Comprehensive plasma proteomics in heart failure patients: findings and future directions

Patients with heart failure (HF) experience a variety of incapacitating symptoms, including breathlessness, fatigue, fluid accumulation and a significantly impaired quality of life with a 20% 1-year mortality. Globally, prevalence of HF has reached epidemic proportions, affecting an estimated 64 million individuals, and posing a escalating public health crisis with substantial financial implications for healthcare systems. Plasma samples from 512 heart failure patients were subjected to proteomic analysis using SEER Bio's proprietary nanoparticle platform employing custom-made nanoparticles to enrich low abundance plasma proteins, enhancing coverage of the plasma proteome. The mass spectrometry (MS) data was recorded on the latest Thermo Astral instrument with Data Independent Acquisition methodology and searched against an in-silico generated spectral library using DIA-NN 1.81. Processing, normalization, univariate and multivariate analyses (PCA, UMAP, t-SNE) of the search results were performed using a combination of R and Perseus. Functional enrichment analyses, based on clinical parameters including NYAH grade, LV ejection fraction, and HD etiology, were conducted to detect abnormal molecular pathways and other annotated biological processes using a compendium of publicly available databases such as Gene Ontology, KEGG, MSigDB, NCI Nature PID, NetPath, Panther, and Reactome. In excess of 7500 plasma proteins were identified. Statistical and bioinformatic analyses revealed hundreds of potential candidate proteins and biological pathways. These findings highlighted differences in patient characteristics such as NYHA grade, LV ejection fraction, and HF etiology. Consequently, this study provides a powerful resource and reference dataset for an unbiased global analysis of the circulating proteome in patients with heart failure, offering valuable insights into disease mechanisms and potential biomarkers.