Evidence map›Paper›PMID 35110534›Full record

ArticleNature communications2022

A pan-CRISPR analysis of mammalian cell specificity identifies ultra-compact sgRNA subsets for genome-scale experiments.

Boyang Zhao, Yiyun Rao, Scott Leighow, Edward P O'Brien, Luke Gilbert, Justin R Pritchard

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 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.7field-weighted citation impact, top 34% 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

6 citing papers in PubMed, 8 citations in OpenAlex.

  1. 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

6 authors at 2 institutions in 1 country.

Boyang ZhaoDepartment of Biomedical Engineering, Pennsylvania State University, State College, PA, USA. bozhao@alum.mit.edu.ORCID 0000-0003-4610-1707
Yiyun RaoHuck Institute for the Life Sciences, Pennsylvania State University, State College, PA, USA.
Scott LeighowDepartment of Biomedical Engineering, Pennsylvania State University, State College, PA, USA.
Edward P O'BrienDepartment of Chemistry, Pennsylvania State University, State College, PA, USA.ORCID 0000-0001-9809-3273
Luke GilbertDepartment of Urology, University of California at San Francisco, San Francisco, CA, USA.ORCID 0000-0001-5854-0825
Justin R PritchardDepartment of Biomedical Engineering, Pennsylvania State University, State College, PA, USA. jrp94@psu.edu.ORCID 0000-0001-7749-4473
Pennsylvania State University · USUniversity of California, San Francisco · US

Funding

Translation Kinetics and their Effects on Protein Structure and Function, mRNA half-lives, and Cellular PhenotypeR35GM124818 · NIGMS · PENNSYLVANIA STATE UNIVERSITY, THE · PI Edward Patrick O'Brien · 2017 to 2026
$4.0M
Personalization and Failure Testing of Dual Switch Gene Drives in Lung CancerU01CA265709 · NCI · PENNSYLVANIA STATE UNIVERSITY, THE · PI PRITCHARD, JUSTIN · 2021 to 2025
$2.6M
A GENETIC INTERACTION MAP OF THE HUMAN NUCLEUSDP2CA239597 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GILBERT, LUKE · 2018 to 2018
$2.4M
Model Driven Construction of Dual-switch Selection Gene Drives to Combat Drug ResistanceR21EB026617 · NIBIB · PENNSYLVANIA STATE UNIVERSITY, THE · PI PRITCHARD, JUSTIN · 2019 to 2021
$628k
NCI NIH HHS DP2 CA239597NCI NIH HHS U01 CA265709NIBIB NIH HHS R21 EB026617NIGMS NIH HHS R35 GM124818
6 · The paper itself

Abstract

A genetic knockout can be lethal to one human cell type while increasing growth rate in another. This context specificity confounds genetic analysis and prevents reproducible genome engineering. Genome-wide CRISPR compendia across most common human cell lines offer the largest opportunity to understand the biology of cell specificity. The prevailing viewpoint, synthetic lethality, occurs when a genetic alteration creates a unique CRISPR dependency. Here, we use machine learning for an unbiased investigation of cell type specificity. Quantifying model accuracy, we find that most cell type specific phenotypes are predicted by the function of related genes of wild-type sequence, not synthetic lethal relationships. These models then identify unexpected sets of 100-300 genes where reduced CRISPR measurements can produce genome-scale loss-of-function predictions across >18,000 genes. Thus, it is possible to reduce in vitro CRISPR libraries by orders of magnitude-with some information loss-when we remove redundant genes and not redundant sgRNAs.

Indexed as

Clustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Cas SystemsGenetic EngineeringMachine LearningAnimalsCell LineGene Knockout TechniquesGenomicsHumansSynthetic Lethal Mutations

Identifiers

PMID35110534
PMCPMC8810922
OpenAlexW4210349800

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.