DORSSAA: Drug-target interactOmics Resource based on Stability/Solubility Alteration Assay

ABSTRACT Advancements in high-throughput techniques such as Thermal Proteome Profiling (TPP) and the high-throughput Proteome Integral Solubility Alteration (PISA) assay have revolutionized our understanding of drug-protein interactions. Despite these innovations, the absence of an integrative platform for cross-study analysis of stability and solubility alteration data represents a significant bottleneck. To address this gap, we introduce DORSSAA (Drug-target interactOmics Resource based on Stability/Solubility Alteration Assay), an interactive and expandable web-based platform for the systematic analysis and visualization of proteome stability and solubility alteration assay datasets. Currently, DORSSAA features 1,135,985 records spanning 38 cell lines and organisms, 135 compounds, and 480,456 potential protein targets. Through its user-friendly interface, the resource supports comparative drug-protein interaction analysis and facilitates the discovery of actionable therapeutic targets. Through two case studies; methotrexate target profiling in A549 cells and combinatorial-therapy drug–target interactions in leukemia cell lines, we demonstrate DORSSAA’s utility for identifying protein–drug interactions across diverse experimental contexts. This resource empowers researchers to accelerate drug discovery and enhance our understanding of protein behavior. Unlike data repositories and interaction knowledgebases, DORSSAA provides assay-native, protein-level MoA evidence with rigorous per-study FDR control, enabling context-specific target nomination, off-target deconvolution, and combination-aware discovery. Abstract Figure