Clinical-transcriptional prioritization of the circulating proteome in human heart failure

Given expanding studies in epidemiology and disease-oriented human studies offering hundreds of associations between the human “ome” and disease, prioritizing molecules relevant to disease mechanisms among this growing breadth is important. Here, we link the circulating proteome to human heart failure (HF) propensity (via echocardiographic phenotyping and clinical outcomes) across the lifespan, demonstrating key pathways of fibrosis, inflammation, metabolism, and hypertrophy. We observe a broad array of genes encoding proteins linked to HF phenotypes and outcomes in clinical populations dynamically expressed at a transcriptional level in human myocardium during HF and cardiac recovery (several in a cell-specific fashion). Many identified targets do not have wide precedent in large-scale genomic discovery or human studies, highlighting the complementary roles for proteomic and tissue transcriptomic discovery to focus epidemiological targets to those relevant in human myocardium for further interrogation. [Display omitted] •Expanding studies in epidemiology identify many molecular targets in heart failure•Prioritizing among these targets for downstream studies is critical•We link a proteome to cardiac structure, function, outcomes, and transcription•This offers a complementary proteomic-transcriptional path for discovery Studies in epidemiology have identified many targets in heart failure, fueling the need to identify ways to prioritize among them for discovery. Here, Perry et al. enlist a combined proteomic-transcriptional approach to identify biological targets in human heart failure. This approach offers a complementary path for target discovery for future studies.