Understanding multicellular function and disease with human tissue-specific networks.
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.
1] Department of Genetics, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USA. [2] Dartmouth-Hitchcock Norris Cotton Cancer Center, Lebanon, New Hampshire, USA. [3] Institute for Quantitative Biomedical Sciences, Dartmouth College, Hanover, New Hampshire, USA.
Casey S
0000000187139213
CS
Greene
Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, USA.
Arjun
A
Krishnan
Department of Computer Science, Princeton University, Princeton, New Jersey, USA.
Aaron K
AK
Wong
1] Department of Pharmacology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. [2] Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Emanuela
E
Ricciotti
Department of Genetics, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USA.
Rene A
RA
Zelaya
Biology and Medical Informatics, University of California, San Francisco, San Francisco, California, USA.
Daniel S
DS
Himmelstein
Department of Molecular Biology, Princeton University, Princeton, New Jersey, USA.
Ran
R
Zhang
Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Boris M
BM
Hartmann
Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Elena
E
Zaslavsky
Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Stuart C
SC
Sealfon
Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Daniel I
DI
Chasman
1] Department of Pharmacology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. [2] Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Garret A
GA
FitzGerald
Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, USA.
Kara
K
Dolinski
1] Department of Pharmacology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. [2] Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Tilo
T
Grosser
1] Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, USA. [2] Department of Computer Science, Princeton University, Princeton, New Jersey, USA. [3] Simons Center for Data Analysis, Simons Foundation, New York, New York, USA.
Olga G
OG
Troyanskaya
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism; D001499:Bayes Theorem; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D063990:Gene Ontology; D053263:Gene Regulatory Networks; D055106:Genome-Wide Association Study; D006801:Humans; D006973:Hypertension / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D032389:Myocytes, Smooth Muscle / Q000502:physiology; D009928:Organ Specificity; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism; D060066:Protein Interaction Maps