Evidence map›Paper›PMID 33189395›Full record

ArticleChemosphere2021

Applying genome-wide CRISPR to identify known and novel genes and pathways that modulate formaldehyde toxicity.

Yun Zhao, Linqing Wei, Abderrahmane Tagmount, Alex Loguinov, Amin Sobh, Alan Hubbard, Cliona M McHale, Christopher J Chang, Chris D Vulpe, Luoping Zhang

Open access · greenAbstract read
In one paragraph

Article in Chemosphere, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed, 1 pooled it
1.6field-weighted citation impact, top 17% 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

21 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.

  1. Pooled it
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  13. State of the Art of Genomic Technology in Toxicology: A Review.International journal of molecular sciences · 2023
    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

10 authors at 3 institutions in 3 countries.

Yun ZhaoSchool of Public Health, University of California, Berkeley, CA, United States; Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan, PR China.
Linqing WeiSchool of Public Health, University of California, Berkeley, CA, United States.
Abderrahmane TagmountDepartment of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL, United States.
Alex LoguinovDepartment of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL, United States.
Amin SobhDepartment of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL, United States.
Alan HubbardSchool of Public Health, University of California, Berkeley, CA, United States.
Cliona M McHaleSchool of Public Health, University of California, Berkeley, CA, United States.
Christopher J ChangDepartment of Chemistry, University of California, Berkeley, CA, United States.
Chris D VulpeDepartment of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL, United States. Electronic address: cvulpe@ufl.edu.
Luoping ZhangSchool of Public Health, University of California, Berkeley, CA, United States. Electronic address: luoping@berkeley.edu.
University of California, Berkeley · USUniversity of Florida · USCentral China Normal University · CN

Funding

Training CoreP42ES004705 · NIEHS · UNIVERSITY OF CALIFORNIA BERKELEY · PI MCHALE, CLIONA · 1987 to 2025
$74.6M
NIEHS NIH HHS P42 ES004705
6 · The paper itself

Abstract

Formaldehyde (FA), a ubiquitous environmental pollutant, is classified as a Group I human carcinogen by the International Agency for Research on Cancer. Previously, we reported that FA induced hematotoxicity and chromosomal aneuploidy in exposed workers and toxicity in bone marrow and hematopoietic stem cells of experimental animals. Using functional toxicogenomic profiling in yeast, we identified genes and cellular processes modulating eukaryotic FA cytotoxicity. Although we validated some of these findings in yeast, many specific genes, pathways and mechanisms of action of FA in human cells are not known. In the current study, we applied genome-wide, loss-of-function CRISPR screening to identify modulators of FA toxicity in the human hematopoietic K562 cell line. We assessed the cellular genetic determinants of susceptibility and resistance to FA at 40, 100 and 150 μM (IC10, IC20 and IC60, respectively) at two time points, day 8 and day 20. We identified multiple candidate genes that increase sensitivity (e.g. ADH5, ESD and FANC family) or resistance (e.g. FASN and KDM6A) to FA when disrupted. Pathway analysis revealed a major role for the FA metabolism and Fanconi anemia pathway in FA tolerance, consistent with findings from previous studies. Additional network analyses revealed potential new roles for one-carbon metabolism, fatty acid synthesis and mTOR signaling in modulating FA toxicity. Validation of these novel findings will further enhance our understanding of FA toxicity in human cells. Our findings support the utility of CRISPR-based functional genomics screening of environmental chemicals.

Indexed as

Fanconi AnemiaRespiratory HypersensitivityAnimalsClustered Regularly Interspaced Short Palindromic RepeatsFormaldehydeHumansFormaldehydeCRISPR ScreenDNA RepairFanconi anemiaFormaldehydeFormaldehyde metabolism

Identifiers

PMID33189395
PMCPMC7904579
OpenAlexW3093723447

What OpenQuestion holds

Textmetadata
LicenceTDM
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.