Understanding multicellular function and disease with human tissue-specific networks

Casey S. Greene, Arjun Krishnan, Aaron K. Wong, Emanuela Ricciotti, Rene A. Zelaya, Daniel S. Himmelstein, Ran Zhang, Boris M. Hartmann, Elena Zaslavsky, Stuart C. Sealfon, Daniel I. Chasman, Garret A. Fitzgerald, Kara Dolinski, Tilo Grosser, Olga G. Troyanskaya

Research output: Contribution to journalArticle

294 Scopus citations

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, identify the changing functional roles of genes across tissues and illuminate relationships among diseases. We introduce NetWAS, which combines genes with nominally significant genome-wide association study (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 a hundred human tissues and cell types.

Original languageEnglish (US)
Pages (from-to)569-576
Number of pages8
JournalNature Genetics
Volume47
Issue number6
DOIs
StatePublished - May 27 2015

All Science Journal Classification (ASJC) codes

  • Genetics

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    Greene, C. S., Krishnan, A., Wong, A. K., Ricciotti, E., Zelaya, R. A., Himmelstein, D. S., Zhang, R., Hartmann, B. M., Zaslavsky, E., Sealfon, S. C., Chasman, D. I., Fitzgerald, G. A., Dolinski, K., Grosser, T., & Troyanskaya, O. G. (2015). Understanding multicellular function and disease with human tissue-specific networks. Nature Genetics, 47(6), 569-576. https://doi.org/10.1038/ng.3259