GenoLink: a graph-based querying and browsing system for investigating the function of genes and proteins-6

<p><b>Copyright information:</b></p><p>Taken from "GenoLink: a graph-based querying and browsing system for investigating the function of genes and proteins"</p><p>BMC Bioinformatics 2006;7():21-21.</p><p>Published online 17 Jan 2006</p><p>PMCID:PMC1382257.</p><p>Copyright © 2006 Durand et al; licensee BioMed Central Ltd.</p> it. This snapshot shows an example of result sub-graph corresponding to the Query Q7 (Table 1 [see ] and Figure 5). The edge linking the two Polypeptides corresponds to a physical interaction (HPIW). The red crosshair on the top-right of some vertices denotes that they are linked to some others that are not currently shown. These vertices may therefore be further expanded to gain more information about the full data graph. In this example, this operation has been performed on vertices holA and holB (from ) in order to display the corresponding Polypeptides (DNA polymerase III) that were not part of the query (see Figure 5)

GenoLink: a graph-based querying and browsing system for investigating the function of genes and proteins-5

<p><b>Copyright information:</b></p><p>Taken from "GenoLink: a graph-based querying and browsing system for investigating the function of genes and proteins"</p><p>BMC Bioinformatics 2006;7():21-21.</p><p>Published online 17 Jan 2006</p><p>PMCID:PMC1382257.</p><p>Copyright © 2006 Durand et al; licensee BioMed Central Ltd.</p>orresponds to a result sub-graph. Each column's header contains two lines: the first one indicates the label of a vertex from the query graph (see Figure 5); the second line indicates the name of an attribute of this vertex (the user can select which attributes to display: in this example only the "Name" attributes have been selected)

GenoLink: a graph-based querying and browsing system for investigating the function of genes and proteins-2

<p><b>Copyright information:</b></p><p>Taken from "GenoLink: a graph-based querying and browsing system for investigating the function of genes and proteins"</p><p>BMC Bioinformatics 2006;7():21-21.</p><p>Published online 17 Jan 2006</p><p>PMCID:PMC1382257.</p><p>Copyright © 2006 Durand et al; licensee BioMed Central Ltd.</p> protein-protein interactions where at least one of the two proteins has an annotated known function (Name !: "hypothetical"). (b) The GQL script describing the same query. GQL reserved keywords are indicated in bold. In the declaration of variable , the expression located to the right of the 'where' clause is a local constraint (here: the name must not contain ). In the declaration of , the expression located to the right of the 'where' clause is the global constraint (here: the two names must be different). (c) Result obtained by executing this query against the data graph shown in Figure 4b. When applied to the entire strain 26695 data set, this query yields 896 different answers

GenoLink: a graph-based querying and browsing system for investigating the function of genes and proteins-3

<p><b>Copyright information:</b></p><p>Taken from "GenoLink: a graph-based querying and browsing system for investigating the function of genes and proteins"</p><p>BMC Bioinformatics 2006;7():21-21.</p><p>Published online 17 Jan 2006</p><p>PMCID:PMC1382257.</p><p>Copyright © 2006 Durand et al; licensee BioMed Central Ltd.</p>ided with GenoLink. Classes are indicated by boxes (white arrows indicate inheritance) and association names are indicated in italics. For clarity, class and association attributes have not been indicated (an example is shown to the right part of the figure, with the Polypeptide class). The complete diagram is distributed with the GenoLink software documentation. (b) An example of data graph based on this data model. It represents a portion of the genome of the bacterium strain 26695 (NCBI RefSeq entry no. NC000915); IRO, ILO, ICF, IIG, HPA, CD and HPIW stand for edges that are instances of associations: IsRepliconOf, IsLocatedOn, IsCodingFor, IsInGeneOrtholog, HasPolypeptideAnnotation, ContainsDomain and HasPhysicalInteractionWith. The entire data graph for this genome actually contains 3197 vertices (1 Organism, 1 Replicon, 1576 ProteinGenes, 43 RNAGenes, 1576 Polypeptides) and 4664 edges (1 IsRepliconOf, 1619 IsLocatedOn, 1576 IsCodingFor and 1468 HasPhysicalInteractionWith). The dashed box displays the attributes for the Polypeptide ureB. COG, EC and IPR data are from the COG database [21], the Enzyme Commission database [24], and the InterPro database [23], respectively. Protein-protein interactions are public data available from Hybrigenics [30] and distributed with GenoLink

PCA after SNPClust application.

