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bioRxiv · 10.64898/2026.07.17.739174

IntraTalker - Modelling Intracellular Signalling in1 Cellular Crosstalk

Kloker, V.·Nagai, J. S.·Feng, Z.·Mavrommatis, L.·Hermanns, L.·Moscoso, J. M. J.·Ruiz, M.·Kuppe, C.·Costa, I. G.
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Abstract

Single-cell sequencing has advanced the study of cell-cell communication, yet most methods focus on intercellular ligand-receptor interactions while neglecting downstream intracellular signalling cascades and the possibility that downstream target genes themselves encode ligands, thereby propagating communication across multiple cells. We present IntraTalker+CrossTalkeR that combines intracellular (IntraTalker) and intercellular (CrossTalkeR) signalling from multimodal single-cell data. IntraTalker infers cell-type-specific transcription factor activities and constructs receptomes that link receptors to downstream target genes, which are then integrated with ligand-receptor predictions in CrossTalkeR. To prioritize signalling receptors, the framework performs in silico receptor perturbation. In a murine bone marrow dataset, this recovered the known function of the Il1r1 receptor in driving myeloid progenitor cell-state changes. In a human myocardial infarction dataset, it predicted a novel role for IGF1R signalling in driving the differentiation of fibroblasts towards progenitor fibroblast states.

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Kloker, V., Nagai, J. S., Feng, Z., Mavrommatis, L., Hermanns, L., Moscoso, J. M. J., Ruiz, M., Kuppe, C., Costa, I. G.. 2026-07-22. IntraTalker - Modelling Intracellular Signalling in1 Cellular Crosstalk. https://doi.org/10.64898/2026.07.17.739174

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