Cell signaling pathways discovery from multi-modal data

Journal: bioRxiv
Published Date:

Abstract

Deciphering cell signaling pathways is key to understanding biology, disease mechanisms, and developing new therapies. Although advances in multi-omics technologies provide richer insight into signaling, the data remain high-dimensional, heterogeneous, and difficult to interpret, and current computational tools for inferring signaling pathways are limited. To address this, we developed Incytr, a method for efficient discovery of cell signaling pathways through integration of diverse data modalities, including transcriptomics, ATAC-seq, proteomics, phosphoproteomics, and kinomics. We demonstrate its application in COVID-19, Alzheimer's disease, and cancer, where it successfully recovers known pathways and generates novel, cell-type-specific hypotheses supported by multiple data types. We further show how integrating Incytr-derived pathways with biomarker and drug databases can support target and drug discovery. Finally, we show that using Incytr-derived signaling pathways as training data for simple natural language processing models can deepen our understanding of cell-cell communication and immune cell dynamics, while helping identify new therapeutic targets.

Authors

  • He
  • C.; Simpson
  • C.; Cossentino
  • I.; Zhang
  • B.; Tkachev
  • S.; Eddins
  • D. J.; Kosters
  • A.; Yang
  • J.; Sheth
  • S.; Levy
  • T.; Possemato
  • A.; Huang
  • L.; Tabatsky
  • E.; Lee
  • S. H.; Ghosh
  • D.; George
  • A.; Gregoretti
  • I.; Ariss
  • M.; Dandekar
  • D.; Ausekar
  • A.; Roan
  • N. R.; Ghosn
  • E. E. B.; Colonna
  • M.; Rikova
  • K.; Nie
  • Q.; Orlova
  • D.

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