De Novo Multi-Omics Pathway Analysis Designed for Prior Data Independent Inference of Cell Signaling Pathways
: Vaparanta, Katri; Merilahti, Johannes A.M.;, Ojala, Veera K.;, Elenius, Klaus
Publisher: Elsevier
: 2024
: Molecular and Cellular Proteomics
: Molecular & Cellular Proteomics
: 100780
: 23
: 7
: 1535-9476
: 1535-9484
DOI: https://doi.org/10.1016/j.mcpro.2024.100780
: https://doi.org/10.1016/j.mcpro.2024.100780
: https://research.utu.fi/converis/portal/detail/Publication/393421821
New tools for cell signaling pathway inference from multi-omics data that are independent of previous knowledge are needed. Here we propose a new de novo method, the de novo multi-omics pathway analysis (DMPA), to model and combine omics data into network modules and pathways. DMPA was validated with published omics data and was found accurate in discovering reported molecular associations in transcriptome, interactome, phosphoproteome, methylome, and metabolomics data and signaling pathways in multi-omics data. DMPA was benchmarked against module discovery and multi-omics integration methods and outperformed previous methods in module and pathway discovery especially when applied to datasets with relatively low sample sizes. Transcription factor, kinase, subcellular location and function prediction algorithms were devised for transcriptome, phosphoproteome and interactome modules and pathways, respectively. To apply DMPA in a biologically relevant context, interactome, phosphoproteome, transcriptome and proteome data were collected from analyses carried out using melanoma cells to address gamma-secretase cleavage-dependent signaling characteristics of the receptor tyrosine kinase TYRO3. The pathways modeled with DMPA reflected the predicted function and its direction in validation experiments.
:
This work was supported by the Academy of Finland, Cancer Foundation Finland, the Sigrid Juselius Foundation, the Turku University Central Hospital, the Turku University Foundation, Orion Research Foundation, K. Albin Johanssons Foundation, the Cancer Society of Southwestern Finland, the Jenny and Antti Wihuri Foundation, the Maud Kuistila memorial Foundation, Emil Aaltonen Foundation, the Finnish Foundation for Cardiovascular Research, the Paavo Nurmi Foundation, the Aarne Koskelo Foundation, the Paulo Foundation, the Oskar Öflunds Stiftelse, the Ida Montinin säätiö, the Finnish Cultural Foundation and the Varsinais-Suomi Regional Fund of the Finnish Cultural Foundation.
