RT Journal Article
SR Electronic
T1 A community overlap strategy reveals central genes and networks in heart failure
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 038174
DO 10.1101/038174
A1 Pablo Cordero
A1 Ayca Erbilgin
A1 Ching Shang
A1 Michael P Morley
A1 Mathew Wheeler
A1 Frederick Dewey
A1 Kevin S Smith
A1 Ray Hu
A1 Jeffrey Brandimarto
A1 Yichuan Liu
A1 Mingyao Li
A1 Hongzhe Li
A1 Scott Ritter
A1 Sihai D Zhao
A1 Komal S Rathi
A1 Liming Qu
A1 Avinash Das
A1 Stephen Montgomery
A1 Sridhar Hannenhalli
A1 Christine S Moravec
A1 Wilson H Tang
A1 Kenneth B Margulies
A1 Thomas P Cappola
A1 Euan A Ashley
YR 2016
UL http://biorxiv.org/content/early/2016/01/28/038174.abstract
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.