF SUMMARY

Demonstrated herein in an exemplary embodiment is a method for diagnosing the status of periodontitis disease. The method includes providing at least one of a gingival crevicular fluid (GCF) sample and a saliva sample, selecting a set of protein biomarkers for identifying a particular state of periodontitis, and determining the expression levels in the selected set of protein biomarkers to diagnose the status of periodontitis disease.

In an aspect of the method, the set of protein biomarkers is selected for distinguishing between a gingivitis state and a periodontitis state.

In another aspect of the method, the set of protein biomarkers is selected for distinguishing between a periodontal health and a disease state.

In yet another aspect of the method, the set of protein biomarkers is selected for distinguishing between a mild periodontitis state and a severe periodontitis state.

In some aspects of the method, the set of protein biomarkers includes at least one protein selected from the group consisting of haemoglobin chains alpha and beta, carbonic anhydrase 1 (International Protein Index or “IPI” #IPI00980674), and plastin 1.

In another aspect of the method, the set of protein biomarkers includes at least one protein selected from the group consisting of S100-P, transaldolase, S100-A8 (calgranulin-A), myosin-9, Haemoglobin Alpha, and Haemoglobin Beta.

In yet another aspect of the method, the set of protein biomarkers includes at least one protein selected from the group consisting of Alpha-1-acid glycoprotein 1 and 2, matrix metalloproteinase-9, Peptidyl-prolyl cis-trans isomerase A, and Haptoglobin-related protein (IPI00431645.1).

In some aspect of the method, the set of protein biomarkers includes at least one protein selected from the group consisting of NADPH oxidase and Alpha-N-acetylgalactosaminidase.

In an aspect of the method, the set of protein biomarkers includes Alpha-N-acetylgalactosaminidase.

In another aspect of the method, the set of protein biomarkers includes at least one protein selected from the group consisting of Protein S100-A11 (IPI00013895.1), Protein IPI00037070.3, catalase (IPI00465436.4), Choline transporter-like protein 2 derivative (IPI00903245.1), and titin isoform N2-B (IPI00985334.2).

In yet another aspect of the method, the set of protein biomarkers includes two or more biomarkers.

In some aspects of the method, the method further includes providing both the GCF sample and saliva sample, generating a first and second protein profile by analyzing the proteome of a GCF sample and a saliva sample, and determining an overlap region between the first and second protein profiles. The set of protein biomarkers are selected for distinguishing between particular states of periodontitis, including calculating a change in abundance of proteins within the overlap region during different stages of periodontitis and selecting those proteins which are under or over expressed during a single state of periodontitis.

In another aspect of the method, the method further includes generating a protein profile by analyzing the proteome of the at least one oral fluid sample, and clustering the protein profile to determine a set of protein biomarkers.

Demonstrated herein in an exemplary embodiment is a kit for diagnosing the status of periodontitis disease. The kit includes a set of protein biomarkers selected to distinguish between gingivitis and periodontitis.

In an aspect of the kit, the set of protein biomarkers includes at least one protein selected from the group consisting of haemoglobin chains alpha and beta, carbonic anhydrase 1 (International Protein Index or “IPI” #IPI00980674), and plastin-1.

In another aspect of the kit, the kit diagnoses gingivitis or mild periodontitis, and the set of protein biomarkers further includes at least one protein biomarkers from saliva data clusters 1B, 1D, 1A4, and 1A5.

BRIEF DESCRIPTION OF THE DRAWINGS

These and other aspects, features and advantages of which the disclosed methods and kits are capable of will be apparent and elucidated from the following description of embodiments of the methods and kits, reference being made to the accompanying drawings, in which

FIG. 1 is a flow-chart illustration of a method for diagnosing a status of an oral disease according to one embodiment; FIG. 2 is a graph of UV Absorbance (mAU) v. time (min) for a patient saliva sample. The UV trace was obtained as the output of an SCX system recording UV Absorbance at 214 nm.

FIG. 3 is a graph of UV Absorbance (mAU) v. time (min) for a patient GCF sample. The UV trace was obtained as the output of an SCX system recording UV Absorbance at 214 nm.

FIG. 4 is a group average clustering graph showing change in protein abundance (transformed by a base 2 logarithmic scale) vs. six (6) proteomic MS analysis groups (defined in TABLE 3) for GCF sample data. The group average clustering identified six (6) different clusters of protein biomarkers. Cluster 1 contained the majority of the proteins (243 proteins), cluster 2 contained 19 proteins, clusters 3, 5 and 6 each contained only one protein, and cluster 4 contained five proteins.

FIG. 5 is a first round re-clustering graph showing change in protein abundance (transformed by a base 2 logarithmic scale) vs. six (6) proteomic MS analysis groups (defined in TABLE 3) for GCF sample data. Cluster 1 from FIG. 4 was re-clustered into four cluster groups, where Group A contained the majority of the proteins (233), groups B and C contained two proteins each, and group D contained six proteins.

FIG. 6 is a second round clustering graph showing change in protein abundance (transformed by a base 2 logarithmic scale) vs. six (6) proteomic MS analysis groups (defined in TABLE 3) for GCF sample data. Cluster A from FIG. 5 was re-clustered into four cluster groups, where the largest cluster (1A1) still contained 171 proteins, cluster 1A2 contained 50 proteins, 1A3 contained 10 proteins, and 1A4 contained two proteins.

FIG. 7 is a final round clustering graph showing change in protein abundance (transformed by a base 2 logarithmic scale) vs. six (6) proteomic MS analysis groups (defined in TABLE 3) for GCF sample data. Cluster 1A1 from FIG. 6 was re-clustered into four groups. There are no clusters from this analysis which appear to be of interest, as the change in protein abundance is now below 1.0 in magnitude.

FIG. 8 is a group average clustering graph showing change in protein abundance (transformed by a base 2 logarithmic scale) vs. six (6) proteomic MS analysis groups (defined in TABLE 3) for Saliva sample data. The group average clustering identified five (5) different clusters of protein biomarkers. The largest cluster (1) contained 297 proteins, clusters 2 and 5 each contained one protein. Cluster 3 contained 11 proteins and cluster 4 contained three proteins. Cluster 2 appears to distinguish severe periodontitis from milder conditions.

FIG. 9 is a first round re-clustering graph showing change in protein abundance (transformed by a base 2 logarithmic scale) vs. six (6) proteomic MS analysis groups (defined in TABLE 3) for GCF sample data. Cluster 1 from FIG. 8 was re-clustered into four cluster groups, the largest of which contained 166 proteins (cluster 1A). Clusters 1B and 1D contained 14 and one protein respectively. These two groups may distinguish between gingivitis/mild periodontitis and severe periodontitis.

FIG. 10 is a second round re-clustering graph showing change in protein abundance (transformed by a base 2 logarithmic scale) vs. six (6) proteomic MS analysis groups (defined in TABLE 3) for GCF sample data. Cluster 1A from FIG. 9 was re-clustered into 5 cluster groups, the largest containing 150 proteins. There do not appear to be any significant clusters here based on lack of abundance change.

FIG. 11 is a second round re-clustering graph showing change in protein abundance (transformed by a base 2 logarithmic scale) vs. six (6) proteomic MS analysis groups (defined in TABLE 3) for GCF sample data. Cluster 1C from FIG. 9 was re-clustered into three clusters. Cluster 1C2 containing seven proteins show a near linear increase in proteins abundance up to severe periodontitis before a reduction post treatment.

FIG. 12 is a final round re-clustering graph showing change in protein abundance (transformed by a base 2 logarithmic scale) vs. six (6) proteomic MS analysis groups (defined in TABLE 3) for GCF sample data. Cluster 1A1 from FIG. 10. Five clusters were observed with a group of proteins showing an increase in abundance for severe periodontitis (cluster 1A1b) but none of the other groups. There were five proteins identified in this cluster.

FIG. 13 is a Venn diagram showing the overlap between the GCF and Saliva sample datasets.

FIG. 14 is a cluster graph showing Log (2) transformed abundance levels of protein S100-P vs six (6) proteomic MS analysis groups (defined in TABLE 3) in combined GCF and Saliva sample data.

FIG. 15 is a cluster graph showing Log (2) transformed abundance levels of protein S100-A8 vs six (6) proteomic MS analysis groups (defined in TABLE 3) in combined GCF and Saliva sample data.

FIG. 16 is a cluster graph showing Log (2) transformed abundance levels of myosin-9 vs six (6) proteomic MS analysis groups (defined in TABLE 3) in combined GCF and Saliva sample data.

FIG. 17 is a cluster graph showing Log (2) transformed abundance levels of transaldolase vs six (6) proteomic MS analysis groups (defined in TABLE 3) in combined GCF and Saliva sample data.

FIG. 18 is a cluster graph showing Log (2) transformed abundance levels of haemoglobin beta vs six (6) proteomic MS analysis groups (defined in TABLE 3) in combined GCF and Saliva sample data.

DETAILED DESCRIPTION OF EMBODIMENTS

Several embodiments of the methods and kits of the present application will be described in more detail below with reference to the accompanying drawings in order for those skilled in the art to be able to carry out the disclosed methods and kits. The methods and kits may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the disclosed methods and kits to those skilled in the art. The embodiments do not limit the scope of disclosed methods or kits. The embodiments are only limited by the appended patent claims. Furthermore, the terminology used in the detailed description of the particular embodiments illustrated in the accompanying drawings is not intended to be limiting of the disclosed methods or kits.

The present application details methods for diagnosing the status of an oral disease, such as periodontitis. The methods may comprise determining the expression level of a set of biomarkers. The set of protein biomarkers may include one or more protein biomarkers which have been shown to vary in abundance at particular stages of oral disease. Accordingly, the set of protein biomarkers may be identified and quantified in expression in order to distinguish between different states of oral disease.

The methods of the present application demonstrate a role for biomarkers to serve as indicators of periodontitis at varying levels of severity, e.g. gingivitis, mild periodontitis. The work described herein demonstrates that elevated levels of multiple biomarkers can be used as a tool for accurately and rapidly determining the status of an oral disease, for example, periodontitis.

As used herein, the term “periodontal health state” is a threshold criteria based and not simply a vague state of health. Patients with a periodontal health state exhibit <10% sites with G.I. of 1.0 or B.O.P. and no sites with G.I. of 2.0 or 3.0. Additionally, they have no sites with interproximal attachment loss and no sites with ppd>3 mm.

As used herein, the term “gingivitis state” is a threshold criteria based on patients exhibiting generalized gingivitis and is not simply a vague state. Generalized gingivitis is shown in patients exhibiting >30% of sites with G.I. >2.0, no sites with interproximal attachment loss, and no sites with ppd>4 mm.

As used herein, the term “mild periodontitis state” is a threshold criteria based on patients exhibiting mild-moderate periodontitis and is not simply a vague state. Mild-moderate periodontitis is shown in patients exhibiting ppd of 5-7 mm and interproximal CAL of 2-4 mm at >8 teeth).

As used herein, the term “severe periodontics state” is a threshold criteria based on patients exhibiting severe periodontitis and is not simply a vague state. Severe periodontitis is shown in patients exhibiting ppd of >7 mm and an interproximal CAL of >5 mm at >12 teeth.

As used herein, the term “biomarker” means a substance that is measured objectively and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention.

Provided herein is a method to diagnose a status of an oral disease by a measurement of prognostic protein biomarkers indicative of a select status of the oral disease. In an exemplary embodiment, the oral disease is periodontitis, and the protein biomarkers are indicative of either gingivitis, mild periodontitis, or severe periodontitis.

Through a proteomic analysis of gingival cervical fluid (GCF) and saliva samples taken from patients with varying states of oral disease, protein biomarkers may be identified which are increased or decreased in abundance during distinct phases of periodontitis. At least one protein biomarker may be used, alone or in combination, to distinguish between healthy patients, those suffering from gingivitis, and those suffering from mild or severe periodontitis.

Proteomic analysis may be conducted through a combination of liquid chromatography and mass spectrometry techniques. In particular, the proteome of GCF and Saliva oral liquid samples may be analyzed by Fourier Transform—tandem Mass Spectrometry (FT MS/MS). The FT MS/MS proteomic approach may be applied to GCF and Saliva samples collected from periodontally healthy volunteers, those with gingivitis, those with mild and severe periodontitis, and those with no teeth (edentulous controls), in order to try and elucidate a panel of biomarkers that will distinguish between healthy and diseased oral states. In particular, the FT MS/MS approach may be undertaken to discover novel protein biomarkers capable of distinguishing between periodontal health and disease, between gingivitis and periodontitis, and between mild and severe periodontitis, through the use of non-presumptive proteomic analysis of gingival crevicular fluid (GCF) and stimulated saliva.

The inventors have astonishingly found that the expression of a small set of particular protein biomarkers may be determined to identify gingivitis or mild periodontitis. These protein biomarkers show an enhanced change (either increase or decrease) in abundance during gingivitis/mild disease states of periodontitis, and show little changes during severe states of periodontitis. Additionally, the expression of a small set of particular protein biomarkers may be determined to identify severe periodontitis. These protein biomarkers show an enhanced change (either increase or decrease) in abundance during the severe state of periodontitis, and show little changes during gingivitis and mild states of periodontitis. The set of protein biomarkers for identifying and distinguishing severe gingivitis relative to mild periodontitis or gingivitis.

With reference to FIG. 1, a method (S100) for diagnosing a status of an oral disease starts at S101. According to an exemplary embodiment, the oral disease is periodontitis and the status of periodontitis may include periodontal health, gingivitis, mild periodontitis, and severe periodontitis.

At S102, at least one oral fluid sample is provided. According to one embodiment, the oral disease is periodontitis and at least one of a GCF and Saliva sample are provided. The samples may be non-invasively collected from a patient.

At S104, a protein profile is generated by analyzing the proteome of at least one of GCF and Saliva samples. In another embodiment, the protein profile is discovered using LC FT MS/MS.

At S106, the protein profile is clustered to determine those proteins which are best fit to serve in a set of protein biomarkers. Clustering may be performed using a combination of statistical methods including principle component analysis, gamma statistics, and metric multidimensional scaling (MMDS). In one embodiment, group average link hierarchical clustering is employed to determine the set of protein biomarkers. In another embodiment, complete link hierarchical clustering methods are employed to determine the set of protein biomarkers.

At S108, a set of protein biomarkers is selected for distinguishing between different states of an oral disease. In one embodiment, the oral disease is periodontitis and the set of protein biomarkers are selected for distinguishing between gingivitis and periodontitis. In another embodiment, the oral disease is periodontitis and the set of protein biomarkers are selected for distinguishing between mild periodontitis and severe periodontitis.

At S110, the expression levels of the proteins in the selected set of protein biomarkers are determined to diagnose the status of the oral disease.

According to one aspect of the methods, a method for diagnosing the status of an oral disease comprises providing at least one oral fluid sample, generating a protein profile by analyzing the proteome of the at least one oral fluid sample, clustering the protein profile to determine a set of protein biomarkers, selecting a set of protein biomarkers for distinguishing between particular states of an oral disease, and determining the expression levels in the selected set of protein biomarkers to diagnose the status of the oral disease.

According to yet another aspect of the methods, a method for diagnosing the status of periodontitis disease comprises providing at least one of a gingival crevicular fluid (GCF) and a saliva sample, selecting a set of protein biomarkers for identifying a particular state of periodontitis, and determining the expression levels in the selected set of protein biomarkers to diagnose the status of the oral disease.

In some aspect of the methods, the set of biomarkers is selected by analyzing the proteome of gingival crevicular fluid (GCF) and saliva. Proteomic analysis may include Fourier Transform—tandem Mass Spectrometry (FT MS/MS) analysis of proteins which are identified to be over or under expressed in varying states of periodontitis.

Another aspect of the methods, the biomarkers may include only one, or a combination of particular biomarkers which are useful for the diagnosis of a disease state. The expression levels of one, two, or more protein biomarkers are determined to determine a status of an oral disease. In further aspects, three, four, five, or more biomarkers are determined and used to determine the status of an oral disease.

In various aspects of the methods, the one or more protein biomarkers are selected from the group consisting of haemoglobin chains alpha and beta, carbonic anhydrase 1 (International Protein Index or “IPI” #IPI00980674), and plastin 1. The method according to this aspect may be used to distinguish between a healthy state, gingivitis state, a mild state, and a severe state of periodontitis.

In yet another aspect of the methods, one or more protein biomarkers are selected from the group consisting of S100-P, transaldolase, S100-A8 (calgranulin-A), myosin-9, Haemoglobin Alpha, and Haemoglobin Beta. The method according to this aspect may be used to identify the severe state of periodontitis, and distinguish to the severe state of periodontitis from the milder states, e.g. mild periodontitis and gingivitis.

In some aspects of the disclosed methods, one or more protein biomarkers are selected from the group consisting of Alpha-1-acid glycoprotein 1 and 2, matrix metalloproteinase-9, Peptidyl-prolyl cis-trans isomerase A, and Haptoglobin-related protein (IPI00431645.1). The method according to this aspect may be used to identify the severe state of periodontitis, and distinguish to the severe state of periodontitis from the milder states, e.g. mild periodontitis and gingivitis.

