Evidence map›Paper›PMID 34313788›Full record

ArticleNucleic acids research2021

Systematic identification of novel cancer genes through analysis of deep shRNA perturbation screens.

Hesam Montazeri, Mairene Coto-Llerena, Gaia Bianco, Ehsan Zangene, Stephanie Taha-Mehlitz, Viola Paradiso, Sumana Srivatsa, Antoine de Weck, Guglielmo Roma, Manuela Lanzafame and 6 more

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.6field-weighted citation impact, top 40% 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

7 citing papers in PubMed, 9 citations in OpenAlex.

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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

16 authors at 7 institutions in 3 countries.

Hesam MontazeriDepartment of Bioinformatics, Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.
Mairene Coto-LlerenaInstitute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland.
Gaia BiancoInstitute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland.
Ehsan ZangeneDepartment of Bioinformatics, Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.
Stephanie Taha-MehlitzVisceral Surgery and Precision Medicine Research laboratory, Department of Biomedicine, University of Basel, Basel, Switzerland.
Viola ParadisoInstitute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland.
Sumana SrivatsaDepartment of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland.
Antoine de WeckNovartis Institutes for BioMedical Research, Novartis Pharma AG, Basel, Switzerland.
Guglielmo RomaNovartis Institutes for BioMedical Research, Novartis Pharma AG, Basel, Switzerland.
Manuela LanzafameInstitute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland.ORCID 0000-0002-0456-1134
Martin BolliClarunis, Department of Visceral Surgery, University Centre for Gastrointestinal and Liver Diseases, St. Clara Hospital and University Hospital Basel, Switzerland.
Niko BeerenwinkelDepartment of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland.ORCID 0000-0002-0573-6119
Markus von FlüeClarunis, Department of Visceral Surgery, University Centre for Gastrointestinal and Liver Diseases, St. Clara Hospital and University Hospital Basel, Switzerland.
Luigi M TerraccianoDepartment of Pathology, Humanitas Clinical and Research Center, IRCCS, Milan, Italy.
Salvatore PiscuoglioInstitute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland.
Charlotte K Y NgInstitute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland.ORCID 0000-0002-6100-0026
University of Basel · CHNovartis (Switzerland) · CHSIB Swiss Institute of Bioinformatics · CHUniversity Hospital of Basel · CHUniversity of Tehran · IRHumanitas University · ITUniversity of Bern · CH

Funding

European Research Council 609883
6 · The paper itself

Abstract

Systematic perturbation screens provide comprehensive resources for the elucidation of cancer driver genes. The perturbation of many genes in relatively few cell lines in such functional screens necessitates the development of specialized computational tools with sufficient statistical power. Here we developed APSiC (Analysis of Perturbation Screens for identifying novel Cancer genes) to identify genetic drivers and effectors in perturbation screens even with few samples. Applying APSiC to the shRNA screen Project DRIVE, APSiC identified well-known and novel putative mutational and amplified cancer genes across all cancer types and in specific cancer types. Additionally, APSiC discovered tumor-promoting and tumor-suppressive effectors, respectively, for individual cancer types, including genes involved in cell cycle control, Wnt/β-catenin and hippo signalling pathways. We functionally demonstrated that LRRC4B, a putative novel tumor-suppressive effector, suppresses proliferation by delaying cell cycle and modulates apoptosis in breast cancer. We demonstrate APSiC is a robust statistical framework for discovery of novel cancer genes through analysis of large-scale perturbation screens. The analysis of DRIVE using APSiC is provided as a web portal and represents a valuable resource for the discovery of novel cancer genes.

Indexed as

GenomicsApoptosisCell Line, TumorCell Transformation, NeoplasticGene AmplificationGenes, NeoplasmHumansNeoplasmsRNA, Small InterferingSignal TransductionRNA, Small Interfering

Identifiers

PMID34313788
PMCPMC8421231
OpenAlexW3183923959

What OpenQuestion holds

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LicenceCC BY
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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.