Integration of high-throughput proteomic data and complementary omics layers with PriOmics

High-throughput bottom-up proteomic data cover thousands of proteins and related co- and post-translational modifications (CTMs/PTMs). Yet, it remains an open question how to holistically explore such data and their relationship to complementary omics/phenotypic information. Graphical models are particularly suited to study molecular networks and underlying regulatory mechanisms, as they can distinguish direct from indirect relationships, aside from their generalizability to diverse data types. Here, we propose PriOmics to integrate proteomic data with complementary omics and phenotypic data. PriOmics models intensities of individual proteotypic peptides and incorporates their protein affiliation as prior knowledge to resolve statistical relationships between proteins and CTMs/PTMs. This is verified in simulation studies, which also demonstrate that PriOmics can disentangle regulatory effects of protein modifications from those of respective protein abundances. These findings are substantiated in a diffuse large B cell lymphoma (DLBCL) data set in which we integrate SWATH-MS-based proteomics with transcriptomic and phenotypic data.