In still another aspect of the methods, protein biomarker Alpha-N-acetylgalactosaminidase is selected for identifying gingivitis or mild periodontitis state, and distinguishing them from a severe periodontitis state.

In a further aspect of the methods, one or more protein biomarkers are selected from NADPH oxidase and Alpha-N-acetylgalactosaminidase for identifying gingivitis or mild periodontitis, and distinguishing them from a severe periodontitis state.

According to some aspects, the method for diagnosing the status of an oral disease further includes providing the GCF and saliva sample, generating a first and second protein profile by analyzing the proteome of a GCF sample and a saliva sample, and determining an overlap region between the first and second protein profiles. The selecting the set of protein biomarkers for distinguishing between particular states of periodontitis may include calculating a change in abundance of proteins within the overlap region during different stages of periodontitis and selecting those proteins which are under or over expressed during a single state of periodontitis.

In yet another aspect, the method for diagnosing a status of an oral disease as disclosed by the previous embodiments is performed by a diagnostic kit. The diagnostic kit comprises a set of protein biomarkers for identifying the status of an oral disease. The kit includes the necessary reagents to carry out the assays of the disclosed methods.

While the present application has been described in terms of various embodiments and examples, it is understood that variations or improvements will occur to those skilled in the art. Therefore, only such limitations as appear in the claims should be placed on the disclosed embodiments.

EXAMPLES
Example 1

The proteome of gingival crevicular fluid (GCF) and saliva was analyzed to identify biomarkers for different oral disease states, e.g. gingivitis, mild periodontitis, and severe periodontitis. GCF and saliva samples were collected non-invasively from the mouths of several patients. Liquid chromatography techniques coupled with Fourier Transform—tandem Mass Spectrometry (FT MS/MS) were used to separate protein biomarkers from within the samples and to identify the protein biomarkers.

The FT MS/MS proteomic approach was applied to samples collected from periodontally healthy volunteers, those with gingivitis, those with mild and severe periodontitis, and those with no teeth (edentulous controls), in order to try and elucidate a panel of biomarkers that will distinguish between healthy and diseased oral states. In particular, the FTMS/MS approach was undertaken to discover novel protein biomarkers capable of:

1. distinguishing between periodontal health and disease

2. distinguishing between gingivitis and periodontitis

3. distinguishing between mild and severe periodontitis

by non-presumptive proteomic analysis of gingival crevicular fluid (GCF) and stimulated saliva.

Study Design

TABLE 1

Patient Group

Number For

Sample Collection
Oral Disease State

Group 1
Patients with periodontal health (<10% sites with

G.I. of 1.0 or B.O.P. & no sites with G.I. of 2.0

or 3.0. No sites with interproximal attachment loss

and no sites with ppd >3 mm).

Group 2
Patients with generalized gingivitis (>30% of sites

with G.I. >2.0, no sites with interproximal

attachment loss & no sites with ppd >4 mm).

Group 3
Patients with mild-moderate periodontitis (ppd of

5-7 mm and interproximal CAL of 2-4 mm at >8

teeth).

Group 4
Patients with severe periodontitis (ppd of >7 mm &

interproximal CAL of >5 mm at >12 teeth).

Group 5
Edentulous patients (no teeth) with no evidence of

oral ulceration or erosive disease.

Five groups of patient volunteers were recruited as defined in TABLE 1. The study was performed as a cross-sectional study with no interventions planned other than routine therapy that may be clinically indicated. Only 1 visit was required at baseline for sampling, but those in Group 3 and 4 required routine periodontal scaling, root surface debridement and prophylaxis and were therefore re-examined and sampled 3-months following completion of their therapy. Longitudinal analysis was therefore available for groups 3 and 4. The clinical assessments were carried out by a trained study dental surgeon.

Sample Collection

Volunteers were asked to provide 6 samples of GCF collected from the gingival (gum) margin, non-invasively on standard filter papers strips (Periopapers™). They were also asked to provide a stimulated saliva sample by rolling a sterile marble around their mouths for five minutes and expectorating into a graduated sterile glass collection vile for volume measurement.

GCF and saliva were collected from 10 volunteers in each of five clearly defined phenotypic groups: healthy, gingivitis, mild periodontitis, severe periodontitis, and edentulous patients as a -ve control group. A total of 50 patients were therefore recruited and sampled. Volunteers with periodontitis (Groups 3 & 4) were then treated non-surgically in order to remove the periodontal inflammation and restore improved health. GCF and saliva were also collected 3 months post-treatment in these two groups, providing longitudinal data.

Table 2 presents the mean clinical data at a time of baseline and post-therapy obtained from 50 patients representing five phenotypic groups. GCF and Saliva samples were collected from 10 volunteers in each of five clearly defined phenotypic groups: Group I (healthy), Group II (gingivitis), Group III (mild periodontitis), Group IV (severe periodontitis), Group V (edentulous patients as a negative control group), where the phenotypic groups are defined based on predefined clinical data thresholds. Volunteers with periodontitis (Groups 3 & 4) were treated non-surgically in order to remove the periodontal inflammation and restore improved health, and therefore have both “baseline” and “review” clinical data.

TABLE 2

Criteria
Time
Group 1
Group 2
Group 3
Group 4
Group 5

PPD
Baseline
1.31 + 0.65
1.89 + .070
3.35 + 1.67
4.68 + 2.33
—

(mm)
Review
—
—
2.45 + 1.06
3.06 + 1.56
—

REC
Baseline
0.00 + 0.00
0.00 + 0.00
0.70 + 0.86
0.77 + 0.89
—

(mm)
Review
—
—
0.83 + .093
1.34 + 1.07
—

CAL
Baseline
1.31 + 0.65
1.89 + .070
4.05 + 1.88
5.45 + 2.49
—

(mm)
Review
—
—
3.27 + 1.44
4.37 + 1.92
—

BOP d
Baseline
3.60 + 2.24
—
100.57 + 61.28
127.29 + 71.10
—

(% sites)
Review
—
—
29.22 + 18.36
40.13 + 22.07
—

BOP m
Baseline
2.80 + 2.56
27.00 + 24.9
51.70 + 47.40
71.30 + 60.79
—

(% sites)
Review
—
—
15.20 + 13.69
20.60 + 17.02
—

MGI
Baseline
44.00
127.10
189.30
192.90
—

(FM
Review
—
—
83.90
112.70
—

total)

PI
Baseline
—
—
79.80 + 72.72
86.90 + 73.73
—

(% sites)
Review
—
—
55.67 + 50.60
49.80 + 42.38
—

GCF
Baseline
0.10 + 0.08
0.29 + 0.14
0.33 + 0.20
0.49 + 0.27
—

(mean
Review
—
—
0.23 + 0.15
0.32 + 0.23
—

vol μls)

Sample Processing

GFC Samples

GCF samples were collected on periopaper strips from the mesio-buccal sites of six teeth per volunteer, for 30 seconds as is convention and volumes read on a Perotron 8000™ (Chapple et at 1999). These were placed in 400 μL of a 100 mM ammonium bicarbonate buffer in 1.5 mL screw top cryo-tubes. The GCF samples were immediately frozen to −80° C. Prior to analysis GCF was defrosted on ice. The tubes were vortexed for 30 seconds and the solution removed into a clean snaptop eppendorf tube. 200 μL of ammonium bicarbonate (100 mM) was added to the strips. These were re-vortexed for 30 seconds and re-centrifuged at 13,000 RPM for five minutes. The solution was removed and added to the previous. From each sample within a group 150 μL was combined to give a single “pooled” sample per group. Individual patient samples were held back to allow a post-study re-evaluation at a patient-specific level once the preferred biomarker panels had been elucidated. Therefore 6×1.5 mL “population” samples were available for proteomic analysis by MS as indicated in Table 3.

TABLE 3

Group Number

for MS Analysis
Oral Disease State

Group 1
Healthy

Group 2
Gingivitis

Group 3
Mild periodontitis pre-treatment

Group 4
Severe periodontitis pre-treatment

Group 5
Mild periodontitis post-treatment

Group 6
Severe periodontitis post-treatment

Saliva Samples

Saliva production was stimulated using a sterile marble and collected for five minutes into 15 mL Falcon tubes. Tubes were frozen at −80° C. Prior to analysis the saliva was defrosted at 4° C. Additional falcon tubes were weighed prior to defrost to transfer the clarified saliva to. Once defrosted the saliva was aliquoted into 1.5 mL snaptop eppendorf tubes and centrifuged at 13,000 rpm for five minutes. The supernatant was transferred into the pre-weighed tubes. The debris pellet was also retained for potential future analysis. Both the weight and volume of saliva was recorded. 10.5 μL of each saliva sample per group was combined in the same manner as GCF samples. However, unlike GCF, saliva was available from the edentulous patient group (Group 5), therefore a total of 7×105 μL “population” saliva samples resulted. As for GCF the individual patient samples were held back to allow future “patient-level” analysis. The Pooled saliva samples were centrifuged at 13,000 RPM for five minutes and 100 μL retained. This was to ensure no debris was transferred into the final sample. Ammonium bicarbonate (100 μL , 200 mM) was added to each sample.

Sample Analysis by Lc Ft Ms/Ms

Dithiothrietol was added (20 μL , 50 mM) to both GCF and saliva samples, which were incubated with shaking at 60° C. for 45 minutes to reduce any disulphide bonds. The samples were returned to room temperature prior to addition of iodoacetamide (100 μL , 22 mM) and incubation at room temperature in the dark for 25 minutes. Iodoacetamide alkylates free thiol group on cysteine residues. Dithiothrietol (2.8 μL , 50 mM) was added to quench any remaining iodoacetamide. 1 μg of Lys-C (cleaves proteins at the C terminus of lysine residues) was added to each sample (1:100 enzyme:protein) and incubated at 37° C. with shaking for four hours. 2 μg of trypsin (cleaves proteins at the C terminus of lysine and arginine residues) was added and the digest continued over night at 37° C.

The samples were vacuum centrifuged dry prior to desalting (required for iTRAQ labelling). The samples were acidified (200 μL, 0.5% TFA) and desalting was performed using a Macrotrap (Michrom). The trap was wetted with acetonitrile (3×50%, 200 μL) followed by washing with trifluoroacetic acid (3×0.1%, 200 μL). The sample was then loaded through the trap and the elutant passed through the trap again. The trap was washed again with trifluoroacetic acid (3×0.1%, 200 μL), finally the peptides were eluted with acetonitrile (70%, 100 μL). The samples were vacuum centrifuged dry.

The dry samples were labeled with the iTRAQ 8-plex labels as shown in Table 4 below. The labeling allows all samples to be subsequently mixed together and run under one set of conditions in triplicate. Subsequently the individual group samples were identified from the iTRAQ labels.

TABLE 4

ITRAQ

LABELS
SALIVA DISEASE STATE
GCF DISEASE STATE

113
Healthy
Healthy

114
Gingivitis
Gingivitis

115
Mild Periodontitis
Mild Periodontitis

116
Severe Periodontitis
Severe Periodontitis

117
Mild Periodontitis Treated
Mild Periodontitis Treated

118
Severe Periodontitis Treated
Severe Periodontitis Treated

119
Edentulous

The samples were incubated with the labels for two hours at room temperature before all individual samples were mixed together for GCF and Saliva respectively. The combined samples (1 pooled saliva and 1 pooled GCF) were vacuum centrifuged dry. The samples were re-suspended in 100 μL of mobile phase A for the SCX system (10 mM KH₂PO₄, pH 3, 20% MeCN). The peptides were separated using strong cation exchange chromatography using the above mobile phase A and mobile phase B (10 mM KH₂PO₄, 500 mM KCl, pH 3, 20% MeCN). The gradient ran for 90 minutes. 15 fractions were collected. Fractions 15 and 12 were combined as were 13 and 14 to give 13 fractions.

With reference to FIGS. 2 and 3, resulting SCX UV traces with the UV recorded at 214 nm are shown for a Saliva sample and GCF sample respectively. The Saliva and GCF samples were then desalted with the Macrotrap LC column as above, vacuum centrifuged and re-suspended in 200 μL of 0.1% formic acid. 20 μL of the samples were desalted with two ziptips and eluted in 20 μL.

Fraction Analysis

Each fraction was analysed in triplicate by LC-MS/MS. Peptides were loaded onto a 150 mm Acclaim PepMap100 C18 column in mobile phase A (0.1% formic acid). Peptides were separated over a linear gradient from 3.2% to 44% mobile phase B (acetonitrile+0.1% formic acid) with a flow rate of 350n1/min. The column was then washed with 90% mobile phase B before re-equilibrating at 3.2% mobile phase B. The column oven was heated to 35° C. The LC system was coupled to an Advion Triversa Nanomate (Advion, Ithaca, N.Y.) which infused the peptides with a spray voltage of 1.7 kV. Peptides were infused directly into the LTQ-Orbitrap Velos ETD (Thermo Fischer Scientific, Bremen, Germany). The mass spectrometer performed a full FT-MS scan (m/z 380-1600) and subsequent collision induced dissociation (CID) MS/MS scans of the three most abundant ions followed by higher energy collisional dissociation (HCD) of the same three ions. The CID spectra were used to identify the peptides and the HCD spectra were used to quantify them.

Data analysis

The data were analyzed using Proteome Discoverer (V1.2, Thermo Fisher Scientific). Data were analyzed as the technical repeats. The Mascot and SEQUEST algorithms were used to search the data with identical setting used. The database was the IPI human database supplemented with oral bacteria as described by Socransky. This database was concatenated with a reverse version to provide false discovery rates. The data were searched with the following settings: semi-trypsin was selected as the enzyme with a maximum of 2 missed cleavages, 5 ppm mass accuracy for the precursor ion, fragment ion mass tolerance was set to 0.5 Da. Carboxyamidomethylation of cysteine and iTRAQ addition to the N-terminus and lysine residues were set as a static modification. Phosphorylation of serine, threonine and tyrosine was set as a variable modification as was oxidation of methionine and iTRAQ addition to tyrosine.

The search results from each of the technical replicates were combined and proteins which were identified with two or more peptides were classed as identified. Only unique peptides were used for protein quantification and protein grouping was employed (only proteins which contained unique peptides were used).

GCF Analysis Preliminary Results—Discovered Proteins

From the analysis of all GCF samples, 270 proteins were identified with two or more peptides. This included 264 human proteins and 6 bacterial proteins. The identified proteins are shown along with relative quantification values in the Appendix, Supplemental Table 1. All proteins show ratios relative to the Healthy control group (label 113—health). This data was subsequently normalized to collected GCF volumes and also log transformed (base 2) to give positive and negative abundance values.

There were no proteins which were solely identified in any of the disease states. The majority of the proteins showed a decrease in abundance between health, gingivitis and disease (229 proteins were lower abundance in gingivitis compared to health, 195 in mild periodontitis and 174 in severe periodontitis). This decrease in abundance across the groups may be due to an increase in GCF volume as tissues become more inflamed and as evidenced in Table 2. Alternatively, a “non-normalized” analysis of GCF may be performed to address this issue, which is recognized in the literature (Lamster et at 1986, Chapple et at 1994 & 1999).

GCF Clustering Analysis Performed on Discovered Proteins

Discovered proteins were clustered using the PolySNAP 3 software. PolySNAP 3 compares each 1 dimensional protein profile with every other and uses a weighted mean of Pearson parametric and Spearman nonparametric correlation coefficients to produce similarity scores. The profiles were clustered using a combination of statistical methods including principle component analysis, gamma statistics, and metric multidimensional scaling (MMDS). The data were then visualized in dendrograms, PCA plots, and MMDS plots. In this analysis, the group average link hierarchical clustering and complete link hierarchical clustering methods were used to group the data. In all cases, the number of clusters used was automatically set by PolySNAP3.

From the group average clustering three rounds of clustering were performed. The group with the largest number of proteins was re-clustered at each point.

First Round of Clustering

With reference to FIG. 4, the first round of analysis provided 6 clusters. Cluster 1 contained the majority of the proteins (243 proteins), cluster 2 contained 19 proteins, clusters 3, 5 and 6 each contained only one protein and cluster 4 contained five proteins.

With continuing reference to FIG. 4, Cluster 4 may be of interest as it includes a set of proteins which decrease in abundance during disease but do not return to baseline post-resolution. The nineteen proteins identified as cluster 2 show an increase in abundance with gingivitis before returning to baseline like levels in periodontitis. This may be due to one of the GCF samples containing blood, however bleeding is a critical clinical sign of gingivitis and periodontitis and blood-related proteins may be very discriminatory between health and disease. There are several blood related proteins identified in this group including haemoglobin alpha and beta. This could be of interest as a group that could distinguish between gingivitis and periodontitis and health, notwithstanding the possible presence of blood. Clusters 3 and 5 for example appear to distinguish untreated periodontitis from health/gingivitis.

The proteins identified clusters of interest, clusters 3, 4, and 5, are shown in the Appendix, Supplementary Table 2.

