Evidence map›Paper›PMID 29078326›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2017

CRISPR-Cas9-mediated saturated mutagenesis screen predicts clinical drug resistance with improved accuracy.

Leyuan Ma, Jeffrey I Boucher, Janet Paulsen, Sebastian Matuszewski, Christopher A Eide, Jianhong Ou, Garrett Eickelberg, Richard D Press, Lihua Julie Zhu, Brian J Druker and 6 more

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing 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

39 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Article
  6. Article
  7. Article
  8. Review
  9. The Future of Precision Oncology.International journal of molecular sciences · 2023
    Review
  10. Review
  11. Article
  12. Review
  13. Article
  14. Article
  15. Mutational fitness landscape and drug resistance.Current opinion in structural biology · 2023
    Review
  16. Saturation mutagenesis of a predicted ancestral Syk-family kinase.Protein science : a publication of the Protein Society · 2022
    Article
  17. Article
  18. Article
  19. Article
  20. Review
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.

Leyuan MaDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605.
Jeffrey I BoucherDepartment of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605.
Janet PaulsenDepartment of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605.
Sebastian MatuszewskiSchool of Life Sciences, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.ORCID 0000-0002-4393-9283
Christopher A EideKnight Cancer Institute, Division of Hematology and Medical Oncology, Oregon Health & Science University, Portland, OR 97239.
Jianhong OuDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605.
Garrett EickelbergKnight Cancer Institute, Department of Pathology, Oregon Health & Science University, Portland, OR 97239.
Richard D PressKnight Cancer Institute, Department of Pathology, Oregon Health & Science University, Portland, OR 97239.
Lihua Julie ZhuDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605.
Brian J DrukerKnight Cancer Institute, Division of Hematology and Medical Oncology, Oregon Health & Science University, Portland, OR 97239.
Susan BranfordDepartment of Genetics and Molecular Pathology, Centre for Cancer Biology, SA Pathology, Adelaide, SA 5000, Australia.
Scot A WolfeDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605.
Jeffrey D JensenSchool of Life Sciences, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
Celia A SchifferDepartment of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605.
Michael R GreenDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605; Michael.Green@umassmed.edu Dan.Bolon@umassmed.edu.ORCID 0000-0003-3017-3298
Daniel N BolonDepartment of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605; Michael.Green@umassmed.edu Dan.Bolon@umassmed.edu.

Funding

CHRONIC MYELOGENOUS LEUKEMIA AND BCR-ABL SUBSTRATESR01CA065823 · NCI · OREGON HEALTH & SCIENCE UNIVERSITY · PI DRUKER, BRIAN J · 1995 to 2021
$4.7M
Identification and Characterization of Genes that Suppress BCR-ABL+ LeukemiaR01CA163926 · NCI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI GREEN, MICHAEL R · 2013 to 2017
$1.7M
Functional effects of all possible point mutations in oncogenesR21CA175664 · NCI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI BOLON, DANIEL N · 2014 to 2015
$385k
Howard Hughes Medical InstituteNCI NIH HHS R01 CA065823NCI NIH HHS R01 CA163926NCI NIH HHS R21 CA175664
6 · The paper itself

Abstract

Developing tools to accurately predict the clinical prevalence of drug-resistant mutations is a key step toward generating more effective therapeutics. Here we describe a high-throughput CRISPR-Cas9-based saturated mutagenesis approach to generate comprehensive libraries of point mutations at a defined genomic location and systematically study their effect on cell growth. As proof of concept, we mutagenized a selected region within the leukemic oncogene

Indexed as

AnimalsAntineoplastic AgentsCell Line, TumorClustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Cas SystemsDrug Resistance, NeoplasmFusion Proteins, bcr-ablLeukemiaMiceMutagenesisOncogenesPoint MutationAntineoplastic AgentsFusion Proteins, bcr-ablBCR-ABLCRISPR-Cas9–based genome editingdrug resistancesaturated mutagenesistyrosine kinase inhibitors

Identifiers

PMID29078326
PMCPMC5676903

What OpenQuestion holds

Textmetadata
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.