<p>First principal components of the PCA on the 261 SNPs and 331 haplotypes from 5,433 patients, with 95% confidence ellipses. The principal components did not discriminate SLE patients from controls.</p

Initial grouping of genetic data.

<p>Two first principal components of the PCA on 379,190 SNPs from 5,433 European SLE patients and controls with 95% confidence ellipses. Northern and Southern Europeans were discriminated in the first principal component. Eastern and Western Europeans were discriminated in the second. 2,733 individuals (50%) did not have geographic information and were colored in gray.</p

Performances of feature selection methods.

<p>Associations of the input dataset without or with population stratification correction by genomic control and Eigenstrat (with 5 and 10 principal components considered) compared with SNPClust.</p

Selection of strong SNP contributors.

<p><b>(a)</b> The 2,000 most contributing SNPs to each of the first 8 principal components are displayed by chromosomal position and colored by chromosomes. Principal components were driven by large localized SNP groups and the chromosome 6 locus <i>HLA</i> was the strongest and largest contributor in all of the first 8 principal components, except principal component 5. <b>(b)</b> Selection of SNPs by the Gaussian mixtures based method. Selected SNPs are colored in red. SNPs are displayed on the x-axis by rank of chromosomic position, <i>i.e.</i> SNPs are regularly spaced and ordered by chromosome and position.</p

Haplotype summarization of the <i>8p23</i> locus.

<p>The haplotypes estimated from the 875 selected SNPs from chromosome 8 were best fitted by two groups. The resulting three groups, plotted with 95% confidence ellipses, accurately represented the three clusters in principal component 3 and showed that haplotypes preserved information carried by SNPs.</p

Additional file 1: Supplementary Methods. of Alzheimer disease pathology and the cerebrospinal fluid proteome

Table S1. Demographics and clinical characteristics of subjects removed from the statistical analyses. Table S2. Non-AD versus AD CSF biomarker profile group comparison after selection in all subjects of 26 proteins with LASSO. Table S3. Non-AD versus AD CSF biomarker profile group comparison after selection in subjects with cognitive impairment of 18 proteins with LASSO. Table S4. Correlation of CSF proteins with CSF Aβ1-42. Table S5. Correlation of CSF proteins with CSF tau. Table S6. Correlation of CSF proteins with CSF P-tau181. Table S7. Group comparisons of CSF protein measurements for AD versus non-AD CSF biomarker profiles in all subjects. Table S8. Group comparisons of CSF protein measurements for AD versus non-AD CSF biomarker profiles in subjects with cognitive impairment. Figure S1. Box-plots of CSF proteins (selected with LASSO analyses) for positive and negative CSF profiles of AD pathology in all subjects and subjects with cognitive impairment. Figure S2. Pairwise correlation heatmap of the 26 CSF proteins selected with LASSO for classification of non-AD versus AD CSF biomarker profiles for all subjects. Figure S3. Pairwise correlation heatmap of the 18 CSF proteins selected with LASSO for classification of non-AD versus AD CSF biomarker profiles for subjects with cognitive impairment. Figure S4. Correlations of CSF neurogranin and neuromodulin with CSF tau and P-tau181. Figure S5. Chord diagram of the relationships of 59 CSF proteins with CSF tau, P-tau181, and/or Aβ1-42. Figure S6. Venn diagrams of CSF proteins with significant group comparison differences between AD versus non-AD CSF biomarker profiles and those correlating with CSF Aβ1-42, tau, and P-tau181. Figure S7. Venn diagrams of CSF proteins selected with LASSO to classify non-AD versus AD CSF biomarker profiles and those correlating with CSF Aβ1-42, tau, and P-tau181. (DOCX 2575 kb