Enabling single-cell trajectory network enrichment

Alexander G. B. Grønning*, Mhaned Oubounyt, Kristiyan Kanev, Jesper Lund, Tim Kacprowski, Dietmar Zehn, Richard Röttger, Jan Baumbach*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

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
ISSN2662-8457
DOIs
Publication statusPublished - 2021

Fingerprint

Dive into the research topics of 'Enabling single-cell trajectory network enrichment'. Together they form a unique fingerprint.

Cite this