Second Round of Clustering

With reference to FIG. 5, the 243 proteins from cluster 1 of FIG. 4 were re-clustered, which gave a total of four groups. Group 1A contained the majority of the proteins (233), groups 1B and 1C contained two proteins each and group 1D contained six proteins. Group 1D shows little change between health and gingivitis before increasing with periodontitis. There is a fall in relative abundance between mild periodontitis and treated mild periodontitis and a return to baseline in the treated severe periodontitis. The two proteins identified in group 1C appear to follow disease, with a decrease to gingivitis and a larger decrease to the two perio groups before returning towards the baseline in the treated samples. Such proteins could be envisaged as being analyzed as outcome measures of whether treatment was successful or not.

The proteins identified in clusters of interest, clusters 1C and 1D, are shown in the Appendix, Supplementary Table 3.

Third Round of Clustering

With reference to FIG. 6, the 233 proteins from cluster 1A of FIG. 5 were clustered again, resulting in four clusters, though the change in abundance is now less than 2 on the log scale (4 times increase/decrease). The largest cluster (1A1) still contained 171 proteins, cluster 1A2 contained 50 proteins, 1A3 contained 10 and 1A4 contained 2 proteins. Again there appear to be groups of potential interest in this analysis.

The proteins identified in each cluster of interest, 1A3 and 1A4, are shown in the Appendix, Supplementary Table 4.

Final Round of Clustering

With reference to FIG. 7, a final round of clustering was performed the 171 proteins from cluster 1A1 of FIG. 6. This resulted in 4 groups as shown in FIG. 6. There are no clusters from this analysis which appear of interest.

The multiple rounds of clustering analysis suggest that there are some groups of proteins in GCF which may distinguish between different disease states of periodontitis.

Saliva Analysis Preliminary Results—Discovered Proteins

All saliva samples were analyzed similarly to GCF samples. 314 proteins were identified with two or more peptides, including 307 human proteins and 7 bacterial proteins. One protein was identified in only one sample group (edentulous). The identified proteins are shown along with relative quantification values in the Appendix, Supplemental Table 5.

Saliva Clustering Analysis Performed on Discovered Proteins

First Round of Clustering

For the clustering analysis the edentulous samples were not included.

Clustering analysis was performed using PolySNAP3. With reference to FIG. 8, the first round of clustering resulted in five clusters. The largest cluster (1) contained 297 proteins, while clusters 2 and 5 each contained one protein. Cluster 3 contained 11 proteins and cluster 4 contained three proteins. As with the GCF dataset there is a group of proteins which are down-regulated with disease and do not return to baseline following treatment. Cluster 2 appears to distinguish severe periodontitis from milder conditions.

The proteins identified in the cluster of interest, cluster 2, is shown in the Appendix, Supplementary Table 6.

Sound Round of Clustering

With reference to FIG. 9, Cluster 1 from FIG. 8 was re-clustered resulting in an additional 4 groups. The largest group contained 166 proteins (cluster 1A). Clusters 1B and 1D contained 14 and one protein respectively. These two groups may distinguish between gingivitis/mild periodontitis and severe periodontitis. However, in both cases, the signal for severe periodontitis is close to healthy levels, though after treatment an increase in protein abundance for both mild and severe periodontitis occurs. Cluster 1C contained 116 proteins. In this group, little change is shown between health and gingivitis followed by an increase to mild periodontitis before a large increase to severe periodontitis. These values are reduced in the treated samples but still at greater levels than the gingivitis group.

The proteins identified in each cluster of interest, clusters 1B and 1D, are shown in the Appendix, Supplementary Table 7.

Third Round of Clustering

With reference to FIG. 10, cluster 1A from FIG. 9 was re-clustered. Cluster 1A gave resulted in 5 groups, the largest cluster (1A1) containing 150 proteins. There do not appear to be any significant clusters here. Cluster 1A4 provided 3 proteins, and Cluster 1A5 provided one protein. The protein biomarkers in Clusters 1A4 and 1A5 all show an increase or decrease in protein abundance between health and gingivitis which is greater in mild periodontitis but less in severe periodontitis.

The proteins identified in clusters 1A4 and 1A5 are shown in the Appendix, Supplementary Table 8.

With reference to FIG. 11, cluster 1C from FIG. 9 was re-clustered, resulting in three clusters. Cluster 1C2 contained 7 proteins showing a near linear increase in proteins abundance up to severe periodontitis before a reduction post treatment. This group was not clustered any further. The proteins identified in cluster 1C2 are shown in the Appendix, Supplementary Table 9.

Final Round of Clustering

With reference to FIG. 12, cluster 1A1 from FIG. 10 was re-clustered. Five clusters were observed with a group of proteins showing an increase in abundance for severe periodontitis (cluster 1A1b) but none of the other groups. There were five proteins identified in this cluster. The proteins identified in cluster 1A1b are shown in the Appendix, Supplementary Table 10.

Comparison of GCF and Saliva Datasets

The proteins observed in the two data sets were compared to identify protein biomarkers that were discovered in both saliva and GCF samples. With reference to FIG. 13, 95 proteins were identified in both the GCF and saliva, represented by the overlapping region of the Venn diagram of FIG. 13. This is approximately a third of the total number of proteins identified on the GCF dataset.

The proteins which are observed in the overlapping region are shown in the Appendix, Supplemental Table 11. The associated abundance data for the proteins in Supplemental Table 11 was collected and subsequently transformed to portray the log (2) ratios for the protein abundance observed. Additionally, two values for the GCF was measured, one normalized to the volume collected, and the other not.

If it is assumed that GCF is a component of saliva, and when saliva is not normalized to the same GCF volumes, it may be of use to compare the three values. Analysis of these triple values shows some of these proteins to have very similar profile. Some of those protein biomarkers with a large increase or decrease in abundance values are depicted in FIGS. 14-17.

FIG. 14 shows the three traces for protein S100-P. S100-P is involved in the regulation of cell cycle progression and differentiation. It has been observed in both GCF and saliva and has been suggested as a potential biomarker for oral squamous cell carcinoma. As shown in FIG. 14, iTRAQ measured abundance of S100-P protein show there is a large increase between mild periodontitis and severe periodontitis. Accordingly, S100-P may serve as a useful protein biomarker for distinguishing between mild and severe periodontitis.

FIG. 15 shows the three traces for protein S100-A8, which is also known as calgranulin-A. It has antimicrobial activity towards bacteria. It is a pro-inflammatory mediator in inflammation and up-regulates the release of IL8. High levels of S100-A8 have been detected in the plasma of patients with chronic periodontitis. As shown in FIG. 15, iTRAQ measured abundance of S100-A8 protein show there is a large increase between mild periodontitis and severe periodontitis. Accordingly, S100-A8 may serve as a useful protein biomarker for distinguishing between mild and severe periodontitis.

FIG. 16 shows the three traces for protein myosin-9. As shown in FIG. 16, iTRAQ measured abundance of myosin-9 protein show there is a large increase between mild periodontitis and severe periodontitis. Accordingly, myosin-9 may serve as a useful protein biomarker for distinguishing between mild and severe periodontitis.

FIG. 17 shows the three traces for protein transaldolase. As shown in FIG. 17, iTRAQ measured abundance of transaldolase protein show there is a large increase between mild periodontitis and severe periodontitis. Accordingly, transaldolase may serve as a useful protein biomarker for distinguishing between mild and severe periodontitis.

FIG. 18 shows the three traces for protein haemoglobin beta. As shown in FIG. 18, iTRAQ measured abundance of haemoglobin beta protein show there is a large increase between mild periodontitis and severe periodontitis. The traces also increase and decrease throughout the range of all oral disease states. Accordingly, haemoglobin beta (or alpha) may serve as a useful protein biomarker for distinguishing between mild and severe periodontitis, and/or other oral disease states.

DISCUSSION OF RESULTS

Gene ontology analysis using The Database for Annotation, Visualization and Integrated Discovery (DAVID) on the GCF and Saliva datasets shows that the most significantly enriched biological process in the saliva dataset were the defense responses, and in GCF dataset, was cytoskeletal organization. The top twenty processes are shown in the Appendix, Supplemental Table 12. Seven of the twenty are enriched in both GCF and saliva including defense responses, responses to stimuli, and glycolysis.

The analysis of GCF and saliva identified 270 proteins in GCF and 314 proteins in saliva of which 95 were identified in both. All proteins except one (solely identified in edentulous saliva) were quantified over the different disease and resolution phases. Of the proteins which are identified in both GCF and saliva there are several proteins which show increases (in both GCF and Saliva datasets) with disease which could potentially be used to distinguish between health, gingivitis, mild and severe periodontitis and resolution of disease.

According to an exemplary embodiment, a method for diagnosing a status of an oral disease includes selecting at least one protein biomarker from the group consisting of: haemoglobin chains alpha and beta, carbonic anhydrase 1 (IPI00980674), and plastin-1. The method may further include diagnosing the status at least one of a healthy state, gingivitis state, and a mild and/or severe periodontitis state. In another embodiment, the at least one protein biomarker is selected from the group consisting of the protein biomarkers in saliva data cluster 1C2 (Supplemental Table 9): Protein #IPI00016347.5, Protein #IPI00377122.4, haemoglobin subunit alpha (IPI00410714.5), haemoglobin subunit delta (IPI00473011.3), haemoglobin subunit beta (IPI00654755.3), protein # IPI00980674.1, and protein accession number #O83773.

There are also several protein biomarkers which are potential indicators for severe periodontitis by showing increases in abundance in both the GCF and saliva datasets. In an exemplary embodiment, a method for diagnosing severe periodontitis includes selecting at least one protein biomarker from the group consisting of: S100-P, transaldolase, S100-A8 (calgranulin-A), myosin-9, haemoglobin alpha, and haemoglobin beta. In another aspect, the method for diagnosing severe periodontitis includes selecting at least one protein biomarker from the group consisting of the protein biomarkers in saliva data cluster 1A1b (Supplemental Table 10): Protein S100-A11 (IPI00013895.1), Protein IPI00037070.3, catalase (IPI00465436.4), Choline transporter-like protein 2 derivative (IPI00903245.1), and titin isoform N2-B (IPI00985334.2).

In yet another aspect, the method for diagnosing severe periodontitis includes selecting at least one protein biomarker from the group consisting of: S100-P, transaldolase, S100-A8 (calgranulin-A), myosin-9, haemoglobin alpha, and haemoglobin beta, alpha-1-acid glycoprotein 1 and 2, matrix metalloproteinase-9, peptidyl-prolyl cis-trans isomerase A and haptoglobin-related protein (IPI00431645.1).

According to another exemplary embodiment, a method for diagnosing gingivitis or mild periodontitis includes selecting at least one protein biomarker from the group consisting of the protein biomarkers in saliva data clusters 1B, 1D (Supplementary Table 7) and/or in saliva data clusters 1A4, 1A5 (Supplementary Table 8). These protein biomarkers all show an increase or decrease in protein abundance between health and gingivitis which is greater in mild periodontitis but less in severe periodontitis. It may be possible to use these to differentiate between gingivitis and mild periodontitis with severe periodontitis.

According to another aspect, a method for diagnosing gingivitis or mild periodontitis includes selecting at least one protein biomarker from NADPH oxidase activator-1 and alpha-N-acetylgalactosaminidase. NADPH oxidase activator-1 is involved in the production of reactive oxygen species. alpha-N-acetylgalactosaminidase portrays has some of the highest ratios for gingivitis and mild periodontitis compared to severe periodontitis. This protein is involved in the breakdown of glycolipids. In another aspect, the method for diagnosing gingivitis or mild periodontitis includes selecting an Alphaa alpha-N-acetylgalactosaminidase biomarker.

APPENDIX

SUPPLEMENTARY TABLE 1

A6:
A6:
A6:
A6:
A6:

Accession
Description
114/113
115/113
116/113
117/113
118/113

A8AW99
Phosphoenolpyruvate carboxylase
1.091
2.214
2.994
1.390
1.661

OS = Streptococcus gordonii (strain Challis/

ATCC 35105/CH1/DL1/V288) GN = ppc

PE = 3 SV = 1

A7IOP7
Peptide chain release factor 2
2.185
6.140
9.502
1.589
2.120

OS = Campylobacter hominis (strain ATCC BAA-

381/LMG 19568/NCTC 13146/CH001A)

GN = prfB PE = 3 SV = 1-[RF2_CAMHC]

A8AX28
tRNA pseudouridine synthase B
2.447
7.298
12.453
2.095
1.862

OS = Streptococcus gordonii (strain Challis/

ATCC 35105/CH1/DL1/V288) GN = truB

PE = 3 SV = 1-[TRUB_STRGC]

A8AW24
Isoleucine--tRNA ligase OS = Streptococcus
1.378
2.731
3.417
0.891
0.519

gordonii (strain Challis/ATCC 35105/CH1/

DL1/V288) GN = ileS PE = 3 SV = 1

IPI00003269.1
Beta-actin-like protein 2
1.174
2.429
4.466
0.977
1.590

IPI00003935.6
Histone H2B type 2-E
1.704
3.139
7.450
1.589
1.710

IPI00004550.5
Keratin, type I cytoskeletal 24
0.868
2.271
3.037
0.915
1.134

IPI00005721.1
Neutrophil defensin 1
1.062
0.949
1.070
0.923
1.599

IPI00006988.1
Resistin
2.419
0.897
0.642
0.961
2.719

IPI00007047.1
Protein S100-A8
1.545
2.762
3.767
1.515
2.262

IPI00008359.2
Keratin, type II cytoskeletal 2 oral
0.940
1.217
1.617
1.403
1.828

IPI00008405.5
Arylsulfatase F
1.650
3.529
5.536
1.426
2.000

IPI00008895.1
Epithelial membrane protein 2
6.951
13.266
2.545
10.122
6.138

IPI00009724.3
Isoform 1 of EF-hand calcium-binding domain-
1.471
8.313
13.940
1.860
1.369

containing protein 6

IPI00009865.4
Keratin, type I cytoskeletal 10
0.935
1.487
1.166
1.344
1.038

IPI00009866.7
Isoform 1 of Keratin, type I cytoskeletal 13
0.918
1.528
1.612
1.242
1.393

IPI00009867.3
Keratin, type II cytoskeletal 5
1.269
2.339
2.862
1.999
2.119

IPI00010133.3
Coronin-1A
2.069
2.459
4.193
1.629
2.510

IPI00010349.1
Alkyldihydroxyacetonephosphate synthase,
2.729
12.079
12.838
11.323
1.586

peroxisomal

IPI00010471.6
Plastin-2
1.663
3.060
5.513
1.635
2.622

IPI00013163.1
Myeloid cell nuclear differentiation antigen
2.025
2.914
5.563
1.109
1.678

IPI00013890.2
Isoform 1 of 14-3-3 protein sigma
1.877
4.014
7.830
1.566
1.574

IPI00013895.1
Protein S100-A11
1.011
0.550
0.480
1.003
2.233

IPI00017526.1
Protein S100-P
1.411
1.835
4.329
1.192
1.657

IPI00019038.1
Lysozyme C
1.427
2.107
2.605
1.293
1.787

IPI00019359.4
Keratin, type I cytoskeletal 9
1.547
1.827
1.793
1.385
1.341

IPI00019502.3
Isoform 1 of Myosin-9
1.787
2.006
2.761
1.386
2.194

IPI00019580.1
Plasminogen
2.288
1.643
1.937
1.261
1.948

IPI00019869.3
Protein S100-A2
8.362
3.474
4.944
2.218
2.994

IPI00020091.1
Alpha-1-acid glycoprotein 2
1.461
0.453
0.519
0.699
1.969

IPI00021263.3
14-3-3 protein zeta/delta
1.935
2.378
4.007
1.337
2.087

IPI00021439.1
Actin, cytoplasmic 1
1.532
3.145
4.896
1.445
2.320

IPI00021828.1
Cystatin-B
1.026
1.725
1.936
1.094
1.383

IPI00021841.1
Apolipoprotein A-I
2.054
1.828
3.046
1.710
2.498

IPI00022371.1
Histidine-rich glycoprotein
2.157
1.828
2.648
1.880
2.269

IPI00022429.3
Alpha-1-acid glycoprotein 1
1.524
0.515
0.601
0.977
2.217

IPI00022463.2
Serotransferrin
2.035
1.860
2.638
1.763
2.374

IPI00022488.1
Hemopexin
2.864
2.697
3.481
1.933
3.455

IPI00022974.1
Prolactin-inducible protein
1.786
1.298
1.464
1.495
3.193

IPI00025512.2
Heat shock protein beta-1
1.152
1.258
1.517
1.471
2.055

IPI00027462.1
Protein S100-A9
1.380
2.491
2.812
1.513
2.136

IPI00027463.1
Protein S100-A6
2.846
4.107
3.748
2.172
4.088

IPI00027509.5
Matrix metalloproteinase-9
2.216
3.561
3.127
2.021
1.365

IPI00027769.1
Neutrophil elastase
1.836
2.667
9.024
1.281
1.919

IPI00028064.1
Cathepsin G
1.391
1.130
1.206
1.072
1.571

IPI00030362.1
Isoform 1 of Proteolipid protein 2
1.389
2.013
4.137
1.411
1.791

IPI00032294.1
Cystatin-S
0.657
0.573
0.729
0.853
1.867

IPI00037070.3
Uncharacterized protein
2.165
0.946
1.272
1.135
1.887

IPI00081836.3
Histone H2A type 1-H
1.107
0.716
1.909
1.903
3.763

IPI00152758.1
FLJ00198 protein (Fragment)
23.303
4.014
7.989
2.169
2.697

IPI00167191.1
CDNA FLJ25707 fis, clone TST04879
1.935
0.186
0.337
1.789
2.778

IPI00168728.1
FLJ00385 protein (Fragment)
2.284
9.149
13.295
3.104
2.935

IPI00174541.1
Isoform 4 of Interleukin-1 receptor antagonist
1.402
0.948
1.229
1.205
2.084

protein

IPI00177428.1
Isoform 2 of Mitochondrial intermembrane
1.091
0.307
0.335
0.775
0.854

space import and assembly protein 40

IPI00180240.2
Thymosin beta-4-like protein 3
1.819
2.538
4.657
1.818
2.105

IPI00216691.5
Profilin-1
2.126
3.193
4.898
1.993
3.376

IPI00216974.1
Isoform 1 of Probable phospholipid-
37.175
0.920
3.993
1.491
1.460

transporting ATPase IK

IPI00217465.5
Histone H1.2
3.025
3.780
6.682
2.143
3.026

IPI00217468.3
Histone H1.5
1.816
3.043
4.613
1.645
2.749

IPI00217963.3
Keratin, type I cytoskeletal 16
0.906
1.190
1.304
1.299
1.537

IPI00218131.3
Protein S100-A12
1.831
2.688
8.152
1.919
2.218

IPI00218918.5
Annexin A1
1.310
2.384
2.914
1.317
1.806

IPI00219037.5
Histone H2A.x
2.459
3.327
8.477
1.536
2.063

IPI00219208.1
Isoform 2 of Granulocyte-macrophage colony-
1.797
2.298
4.347
1.840
2.175

stimulating factor receptor subunit alpha

IPI00219395.3
Isoform 6 of Voltage-dependent T-type calcium
3.160
6.602
10.369
2.696
4.044

channel subunit alpha-1G

IPI00219502.1
Isoform Short of G1/S-specific cyclin-E2
1.657
1.027
1.319
1.477
4.004

