Enabling single-cell trajectory network enrichment

Research output: Contribution to journalJournal articlepeer-review

  • Grønning, Alexander GB
  • Mhaned Oubounyt
  • Kristiyan Kanev
  • Jesper Lund
  • Tim Kacprowski
  • Dietmar Zehn
  • Richard Röttger
  • Jan Baumbach

Single-cell sequencing (scRNA-seq) technologies allow the investigation of cellular differentiation processes with unprecedented resolution. Although powerful software packages for scRNA-seq data analysis exist, systems biology-based tools for trajectory analysis are rare and typically difficult to handle. This hampers biological exploration and prevents researchers from gaining deeper insights into the molecular control of developmental processes. Here, to address this, we have developed Scellnetor; a network-constraint time-series clustering algorithm. It allows extraction of temporal differential gene expression network patterns (modules) that explain the difference in regulation of two developmental trajectories. Using well-characterized experimental model systems, we demonstrate the capacity of Scellnetor as a hypothesis generator to identify putative mechanisms driving haematopoiesis or mechanistically interpretable subnetworks driving dysfunctional CD8 T-cell development in chronic infections. Altogether, Scellnetor allows for single-cell trajectory network enrichment, which effectively lifts scRNA-seq data analysis to a systems biology level.

Original languageEnglish
JournalNature Computational Science
Volume1
Issue number2
Pages (from-to)153-163
DOIs
Publication statusPublished - 2021

Bibliographical note

Funding Information:
J.B. and A.G.B.G. received funding from J.B.’s VILLUM Young Investigator grant no. 13154. The work of J.B. and T.K. was further funded by H2020 project RepoTrial (no. 777111). The work of R.R. and J.B. was partially funded by H2020 project FeatureCloud (no. 826078). J.B. and T.K. are grateful for financial support from BMBF project Sys_Care. M.O. is grateful for financial support from the Collaborative Research Center SFB924.

Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.

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