Wehling, L. | Search bioRxiv

bioRxiv2025

Talk2Biomodels: AI agent-based open-source LLM initiative for kinetic biological models

In this study, we present Talk2Biomodels (T2B), an open-source1, user-friendly, large language model-based agentic AI platform designed to democratize access to computational models of biological interactions and promote the FAIRification (Findability, Accessibility, Interoperability, and Reusability) of these models. T2B enables users to explore and analyse mathematical models of biological systems using natural language. It eschews the traditional graphical user interface (GUI) and minimally adaptable workflow in favour of a modern agentic framework to provide a dynamic and immersive experience to explore mathematical models of biological interactions through conversations in natural language. T2B supports models encoded in the open-source community format Systems Biology Markup Language (SBML) and is integrated with the BioModels database (https://www.ebi.ac.uk/biomodels/), enabling seamless exploration, simulation, and analysis of curated systems biology models. Use cases in precision medicine, epidemiology, and emergent systems properties of biological networks are presented to demonstrate how experts and non-experts in computational biology can benefit from T2B.

systems biology↗

bioRxiv2022

Spatial modeling reveals nuclear phosphorylation and subcellular shuttling of YAP upon drug-induced liver injury

The Hippo signaling pathway controls cell proliferation and tissue regeneration via its transcriptional effectors yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ). In this context, the canonical pathway topology is characterized by sequential phosphorylation of kinases in the cytoplasm that define the subcellular localization of YAP and TAZ. However, the molecular mechanisms controlling the nuclear/cytoplasmic shuttling dynamics of both factors under physiological and tissue-damaging conditions are poorly understood. By implementing experimental data, partial differential equation (PDE) modeling, as well as automated image analysis, we demonstrate that nuclear phosphorylation contributes to differences between YAP and TAZ localization in the nucleus and cytoplasm. Treatment of hepatocyte-derived cells with hepatotoxic acetaminophen (APAP) overdose induces a biphasic protein phosphorylation eventually leading to nuclear protein enrichment of YAP but not TAZ. APAP-dependent regulation of nuclear/cytoplasmic YAP shuttling is not an unspecific cellular response but relies on the sequential induction of reactive oxygen species (ROS), RAC-alpha serine/threonine-protein kinase (AKT, synonym: protein kinase B), as well as elevated nuclear interaction between YAP and AKT. Mouse experiments confirm this consecutive sequence of events illustrated by the expression of ROS-, AKT-, and YAP-specific gene signatures upon APAP administration. In summary, our data illustrate the importance of nuclear processes in the regulation of Hippo pathway activity. YAP and TAZ exhibit different shuttling dynamics, which explains distinct cellular responses of both factors under physiological and tissue-damaging conditions. SignificanceWe show that canonical view on the Hippo pathway must be extended by additional regulatory processes in cell nuclei. These processes significantly contribute to the activity of YAP and TAZ under unchallenged conditions (e.g., with cell density as physiological regulator of the Hippo kinase cassette) or under cell damaging conditions (e.g., after administration of APAP overdose). APAP-induced cellular damage activates YAP via distinct molecular processes as part of a cell-protective response.

molecular biology↗