IPI00219757.13
Glutathione S-transferase P
1.563
2.730
4.126
1.820
2.059

IPI00220056.1
Kelch domain-containing protein 5
1.232
1.456
2.136
1.420
1.499

IPI00220327.4
Keratin, type II cytoskeletal 1
1.116
1.181
1.449
1.163
1.170

IPI00236554.1
Isoform H14 of Myeloperoxidase
2.434
4.087
10.319
1.735
2.189

IPI00290077.3
Keratin, type I cytoskeletal 15
0.981
0.876
0.777
1.045
1.535

IPI00292579.4
Stabilin-2
5.188
18.978
17.247
7.542
2.843

IPI00293665.9
Keratin, type II cytoskeletal 6B
0.924
1.657
1.791
1.741
1.746

IPI00296215.2
Epithelial cell adhesion molecule
13.055
0.830
1.428
1.586
1.096

IPI00297056.2
Cornulin
1.613
2.387
2.849
1.361
1.963

IPI00297763.4
Retinal-specific ATP-binding cassette
1.662
3.618
7.512
1.030
1.452

transporter

IPI00298497.3
Fibrinogen beta chain
1.627
1.774
2.386
1.309
1.816

IPI00299078.1
Salivary acidic proline-rich phosphoprotein 1/2
0.684
0.967
0.989
1.197
1.396

IPI00299547.4
Isoform 1 of Neutrophil gelatinase-associated
2.854
3.215
8.337
1.534
3.224

lipocalin

IPI00300725.7
Keratin, type II cytoskeletal 6A
0.909
1.345
1.079
2.018
1.701

IPI00305477.6
Cystatin-SN
1.286
1.089
1.617
1.253
2.407

IPI00307770.2
Uncharacterized protein
1.106
1.956
1.584
1.259
1.019

IPI00328296.2
PDZ domain-containing protein GIPC2
0.765
0.759
0.811
0.735
0.923

IPI00334400.2
Isoform 2 of Plakophilin-4
0.374
0.797
1.320
0.616
0.541

IPI00374975.2
Probable phosphoglycerate mutase 4
0.857
0.479
0.362
1.082
2.494

IPI00375293.2
Isoform 2 of High affinity immunoglobulin
2.130
7.149
20.796
0.789
2.361

gamma Fc receptor I

IPI00377081.1
erythrocyte band 7 integral membrane protein
1.951
2.869
5.214
1.399
1.858

isoform b

IPI00384282.2
FERM, C-terminal PH-like domain containing
1.804
2.321
1.684
1.562
2.468

protein

IPI00384444.6
Keratin, type I cytoskeletal 14
1.098
1.767
1.755
1.580
1.937

IPI00384938.1
Putative uncharacterized protein
3.048
3.013
4.415
2.739
3.220

DKFZp686N02209

IPI00385373.1
Truncated proliferating cell nuclear antigen
2.277
5.425
10.797
1.879
3.952

IPI00394951.1
Putative ubiquitin carboxyl-terminal hydrolase
0.794
1.094
1.055
1.100
1.280

17-like protein 1

IPI00397585.1
Isoform 2 of Leucine-rich repeat LGI family
1.485
5.536
11.795
1.242
1.470

member 4

IPI00399007.7
Putative uncharacterized protein
2.176
4.694
8.528
2.583
4.705

DKFZp686I04196 (Fragment)

IPI00402502.2
secernin-2 isoform 2
1.847
3.169
5.171
1.638
1.359

IPI00410714.5
Hemoglobin subunit alpha
19.785
2.146
5.893
1.815
2.553

IPI00418153.1
Putative uncharacterized protein
2.111
9.132
16.172
3.105
3.051

DKFZp686I15212

IPI00418262.5
Fructose-bisphosphate aldolase
2.633
2.420
4.379
1.698
1.846

IPI00419585.9
Peptidyl-prolyl cis-trans isomerase A
1.939
2.634
2.609
1.437
2.073

IPI00423460.3
Putative uncharacterized protein
1.626
1.478
2.635
1.433
2.829

DKFZp686G21220 (Fragment)

IPI00431645.2
31 kDa protein
1.488
2.257
3.870
1.899
3.274

IPI00448925.6
44 kDa protein
2.771
3.473
5.077
2.394
2.905

IPI00449920.1
cDNA FLJ90170 fis, clone MAMMA1000370,
1.596
1.643
2.609
1.548
2.673

highly similar to Ig alpha-1 chain C region

IPI00450768.7
Keratin, type I cytoskeletal 17
1.083
1.815
1.071
1.764
2.427

IPI00453473.6
Histone H4
1.803
2.130
5.598
1.308
1.478

IPI00465248.5
Isoform alpha-enolase of Alpha-enolase
1.791
2.111
2.924
1.807
3.210

IPI00465439.5
Fructose-bisphosphate aldolase A
1.640
3.506
5.165
1.472
2.197

IPI00470476.3
Uncharacterized protein C9orf144A
2.945
33.019
68.061
4.446
4.289

IPI00477227.3
Isoform 1 of Keratin, type II cytoskeletal 78
2.284
2.575
2.759
1.760
1.887

IPI00477597.2
Isoform 1 of Haptoglobin-related protein
1.721
2.349
2.958
1.753
2.713

IPI00478493.3
haptoglobin isoform 2 preproprotein
1.866
2.137
3.510
1.957
3.282

IPI00478837.1
Zinc finger protein 580
1.497
3.258
3.719
3.443
3.763

IPI00479145.3
Keratin, type I cytoskeletal 19
1.384
1.614
2.336
1.525
1.077

IPI00479186.7
Isoform M2 of Pyruvate kinase isozymes
1.817
2.016
3.100
1.343
2.417

M1/M2

IPI00513782.3
cDNA FLJ35478 fis, clone SMINT2007796,
1.795
3.124
4.434
1.432
2.293

highly similar to Gelsolin

IPI00514954.2
Isoform 3 of Membrane-associated guanylate
19.533
2.306
5.063
1.736
2.091

kinase, WW and PDZ domain-containing

protein 3

IPI00552280.2
Bactericidal/permeability-increasing protein
3.490
4.103
6.014
2.387
2.685

IPI00552637.1
G-protein coupled receptor
3.109
9.833
29.016
1.776
3.499

IPI00552768.1
Uncharacterized protein
2.467
3.130
4.076
2.048
2.971

IPI00554648.3
Keratin, type II cytoskeletal 8
0.951
1.135
1.151
1.521
1.629

IPI00554711.3
Junction plakoglobin
2.401
1.725
1.711
1.645
1.444

IPI00556287.1
Putative uncharacterized protein
3.141
9.484
8.840
4.033
1.990

IPI00556432.1
Oxysterol-binding protein (Fragment)
1.367
2.816
2.088
2.288
2.156

IPI00641244.1
11 kDa protein
1.169
1.798
1.727
1.363
1.777

IPI00641737.2
Haptoglobin
1.644
2.777
4.785
2.105
3.097

IPI00642042.3
Putative uncharacterized protein
1.731
1.777
2.490
1.322
2.217

DKFZp686J1372

IPI00642632.2
Ig lambda-7 chain C region
2.102
3.498
6.515
1.678
2.730

IPI00642694.3
cDNA FLJ55428, highly similar to Regulator of
1.823
1.401
2.230
1.511
2.922

G-protein signaling 7

IPI00644534.6
Uncharacterized protein
2.269
3.559
5.442
2.056
3.265

IPI00645801.1
Uncharacterized protein
1.302
1.726
2.340
1.338
1.598

IPI00654755.3
Hemoglobin subunit beta
21.011
1.997
5.888
1.833
2.307

IPI00658130.1
IGL@ protein
2.182
3.474
6.670
1.802
2.970

IPI00658186.1
cDNA FLJ59463, highly similar to
1.685
2.271
2.159
1.803
1.991

Geranylgeranyl pyrophosphate synthetase

IPI00739683.3
Beta-defensin 131
0.976
3.084
7.562
1.011
0.950

IPI00745280.1
Similar to Keratin, type II cytoskeletal 7
4.024
8.529
10.940
3.927
5.645

IPI00745872.2
Isoform 1 of Serum albumin
2.157
2.623
3.404
2.264
2.921

IPI00746352.1
SH3 domain-binding glutamic acid-rich-like
1.700
2.191
3.645
1.565
3.303

protein 3

IPI00748022.2
Actin-like protein (Fragment)
1.391
1.059
0.925
1.449
2.532

IPI00759663.1
Isoform Cytoplasmic + peroxisomal of
3.491
4.923
5.620
3.012
4.002

Peroxiredoxin-5, mitochondrial

IPI00783859.2
Isoform 2 of Vacuolar protein sorting-
4.988
17.839
25.242
7.435
2.409

associated protein 13D

IPI00783987.2
Complement C3 (Fragment)
1.980
3.439
6.345
1.877
2.164

IPI00784295.2
Isoform 1 of Heat shock protein HSP 90-alpha
2.433
2.968
4.964
1.766
1.961

IPI00784950.1
Putative uncharacterized protein
3.468
2.723
5.483
1.624
1.930

DKFZp686L19235

IPI00784985.1
IGK@ protein
2.223
3.329
4.496
2.052
2.583

IPI00789134.5
Glyceraldehyde-3-phosphate dehydrogenase
1.926
2.502
4.779
1.452
2.574

IPI00790172.5
Keratin, type I cuticular Ha5
2.163
12.202
6.334
2.584
1.246

IPI00792677.2
cDNA FLJ60097, highly similar to Tubulin
1.382
1.770
2.776
1.052
1.476

alpha-ubiquitous chain

IPI00793108.2
98 kDa protein
2.020
4.890
11.027
2.183
2.432

IPI00793296.1
MAM domain-containing
1.221
4.266
3.150
1.367
1.463

glycosylphosphatidylinositol anchor protein 2

isoform 2

IPI00795501.3
Low affinity immunoglobulin gamma Fc region
1.571
0.823
0.820
1.112
2.117

receptor III-B

IPI00796727.1
Uncharacterized protein
1.214
1.058
1.307
1.277
1.278

IPI00797270.4
Isoform 1 of Triosephosphate isomerase
1.602
4.407
9.141
1.604
1.199

IPI00807400.2
Isoform 2 of Structural maintenance of
1.721
2.850
4.573
1.550
1.726

chromosomes protein 1B

IPI00815843.1
RPL14 protein (Fragment)
1.016
1.489
1.604
1.720
1.596

IPI00816314.1
Putative uncharacterized protein
3.011
3.313
6.320
2.707
3.279

DKFZp686I15196

IPI00816687.1
FGB protein (Fragment)
1.627
1.774
2.386
1.309
1.816

IPI00816741.1
Complement component 5 variant (Fragment)
1.971
6.126
7.845
2.710
1.725

IPI00829896.1
Hemoglobin Lepore-Baltimore (Fragment)
2.476
2.209
3.061
1.420
1.481

IPI00845508.3
BAH and coiled-coil domain-containing protein 1
2.207
4.497
7.543
2.159
3.719

IPI00848259.1
Merlin variant 14
0.763
3.070
1.933
2.357
1.915

IPI00848276.1
Isoform 1 of Uncharacterized protein C10orf18
0.452
1.711
1.520
0.635
0.597

IPI00853045.1
Anti-RhD monoclonal T125 kappa light chain
2.325
2.720
4.016
1.949
3.138

IPI00853068.2
Hemoglobin alpha-2
46.021
2.885
11.499
2.248
3.976

IPI00853525.1
Uncharacterized protein
1.991
1.067
1.430
1.674
2.615

IPI00855985.2
Mitogen-activated protein kinase kinase kinase 1
1.515
2.157
3.919
1.315
2.010

IPI00872684.2
cDNA FLJ54141, highly similar to Ezrin
1.669
1.861
1.318
1.498
2.844

IPI00878282.1
23 kDa protein
2.295
6.632
15.416
2.522
1.777

IPI00879437.1
Protein
1.872
1.883
2.321
1.522
2.591

IPI00884996.1
Isoform 1 of Dynein heavy chain 6, axonemal
2.020
2.936
5.556
1.342
1.546

IPI00885046.1
Isoform 3 of Dynein heavy chain 1, axonemal
32.735
12.945
42.874
3.459
2.779

IPI00885122.1
Isoform 1 of Diffuse panbronchiolitis critical
2.041
3.306
9.940
1.637
2.026

region protein 1

IPI00888187.2
Putative zinc finger protein 487
8.799
4.879
5.499
3.205
5.113

IPI00893981.1
Uncharacterized protein
1.361
2.469
5.074
1.032
1.852

IPI00902755.1
FGA protein (Fragment)
2.400
2.028
3.058
2.061
2.746

IPI00903112.1
cDNA FLJ36533 fis, clone TRACH2004428,
2.664
3.137
5.644
2.044
2.428

highly similar to Lactotransferrin (Fragment)

IPI00908402.1
cDNA FLJ51275
1.554
0.515
0.526
1.250
2.617

IPI00908776.3
cDNA FLJ61380, highly similar to Alpha-actinin-4
1.971
2.092
2.061
1.342
2.370

IPI00908791.3
L-lactate dehydrogenase
1.690
2.824
5.085
1.566
2.454

IPI00908881.3
Glucose-6-phosphate isomerase
2.095
4.977
9.723
1.670
2.216

IPI00909059.5
cDNA FLJ53910, highly similar to Keratin, type
0.912
1.283
0.913
2.144
2.156

II cytoskeletal 6A

IPI00909509.1
cDNA FLJ59138, highly similar to Annexin A2
1.856
1.005
1.392
1.114
1.521

IPI00909530.1
cDNA FLJ52843, highly similar to Histone H3.3
1.910
3.080
6.500
1.568
2.261

IPI00909658.1
cDNA FLJ52759, highly similar to Plastin-2
1.812
2.489
6.118
1.494
2.698

IPI00910407.1
Peptidyl-prolyl cis-trans isomerase
1.879
2.581
2.584
1.471
1.961

IPI00910544.1
cDNA FLJ57640, highly similar to Serpin B5
1.521
2.576
2.975
1.682
2.259

IPI00910709.1
cDNA FLJ53133, highly similar to Erythrocyte
1.133
3.066
0.904
0.868
1.604

band 7 integral membrane protein

IPI00910754.1
L-lactate dehydrogenase A chain isoform 2
1.618
2.749
4.408
1.422
2.253

IPI00910974.1
Phosphoglycerate kinase
1.486
4.229
10.034
1.340
1.553

IPI00910979.1
pyruvate kinase isozymes M1/M2 isoform e
1.685
1.671
2.448
1.421
2.812

IPI00911039.1
cDNA FLJ54408, highly similar to Heat shock
1.587
1.556
1.862
1.324
1.772

70 kDa protein 1

IPI00914847.2
nebulin isoform 1
0.867
1.322
1.361
1.031
1.161

IPI00916185.2
Isoform 4 of Dynein heavy chain 1, axonemal
17.718
8.329
25.793
2.109
2.507

