Key result
Multi-omic analysis in CAD links 851 plasma proteins to cross-tissue gene regulatory networks.
Why the study?
Identifying the organ of origin for plasma protein biomarkers is critical for establishing their biological relevance in cardiometabolic disorders and coronary artery disease.
Observational (n=532)
Plasma proteins are integral components of cross-tissue gene regulatory networks, providing a biological basis for developing diagnostic markers and therapeutic targets for cardiometabolic disorders and CAD.
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“One of the key findings of this study was that plasma proteins were found to be strongly linked to the activity of gene regulatory networks (GRNs), in particular GRNs comprised of genes spanning multiple tissues. Many of these proteins and GRNs have been implicated in key biological processes and different cardiometabolic and cardiovascular diseases. These findings bring new insight to the possible role of plasma proteins in tissue signalling with potential implications for tissue-informed biomarker discovery.”
Supports plasma proteins as CAD network components; leaves open their utility as biomarkers pending prospective validation.
The plasma proteome has demonstrated promise for identifying diagnostic markers for cardiometabolic disorders (CMDs) and coronary artery disease (CAD). However, identifying the organ of origin for these biomarkers is critical for establishing biological relevance. We performed a multi-omic integrative analysis across multiple tissues from the STARNET study by profiling 974 plasma proteins in 532 CAD patients, integrating RNA sequencing (RNA-seq) data from the arterial wall, major metabolic organs, and blood. We identified 144 cis-protein quantitative trait loci in plasma, colocalizing with tissue cis-expression quantitative trait loci. Additionally, by mapping tissue mRNA "seed genes," we traced 262 plasma proteins to their source organs, primarily the liver. Crucially, we found that 851 plasma proteins are associated with the activity of cross-tissue gene regulatory networks (GRNs), including GRNs implicated in CMD and CAD development. Our findings demonstrate that plasma proteins are integral components of GRNs, with potential for developing reliable diagnostics and precise therapeutic targets. A record of this paper's transparent peer review process is included in the supplemental information.
No takes yet. Share an insight, caveat, or question.
Bankier et al. (2026) conducted an observational in Coronary artery disease (CAD) (n=532). Plasma protein profiling and RNA-seq integration was evaluated on Identification of cis-protein quantitative trait loci and association with cross-tissue gene regulatory networks. Multi-omic integrative analysis of 532 CAD patients traced 262 plasma proteins to their source organs and found 851 plasma proteins associated with cross-tissue gene regulatory networks.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: