Evidence map›Paper›PMID 41174235›Full record

ArticleNature chemical biology2026

Click-code-seq reveals strand biases of DNA oxidation and depurination in human genome.

Vakil Takhaveev, Nikolai J L Püllen, Navnit K Singh, Lucie Lefevre, Emilie A Aghajani, Sabrina M Huber, Stefan Schauer, Hailey L Gahlon, Anna R Poetsch, Shana J Sturla

Registry-linked trialAbstract read
In one paragraph

Article in Nature chemical biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07664540 (Targeting Autophagy in Depression), which is not on this map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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.

NCT07664540 nanot yet recruitingnot on this map

Targeting Autophagy in Depression: Fasting, Exercise, Diet

TypeinterventionalSponsorUniversity of ZurichRan2026 to 2029Enrolled120ConditionsDepression - Major Depressive Disorder, Overweight (BMI > 25)ArmsPerformance test
3 · Its place in the literature

Who cites it

8 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
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  8. Article
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.

Vakil TakhaveevDepartment of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland.ORCID http://orcid.org/0000-0002-3474-5241
Nikolai J L PüllenDepartment of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland.ORCID http://orcid.org/0000-0002-9446-1670
Navnit K SinghDepartment of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland.ORCID http://orcid.org/0009-0007-1837-144X
Lucie LefevreDepartment of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland.ORCID http://orcid.org/0009-0001-5527-280X
Emilie A AghajaniDepartment of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland.ORCID http://orcid.org/0009-0008-4650-7188
Sabrina M HuberDepartment of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland.
Stefan SchauerFunctional Genomics Center Zurich, ETH Zurich, University of Zurich, Zurich, Switzerland.
Hailey L GahlonDepartment of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland.
Anna R PoetschBiomedical Genomics, Biotechnology Center, Center for Molecular and Cellular Bioengineering, Technische Universität, Dresden, Germany.
Shana J SturlaDepartment of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland. sturlas@ethz.ch.ORCID http://orcid.org/0000-0001-6808-5950

Funding

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation) 185020Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation) 186332
6 · The paper itself

Abstract

DNA modifications drive aging, neurodegeneration, carcinogenesis and chemotherapy drug action. Accurate mapping of diverse DNA modifications with single-nucleotide precision in complex genomes remains challenging. We upgraded click-code-seq, a click-chemistry-aided DNA-modification mapping strategy, to enable its first application for sequencing oxidation and depurination in the human genome. We developed a companion fluorescence assay, click-fluoro-quant, to rapidly quantify common DNA modifications and novel adaptors to minimize false positives and assess modification frequency. We uncovered that endogenous DNA oxidation in a human cell line mirrors cancer mutational signatures linked to oxidative stress. The chemotherapy drug irofulven preferentially induces depurination in ApA dimers and promoters. Notably, oxidized guanines and apurinic sites, both irofulven induced and endogenous, are depleted in gene transcribed strands, with the strand bias increasing with gene expression. This work substantially advances click-code-seq for deciphering the impacts of key modifications in human DNA on cellular physiology and toxicological responses.

Indexed as

Click ChemistryDNAGenome, HumanHumansOxidation-ReductionOxidative StressDNA

Identifiers

PMID41174235
PMCPMC13128490

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Registered trials

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.