IPI00916517.2
28 kDa protein
1.997
3.800
4.818
1.948
3.008

IPI00917176.1
Isoform 5 of Dynein heavy chain 1, axonemal
21.419
5.385
11.708
1.394
1.894

IPI00922216.1
Adenylyl cyclase-associated protein
1.669
2.359
2.792
1.493
2.233

IPI00922673.1
cDNA FLJ55309
11.198
2.427
5.107
7.320
5.842

IPI00924436.1
Uncharacterized protein
0.855
0.734
0.950
1.141
1.961

IPI00924608.1
vacuolar protein sorting-associated protein 13D
4.375
15.621
22.791
6.247
2.323

isoform 1

IPI00925547.2
Uncharacterized protein
2.438
2.568
4.876
1.556
1.963

IPI00927887.1
Histone H2A
1.023
0.668
0.793
0.664
1.378

IPI00930073.1
cDNA, FLJ93744, highly similar to Homo
0.878
1.278
1.048
2.277
2.347

sapiens keratin 6E (KRT6E), mRNA

IPI00930144.1
Histone H2A
1.101
0.772
0.843
0.711
1.325

IPI00930351.1
Hbbm fused globin protein (Fragment)
5.696
2.581
4.831
1.515
1.644

IPI00930442.1
Putative uncharacterized protein
1.532
1.295
1.792
1.656
2.465

DKFZp686M24218

IPI00930614.1
GUCA1B protein (Fragment)
0.943
1.457
1.403
1.085
1.278

IPI00939521.1
10 kDa protein
3.468
2.723
5.483
1.624
1.930

IPI00940399.2
Uncharacterized protein
0.596
0.553
1.176
0.232
0.414

IPI00940673.2
cDNA FLJ36348 fis, clone THYMU2007025,
2.356
2.516
4.369
1.762
2.641

highly similar to TRANSKETOLASE

IPI00945626.2
cDNA FLJ54029, highly similar to
2.124
1.674
2.181
1.819
2.673

Serotransferrin

IPI00946655.1
Isoform 1 of Actin-related protein 3C
3.030
8.158
11.061
3.034
2.477

IPI00947307.1
cDNA FLJ58075, highly similar to Ceruloplasmin
3.799
2.779
4.874
2.259
4.018

IPI00964070.1
Uncharacterized protein
2.290
4.252
7.797
1.974
2.200

IPI00964635.1
Uncharacterized protein
1.843
1.324
1.650
1.286
1.907

IPI00965713.3
fibrinogen beta chain isoform 2 preproprotein
1.488
1.582
2.102
1.172
1.673

IPI00966664.1
Uncharacterized protein
2.641
1.602
2.256
1.275
2.020

IPI00967416.1
Uncharacterized protein
2.167
1.776
2.853
1.556
2.101

IPI00967791.1
Protein
1.582
2.155
2.671
1.559
2.464

IPI00972963.1
Lambda light chain of human immunoglobulin
2.264
2.955
4.213
2.075
3.259

surface antigen-related protein (Fragment)

IPI00973588.1
Full-length cDNA clone CS0DI019YF20 of
2.706
9.806
15.041
3.359
2.641

Placenta of Homo sapiens (Fragment)

IPI00974274.1
Uncharacterized protein
1.968
2.167
2.275
1.697
2.331

IPI00974428.1
Uncharacterized protein
55.064

1.529
2.624
4.044

IPI00975690.1
Vimentin variant 3
2.191
3.482
6.483
1.417
1.796

IPI00975801.1
Uncharacterized protein
1.883
0.863
0.946
1.047
2.470

IPI00976599.1
Uncharacterized protein
1.596
0.743
1.063
0.907
3.364

IPI00977575.1
Uncharacterized protein
39.712
4.075
22.681
1.709
1.810

IPI00978296.1
Uncharacterized protein
28.145
0.255
1.653
1.637
2.836

IPI00978338.1
Wilms tumor 1
5.475
3.551
10.012
1.042
1.521

IPI00978796.1
17 kDa protein
1.740
3.718
5.675
1.139
2.307

IPI00980674.1
Uncharacterized protein
13.509
1.040
2.885
1.677
2.479

IPI00981317.1
cDNA FLJ75025, highly similar to Homo sapiens
2.557
3.259
4.123
1.803
2.636

peptidylprolyl isomerase A (cyclophilin A)

(PPIA), transcript variant 2, mRNA

IPI00981659.1
Similar to Cold agglutinin FS-1 H-chain
1.504
1.967
3.733
0.982
1.173

IPI00981943.1
Uncharacterized protein
2.022
0.885
1.226
1.067
1.914

IPI00982472.1
Transaldolase
1.870
2.506
4.255
1.583
2.420

IPI00984226.2
Uncharacterized protein
2.988
0.950
1.276
1.116
1.606

IPI00985334.2
titin isoform N2-B
6.506
1.481
3.001
2.668
2.421

IPI01009324.2
Uncharacterized protein
2.015
2.419
3.996
1.458
2.271

IPI01009332.1
cDNA FLJ61543, highly similar to Desmoplakin
0.973
1.588
1.597
1.892
1.943

IPI01009809.1
51 kDa protein
1.093
1.572
1.574
1.323
1.570

IPI01010323.1
cDNA FLJ38286 fis, clone FCBBF3008153,
1.005
0.681
0.714
0.941
2.218

highly similar to ALPHA-AMYLASE 2B

IPI01011210.1
Isoform 4 of Potassium voltage-gated channel
1.865
4.165
6.680
1.856
3.342

subfamily C member 2

IPI01011319.1
annexin A6 isoform 2
2.030
2.117
2.293
1.766
2.373

IPI01011344.1
Uncharacterized protein
1.549
3.576
4.754
1.731
2.201

IPI01011530.1
Uncharacterized protein
1.711
3.147
4.479
1.649
2.247

IPI01011804.1
Uncharacterized protein
1.378
2.425
4.677
1.082
2.089

IPI01011912.1
Phosphoglycerate kinase
1.462
3.359
8.933
1.331
1.826

IPI01011970.1
6-phosphogluconate dehydrogenase,
1.477
1.984
3.160
1.281
1.592

decarboxylating

IPI01012623.1
Uncharacterized protein
2.982
6.695
10.668
2.551
3.922

IPI01012744.1
Uncharacterized protein
1.935
11.056
8.458
3.207
1.616

IPI01013112.1
Uncharacterized protein
2.596
8.476
17.899
2.424
3.131

IPI01013314.1
cDNA FLJ53395, highly similar to Prolyl 3-
18.301
27.571
55.459
16.630
3.594

hydroxylase 1

IPI01013441.1
Uncharacterized protein
2.293
1.376
1.354
1.366
2.016

IPI01013543.1
Triosephosphate isomerase
1.583
2.620
3.451
1.544
1.736

IPI01014005.1
AMY1A protein (Fragment)
1.105
0.879
0.901
1.148
2.442

IPI01014138.1
Uncharacterized protein
1.679
2.739
3.783
1.830
2.511

IPI01014668.1
Isoform 6 of Afadin
0.392
0.686
0.648
0.467
0.630

IPI01014975.1
Uncharacterized protein
2.447
1.090
1.955
1.969
2.527

IPI01015050.2
Uncharacterized protein
1.539
2.230
3.161
1.285
2.343

IPI01015738.1
Uncharacterized protein
1.962
2.414
2.212
1.611
2.282

IPI01018060.1
Ig lambda-3 chain C regions
2.143
3.807
6.225
2.172
3.213

IPI01018799.1
Isoform 2 of Dystonin
2.614
2.861
4.054
2.074
3.431

IPI01020720.1
cDNA FLJ54328, highly similar to Heat shock
2.232
3.358
5.006
1.677
2.299

70 kDa protein 1

IPI01021999.1
Uncharacterized protein
1.813
5.475
6.467
1.970
1.650

IPI01022175.1
cDNA FLJ55805, highly similar to Keratin, type
0.807
1.416
1.443
1.087
1.078

II cytoskeletal 4

IPI01022327.1
keratin, type II cytoskeletal 4
0.861
1.347
1.387
1.043
1.078

IPI01025024.1
27 kDa protein
1.850
1.722
2.055
1.495
2.357

IPI01025103.1
20 kDa protein
1.454
2.261
3.413
1.400
2.351

IPI01026451.1
Protein
2.571
7.608
26.692
0.218
0.825

IPI00019779.3
Putative uncharacterized protein
1.964
7.204
22.332
0.817
2.105

DKFZp686B0790

Q73NE3
ATP-dependent protease ATPase subunit HsIU
2.283
4.788
10.385
2.164
3.335

OS = Treponema denticola (strain ATCC 35405/

CIP 103919/DSM 14222) GN = hsIU PE = 3

SV = 1-[HSLU_TREDE]

Q97QZ6
Putative lipid kinase SP_1045
1.346
2.270
6.525
0.712
1.261

OS = Streptococcus pneumoniae GN = SP_1045

PE = 1 SV = 1-[Y1045_STRPN]

SUPPLEMENTARY TABLE 2

CLUSTER 3

Sample # 52:
IPI00167191.1
CDNA FLJ25707 fis, clone TST04879

CLUSTER 4

Sample # 4:
A8AW24
Isoleucine-tRNA ligase OS =

Streptococcus gordonii

(strain Challis/ATCC 35105/

CH1/DL1/V288) GN = ileS PE = 3

SV = 1

Sample # 85:
IPI00334400.2
Isoform 2 of Plakophilin-4

Sample # 163:
IPI00848276.1
Isoform 1 of Uncharacterized protein

C10orf18

Sample # 209:
IPI00940399.2
Uncharacterized protein

Sample # 257:
IPI01014668.1
Isoform 6 of Afadin

CLUSTER 5

Sample # 269:
IPI01026451.1
Protein

SUPPLEMENTARY TABLE 3

CLUSTER 1C

Sample # 49:
IPI00177428.1
Isoform 2 of Mitochondrial

intermembrane space import and

assembly protein 40

Sample # 76:
IPI00328296.2
PDZ domain-containing protein GIPC2

CLUSTER 1D

Sample # 17:
IPI00010349.1
Alkyldihydroxyacetonephosphate

synthase, peroxisomal

Sample # 66:
IPI00292579.4
Stabilin-2

Sample # 99:
IPI00470476.3
Uncharacterized protein C9orf144A

Sample # 125:
IPI00745280.1
Similar to Keratin, type II cytoskeletal 7

Sample # 130:
IPI00783859.2
Isoform 2 of Vacuolar protein sorting-

associated protein 13D

Sample # 181:
IPI00924608.1
vacuolar protein sorting-associated

protein 13D isoform 1

SUPPLEMENTARY TABLE 4

CLUSTER 1A3

Sample # 12:
IPI00009724.3
Isoform 1 of EF-hand calcium-binding

domain-containing protein 6

Sample # 46:
IPI00168728.1
FLJ00385 protein (Fragment)

Sample # 84:
IPI00418153.1
Putative uncharacterized protein

DKFZp686I15212

Sample # 103:
IPI00552637.1
G-protein coupled receptor

Sample # 108:
IPI00556287.1
Putative uncharacterized protein

Sample # 129:
IPI00790172.5
Keratin, type I cuticular Ha5

Sample # 183:
IPI00946655.1
Isoform 1 of Actin-related protein 3C

Sample # 192:
IPI00973588.1
Full-length cDNA clone

CS0DI019YF20 of Placenta of

Homo sapiens (Fragment)

Sample # 215:
IPI01012744.1
Uncharacterized protein

Sample # 216:
IPI01013112.1
Uncharacterized protein

CLUSTER 1A4

Sample # 74:
IPI00375293.2
Isoform 2 of High affinity

immunoglobulin gamma Fc receptor I

Sample # 232:
O83773
Uncharacterized protein TP_0795 OS =

Treponema pallidum (strain Nichols)

GN = TP_0795 PE = 4 SV =

1 − [Y795_TREPA]

SUPPLEMENTARY TABLE 5

Number

of quant
A6:
A6:
A6:
A6:
A6:
A6:

Accession
Description
peptides
114/113
115/113
116/113
117/113
118/113
119/113

A7I3U7
Elongation factor Tu
1
1.334
1.068
1.383
0.931
0.965
0.909

OS = Campylobacter hominis

(strain ATCC BAA-381/LMG

19568/NCTC 13146/

CH001A) GN = tuf PE = 3 SV = 1-

[EFTU_CAMHC]

IPI00002557.1
Coatomer subunit gamma-2
3
2.422
3.431
5.719
1.270
1.857
0.973

IPI00002851.1
Cystatin-D
45
1.067
1.155
1.212
1.946
1.669
2.013

IPI00003269.1
Beta-actin-like protein 2
1
1.133
1.512
1.605
1.476
1.238
1.541

IPI00003935.6
Histone H2B type 2-E
5
1.265
1.484
1.633
0.388
0.634
0.551

IPI00004573.2
Polymeric immunoglobulin
344
1.355
1.004
1.141
1.339
1.164
2.048

receptor

IPI00004656.3
Beta-2-microglobulin
12
1.151
0.818
1.107
1.181
0.921
1.456

IPI00005721.1
Neutrophil defensin 1
31
1.339
1.818
3.735
1.321
1.880
0.325

IPI00007047.1
Protein S100-A8
105
2.089
3.485
5.821
3.001
3.414
0.761

IPI00007797.3
Fatty acid-binding protein,
37
0.869
0.659
1.116
0.868
0.730
1.118

epidermal

IPI00008405.5
Arylsulfatase F
1
2.459
1.617
2.073
1.893
1.433
1.685

IPI00008895.1
Epithelial membrane protein 2
2
1.432
1.014
1.025
0.465
0.654
0.343

IPI00009650.1
Lipocalin-1
88
0.821
0.659
0.774
0.770
0.849
1.003

IPI00010182.4
Isoform 1 of Acyl-CoA-
2
0.541
0.683
1.343
0.535
0.586
1.083

binding protein

IPI00010471.6
Plastin-2
60
1.927
2.427
3.986
1.449
1.981
0.749

IPI00010796.1
Protein disulfide-isomerase
22
1.158
1.242
1.913
1.246
1.360
1.128

IPI00010896.3
Chloride intracellular channel
1
1.302
2.597
4.398
1.171
1.693
0.000

protein 1

IPI00012024.1
Histatin-1
19
1.681
2.703
1.813
8.008
3.163
5.536

IPI00012199.1
Coiled-coil domain-containing
5
3.494
1.199
0.471
2.583
1.608
9.492

protein 86

IPI00012525.1
Putative uncharacterized
3
0.923
1.037
0.621
1.198
0.931
2.992

protein (Fragment)

IPI00012796.1
Glutamate decarboxylase 2
6
0.524
0.591
0.909
0.338
0.252
0.342

IPI00013382.1
Cystatin-SA
154
1.612
2.447
1.976
3.388
3.313
2.284

IPI00013885.1
Caspase-14
4
0.821
0.982
1.293
0.866
1.008
1.908

IPI00013890.2
Isoform 1 of 14-3-3 protein
2
0.749
0.478
0.614
0.806
0.626
1.215

sigma

IPI00013895.1
Protein S100-A11
3
0.964
0.923
2.966
0.659
0.985
1.115

IPI00016347.5
Isoform 3 of Uncharacterized
1
4.154
8.928
16.772
1.275
2.398
1.915

protein C2orf54

IPI00017526.1
Protein S100-P
8
1.552
2.065
4.222
1.358
1.880
0.603

IPI00017672.4
cDNA FLJ25678 fis, clone
5
0.918
1.218
5.022
1.120
1.446
0.815

TST04067, highly similar to

PURINE NUCLEOSIDE

PHOSPHORYLASE

IPI00019038.1
Lysozyme C
4
2.326
1.456
2.240
1.721
1.671
3.324

IPI00019449.1
Non-secretory ribonuclease
2
1.376
2.430
3.652
1.226
1.337
1.147

IPI00019502.3
Isoform 1 of Myosin-9
2
2.000
3.924
8.217
1.892
3.411
0.808

IPI00020008.1
NEDD8
3
1.428
1.588
2.203
1.005
1.461
1.352

IPI00020091.1
Alpha-1-acid glycoprotein 2
17
1.535
1.385
4.699
1.421
1.782
1.147

IPI00021085.1
Peptidoglycan recognition
5
1.221
1.458
2.897
0.970
1.046
0.753

protein 1

IPI00021263.3
14-3-3 protein zeta/delta
3
1.178
1.027
1.446
1.289
1.279
1.287

IPI00021304.1
Keratin, type II cytoskeletal 2
5
0.982
1.009
1.276
1.151
3.128
1.063

epidermal

IPI00021447.1
Alpha-amylase 2B
3
1.079
0.862
0.705
1.222
0.933
2.067

IPI00021828.1
Cystatin-B
81
0.828
0.544
0.876
0.676
0.686
1.099

IPI00021841.1
Apolipoprotein A-I
18
0.835
0.832
1.867
0.694
0.860
0.745

IPI00022429.3
Alpha-1-acid glycoprotein 1
53
1.424
1.537
4.423
1.523
1.798
0.917

IPI00022463.2
Serotransferrin
146
1.459
1.092
2.155
1.029
1.126
0.881

IPI00022488.1
Hemopexin
32
1.404
1.403
2.394
0.981
1.138
0.948

IPI00022974.1
Prolactin-inducible protein
246
1.227
1.209
1.292
1.748
1.622
1.103

