IntraTalker - Modelling Intracellular Signalling in1 Cellular Crosstalk

Authors

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

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.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 23 Jul 2026.

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