Topology identifies concurrent cyclic processes in single-cell transcriptomics and androgen receptor function
Kelly MaggsiD, Markus K. YoussefiD, Cyril PulveriD, Jovan IsmaiD, Tâm J. Nguyên, Matthias Arzt, Wouter R. KarthausiD, Heather A. Harrington, Kathryn P. HessiD, G. Paolo Dotto
Abstract
Standard single-cell RNA-seq analysis frameworks aggregate over-lapping biological processes and impose a single parametrization, conflating distinct programs. Here, we introduce a topological framework that detects and disentangles multiple cyclic processes directly from single-cell transcriptomic data. We validate this approach on synthetic datasets and scRNA-seq profiles of human dermal fibroblasts under control conditions and following androgen receptor (AR) silencing, as well as in vivo mouse prostate regeneration under androgen receptor add-back. We show robust cell cycle structure across conditions, identify an unbiased AR-linked stress signature related to the senescence and proliferation across organisms, and uncover cholesterol homeostasis as an AR-linked program in tissue regeneration. This framework enables identification and separation of concurrent cyclic processes from snapshot single-cell data, revealing complex multi-dimensional regulatory dynamics inaccessible to standard clustering analysis.
02 /Specification & Classification
Click any tag to browse matching papers- Citations
- 0
- Organism
- Assay
- Research Focus
- Approach
Reproducibility ledger
Nobody has reported trying to reproduce this paper yet. Did you replicate an experiment or run the code? Your report saves the next lab a week.
Sign in to file a reproducibility report.
Related papers
- Quantifying landscape-flux via single-cell transcriptomics uncovers the underlying mechanism of cell cycle
Ligang Zhu, Jin Wang·Advanced SciencePeer-reviewed·Feb 14, 2024
- Cell cycle gene regulation dynamics revealed by RNA velocity and deep-learning
Andrea Riba, Attila Oravecz, … Nacho Molina·Nature CommunicationsPeer-reviewed·May 23, 2022
- Detecting Rhythmic Gene Expression in Single Cell Transcriptomics
Bingxian Xu, Dingbang Ma, … Rosemary Braun·Journal of Biological RhythmsPeer-reviewed·Oct 8, 2024
- A Cell Cycle-aware Network for Data Integration and Label Transferring of Single-cell RNA-seq and ATAC-seq
Jiajia Liu, Jian Ma, … Xiaobo Zhou·Advanced SciencePeer-reviewed·Jun 17, 2024
- Latent periodic process inference from single-cell RNA-seq data
Shaoheng Liang, Fang Wang, … Ken Chen·Nature CommunicationsPeer-reviewed·Mar 18, 2020
- CycleVI: Isolating cell cycle variation with an interpretable deep generative model
Pia Mozdzanowski, Marcel Tarbier, Gustavo S. Jeuken·BioinformaticsPeer-reviewed·Jun 1, 2026