IPI00022990.1
Statherin
7
1.429
2.406
2.568
3.207
2.496
2.384

IPI00023011.2
Submaxillary gland
90
1.742
2.454
2.287
2.367
2.098
2.577

androgen-regulated protein

3B

IPI00023038.2
Basic salivary proline-rich
4
1.218
0.961
1.368
1.927
1.498
3.110

protein 1

IPI00027462.1
Protein S100-A9
96
1.798
3.205
6.274
2.954
3.150
1.038

IPI00027463.1
Protein S100-A6
2
2.194
2.125
3.066
1.586
2.024
1.628

IPI00027509.5
Matrix metalloproteinase-9
10
1.467
1.875
4.619
1.046
1.606
0.603

IPI00027769.1
Neutrophil elastase
12
1.439
2.081
3.690
0.986
1.648
0.671

IPI00028064.1
Cathepsin G
2
1.820
1.721
2.885
1.107
2.606
0.827

IPI00028931.2
Desmoglein-2
5
0.928
1.331
0.424
0.680
0.401
1.298

IPI00031983.4
UDP-GlcNAc:betaGal beta-
1
1.175
1.644
1.973
1.315
1.081
1.234

1,3-N-

acetylglucosaminyltransferase 3

IPI00032220.3
Angiotensinogen
3
1.522
0.794
2.030
0.934
1.162
1.027

IPI00032293.1
Cystatin-C
25
1.258
1.117
1.166
1.533
1.176
1.776

IPI00032294.1
Cystatin-S
234
1.385
1.513
1.441
2.037
1.440
1.319

IPI00037070.3
Uncharacterized protein
1
0.603
0.706
3.183
0.527
0.552
0.625

IPI00060800.5
Zymogen granule protein 16
154
2.141
1.224
0.812
1.888
1.294
0.914

homolog B

IPI00065475.6
Isoform 2 of UPF0585 protein
1
1.307
1.489
2.017
1.064
0.979
1.041

C16orf13

IPI00103636.1
Isoform 2 of WAP four-
11
1.213
0.761
1.013
1.286
1.328
2.436

disulfide core domain protein 2

IPI00141938.4
histone H2A.V isoform 2
7
1.184
1.149
1.390
0.377
0.633
0.822

IPI00152154.2
Mucin-7
11
1.390
1.341
1.362
1.481
1.205
0.846

IPI00166729.4
Zinc-alpha-2-glycoprotein
126
1.184
0.986
1.046
1.204
1.017
1.645

IPI00169244.1
106 kDa protein
1
1.285
1.692
1.105
1.831
1.341
2.026

IPI00171196.2
Isoform 3 of Keratin, type I
28
0.997
2.372
3.765
0.914
0.921
0.784

cytoskeletal 13

IPI00174541.1
Isoform 4 of Interleukin-1
27
0.951
0.847
0.969
0.874
0.848
1.522

receptor antagonist protein

IPI00178926.2
Immunoglobulin J chain
48
1.411
0.946
1.422
1.191
1.292
1.833

IPI00180240.2
Thymosin beta-4-like protein 3
4
1.890
2.250
5.361
1.801
2.320
1.482

IPI00182138.4
Isoform 2 of Granulins
8
1.159
1.156
2.207
1.104
1.212
0.833

IPI00215628.1
Isoform V1 of Versican core
4
0.753
0.233
0.118
0.868
0.167
2.209

protein

IPI00216298.6
Thioredoxin
20
0.714
0.530
0.903
0.637
0.618
0.868

IPI00216691.5
Profilin-1
43
2.306
2.912
7.249
1.671
2.447
0.862

IPI00216835.2
Isoform 2 of NADPH oxidase
2
4.163
3.228
1.127
3.132
3.034
4.653

activator 1

IPI00217473.5
Hemoglobin subunit zeta
1
2.065
4.113
2.853
5.036
4.045
3.416

IPI00217846.3
Isoform 4 of Uncharacterized
6
1.208
1.328
2.126
1.044
0.906
1.302

protein C5orf25

IPI00217963.3
Keratin, type I cytoskeletal
1
1.136
1.173
1.859
1.552
1.383
0.770

16

IPI00217966.9
Isoform 1 of L-lactate
7
1.420
1.287
3.600
1.170
1.608
1.021

dehydrogenase A chain

IPI00218131.3
Protein S100-A12
7
2.018
2.382
5.247
1.969
3.303
0.870

IPI00218918.5
Annexin A1
6
0.901
0.866
1.135
0.842
1.134
1.151

IPI00219018.7
Glyceraldehyde-3-phosphate
7
1.890
2.015
3.068
2.405
3.303
1.254

dehydrogenase

IPI00219365.3
Moesin
5
2.446
3.238
5.521
1.827
2.468
1.272

IPI00219757.13
Glutathione S-transferase P
5
1.167
1.143
2.071
0.961
1.121
1.127

IPI00220327.4
Keratin, type II cytoskeletal 1
10
1.379
1.390
1.249
1.338
2.501
1.922

IPI00221362.3
Isoform 3 of Apoptosis-
3
1.298
1.275
2.918
0.872
1.230
0.674

associated speck-like protein

containing a CARD

IPI00236554.1
Isoform H14 of
7
0.972
1.284
1.511
0.698
0.702
0.622

Myeloperoxidase

IPI00255103.8
Isoform 3 of Contactin-
1
0.804
0.796
1.113
0.715
0.650
0.736

associated protein-like 3B

IPI00290077.3
Keratin, type I cytoskeletal
3
0.713
1.001
1.373
0.894
1.092
0.636

15

IPI00291410.3
Isoform 1 of Long palate,
5
0.565
0.499
0.630
0.648
0.723
0.588

lung and nasal epithelium

carcinoma-associated protein 1

IPI00291922.2
Proteasome subunit alpha
2
1.205
1.447
3.311
1.219
1.520
0.848

type-5

IPI00293276.10
Macrophage migration
2
1.102
1.154
3.849
0.903
1.245
0.864

inhibitory factor

IPI00295105.3
cDNA FLJ60163, highly
89
1.200
0.995
0.740
1.345
0.973
1.944

similar to Carbonic anhydrase 6

IPI00296654.2
Bactericidal/permeability-
102
1.038
0.964
1.128
1.036
1.059
0.979

increasing protein-like 1

IPI00298497.3
Fibrinogen beta chain
3
1.271
1.495
2.748
1.090
1.251
0.768

IPI00299078.1
Salivary acidic proline-rich
105
1.717
1.175
0.948
1.780
0.958
2.336

phosphoprotein 1/2

IPI00299547.4
Isoform 1 of Neutrophil
10
1.335
1.374
4.163
0.862
1.261
1.122

gelatinase-associated

lipocalin

IPI00299729.4
Transcobalamin-1
11
1.254
1.092
1.409
1.080
0.911
1.048

IPI00300376.5
Protein-glutamine gamma-
4
1.381
1.362
1.519
0.934
1.308
1.472

glutamyltransferase E

IPI00300786.1
Alpha-amylase 1
1385
1.018
0.914
0.835
1.024
0.877
2.316

IPI00301058.5
Vasodilator-stimulated
6
1.831
2.325
3.191
1.358
1.822
1.087

phosphoprotein

IPI00301658.7
Isoform 3 of Protein
2
1.908
1.390
1.034
0.892
2.194
1.993

FAM194A

IPI00304557.2
Short palate, lung and nasal
117
0.967
0.839
0.582
1.462
1.133
1.411

epithelium carcinoma-

associated protein 2

IPI00304808.4
Isoform 1 of Kallikrein-1
33
1.143
1.071
1.088
1.193
0.996
2.770

IPI00305477.6
Cystatin-SN
328
1.029
1.165
1.402
1.480
1.224
1.340

IPI00373937.3
Suprabasin
3
1.089
1.447
1.976
1.499
1.271
1.150

IPI00374315.1
UPF0762 protein C6orf58
35
1.219
0.889
0.891
0.899
0.814
0.628

IPI00375307.2
peroxiredoxin-5,
1
2.176
1.892
2.076
2.669
2.607
2.187

mitochondrial isoform c

precursor

IPI00377122.4
Isoform 2 of WD repeat-
2
3.250
8.184
9.606
1.741
5.015
1.041

containing protein KIAA1875

IPI00383627.1
Pituitary tumor transforming
1
1.664
1.085
0.789
2.088
1.348
3.280

gene protein

IPI00383981.3
AZU1 protein (Fragment)
1
1.239
1.215
1.506
1.029
1.043
1.587

IPI00384251.1
Isoform 2 of Guanine
2
2.806
4.222
2.254
2.408
1.972
0.903

nucleotide exchange factor

for Rab-3A

IPI00384382.1
AngRem52
2
5.427
4.310
0.488
5.921
5.682
13.414

IPI00384444.6
Keratin, type I cytoskeletal
9
0.828
1.020
1.545
1.135
1.213
0.629

14

IPI00384975.4
Uncharacterized protein
3
1.703
1.882
3.972
1.491
1.887
1.072

IPI00385252.1
Ig kappa chain V-III region
1
1.122
1.376
1.627
0.603
0.797
0.991

GOL

IPI00386132.1
Ig kappa chain V-IV region JI
3
1.135
1.470
2.104
1.164
1.192
1.304

IPI00386879.1
cDNA FLJ14473 fis, clone
35
1.468
0.875
1.253
1.497
1.229
2.044

MAMMA1001080, highly

similar to Homo sapiens

SNC73 protein (SNC73)

mRNA

IPI00397768.5
Isoform 2 of
2
1.697
1.040
0.494
0.974
0.716
0.626

Ribonucleoprotein PTB-

binding 2

IPI00399007.7
Putative uncharacterized
22
1.366
1.235
3.744
1.003
1.606
0.685

protein DKFZp686I04196

(Fragment)

IPI00399260.2
basic salivary proline-rich
4
0.817
0.602
0.858
1.338
0.896
2.761

protein 1 isoform 3

preproprotein

IPI00410714.5
Hemoglobin subunit alpha
295
3.564
5.378
11.480
1.052
1.813
1.174

IPI00411765.3
Isoform 2 of 14-3-3 protein
1
0.669
0.409
0.557
0.667
0.485
1.131

sigma

IPI00414909.1
Alpha-N-
2
2.859
3.040
0.525
3.474
2.633
17.162

acetylgalactosaminidase

IPI00419215.6
Alpha-2-macroglobulin-like
6
0.874
0.695
1.359
0.997
0.806
1.642

protein 1

IPI00419585.9
Peptidyl-prolyl cis-trans
14
1.235
1.302
2.881
0.983
1.272
0.902

isomerase A

IPI00423460.3
Putative uncharacterized
68
1.253
0.886
1.122
1.420
1.036
2.031

protein DKFZp686G21220

(Fragment)

IPI00426051.3
Putative uncharacterized
6
1.301
1.325
3.380
1.042
1.585
0.771

protein DKFZp686C15213

IPI00431645.2
31 kDa protein
19
1.534
1.353
3.752
1.022
1.684
1.119

IPI00448925.6
44 kDa protein
39
1.816
1.994
4.028
1.449
1.637
1.038

IPI00451401.3
Isoform 2 of Triosephosphate
11
0.939
0.943
1.929
0.911
0.914
0.938

isomerase

IPI00453473.6
Histone H4
19
0.940
1.178
1.774
0.294
0.442
0.599

IPI00465248.5
Isoform alpha-enolase of
77
1.577
1.636
3.750
1.376
1.676
1.053

Alpha-enolase

IPI00465436.4
Catalase
3
0.849
0.892
4.163
0.689
0.719
0.588

IPI00465439.5
Fructose-bisphosphate
8
1.126
1.108
2.388
0.895
1.034
0.932

aldolase A

IPI00472974.2
PR domain zinc finger protein
1
1.322
0.782
0.594
0.499
0.606
0.826

2 isoform c

IPI00473011.3
Hemoglobin subunit delta
10
2.137
4.652
11.181
0.891
1.396
1.521

IPI00477265.2
archaemetzincin-2 isoform 2
2
1.045
1.803
1.409
1.232
1.202
1.036

IPI00478003.3
Alpha-2-macroglobulin
32
1.781
1.541
2.997
1.162
1.369
1.261

IPI00478493.3
haptoglobin isoform 2
22
1.618
1.346
3.690
1.046
1.698
1.126

preproprotein

IPI00479186.7
Isoform M2 of Pyruvate
9
1.071
1.140
4.945
1.178
1.376
0.947

kinase isozymes M1/M2

IPI00479708.6
Full-length cDNA clone
25
1.453
1.136
1.956
1.318
1.367
1.145

CS0DD006YL02 of

Neuroblastoma of Homo

sapiens

IPI00549413.2
Uncharacterized protein
7
0.823
0.790
0.992
0.864
1.115
1.100

IPI00550731.2
Putative uncharacterized
162
1.388
1.056
1.827
1.336
1.377
1.778

protein

IPI00552432.3
Basic salivary proline-rich
13
1.468
1.308
2.302
2.485
2.204
4.018

protein 2

IPI00552768.1
Uncharacterized protein
44
0.725
0.542
0.941
0.661
0.638
0.878

IPI00553177.1
Isoform 1 of Alpha-1-
1
2.622
1.595
2.982
3.246
2.000
9.201

antitrypsin

IPI00554696.2
Uncharacterized protein
141
1.153
0.946
0.733
1.287
0.901
1.893

IPI00555812.5
vitamin D-binding protein
2
1.540
0.864
1.313
0.642
0.864
0.776

isoform 1 precursor

IPI00640006.1
rab GDP dissociation inhibitor
2
1.094
1.139
2.142
0.875
0.960
1.079

beta isoform 2

IPI00640335.1
Protein
2
1.020
1.000
1.104
0.715
0.763
1.381

IPI00641047.5
Uncharacterized protein
2
1.030
1.256
2.841
0.875
1.109
0.724

IPI00641737.2
Haptoglobin
9
1.558
1.456
3.624
1.039
1.631
1.146

IPI00642247.1
Uncharacterized protein
1
1.345
1.142
1.335
1.592
1.976
3.355

IPI00642414.1
Adenylyl cyclase-associated
8
1.525
1.749
4.087
1.080
1.601
0.632

protein

IPI00643231.1
Uncharacterized protein
7
0.799
0.724
0.856
0.806
0.949
1.048

IPI00645363.2
Putative uncharacterized
13
1.731
1.816
3.774
1.500
1.768
1.103

protein DKFZp686P15220

IPI00646265.2
58 kDa protein
1
0.446
0.419
0.711
0.756
0.440
2.129

IPI00654755.3
Hemoglobin subunit beta
206
5.138
7.744
19.343
0.958
2.207
1.176

IPI00658053.1
Uncharacterized protein
3
1.025
0.706
1.138
1.215
1.057
1.976

IPI00658218.1
Isoform 5 of Deleted in
33
1.134
0.848
1.072
1.484
1.104
2.882

malignant brain tumors 1

protein

IPI00719452.1
IGL@ protein
3
1.619
1.410
2.306
1.524
1.564
1.899

IPI00735451.4
Immunolgoobulin heavy
3
1.458
1.342
1.931
1.375
1.529
1.614

chain

IPI00740545.1
POTE ankyrin domain family
1
1.544
1.863
5.939
1.646
1.829
1.201

member I

IPI00742775.1
Bardet-Biedl syndrome 10
3
1.797
1.054
0.649
1.610
1.479
3.659

protein

IPI00745872.2
Isoform 1 of Serum albumin
1199
1.253
1.073
1.906
0.893
1.020
0.693

IPI00748022.2
Actin-like protein (Fragment)
3
0.658
0.450
15.108
0.904
1.215
0.342

IPI00748184.4
Uncharacterized protein
1
1.190
0.580
0.806
0.721
0.783
1.577

IPI00759663.1
Isoform
3
2.019
1.866
2.939
2.017
2.349
1.436

Cytoplasmic + peroxisomal of

Peroxiredoxin-5,

mitochondrial

IPI00759832.1
Isoform Short of 14-3-3
4
1.613
1.872
2.478
1.732
2.004
1.079

protein beta/alpha

IPI00782983.3
Immunglobulin heavy chain
1
1.274
0.966
1.380
0.984
1.124
1.435

variable region

IPI00783192.1
Isoform 2 of
2
1.835
2.502
4.115
0.957
1.295
0.426

Lysophospholipid

acyltransferase LPCAT4

IPI00783287.1
Immunglobulin heavy chain
6
1.370
1.178
1.908
1.273
1.351
1.855

variable region (Fragment)

IPI00783987.2
Complement C3 (Fragment)
31
1.310
1.335
1.824
1.083
1.300
0.939

IPI00784430.5
Ig kappa chain V-III region
3
1.432
1.606
2.025
1.687
1.269
1.802

VG (Fragment)

