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PLoS One. 2013 Oct 23;8(10):e77478. doi: 10.1371/journal.pone.0077478. eCollection 2013.

Inference of gene-phenotype associations via protein-protein interaction and orthology.

Author information

1
Department of Biochemistry, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China ; Shenzhen Institute of Research and Innovation, The University of Hong Kong, Shenzhen, China.

Abstract

One of the fundamental goals of genetics is to understand gene functions and their associated phenotypes. To achieve this goal, in this study we developed a computational algorithm that uses orthology and protein-protein interaction information to infer gene-phenotype associations for multiple species. Furthermore, we developed a web server that provides genome-wide phenotype inference for six species: fly, human, mouse, worm, yeast, and zebrafish. We evaluated our inference method by comparing the inferred results with known gene-phenotype associations. The high Area Under the Curve values suggest a significant performance of our method. By applying our method to two human representative diseases, Type 2 Diabetes and Breast Cancer, we demonstrated that our method is able to identify related Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways. The web server can be used to infer functions and putative phenotypes of a gene along with the candidate genes of a phenotype, and thus aids in disease candidate gene discovery. Our web server is available at http://jjwanglab.org/PhenoPPIOrth.

PMID:
24194887
PMCID:
PMC3806783
DOI:
10.1371/journal.pone.0077478
[Indexed for MEDLINE]
Free PMC Article

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