Evidence map›Paper›PMID 39971994›Full record

ArticleNature communications2025

Systematic representation and optimization enable the inverse design of cross-species regulatory sequences in bacteria.

Pengcheng Zhang, Qixiu Du, Ye Wang, Lei Wei, Xiaowo Wang

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 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing 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

9 citing papers in PubMed.

  1. Article
  2. PlantGFM: A Genomic Foundation Model for Discovery and Creation of Plant Genes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  3. Article
  4. Review
  5. Review
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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

5 authors.

Pengcheng Zhang *Ministry of Education Key Laboratory of Bioinformatics; Center for Synthetic and Systems Biology; Bio-informatics Division, Beijing National Research Center for Information Science and Technology; Department of Automation, Tsinghua University, Beijing, 100084, China.ORCID http://orcid.org/0000-0003-3524-3478
Qixiu Du *Ministry of Education Key Laboratory of Bioinformatics; Center for Synthetic and Systems Biology; Bio-informatics Division, Beijing National Research Center for Information Science and Technology; Department of Automation, Tsinghua University, Beijing, 100084, China.ORCID http://orcid.org/0009-0008-8351-618X
Ye Wang *Ministry of Education Key Laboratory of Bioinformatics; Center for Synthetic and Systems Biology; Bio-informatics Division, Beijing National Research Center for Information Science and Technology; Department of Automation, Tsinghua University, Beijing, 100084, China.
Lei WeiMinistry of Education Key Laboratory of Bioinformatics; Center for Synthetic and Systems Biology; Bio-informatics Division, Beijing National Research Center for Information Science and Technology; Department of Automation, Tsinghua University, Beijing, 100084, China.ORCID http://orcid.org/0000-0002-1546-6458
Xiaowo WangMinistry of Education Key Laboratory of Bioinformatics; Center for Synthetic and Systems Biology; Bio-informatics Division, Beijing National Research Center for Information Science and Technology; Department of Automation, Tsinghua University, Beijing, 100084, China. xwwang@tsinghua.edu.cn.ORCID http://orcid.org/0000-0003-2965-8036

Funding

National Natural Science Foundation of China (National Science Foundation of China) 62225307National Natural Science Foundation of China (National Science Foundation of China) 62250007
6 · The paper itself

Abstract

Regulatory sequences encode crucial gene expression signals, yet the sequence characteristics that determine their functionality across species remain obscure. Deep generative models have demonstrated considerable potential in various inverse design applications, especially in engineering genetic elements. Here, we introduce DeepCROSS, a generative artificial intelligence framework for the inverse design of cross-species and species-preferred 5' regulatory sequences in bacteria. DeepCROSS constructs a meta-representation using 1.8 million regulatory sequences from thousands of bacterial genomes to depict the general constraints of regulatory sequences, employs artificial intelligence-guided massively parallel reporter assay experiments in E. coli and P. aeruginosa to explore the potential sequence space, and performs multi-task optimization to obtain de novo regulatory sequences. The optimized regulatory sequences achieve similar or better performance to functional natural regulatory sequences, with high success rates and low sequence similarities with the natural genome. Collectively, DeepCROSS efficiently navigates the sequence-function landscape and enables the inverse design of cross-species and species-preferred 5' regulatory sequences.

Indexed as

BacteriaEscherichia coliPseudomonas aeruginosaRegulatory Sequences, Nucleic AcidArtificial IntelligenceGene Expression Regulation, BacterialGenome, BacterialSpecies Specificity

Identifiers

PMID39971994
PMCPMC11840067

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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 OpenQuestion graph.