Evidence map›Paper›PMID 27632082›Full record

ArticlePLoS computational biology2016

Systems Biology-Based Investigation of Cellular Antiviral Drug Targets Identified by Gene-Trap Insertional Mutagenesis.

Feixiong Cheng, James L Murray, Junfei Zhao, Jinsong Sheng, Zhongming Zhao, Donald H Rubin

Open access · goldAbstract read
In one paragraph

Article in PLoS computational biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
3.1field-weighted citation impact, top 8% of its field
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

29 citing papers in PubMed, 70 citations in OpenAlex.

  1. Review
  2. AΙ-Driven Drug Repurposing: Applications and Challenges.Medicines (Basel, Switzerland) · 2025
    Review
  3. Review
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  5. Article
  6. A Yeast BiFC-seq Method for Genome-wide Interactome Mapping.Genomics, proteomics & bioinformatics · 2022
    Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Emerging strategies on in silico drug development against COVID-19: challenges and opportunities.European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences · 2020
    Review
  13. Article
  14. Observational
  15. Article
  16. Article
  17. Shotgun drug repurposing biotechnology to tackle epidemics and pandemics.ChemRxiv : the preprint server for chemistry · 2020
    Article
  18. Article
  19. Article
  20. Article
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

6 authors at 2 institutions in 2 countries.

Feixiong ChengState Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, Sichuan, China.ORCID 0000-0002-1251-3116
James L MurrayZirus, Incorporated, Buford, Georgia, United States of America.
Junfei ZhaoCenter for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, Texas, United States of America.
Jinsong ShengDivision of Infectious Disease, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
Zhongming ZhaoDepartment of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.ORCID 0000-0002-3477-0914
Donald H RubinDivision of Infectious Disease, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
Vanderbilt University · USThe University of Texas Health Science Center at Houston · US

Funding

Tumor Immunology and Microenvironment Research ProgramP30CA068485 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI STACIE B DUSETZINA · 1995 to 2026
$172.8M
TISSUE CoreP50CA098131 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI PARK, BEN HO, PIETENPOL, JENNIFER A · 2003 to 2024
$48.7M
Understanding and Controlling p120 Dysfunction in CRCP50CA095103 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI COFFEY, ROBERT J. · 2002 to 2017
$33.6M
Mapping the Genetic Architecture of Complex Disease via RNA-seq and GWAS DataR01LM011177 · NLM · VANDERBILT UNIVERSITY · PI WANG, LILY, ZHAO, ZHONGMING · 2012 to 2014
$1.0M
NCI NIH HHS P30 CA068485NCI NIH HHS P50 CA095103NCI NIH HHS P50 CA098131NLM NIH HHS R01 LM011177
6 · The paper itself

Abstract

Viruses require host cellular factors for successful replication. A comprehensive systems-level investigation of the virus-host interactome is critical for understanding the roles of host factors with the end goal of discovering new druggable antiviral targets. Gene-trap insertional mutagenesis is a high-throughput forward genetics approach to randomly disrupt (trap) host genes and discover host genes that are essential for viral replication, but not for host cell survival. In this study, we used libraries of randomly mutagenized cells to discover cellular genes that are essential for the replication of 10 distinct cytotoxic mammalian viruses, 1 gram-negative bacterium, and 5 toxins. We herein reported 712 candidate cellular genes, characterizing distinct topological network and evolutionary signatures, and occupying central hubs in the human interactome. Cell cycle phase-specific network analysis showed that host cell cycle programs played critical roles during viral replication (e.g. MYC and TAF4 regulating G0/1 phase). Moreover, the viral perturbation of host cellular networks reflected disease etiology in that host genes (e.g. CTCF, RHOA, and CDKN1B) identified were frequently essential and significantly associated with Mendelian and orphan diseases, or somatic mutations in cancer. Computational drug repositioning framework via incorporating drug-gene signatures from the Connectivity Map into the virus-host interactome identified 110 putative druggable antiviral targets and prioritized several existing drugs (e.g. ajmaline) that may be potential for antiviral indication (e.g. anti-Ebola). In summary, this work provides a powerful methodology with a tight integration of gene-trap insertional mutagenesis testing and systems biology to identify new antiviral targets and drugs for the development of broadly acting and targeted clinical antiviral therapeutics.

Indexed as

AnimalsAntiviral AgentsCell CycleCell LineDogsDrug Delivery SystemsDrug DiscoveryHep G2 CellsHost-Pathogen InteractionsHumansMadin Darby Canine Kidney CellsMutagenesis, InsertionalProtein Interaction MapsSystems BiologyVirus ReplicationAntiviral Agents

Identifiers

PMID27632082
PMCPMC5025164
OpenAlexW2520699286

What OpenQuestion holds

Textmetadata
LicenceCC0
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 OpenQuestion graph.