BACKGROUND: Personalized and precision medicine aim to identify predictive biomarkers from patient-specific proteogenomic profiles and to uncover tailored therapeutic strategies by targeting deregulated proteins driving disease phenotypes. METHODS: To address these challenges, we developed MultiOmicsXplorer, a freely available and interactive R-based Shiny application designed to facilitate the exploration and analysis of multi-omics cancer datasets with a user-friendly interface. At its core, MultiOmicsXplorer builds on our recently developed SignalingProfiler pipeline to extract protein activities from proteogenomic data, thereby reducing data complexity and dimensionality while enabling mechanistic hypothesis generation. RESULTS: The application integrates two core functionalities. The first, OncoXplorer, enables the systematic inference and comparison of protein activities from 1492 samples corresponding to approximately 1000 patients across ten cancer types, leveraging harmonized datasets from the CPTAC portal to provide a functional and mechanistic interpretation of multi-layered data. Importantly, beyond activity estimation, it allows for comparative analysis of transcriptomic, proteomic, and phosphoproteomic data. The second module, Extract Protein Activity from Your Data, enables users to infer the activity of kinases, phosphatases, and transcription factors from custom multi-modal datasets. CONCLUSIONS: Overall, MultiOmicsXplorer facilitates the exploration and interpretation of CPTAC multi-omics cancer datasets, supporting comparative analyses and protein activity inference within a unified and user-friendly environment.

MOTIVATION: Phosphoproteomics measurements are widely applied in cellular biology to detect changes in signalling dynamics. However, due to the inherent complexity of phosphorylation patterns and the lack of knowledge on how phosphorylations are related to functions, it is often not possible to directly deduce protein activities from those measurements. Here, we present a heuristic machine learning algorithm that infers the activities of kinases from Phosphoproteomics data using kinase-target information from the PhosphoSitePlus database. By comparing the estimated kinase activity profiles to the measured phosphosite profiles, it is furthermore possible to derive the kinases that are most likely to phosphorylate the respective phosphosite. RESULTS: We apply our approach to published datasets of the human cell cycle generated from HeLaS3 cells, and insulin signalling dynamics in mouse hepatocytes. In the first case, we estimate the activities of 118 at six cell cycle stages and derive 94 new kinase-phosphosite links that can be validated through either database or motif information. In the second case, the activities of 143 kinases at eight time points are estimated and 49 new kinase-target links are derived. AVAILABILITY AND IMPLEMENTATION: The algorithm is implemented in Matlab and be downloaded from github. It makes use of the Optimization and Statistics toolboxes. https://github.com/marcel-mischnik/IKAP.git. CONTACT: [email protected] SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.