MetaPlaq: Integrative Single-Cell Meta-Analysis for Atherosclerosis
This network will establish a multi-omic single-cell atlas of adult human coronary and carotid artery atherosclerosis by meta-analyzing publicly available datasets across age, sex, and ancestries. The primary purpose of this atlas, called MetaPlaq, will be to map the consensus cell types and transition cell subtypes involved in both early and advanced stages of atherosclerosis, a disease of the arteries involving plaque buildup. In particular, this atlas will provide mechanistic clues for vascular and immune cells and their transition cell types responsible for plaque initiation, progression, and stability. Importantly, this work will involve critical benchmarking of software tools for automated cell type annotation, trajectory and network inference, as well as in-depth cis-regulatory element and quantitative trait locus discovery, bias correction and data integration.
Finally, the atlas will serve as a key reference for the single-cell and genetics communities by integrating publicly available genome-wide association study datasets. These integrated datasets will contribute to an expanded open-source single-cell web portal for atherosclerosis, called PlaqView, which is designed to empower scientists and clinicians. These resources will enable a diverse set of researchers to extract biologically and clinically-relevant insights in better understanding the target cell types, regulatory mechanisms and druggable targets for atherosclerosis. Given the role of atherosclerosis in driving the risk for heart attack, stroke and peripheral artery disease, this atlas has the potential to inform new prognostic and therapeutic strategies for these debilitating diseases.