BACKGROUND: Quantitative kinetic models of biological regulatory processes play an important role in understanding disease mechanisms. However, their simulation and analysis require specialized domain expertise. RESULTS: In this study, we present Talk2Biomodels (T2B), an open-source, user-friendly, large language model-based agentic AI platform designed to facilitate access to computational models of biological systems and promote the FAIRification (Findability, Accessibility, Interoperability, and Reusability) principles in systems biology. T2B allows users to interact with and analyse mathematical models of biological systems through conversations in natural language, thereby lowering the barrier to entry for model interpretation and hypothesis-driven exploration. The platform natively supports models encoded in the Systems Biology Markup Language, a widely adopted standard in the computational biology community. T2B is integrated with the BioModels database ( https://www.ebi.ac.uk/biomodels/ ), enabling retrieval, simulation, and analysis of curated systems biology models. We illustrate the platform's capabilities through use cases in precision medicine, infectious disease epidemiology, and the study of emergent network-level properties in cellular systems - demonstrating how both computational experts and domain scientists without formal modelling training can derive actionable insights from complex biological models. Talk2Biomodels is available at https://github.com/VirtualPatientEngine/AIAgents4Pharma . Detailed documentation and use cases are available at https://virtualpatientengine.github.io/AIAgents4Pharma/talk2biomodels/intro/ . CONCLUSIONS: In summary, T2B lowers the barrier for non-experts to engage with and extract insights from computational models of biological systems, while simultaneously providing experts with a streamlined interface for analysing models and overall contributes to the FAIRification of models.

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.

SUMMARY: Drug versus Disease (DvD) provides a pipeline, available through R or Cytoscape, for the comparison of drug and disease gene expression profiles from public microarray repositories. Negatively correlated profiles can be used to generate hypotheses of drug-repurposing, whereas positively correlated profiles may be used to infer side effects of drugs. DvD allows users to compare drug and disease signatures with dynamic access to databases Array Express, Gene Expression Omnibus and data from the Connectivity Map. AVAILABILITY AND IMPLEMENTATION: R package (submitted to Bioconductor) under GPL 3 and Cytoscape plug-in freely available for download at www.ebi.ac.uk/saezrodriguez/DVD/.