Systems analysis of de novo mutations in congenital heart diseases identified a protein network in the hypoplastic left heart syndrome.

ABSTRACT: Despite a strong genetic component, only a few genes have been identified in congenital heart diseases (CHDs). We introduced systems analyses to uncover the hidden organization on biological networks of mutations in CHDs and leveraged network analysis to integrate the protein interactome, patient exomes, and single-cell transcriptomes of the developing heart. We identified a CHD network regulating heart development and observed that a sub-network also regulates fetal brain development, thereby providing mechanistic insights into the clinical comorbidities between CHDs and neurodevelopmental conditions. At a small scale, we experimentally verified uncharacterized cardiac functions of several proteins. At a global scale, our study revealed developmental dynamics of the network and observed i

SUBMITTER: Wang YJ 

PROVIDER: S-EPMC9671831 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature