Evidence map›Paper›PMID 37246643›Full record

ArticleNucleic acids research2023

Gene knockout inference with variational graph autoencoder learning single-cell gene regulatory networks.

Yongjian Yang, Guanxun Li, Yan Zhong, Qian Xu, Bo-Jia Chen, Yu-Te Lin, Robert S Chapkin, James J Cai

Abstract read
In one paragraph

Article in Nucleic acids research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed, 1 pooled it
–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

24 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  18. A mini-review on perturbation modelling across single-cell omic modalities.Computational and structural biotechnology journal · 2024
    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

8 authors.

Yongjian YangDepartment of Electrical and Computer Engineering, Texas A&M University, College Station, TX 77843, USA.ORCID 0000-0002-4135-5014
Guanxun LiDepartment of Statistics, Texas A&M University, College Station, TX 77843, USA.
Yan ZhongKey Laboratory of Advanced Theory and Application in Statistics and Data Science-MOE, School of Statistics, East China Normal University, 3663 North Zhongshan Road, Shanghai 200062, China.
Qian XuDepartment of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX 77843, USA.
Bo-Jia ChenGraduate Institute of Microbiology and Public Health, College of Veterinary Medicine, National Chung Hsing University, Taichung 402, Taiwan.
Yu-Te LinGraduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan.
Robert S ChapkinProgram in Integrative & Complex Diseases, Department of Nutrition, Texas A&M University, College Station, TX 77843, USA.
James J CaiDepartment of Electrical and Computer Engineering, Texas A&M University, College Station, TX 77843, USA.ORCID 0000-0002-8081-6725

Funding

Texas A&M Center for Environmental Health Research (TiCER)P30ES029067 · NIEHS · TEXAS A&M UNIVERSITY · PI Sakhila Banu · 2019 to 2026
$13.0M
Plasma membrane therapy: Disruption of Wnt associated receptor spatiotemporal organization by membrane targeted dietary bioactives (MTDB)R35CA197707 · NCI · TEXAS A&M AGRILIFE RESEARCH · PI CHAPKIN, ROBERT STEPHEN · 2016 to 2022
$6.3M
Targeting plasma membrane spatial dynamics to suppress aberrant Wnt signalingR01CA244359 · NCI · TEXAS A&M AGRILIFE RESEARCH · PI CHAPKIN, ROBERT STEPHEN, KARPAC, JASON S · 2020 to 2024
$2.7M
NR4A1 Antagonists Inhibit Colorectal Cancer Growth and Enhance Immune SurveillanceR01CA269580 · NCI · TEXAS A&M UNIVERSITY · PI MAEN ABDELRAHIM, James Jing Cai · 2023 to 2026
$2.3M
The selective advantage of mismatch repair loss in colonic stem cellsR01CA245514 · NCI · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI HEINEN, CHRISTOPHER D. · 2021 to 2025
$2.3M
NCI NIH HHS R01 CA245514NCI NIH HHS R01 CA269580NCI NIH HHS R35 CA197707NIEHS NIH HHS P30 ES029067
6 · The paper itself

Abstract

In this paper, we introduce Gene Knockout Inference (GenKI), a virtual knockout (KO) tool for gene function prediction using single-cell RNA sequencing (scRNA-seq) data in the absence of KO samples when only wild-type (WT) samples are available. Without using any information from real KO samples, GenKI is designed to capture shifting patterns in gene regulation caused by the KO perturbation in an unsupervised manner and provide a robust and scalable framework for gene function studies. To achieve this goal, GenKI adapts a variational graph autoencoder (VGAE) model to learn latent representations of genes and interactions between genes from the input WT scRNA-seq data and a derived single-cell gene regulatory network (scGRN). The virtual KO data is then generated by computationally removing all edges of the KO gene-the gene to be knocked out for functional study-from the scGRN. The differences between WT and virtual KO data are discerned by using their corresponding latent parameters derived from the trained VGAE model. Our simulations show that GenKI accurately approximates the perturbation profiles upon gene KO and outperforms the state-of-the-art under a series of evaluation conditions. Using publicly available scRNA-seq data sets, we demonstrate that GenKI recapitulates discoveries of real-animal KO experiments and accurately predicts cell type-specific functions of KO genes. Thus, GenKI provides an in-silico alternative to KO experiments that may partially replace the need for genetically modified animals or other genetically perturbed systems.

Indexed as

Gene Regulatory NetworksSingle-Cell AnalysisAnimalsGene Expression ProfilingGene Expression RegulationGene Knockout TechniquesSequence Analysis, RNA

Identifiers

PMID37246643
PMCPMC10359630

What Socratic holds

Textmetadata
LicenceCC BY
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.