Understanding multicellular function and disease with human tissue-specific networks
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Author
Greene, Casey S.
Krishnan, Arjun
Wong, Aaron K.
Ricciotti, Emanuela
Zelaya, Rene A.
Himmelstein, Daniel S.
Zhang, Ran
Hartmann, Boris M.
Zaslavsky, Elena
Sealfon, Stuart C.
FitzGerald, Garret A.
Dolinski, Kara
Grosser, Tilo
Troyanskaya, Olga G.
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.1038/ng.3259Metadata
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Greene, C. S., A. Krishnan, A. K. Wong, E. Ricciotti, R. A. Zelaya, D. S. Himmelstein, R. Zhang, et al. 2016. “Understanding multicellular function and disease with human tissue-specific networks.” Nature genetics 47 (6): 569-576. doi:10.1038/ng.3259. http://dx.doi.org/10.1038/ng.3259.Abstract
Tissue and cell-type identity lie at the core of human physiology and disease. Understanding the genetic underpinnings of complex tissues and individual cell lineages is crucial for developing improved diagnostics and therapeutics. We present genome-wide functional interaction networks for 144 human tissues and cell types developed using a data-driven Bayesian methodology that integrates thousands of diverse experiments spanning tissue and disease states. Tissue-specific networks predict lineage-specific responses to perturbation, reveal genes’ changing functional roles across tissues, and illuminate disease-disease relationships. We introduce NetWAS, which combines genes with nominally significant GWAS p-values and tissue-specific networks to identify disease-gene associations more accurately than GWAS alone. Our webserver, GIANT, provides an interface to human tissue networks through multi-gene queries, network visualization, analysis tools including NetWAS, and downloadable networks. GIANT enables systematic exploration of the landscape of interacting genes that shape specialized cellular functions across more than one hundred human tissues and cell types.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4828725/pdf/Terms of Use
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