Evidence map›Paper›PMID 36968528›Full record

ArticleACS central science2023

Quantification and Mapping of Alkylation in the Human Genome Reveal Single Nucleotide Resolution Precursors of Mutational Signatures.

Yang Jiang, Cécile Mingard, Sabrina M Huber, Vakil Takhaveev, Maureen McKeague, Seiichiro Kizaki, Mirjam Schneider, Nathalie Ziegler, Vera Hürlimann, Julia Hoeng and 3 more

Erratum issuedOpen access · diamondFull text read
In one paragraph

Article in ACS central science, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
2.8field-weighted citation impact, top 10% 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

13 citing papers in PubMed, 18 citations in OpenAlex.

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  10. HMGB3 and SUB1 Bind to and Facilitate the Repair ofJournal of the American Chemical Society · 2024
    Article
  11. Activity of DNA polymerase κ across the genome in human fibroblasts.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  12. Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 2 institutions in 2 countries.

Yang JiangDepartment of Health Sciences and Technology, ETH Zurich, Schmelzbergstrasse 9, Zurich 8092, Switzerland.ORCID https://orcid.org/0000-0002-9078-3453
Cécile MingardDepartment of Health Sciences and Technology, ETH Zurich, Schmelzbergstrasse 9, Zurich 8092, Switzerland.ORCID https://orcid.org/0000-0002-2808-0204
Sabrina M HuberDepartment of Health Sciences and Technology, ETH Zurich, Schmelzbergstrasse 9, Zurich 8092, Switzerland.ORCID https://orcid.org/0000-0001-9204-5537
Vakil TakhaveevDepartment of Health Sciences and Technology, ETH Zurich, Schmelzbergstrasse 9, Zurich 8092, Switzerland.ORCID https://orcid.org/0000-0002-3474-5241
Maureen McKeagueDepartment of Health Sciences and Technology, ETH Zurich, Schmelzbergstrasse 9, Zurich 8092, Switzerland.ORCID https://orcid.org/0000-0002-3750-6027
Seiichiro KizakiDepartment of Health Sciences and Technology, ETH Zurich, Schmelzbergstrasse 9, Zurich 8092, Switzerland.
Mirjam SchneiderDepartment of Health Sciences and Technology, ETH Zurich, Schmelzbergstrasse 9, Zurich 8092, Switzerland.
Nathalie ZieglerDepartment of Health Sciences and Technology, ETH Zurich, Schmelzbergstrasse 9, Zurich 8092, Switzerland.ORCID https://orcid.org/0000-0003-1152-0645
Vera HürlimannDepartment of Health Sciences and Technology, ETH Zurich, Schmelzbergstrasse 9, Zurich 8092, Switzerland.
Julia HoengPhilip Morris Products SA, Quai Jeanrenaud 3, Neuchatel 2000, Switzerland.
Nicolas SierroPhilip Morris Products SA, Quai Jeanrenaud 3, Neuchatel 2000, Switzerland.
Nikolai V IvanovPhilip Morris Products SA, Quai Jeanrenaud 3, Neuchatel 2000, Switzerland.ORCID https://orcid.org/0000-0002-2052-4333
Shana J SturlaDepartment of Health Sciences and Technology, ETH Zurich, Schmelzbergstrasse 9, Zurich 8092, Switzerland.ORCID https://orcid.org/0000-0001-6808-5950
ETH Zurich · CHPhilip Morris International (Switzerland) · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Chemical modifications to DNA bases, including DNA adducts arising from reactions with electrophilic chemicals, are well-known to impact cell growth, miscode during replication, and influence disease etiology. However, knowledge of how genomic sequences and structures influence the accumulation of alkylated DNA bases is not broadly characterized with high resolution, nor have these patterns been linked with overall quantities of modified bases in the genome. For benzo(a) pyrene (BaP), a ubiquitous environmental carcinogen, we developed a single-nucleotide resolution damage sequencing method to map in a human lung cell line the main mutagenic adduct arising from BaP. Furthermore, we combined this analysis with quantitative mass spectrometry to evaluate the dose-response profile of adduct formation. By comparing damage abundance with DNase hypersensitive sites, transcription levels, and other genome annotation data, we found that although overall adduct levels rose with increasing chemical exposure concentration, genomic distribution patterns consistently correlated with chromatin state and transcriptional status. Moreover, due to the single nucleotide resolution characteristics of this DNA damage map, we could determine preferred DNA triad sequence contexts for alkylation accumulation, revealing a characteristic DNA damage signature. This new BaP damage signature had a profile highly similar to mutational signatures identified previously in lung cancer genomes from smokers. Thus, these data provide insight on how genomic features shape the accumulation of alkylation products in the genome and predictive strategies for linking single-nucleotide resolution in vitro damage maps with human cancer mutations.

Identifiers

PMID36968528
PMCPMC10037492
OpenAlexW4321494608

What OpenQuestion holds

Textfull text, public
LicenceCC BY
measurements read22
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.