IPI00784830.1
cDNA FLJ41981 fis, clone
20
1.313
0.969
1.755
1.137
1.364
1.729

SMINT2011888, highly

similar to Protein Tro alpha1

H, myeloma

IPI00784842.1
Putative uncharacterized
5
1.677
1.158
2.049
1.110
1.290
1.805

protein DKFZp686G11190

IPI00784950.1
Putative uncharacterized
34
1.385
1.031
1.794
1.307
1.680
1.966

protein DKFZp686L19235

IPI00784985.1
IGK@ protein
4
1.659
1.619
2.137
1.341
1.216
1.390

IPI00789337.4
cDNA, FLJ79516, highly
11
1.014
0.979
1.408
1.077
1.151
1.104

similar to 14-3-3 protein

zeta/delta

IPI00793319.1
Uncharacterized protein
15
1.056
0.817
1.892
0.803
0.955
1.135

IPI00793812.3
Isoform 3 of Leukotriene A-4
2
2.073
3.756
2.090
2.556
3.836
1.378

hydrolase

IPI00795257.3
Glyceraldehyde-3-phosphate
20
1.906
2.414
4.423
2.475
3.309
1.095

dehydrogenase

IPI00796776.2
cDNA FLJ54081, highly
8
0.956
1.653
2.132
1.055
1.262
0.895

similar to Keratin, type II

cytoskeletal 5

IPI00796823.1
Uncharacterized protein
3
1.332
1.018
1.531
1.274
1.060
1.634

IPI00797270.4
Isoform 1 of Triosephosphate
12
0.954
0.958
1.977
0.942
0.936
0.954

isomerase

IPI00807428.1
Putative uncharacterized
11
1.663
1.256
2.096
1.521
1.622
2.108

protein

IPI00816687.1
FGB protein (Fragment)
2
1.256
1.455
2.629
1.158
1.171
0.861

IPI00829697.1
13 kDa protein
2
1.291
1.053
1.273
1.258
1.076
1.344

IPI00844600.1
9 kDa protein
34
1.819
1.908
4.485
1.795
3.045
0.855

IPI00847989.3
Pyruvate kinase
7
1.034
1.075
5.892
1.073
1.314
0.992

IPI00853525.1
Uncharacterized protein
32
0.974
0.952
2.041
0.787
0.978
0.740

IPI00854743.1
Immunglobulin heavy chain
3
1.793
1.577
2.106
1.672
1.477
1.621

variable region

IPI00869004.1
Isoform 3 of Alpha-1-
3
2.465
1.626
3.011
3.218
2.013
8.595

antitrypsin

IPI00872278.1
Isoform 7 of Deleted in
73
1.096
0.859
1.032
1.459
1.193
2.904

malignant brain tumors 1

protein

IPI00876888.1
cDNA FLJ78387
24
1.938
2.052
4.124
1.445
1.739
1.089

IPI00878551.2
cDNA FLJ59430, highly
6
1.132
1.179
1.789
1.162
1.248
1.130

similar to Protein disulfide-

isomerase

IPI00879084.2
Uncharacterized protein
2
0.869
0.734
1.657
0.639
0.844
0.847

IPI00879437.1
Protein
6
1.140
1.244
2.007
1.342
1.500
1.118

IPI00879438.1
Uncharacterized protein
7
1.599
1.349
2.028
1.286
1.446
1.754

IPI00883885.3
PRB3 protein
2
1.958
4.184
10.696
4.152
5.160
3.582

IPI00884451.2
basic salivary proline-rich
4
1.487
1.901
1.782
3.621
2.533
6.502

protein 4 precursor

IPI00892657.1
Protein
3
1.054
0.900
0.852
0.988
0.843
1.529

IPI00893981.1
Uncharacterized protein
15
1.884
3.572
9.128
1.543
2.690
0.933

IPI00902602.1
cDNA FLJ33251 fis, clone
2
0.931
0.313
0.160
1.079
0.232
2.915

ASTRO2005242, highly

similar to Rho guanine

nucleotide exchange factor 5

IPI00902755.1
FGA protein (Fragment)
13
1.306
1.305
2.165
0.863
1.298
0.851

IPI00903112.1
cDNA FLJ36533 fis, clone
35
1.075
1.133
1.275
0.905
0.900
1.574

TRACH2004428, highly

similar to Lactotransferrin

(Fragment)

IPI00903245.1
cDNA FLJ44586 fis, clone
3
1.185
1.237
3.194
0.543
1.024
0.603

ASTRO2015162, highly

similar to Choline

transporter-like protein 2

IPI00908402.1
cDNA FLJ51275
21
0.875
0.775
1.042
0.763
0.863
1.697

IPI00908746.1
cDNA FLJ51535, highly
2
1.215
1.080
1.494
0.992
0.979
1.399

similar to

Phosphatidylethanolamine-

binding protein 1

IPI00908881.3
Glucose-6-phosphate
21
1.390
1.889
4.093
1.235
1.632
0.778

isomerase

IPI00909239.1
Isoform 2 of Alpha-actinin-1
2
0.959
1.185
3.107
0.847
0.983
0.761

IPI00909530.1
cDNA FLJ52843, highly
2
0.863
1.184
1.638
0.284
0.466
0.389

similar to Histone H3.3

IPI00909737.1
cDNA FLJ55140, highly
3
1.576
1.040
1.195
1.687
1.148
1.266

similar to SPARC-like protein 1

IPI00910407.1
Peptidyl-prolyl cis-trans
4
1.257
1.380
2.526
1.134
1.306
1.122

isomerase

IPI00910819.2
cDNA FLJ60194, highly
2
0.419
0.169
0.340
0.174
0.162
0.819

similar to WW domain-

binding protein 11

IPI00911039.1
cDNA FLJ54408, highly
24
1.286
1.230
2.977
0.919
1.177
1.015

similar to Heat shock 70 kDa

protein 1

IPI00914858.1
Isoform 3 of WD repeat- and
1
0.710
0.782
2.267
0.797
0.708
0.764

FYVE domain-containing

protein 4

IPI00915959.2
Uncharacterized protein
1
1.027
0.847
1.058
0.822
1.078
1.278

IPI00916434.1
Anti-(ED-B) scFV (Fragment)
22
1.451
1.070
1.836
1.129
1.270
1.745

IPI00916818.1
Phosphoglycerate kinase
3
1.905
2.138
4.346
1.691
2.285
1.158

IPI00918002.1
Mucin 5AC, oligomeric
148
0.803
0.649
0.774
0.894
0.946
0.792

mucus/gel-forming

IPI00921945.1
cDNA FLJ57374
3
2.551
1.937
1.257
2.959
2.453
5.295

IPI00922262.1
cDNA FLJ56822, highly
3
1.453
1.413
2.569
1.226
1.486
0.917

similar to Alpha-2-HS-

glycoprotein

IPI00924751.1
Protein
2
6.044
5.591
1.745
9.960
7.333
6.159

IPI00927887.1
Histone H2A
6
1.166
1.117
1.335
0.340
0.595
0.859

IPI00929669.1
Similar to Keratin 16
1
0.846
0.939
1.745
1.197
1.161
0.460

IPI00930072.1
Putative uncharacterized
9
1.493
1.318
4.185
1.146
1.974
0.697

protein DKFZp686E23209

IPI00930226.1
cDNA FLJ57283, highly
144
1.614
2.170
5.681
1.448
1.915
0.897

similar to Actin, cytoplasmic 2

IPI00930442.1
Putative uncharacterized
10
1.357
1.336
3.471
0.849
1.304
0.710

protein DKFZp686M24218

IPI00936444.2
cDNA FLJ59081, highly
375
0.767
0.618
0.731
0.872
0.943
0.744

similar to Mucin-5B

IPI00939521.1
10 kDa protein
11
1.417
1.299
1.919
1.323
1.499
1.796

IPI00940673.2
cDNA FLJ36348 fis, clone
27
1.263
1.421
2.558
1.151
1.346
1.090

THYMU2007025, highly

similar to TRANSKETOLASE

IPI00942117.2
cysteine-rich secretory
3
1.602
1.679
1.851
2.268
1.658
1.236

protein 3 isoform 1 precursor

IPI00942257.3
Uncharacterized protein
8
0.831
1.298
2.436
1.171
1.063
0.668

IPI00942979.1
Transketolase
56
1.799
2.383
4.969
1.448
2.125
0.778

IPI00943894.1
glycogen phosphorylase, liver
3
1.700
2.112
8.124
2.052
2.690
0.942

form isoform 2

IPI00945694.1
Uncharacterized protein
4
2.032
1.446
1.134
0.943
2.198
2.126

IPI00946655.1
Isoform 1 of Actin-related
6
1.390
1.496
5.005
1.472
2.156
0.949

protein 3C

IPI00947240.1
24 kDa protein
3
0.683
0.962
0.883
0.531
0.547
0.793

IPI00964000.1
Uncharacterized protein
110
1.452
0.954
1.354
1.277
1.294
1.901

IPI00965100.1
Uncharacterized protein
20
1.738
2.050
1.646
3.357
2.292
1.017

IPI00965713.3
fibrinogen beta chain isoform
2
1.515
1.521
3.117
1.023
1.453
0.671

2 preproprotein

IPI00966755.1
Uncharacterized protein
2
1.956
1.775
1.376
1.277
1.506
0.649

IPI00967145.1
Uncharacterized protein
5
0.920
0.286
0.265
1.014
0.277
2.146

IPI00968182.1
Uncharacterized protein
5
0.702
0.698
1.209
0.588
0.762
0.850

IPI00969578.1
Salivary proline-rich protein 2
3
0.384
0.298
0.467
0.428
0.296
2.190

(Fragment)

IPI00972963.1
Lambda light chain of human
28
1.623
1.250
2.236
1.587
1.700
2.028

immunoglobulin surface

antigen-related protein

(Fragment)

IPI00973998.1
Uncharacterized protein
4
0.855
1.217
1.587
0.311
0.383
0.315

IPI00974112.1
22 kDa protein
3
1.518
1.547
1.709
2.228
1.636
1.129

IPI00974544.1
Isoform SV of 14-3-3 protein
4
1.198
1.054
1.576
0.983
1.235
0.878

epsilon

IPI00975690.1
Vimentin variant 3
5
1.490
2.426
3.841
1.423
1.455
0.479

IPI00975820.1
Uncharacterized protein
3
1.341
0.908
0.965
1.223
0.866
0.639

IPI00976039.1
Uncharacterized protein
7
1.316
1.174
1.162
1.623
1.390
1.853

IPI00976187.1
Similar to Rheumatoid factor
5
1.343
0.913
1.190
0.948
1.033
1.320

G9 heavy chain

IPI00976928.1
Similar to Myosin-reactive
4
1.848
1.462
1.590
1.501
1.147
1.387

immunoglobulin heavy chain

variable region

IPI00977041.1
Isoform 1 of Immunoglobulin
5
1.510
1.304
1.783
1.427
1.426
1.854

lambda-like polypeptide 5

IPI00977297.1
Similar to VH4 heavy chain
6
1.179
0.809
1.325
0.893
0.986
1.307

variable region precursor

IPI00977405.1
Similar to Ig kappa chain V-
5
1.476
1.645
2.074
1.634
1.205
1.807

III region VG precursor

IPI00977704.1
Uncharacterized protein
1
1.794
2.829
5.564
0.908
1.354
1.299

IPI00977788.1
Similar to Hepatitis B virus
6
1.015
0.952
1.480
1.052
0.982
1.314

receptor binding protein

IPI00978315.1
Conserved hypothetical
2
0.987
0.913
1.992
0.499
0.712
0.576

protein

IPI00979837.1
Conserved hypothetical
3
1.470
1.866
3.592
1.451
1.808
0.801

protein

IPI00980674.1
Uncharacterized protein
11
2.724
4.406
9.159
0.884
1.734
1.214

IPI00980807.1
5 kDa protein
4
1.304
3.346
1.734
6.962
3.179
3.962

IPI00981659.1
Similar to Cold agglutinin FS-
11
1.775
1.889
4.199
1.191
1.455
0.898

1 H-chain

IPI00982472.1
Transaldolase
19
1.276
1.416
3.039
1.011
1.238
0.745

IPI00982588.1
Protein
2
1.404
1.095
1.125
1.587
1.258
2.002

IPI00984004.1
Similar to Ig kappa chain V-
1
1.345
1.206
1.794
1.449
1.176
1.690

III region WOL

IPI00984370.1
Uncharacterized protein
1
1.681
2.137
2.999
2.333
2.090
2.109

IPI00984640.1
Similar to Immunglobulin
15
2.300
2.083
2.111
1.618
1.775
1.900

heavy chain variable region

IPI00984835.1
16 kDa protein
2
4.667
1.241
0.485
3.896
1.002
12.522

IPI00985334.2
titin isoform N2-B
3
1.057
1.108
2.004
0.654
1.002
0.621

IPI00985505.1
Uncharacterized protein
3
0.795
1.052
0.653
1.359
0.731
2.521

IPI01009389.1
DNA methyltransferase
3
4.745
3.371
0.401
6.191
4.063
12.096

IPI01009456.2
34 kDa protein
3
1.200
1.522
3.292
1.059
1.495
0.874

IPI01009563.1
Adenylyl cyclase-associated
3
1.488
1.598
4.019
1.105
1.534
0.762

protein

IPI01010684.1
Uncharacterized protein
7
0.855
0.667
1.161
1.015
0.862
2.082

IPI01011090.1
Uncharacterized protein
2
1.759
2.275
2.702
1.622
1.984
1.655

IPI01011344.1
Uncharacterized protein
35
1.710
2.297
4.424
1.556
2.008
0.946

IPI01011676.1
Uncharacterized protein
4
1.390
1.652
2.651
0.848
1.032
1.002

IPI01011820.1
Uncharacterized protein
4
1.286
1.318
2.605
1.057
1.352
0.779

IPI01011970.1
6-phosphogluconate
12
1.270
1.514
2.734
1.340
1.478
0.906

dehydrogenase,

decarboxylating

IPI01012346.1
Uncharacterized protein
2
1.617
2.046
5.188
1.135
1.631
0.652

IPI01012426.1
Uncharacterized protein
2
1.070
1.154
2.030
0.831
0.852
0.952

IPI01012504.1
6-phosphogluconate
38
1.359
1.542
3.026
1.406
1.599
0.918

dehydrogenase,

decarboxylating

IPI01012528.1
Uncharacterized protein
15
1.690
1.785
3.294
1.624
1.882
1.142

IPI01013019.1
Airway lactoperoxidase
24
0.882
0.733
1.101
1.167
0.906
2.216

IPI01013112.1
Uncharacterized protein
2
1.502
1.616
3.136
1.163
1.581
0.786

IPI01013441.1
Uncharacterized protein
37
1.478
1.614
3.728
1.113
1.452
0.624

IPI01013537.1
Uncharacterized protein
8
1.128
0.999
1.396
1.072
0.980
1.148

IPI01013543.1
Triosephosphate isomerase
3
0.553
0.639
1.933
0.614
0.563
0.726

IPI01014238.1
cDNA FLJ53963, highly
3
1.093
0.902
0.940
1.238
1.013
1.197

similar to Leukocyte elastase

inhibitor

IPI01014975.1
Uncharacterized protein
4
1.298
1.759
6.183
1.213
1.747
0.620

IPI01015050.2
Uncharacterized protein
10
1.075
1.221
3.161
0.882
1.159
0.708

IPI01015184.1
Uncharacterized protein
2
1.649
1.436
1.903
1.081
1.226
1.151

IPI01015504.1
Uncharacterized protein
5
1.726
1.551
2.266
1.769
1.763
2.780

IPI01015565.1
Uncharacterized protein
3
2.337
2.119
2.126
1.706
1.583
1.924

IPI01015921.1
cDNA FLJ55361, highly
5
3.253
6.211
2.964
1.562
1.872
2.294

similar to Nucleolar protein

11

IPI01018060.1
Ig lambda-3 chain C regions
23
1.272
0.992
1.609
1.476
1.335
1.720

IPI01019128.1
Uncharacterized protein
1
1.461
1.790
1.194
0.640
0.973
1.539

IPI01021118.1
Uncharacterized protein
1
0.671
0.503
0.728
0.286
0.369
1.274

IPI01022175.1
cDNA FLJ55805, highly
13
0.751
3.532
8.674
0.944
0.728
0.836

similar to Keratin, type II

cytoskeletal 4

IPI01022408.1
Uncharacterized protein
3
1.609
1.588
2.160
1.128
1.363
1.526

IPI01022662.1
Uncharacterized protein
3
1.561
1.720
1.533
1.291
1.122
1.085

IPI01023021.1
Uncharacterized protein
2
2.702
1.781
2.674
1.532
1.735
1.014

IPI01024806.1
Alpha-actinin 1
5
1.098
1.431
3.435
1.031
1.276
0.762

IPI01026033.1
9 kDa protein
2
0.604
0.402
0.671
0.552
0.550
1.382

IPI01026288.1
Uncharacterized protein
14
1.097
1.071
1.045
1.123
1.014
2.762

O83224
50S ribosomal protein L22
2
2.132
3.140
3.922
1.528
2.328
1.160

OS = Treponema pallidum

(strain Nichols) GN = rpIV

PE = 3 SV = 1-[RL22_TREPA]

