IntraTalker - Modelling Intracellular Signalling in Cellular Crosstalk

bioRxiv (Cold Spring Harbor Laboratory)

Abstract

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.

Authors 8

1. Vanessa Klöker Aachen Center for Computational Life Sciences Institute for Computational Genomics

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Center for Computational Life Sciences, RWTH Aachen, Aachen, Germany

   Institute for Computational Genomics, RWTH Aachen University Hospital, Aachen, Germany

2. James S. Nagai Aachen Center for Computational Life Sciences Institute for Computational Genomics

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Center for Computational Life Sciences, RWTH Aachen, Aachen, Germany

   Institute for Computational Genomics, RWTH Aachen University Hospital, Aachen, Germany

3. Lampros Mavrommatis Aachen Center for Computational Life Sciences

   RWTH Aachen University

   Affiliation as printed

   Center for Computational Life Sciences, RWTH Aachen, Aachen, Germany

4. Larissa Hermanns Aachen Institute for Computational Genomics

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Institute for Computational Genomics, RWTH Aachen University Hospital, Aachen, Germany

5. Jacqueline Michelle Jara Moscoso Aachen Institute for Computational Genomics

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Institute for Computational Genomics, RWTH Aachen University Hospital, Aachen, Germany

6. Mayra Ruiz Aachen Institute for Computational Genomics

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Institute for Computational Genomics, RWTH Aachen University Hospital, Aachen, Germany

7. Christoph Kuppe Aachen Center for Computational Life Sciences Division of Nephrology and Clinical Immunology

   RWTH Aachen University

   Affiliation as printed

   Center for Computational Life Sciences, RWTH Aachen, Aachen, Germany

   Division of Nephrology and Clinical Immunology, RWTH Aachen University, Medical Faculty, Aachen, Germany

8. Ivan G. Costa corresponding Aachen Center for Computational Life Sciences Institute for Computational Genomics

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Center for Computational Life Sciences, RWTH Aachen, Aachen, Germany

   Institute for Computational Genomics, RWTH Aachen University Hospital, Aachen, Germany