Genome-wide prioritization of disease genes and identification of disease-disease associations from an integrated human functional linkage network.
We integrate 16 genomic features to construct an evidence-weighted functional-linkage network comprising 21,657 human genes. The functional-linkage network is used to prioritize candidate genes for 110 diseases, and to reliably disclose hidden associations between disease pairs having dissimilar phenotypes, such as hypercholesterolemia and Alzheimer's disease. Many of these disease-disease associations are supported by epidemiology, but with no previous genetic basis. Such associations can drive novel hypotheses on molecular mechanisms of diseases and therapies.
Linghu
Bolan
B
Bioinformatics Program, Boston University, 24 Cummington Street, Boston, MA 02215, USA. blinghu@bu.edu
Snitkin
Evan S
ES
Hu
Zhenjun
Z
Xia
Yu
Y
Delisi
Charles
C
D000465:Algorithms; D053263:Gene Regulatory Networks; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D015894:Genome, Human / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods*; D023281:Genomics / Q000379:methods; D006801:Humans; D025941:Protein Interaction Mapping / Q000379:methods; D015203:Reproducibility of Results; D012984:Software