O83465
Uncharacterized protein
2
4.618
3.313
1.304
3.726
3.516
5.718

TP_0451 OS = Treponema

pallidum (strain Nichols)

GN = TP_0451 PE = 4 SV = 1-

[Y451_TREPA]

O83773
Uncharacterized protein
2
4.450
9.222
10.821
1.969
4.533
0.810

TP_0795 OS = Treponema

pallidum (strain Nichols)

GN = TP_0795 PE = 4 SV = 1-

[Y795_TREPA]

P24366
Phosphocarrier protein HPr
3
0.735
0.259
0.797
0.316
0.262
1.029

OS = Streptococcus salivarius

GN = ptsH PE = 1 SV = 2-

[PTHP_STRSL]

P96119
Zinc transport system
3
1.209
1.223
1.320
1.302
2.272
1.126

membrane protein troD

OS = Treponema pallidum

(strain Nichols) GN = troD

PE = 3 SV = 1-[TROD_TREPA]

Q9AIM3
3-isopropylmalate
2
2.397
1.049
0.615
1.752
0.661
5.701

dehydratase large subunit

(Fragment)

OS = Streptococcus gordonii

GN = leuC PE = 3 SV = 1-

[LEUC_STRGN]

SUPPLEMENTARY TABLE 6

CLUSTER 2

Protein # 165:
IPI00748022.2
Actin-like protein (Fragment)

SUPPLEMENTARY TABLE 7

CLUSTER 1B

Protein # 19:
IPI00012199.1
Coiled-coil domain-containing protein

86

Protein # 58:
IPI00060800.5
Zymogen granule protein 16 homolog B

Protein # 73:
IPI00216835.2
Isoform 2 of NADPH oxidase activator

1

Protein # 94:
IPI00299078.1
Salivary acidic proline-rich

phosphoprotein 1/2

Protein # 108:
IPI00383627.1
Pituitary tumor transforming gene

protein

Protein # 110:
IPI00384251.1
Isoform 2 of Guanine nucleotide

exchange factor for Rab-3A

Protein # 111:
IPI00384382.1
AngRem52

Protein # 122:
IPI00414909.1
Alpha-N-acetylgalactosaminidase

Protein # 163:
IPI00742775.1
Bardet-Biedl syndrome 10 protein

Protein # 221:
IPI00921945.1
cDNA FU57374

Protein # 270:
IPI00984835.1
16 kDa protein

Protein # 273:
IPI00985334.2
titin isoform N2-B

Protein # 297:
IPI01015921.1
cDNA FLJ55361, highly similar to

Nucleolar protein 11

Protein # 309:
O83465
Uncharacterized protein TP_0451 OS =

Treponema pallidum (strain Nichols)

GN = TP_0451 PE = 4 SV =

1 − [Y451_TREPA]

CLUSTER 1D

Protein # 212:
IPI00909737.1
cDNA FLJ55140, highly similar to

SPARC-like protein 1

SUPPLEMENTARY TABLE 8

CLUSTER 1A4

Protein # 21:
IPI00012796.1
Glutamate decarboxylase 2

Protein # 300:
IPI01021118.1
Uncharacterized protein

Protein # 311:
P24366
Phosphocarrier protein HPr OS =

Streptococcus salivarius

GN = ptsH PE = 1

SV = 2 − [PTHP_STRSL]

CLUSTER 1A5

Protein # 245:
IPI00969578.1
Salivary proline-rich protein 2

(Fragment)

SUPPLEMENTARY TABLE 9

CLUSTER 1C2

Protein # 26:
IPI00016347.5
Isoform 3 of Uncharacterized

protein C2orf54

Protein# 107:
IPI00377122.4
Isoform 2 of WD repeat-containing

protein KIAA1875

Protein# 120:
IPI00410714.5
Hemoglobin subunit alpha

Protein# 135:
IPI00473011.3
Hemoglobin subunit delta

Protein# 157:
IPI00654755.3
Hemoglobin subunit beta

Protein # 262:
IPI00980674.1
Uncharacterized protein

Protein # 310:
O83773
Uncharacterized protein TP_0795 OS =

Treponema pallidum (strain Nichols)

GN = TP_0795 PE = 4 SV =

1 − [Y795_TREPA]

SUPPLEMENTAL TABLE 10

CLUSTER 1A1b

Protein# 25:
IPI00013895.1
Protein S100-A11

Protein # 57:
IPI00037070.3
Uncharacterized protein

Protein # 132:
IPI00465436.4
Catalase

Protein # 206:
IPI00903245.1
cDNA FU44586 fis, clone

ASTRO2015162, highly

similar to Choline

transporter-like protein 2

Protein # 271:
IPI00985334.2
titin isoform N2-B

SUPPLEMENTAL TABLE 11

Description
Accession
gene
Description

Beta-actin-like protein 2
IPI00003269.1
ACTBL2
Beta-actin-like protein 2

Histone H2B type 2-E
IPI00003935.6
HIST2H2BE
Histone H2B type 2-E

Neutrophil defensin 1
IPI00005721.1
DEFA1
Neutrophil defensin 1

Protein S100-A8
IPI00007047.1
S100A8
Protein S100-A8

Arylsulfatase F
IPI00008405.5
ARSF
Arylsulfatase F

Epithelial membrane protein 2
IPI00008895.1
EMP2
Epithelial membrane protein 2

Plastin-2
IPI00010471.6
LCP1
Plastin-2

Isoform 1 of 14-3-3 protein sigma
IPI00013890.2
SFN
Isoform 1 of 14-3-3 protein sigma

Protein S100-A11
IPI00013895.1
S100A11
Protein S100-A11

Protein S100-P
IPI00017526.1
S100P
Protein S100-P

Lysozyme C
IPI00019038.1
LYZ
Lysozyme C

Isoform 1 of Myosin-9
IPI00019502.3
MYH9
Isoform 1 of Myosin-9

Alpha-1-acid glycoprotein 2
IPI00020091.1
ORM2
Alpha-1-acid glycoprotein 2

14-3-3 protein zeta/delta
IPI00021263.3
YWHAZ
14-3-3 protein zeta/delta

Cystatin-B
IPI00021828.1
CSTB
Cystatin-B

Apolipoprotein A-I
IPI00021841.1
APOA1
Apolipoprotein A-I

Alpha-1-acid glycoprotein 1
IPI00022429.3
ORM1
Alpha-1-acid glycoprotein 1

Serotransferrin
IPI00022463.2
TF
Serotransferrin

Hemopexin
IPI00022488.1
HPX
Hemopexin

Prolactin-inducible protein
IPI00022974.1
PIP
Prolactin-inducible protein

Protein S100-A9
IPI00027462.1
S100A9
Protein S100-A9

Protein S100-A6
IPI00027463.1
S100A6
Protein S100-A6

Matrix metalloproteinase-9
IPI00027509.5
MMP9
Matrix metalloproteinase-9

Neutrophil elastase
IPI00027769.1
ELANE
Neutrophil elastase

Cathepsin G
IPI00028064.1
CTSG
Cathepsin G

Cystatin-S
IPI00032294.1
CST4
Cystatin-S

Uncharacterized protein
IPI00037070.3
HSPA8
Uncharacterized protein

Isoform 4 of Interleukin-1
IPI00174541.1
IL1RN
Isoform 4 of Interleukin-1

receptor antagonist protein

receptor antagonist protein

Thymosin beta-4-like protein 3
IPI00180240.2
TMSL3
Thymosin beta-4-like protein 3

Profilin-1
IPI00216691.5
PFN1
Profilin-1

Keratin, type I cytoskeletal 16
IPI00217963.3
KRT16
Keratin, type I cytoskeletal 16

Protein S100-A12
IPI00218131.3
S100A12
Protein S100-A12

Annexin A1
IPI00218918.5
ANXA1
Annexin Al

Glutathione S-transferase P
IPI00219757.13
GSTP1
Glutathione S-transferase P

Keratin, type II cytoskeletal 1
IPI00220327.4
KRT1
Keratin, type II cytoskeletal 1

Isoform H14 of Myeloperoxidase
IPI00236554.1
MPO
Isoform H14 of Myeloperoxidase

Keratin, type I cytoskeletal 15
IPI00290077.3
KRT15
Keratin, type I cytoskeletal 15

Fibrinogen beta chain
IPI00298497.3
FGB
Fibrinogen beta chain

Salivary acidic proline-rich
IPI00299078.1
PRH1
Salivary acidic proline-rich

phosphoprotein 1/2

phosphoprotein 1/2

Isoform 1 of Neutrophil gelatinase-
IPI00299547.4
LCN2
Isoform 1 of Neutrophil gelatinase-

associated lipocalin

associated lipocalin

Cystatin-SN
IPI00305477.6
CST1
Cystatin-SN

Keratin, type I cytoskeletal 14
IPI00384444.6
KRT14
Keratin, type I cytoskeletal 14

Putative uncharacterized protein
IPI00399007.7
IGHG2
Putative uncharacterized

DKFZp686I04196 (Fragment)

protein DKFZp686I04196 (Fragment)

Hemoglobin subunit alpha
IPI00410714.5
HBA1
Hemoglobin subunit alpha

Peptidyl-prolyl cis-trans isomerase A
IPI00419585.9
PPIA
Peptidyl-prolyl cis-trans isomerase A

Putative uncharacterized protein
IPI00423460.3
IGHA1
Putative uncharacterized protein

DKFZp686G21220 (Fragment)

DKFZp686G21220 (Fragment)

31 kDa protein
IPI00431645.2
HPR
31 kDa protein

44 kDa protein
IPI00448925.6
IGHG1
44 kDa protein

Histone H4
IPI00453473.6
HIST4H4
Histone H4

Isoform alpha-enolase of Alpha-
IPI00465248.5
ENO1
Isoform alpha-enolase of Alpha-

enolase

enolase

Fructose-bisphosphate aldolase A
IPI00465439.5
ALDOA
Fructose-bisphosphate aldolase A

haptoglobin isoform 2 preproprotein
IPI00478493.3
HPR
haptoglobin isoform 2 preproprotein

Isoform M2 of Pyruvate kinase
IPI00479186.7
PKM2
Isoform M2 of Pyruvate kinase

isozymes M1/M2

isozymes M1/M2

Uncharacterized protein
IPI00552768.1
TXN
Uncharacterized protein

Haptoglobin
IPI00641737.2
HP
Haptoglobin

Hemoglobin subunit beta
IPI00654755.3
HBB
Hemoglobin subunit beta

Isoform 1 of Serum albumin
IPI00745872.2
ALB
Isoform 1 of Serum albumin

Actin-like protein (Fragment)
IPI00748022.2
LOC727848
Actin-like protein (Fragment)

Isoform Cytoplasmic + peroxisomal
IPI00759663.1
PRDX5
Isoform Cytoplasmic + peroxisomal

of Peroxiredoxin-5, mitochondrial

of Peroxiredoxin-5, mitochondrial

Complement C3 (Fragment)
IPI00783987.2
C3
Complement C3 (Fragment)

Putative uncharacterized protein
IPI00784950.1
IGHA2
Putative uncharacterized protein

DKFZp686L19235

DKFZp686L19235

IGK@ protein
IPI00784985.1
IGK@
IGK@ protein

Isoform 1 of Triosephosphate
IPI00797270.4
TPI1P1
Isoform 1 of Triosephosphate

isomerase

isomerase

FGB protein (Fragment)
IPI00816687.1
FGB
FGB protein (Fragment)

Uncharacterized protein
IPI00853525.1
APOA1
Uncharacterized protein

Protein
IPI00879437.1
P4HB
Protein

Uncharacterized protein
IPI00893981.1
ACTB
Uncharacterized protein

FGA protein (Fragment)
IPI00902755.1
FGA
FGA protein (Fragment)

cDNA FLJ36533 fis, clone
IPI00903112.1
LTF
cDNA FLJ36533 fis, clone

TRACH2004428, highly similar to

TRACH2004428, highly similar to

Lactotransferrin (Fragment)

Lactotransferrin (Fragment)

cDNA FLJ51275
IPI00908402.1
CRNN
cDNA FLJ51275

Glucose-6-phosphate isomerase
IPI00908881.3
GPI
Glucose-6-phosphate isomerase

cDNA FLJ52843, highly similar to
IPI00909530.1
LOC644914
cDNA FLJ52843, highly similar to

Histone H3.3

Histone H3.3

Peptidyl-prolyl cis-trans isomerase
IPI00910407.1
PPIA
Peptidyl-prolyl cis-trans

isomerase

cDNA FLJ54408, highly similar to Heat
IPI00911039.1
HSPA1A
cDNA FLJ54408, highly similar to Heat

shock 70 kDa protein 1

shock 70 kDa protein 1

Histone H2A
IPI00927887.1
H2AFV
Histone H2A

Putative uncharacterized protein
IPI00930442.1
IGHG4
Putative uncharacterized protein

DKFZp686M24218

DKFZp686M24218

10 kDa protein
IPI00939521.1

10 kDa protein

cDNA FLJ36348 fis, clone
IPI00940673.2
TKT
cDNA FLJ36348 fis, clone

THYMU2007025, highly similar to

THYMU2007025, highly similar to

TRANSKETOLASE

TRANSKETOLASE

Isoform 1 of Actin-related protein 3C
IPI00946655.1
ACTR3C
Isoform 1 of Actin-related protein 3C

fibrinogen beta chain isoform 2
IPI00965713.3
FGB
fibrinogen beta chain isoform 2

preproprotein

preproprotein

Lambda light chain of human
IPI00972963.1
IgLC-rG
Lambda light chain of human

immunoglobulin surface antigen-

immunoglobulin surface antigen-

related protein (Fragment)

related protein (Fragment)

Vimentin variant 3
IPI00975690.1
VIM
Vimentin variant 3

Uncharacterized protein
IPI00980674.1
CA1
Uncharacterized protein

Similar to Cold agglutinin FS-
IPI00981659.1
IGH@
Similar to Cold agglutinin FS-

1 H-chain

1 H-chain

Transaldolase
IPI00982472.1
TALDO1
Transaldolase

titin isoform N2-B
IPI00985334.2
TTN
titin isoform N2-B

Uncharacterized protein
IPI01011344.1
ACTG1
Uncharacterized protein

6-phosphogluconate dehydrogenase,
IPI01011970.1
PGD
6-phosphogluconate dehydrogenase,

decarboxylating

decarboxylating

Uncharacterized protein
IPI01013112.1
ARHGDIB
Uncharacterized protein

Uncharacterized protein
IPI01013441.1
PRTN3
Uncharacterized protein

Triosephosphate isomerase
IPI01013543.1
TPI1
Triosephosphate isomerase

Uncharacterized protein
IPI01014975.1
TLN1
Uncharacterized protein

Uncharacterized protein
IPI01015050.2
GSN
Uncharacterized protein

Ig lambda-3 chain C regions
IPI01018060.1
IGLC3
Ig lambda-3 chain C regions

cDNA FLJ55805, highly similar to
IPI01022175.1
KRT4
cDNA FLJ55805, highly similar to

Keratin, type II cytoskeletal 4

Keratin, type II cytoskeletal 4

SUPPLEMENTAL TABLE 12

Count

Biological process
(genes)
P-value

GCF
cytoskeleton organization
29
1.90E−12

glucose catabolic process
12
1.60E−10

actin cytoskeleton organization
19
7.50E−10

hexose catabolic process
12
1.20E−09

monosaccharide catabolic process
12
1.60E−09

actin filament-based process
19
2.10E−09

alcohol catabolic process
12
6.70E−09

glycolysis
10
7.20E−09

organelle organization
44
1.10E−08

cellular carbohydrate catabolic process
12
1.10E−08

defense response
28
2.30E−08

ectoderm development
16
4.40E−08

response to stimulus
79
6.40E−08

cellular component organization
63
7.00E−08

carbohydrate catabolic process
12
1.60E−07

cellular component assembly
31
1.10E−06

response to stress
46
1.20E−06

tissue development
26
1.40E−06

response to external stimulus
31
1.90E−06

Saliva
defense response
32
1.60E−10

glucose catabolic process
11
4.40E−09

response to stimulus
83
1.50E−08

cellular carbohydrate catabolic process
12
1.70E−08

carbohydrate catabolic process
13
2.40E−08

hexose catabolic process
11
2.50E−08

monosaccharide catabolic process
11
3.30E−08

response to stress
50
8.60E−08

response to inorganic substance
16
1.10E−07

alcohol catabolic process
11
1.20E−07

response to wounding
25
1.70E−07

glycolysis
9
1.80E−07

inflammatory response
19
3.70E−07

response to external stimulus
33
4.80E−07

tissue development
27
8.60E−07

actin cytoskeleton organization
15
2.10E−06

defense response to bacterium
11
2.50E−06

ectoderm development
14
2.80E−06

immune system process
33
3.20E−06

ANALYSIS OF SALIVA PROTEOME FOR BIOMARKERS OF GINGIVITIS AND PERIODONTITIS USING FT-ICR-MS/MS

Information

Publication Number

Date Filed

Date Published

Inventors

Original Assignees

CPC

International Classifications

Abstract

Description

Claims

PCT Information

Provisional Applications (1)