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Atlas of Computational Cell Reprogramming

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L1 · Network-informed inverse design heuristics D

SwitchTFI

Martini P, Hartebrodt A, de Almeida GP, Hackstein CP, Zehn D, Blumenthal DB

2025 · Genome biology

Many methods exist that infer cell differentiation trajectories from single-cell RNA sequencing data, but only few determine which mechanisms drive the inferred differentiation dynamics.

Abstract

From the original paper, Genome biology · PubMed

Many methods exist that infer cell differentiation trajectories from single-cell RNA sequencing data, but only few determine which mechanisms drive the inferred differentiation dynamics. To close this gap, we developed the algorithm and Python package SwitchTFI. Utilizing regression stump learning, permutation-based family-wise error rate control, and node centrality measures, SwitchTFI identifies differentiation-driving gene regulatory networks and the key transcription factors involved in them. Comprehensive tests on pancreatic endocrinogenesis, erythrocyte differentiation, and T cell exhaustion datasets show that SwitchTFI can rediscover known differentiation factors, that it can discover novel biologically plausible hypotheses, and that it compares favorably to competitor methods. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13059-025-03876-0.

Summary

Editorial summary pending review by the maintainer. The paper's own abstract appears above; the Atlas summary in the maintainer's voice will explain how SwitchTFI relates to the cross-modality inverse-design framework of the review.

Why this level

Level 1 because the method scores candidate interventions through static regulatory-network influence relative to a target GRN, without computing the post-intervention state P^S,u\hat P_{S,u}. Representation family is regulatory-network influence. Cited in §3.2 of the review. Editorial rationale pending review by the maintainer.

Classification

Level
L1
Representation
Regulatory-network influence
Modalities
D
Intervention
Transcription factors
Framework
Static network analysis

Software

Reproducibility
4 of 4
FAIR4RS
4 of 5

Last audited 2026-05-24

Citation

Martini P et al. (2025). SwitchTFI: identifying transcription factors driving cell differentiation., Genome biology.

DOI: 10.1186/s13059-025-03876-0

PMID: 41331466

BibTeX
@article{switchtfi2025,
  title  = {SwitchTFI: identifying transcription factors driving cell differentiation.},
  author = {Martini P et al.},
  year   = {2025},
  journal = {Genome biology},
  pmid = {41331466},
  doi  = {10.1186/s13059-025-03876-0}
}