Whole blood transcriptomics atlas across human diseases

We present a WBT Atlas, comprising 4444 WBT samples across 98 distinct health conditions, enabling systematic exploration of disease-associated transcriptomic signatures. Health condition-specific profiles are characterized across immune, metabolic, and cell-type specific features at the gene, gene module, and pathway levels. By integrating matched plasma proteomics data from 1280 participants across 28 health conditions, we further assess blood RNA-protein relationships and demonstrate their complementary biological roles. By integrating RNA and protein signatures, we develop multi-class classification models that accurately distinguish among a wide range of health conditions, with integrated models consistently outperforming those based on single-omics data alone. The identified RNA and protein signatures are validated across ten independent WBT cohorts and the UK Biobank. Together, the WBT Atlas provides a genome-wide resource that enables translational discovery in precision medicine.