PT  - JOURNAL ARTICLE
AU  - Pablo Cordero
AU  - Ayca Erbilgin
AU  - Ching Shang
AU  - Michael P Morley
AU  - Mathew Wheeler
AU  - Frederick Dewey
AU  - Kevin S Smith
AU  - Ray Hu
AU  - Jeffrey Brandimarto
AU  - Yichuan Liu
AU  - Mingyao Li
AU  - Hongzhe Li
AU  - Scott Ritter
AU  - Sihai D Zhao
AU  - Komal S Rathi
AU  - Liming Qu
AU  - Avinash Das
AU  - Stephen Montgomery
AU  - Sridhar Hannenhalli
AU  - Christine S Moravec
AU  - Wilson H Tang
AU  - Kenneth B Margulies
AU  - Thomas P Cappola
AU  - Euan A Ashley
TI  - A community overlap strategy reveals central genes and networks in heart failure
AID  - 10.1101/038174
DP  - 2016 Jan 01
TA  - bioRxiv
PG  - 038174
4099  - http://biorxiv.org/content/early/2016/01/28/038174.short
4100  - http://biorxiv.org/content/early/2016/01/28/038174.full
AB  - Heart failure is one of the leading causes of mortality worldwide, but its underlying molecular mechanisms are poorly understood. To obtain a systems view of the molecular networks that underlie heart failure, we harvested 1352 samples from 313 healthy and failing hearts directly from transplant operating rooms and obtained left-ventricular whole-genome gene expression and genotype measurements. From these data, we built directed regulatory gene networks and gene communities using an approach that combines network and community inference in one framework. Differences in co-expression and global and local centrality parameters pinpointed changes in the molecular interaction network associated with heart failure, as well as its network-wise genetic determinants. Connectivity of one gene, PPP1R3A, previously unassociated with heart failure, changed significantly between healthy and diseased states. Perturbation of in vitro and in vivo systems via time series transcriptome sequencing and murine cardiovascular phenotyping revealed that ablation of PPP1R3A alters disease progression.