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Each gene is subsequently annotated with its associated biological pathways, obtained from KEGG, a collection of manually drawn pathway maps representing the molecular interaction and reaction networks for 1) metabolism, 2) genetic information processing 3) environmental information processing, 4) cellular processes, 5) organismal systems and 6) human diseases.
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We first tested biomarkers based on the 200 KEGG [ 30] human pathways obtained from MSigDB version 2.5 [ 16] and compared them to an alternative set of aggregate biomarkers consisting of 522 functional gene sets (selected on the basis of pathway membership and other biological criteria) from MSigDB version 2.5 (data set C2 [ 16]).
As an example, consider the name of the biological process, "classic complement activation pathway" obtained from Gene Ontology (GO).
Information from gene sets representing biological pathways were obtained from REACTOME (Croft et al., 2011), which are also provided in the Molecular Signature Database (Subramanian et al., 2005).
By comparing a few biological parameters such as total number of networks and common genes among pathways, they determined the statistical threshold by the amount of biological information obtained from the DEGs [ 32].
As a result, 33 unique pathways were obtained from the shared pathways by GWAS datasets or PBA tools.
The topology of the pathway, which determines whether a given molecule lies upstream or downstream from another reference molecule, is generally dependent on the biological information obtained from studies using mutants or inhibitors of specific molecules.
Samples were collected from multiple, pooled biological samples obtained from clonal copies growing in northern Sweden.
Cell cycle and DNA damage repair pathways were obtained from the KEGG pathway database [ 53].
Gene sets from GO, BBID (Biological Biochemical Image Database), Biocarta, and Kegg pathways were obtained from DAVID Bioinformatics Resource (http://david.abcc.ncifcrf.gov).abcc.ncifcrf.gov
Transcripts were classified according to different biological processes, as obtained from LocusLink (www.ncbi.nlm.nih.gov/LocusLink/): extracellular matrix proteins/phosphate transport, cell adhesion, muscle development, transcription factors, signaling pathways, metabolic process, transport, ubiquitin cycle, and other functions.
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