Evidence mapPaperPMID 39900922Full record

ArticleNature communications2025

A mechanism-informed deep neural network enables prioritization of regulators that drive cell state transitions.

Xi Xi, Jiaqi Li, Jinmeng Jia, Qiuchen Meng, Chen Li, Xiaowo Wang, Lei Wei, Xuegong Zhang

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed.

  1. Article
  2. Cell lineage tracing: Methods, applications, and challenges.Quantitative biology (Beijing, China) · 2025
    Review
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Pathway-guided architectures for interpretable AI in biological research.Computational and structural biotechnology journal · 2025
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Xi XiMOE Key Laboratory of Bioinformatics and Bioinformatics Division, BNRIST / Department of Automation, Tsinghua University, Beijing, China.ORCID http://orcid.org/0000-0002-9207-1804
Jiaqi LiMOE Key Laboratory of Bioinformatics and Bioinformatics Division, BNRIST / Department of Automation, Tsinghua University, Beijing, China.ORCID http://orcid.org/0000-0001-9038-9010
Jinmeng JiaMOE Key Laboratory of Bioinformatics and Bioinformatics Division, BNRIST / Department of Automation, Tsinghua University, Beijing, China.
Qiuchen MengMOE Key Laboratory of Bioinformatics and Bioinformatics Division, BNRIST / Department of Automation, Tsinghua University, Beijing, China.ORCID http://orcid.org/0000-0001-6013-9475
Chen LiMOE Key Laboratory of Bioinformatics and Bioinformatics Division, BNRIST / Department of Automation, Tsinghua University, Beijing, China.
Xiaowo WangMOE Key Laboratory of Bioinformatics and Bioinformatics Division, BNRIST / Department of Automation, Tsinghua University, Beijing, China.ORCID http://orcid.org/0000-0003-2965-8036
Lei WeiMOE Key Laboratory of Bioinformatics and Bioinformatics Division, BNRIST / Department of Automation, Tsinghua University, Beijing, China.ORCID http://orcid.org/0000-0002-1546-6458
Xuegong ZhangMOE Key Laboratory of Bioinformatics and Bioinformatics Division, BNRIST / Department of Automation, Tsinghua University, Beijing, China. zhangxg@tsinghua.edu.cn.ORCID http://orcid.org/0000-0002-9684-5643

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cells are regulated at multiple levels, from regulations of individual genes to interactions across multiple genes. Some recent neural network models can connect molecular changes to cellular phenotypes, but their design lacks modeling of regulatory mechanisms, limiting the decoding of regulations behind key cellular events, such as cell state transitions. Here, we present regX, a deep neural network incorporating both gene-level regulation and gene-gene interaction mechanisms, which enables prioritizing potential driver regulators of cell state transitions and providing mechanistic interpretations. Applied to single-cell multi-omics data on type 2 diabetes and hair follicle development, regX reliably prioritizes key transcription factors and candidate cis-regulatory elements that drive cell state transitions. Some regulators reveal potential new therapeutic targets, drug repurposing possibilities, and putative causal single nucleotide polymorphisms. This method to analyze single-cell multi-omics data demonstrates how the interpretable design of neural networks can better decode biological systems.

Indexed as

Neural Networks, ComputerAnimalsDiabetes Mellitus, Type 2Gene Expression RegulationGene Regulatory NetworksHair FollicleHumansMicePolymorphism, Single NucleotideSingle-Cell AnalysisTranscription FactorsTranscription Factors

Identifiers

PMID39900922
PMCPMC11790924

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.