Evidence map›Paper›PMID 35927228›Full record

ArticleNature communications2022

Accurate determination of CRISPR-mediated gene fitness in transplantable tumours.

Peter Eirew, Ciara O'Flanagan, Jerome Ting, Sohrab Salehi, Jazmine Brimhall, Beixi Wang, Justina Biele, Teresa Algara, So Ra Lee, Corey Hoang and 17 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2022. 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
0.7field-weighted citation impact, top 33% 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, 8 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

27 authors at 7 institutions in 2 countries.

Peter EirewDepartment of Molecular Oncology, BC Cancer, Vancouver, BC, Canada.
Ciara O'FlanaganDepartment of Molecular Oncology, BC Cancer, Vancouver, BC, Canada.
Jerome TingDepartment of Molecular Oncology, BC Cancer, Vancouver, BC, Canada.
Sohrab SalehiDepartment of Molecular Oncology, BC Cancer, Vancouver, BC, Canada.
Jazmine BrimhallDepartment of Molecular Oncology, BC Cancer, Vancouver, BC, Canada.
Beixi WangDepartment of Molecular Oncology, BC Cancer, Vancouver, BC, Canada.
Justina BieleDepartment of Molecular Oncology, BC Cancer, Vancouver, BC, Canada.
Teresa AlgaraDepartment of Molecular Oncology, BC Cancer, Vancouver, BC, Canada.
So Ra LeeDepartment of Molecular Oncology, BC Cancer, Vancouver, BC, Canada.
Corey HoangDepartment of Molecular Oncology, BC Cancer, Vancouver, BC, Canada.
Damian YapDepartment of Molecular Oncology, BC Cancer, Vancouver, BC, Canada.ORCID 0000-0002-5370-4592
Steven McKinneyDepartment of Molecular Oncology, BC Cancer, Vancouver, BC, Canada.ORCID 0000-0002-1611-0867
Cherie BatesDepartment of Molecular Oncology, BC Cancer, Vancouver, BC, Canada.
Esther KongDepartment of Molecular Oncology, BC Cancer, Vancouver, BC, Canada.ORCID 0000-0002-1315-4311
Daniel LaiDepartment of Molecular Oncology, BC Cancer, Vancouver, BC, Canada.ORCID 0000-0001-9203-6323
Sean BeattyDepartment of Molecular Oncology, BC Cancer, Vancouver, BC, Canada.ORCID 0000-0001-6819-7071
Mirela AndronescuDepartment of Molecular Oncology, BC Cancer, Vancouver, BC, Canada.
Elena ZaikovaDepartment of Molecular Oncology, BC Cancer, Vancouver, BC, Canada.
Tyler FunnellComputational Oncology, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.ORCID 0000-0003-1612-5644
Nicholas CegliaComputational Oncology, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Stephen ChiaDepartment of Medical Oncology, BC Cancer, Vancouver, BC, Canada.
Karen GelmonDepartment of Medical Oncology, BC Cancer, Vancouver, BC, Canada.
Colin MarDepartment of Diagnostic Radiology, BC Cancer, Vancouver, BC, Canada.
Sohrab ShahComputational Oncology, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.ORCID 0000-0001-6402-523X
Andrew RothDepartment of Molecular Oncology, BC Cancer, Vancouver, BC, Canada.ORCID 0000-0003-3422-8823
Alexandre Bouchard-CôtéDepartment of Statistics, University of British Columbia, Vancouver, BC, Canada. bouchard@stat.ubc.ca.
Samuel AparicioDepartment of Molecular Oncology, BC Cancer, Vancouver, BC, Canada. saparicio@bccrc.ca.ORCID 0000-0002-0487-9599
Memorial Sloan Kettering Cancer Center · USAbCellera (Canada) · CABC Cancer Agency · CABritish Columbia Institute of Technology · CASpinal Cord Injury BC · CAUniversity of British Columbia · CAUniversity of British Columbia Hospital · CA

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
Cancer Research UK 21143NCI NIH HHS P30 CA008748
6 · The paper itself

Abstract

Assessing tumour gene fitness in physiologically-relevant model systems is challenging due to biological features of in vivo tumour regeneration, including extreme variations in single cell lineage progeny. Here we develop a reproducible, quantitative approach to pooled genetic perturbation in patient-derived xenografts (PDXs), by encoding single cell output from transplanted CRISPR-transduced cells in combination with a Bayesian hierarchical model. We apply this to 181 PDX transplants from 21 breast cancer patients. We show that uncertainty in fitness estimates depends critically on the number of transplant cell clones and the variability in clone sizes. We use a pathway-directed allelic series to characterize Notch signaling, and quantify TP53 / MDM2 drug-gene conditional fitness in outlier patients. We show that fitness outlier identification can be mirrored by pharmacological perturbation. Overall, we demonstrate that the gene fitness landscape in breast PDXs is dominated by inter-patient differences.

Indexed as

Breast NeoplasmsClustered Regularly Interspaced Short Palindromic RepeatsAnimalsBayes TheoremDisease Models, AnimalFemaleHeterograftsHumansXenograft Model Antitumor Assays

Identifiers

PMID35927228
PMCPMC9352714
OpenAlexW4289780900

What OpenQuestion 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 OpenQuestion graph.