Evidence map›Paper›PMID 42130071›Full record

ArticleNucleic acids research2026

Enriched methylomes of low-input and fragmented DNA using fragment ligation EXclusive methylation sequencing.

Jingru Yu, Lauren S Ahmann, Yvette Y Yao, Angus Toland, Alicia Snowden, Chandler Ho, Netanel Loyfer, Tommy Kaplan, Hannes Vogel, Linlin Wang and 4 more

Abstract read
In one paragraph

Article in Nucleic acids research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. Adapting Clinical Chemistry Plasma as a Source for Liquid Biopsies.medRxiv : the preprint server for health sciences · 2026
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

Jingru YuDepartment of Pathology, School of Medicine, Stanford University, Stanford, CA 94305, United States.ORCID 0000-0002-4157-4647
Lauren S AhmannDepartment of Pathology, School of Medicine, Stanford University, Stanford, CA 94305, United States.
Yvette Y YaoDepartment of Pathology, School of Medicine, Stanford University, Stanford, CA 94305, United States.
Angus TolandDepartment of Pathology, School of Medicine, Stanford University, Stanford, CA 94305, United States.
Alicia SnowdenCollege of Medicine, Howard University, Washington, DC 20059, United States.
Chandler HoClinical Laboratories, Stanford Health Care, Stanford, CA 94305, United States.
Netanel LoyferSchool of Computer Science and Engineering, The Hebrew University of Jerusalem, Jerusalem 9190501, Israel.
Tommy KaplanSchool of Computer Science and Engineering, The Hebrew University of Jerusalem, Jerusalem 9190501, Israel.ORCID 0000-0002-1892-5461
Hannes VogelDepartment of Pathology, School of Medicine, Stanford University, Stanford, CA 94305, United States.
Linlin WangDepartment of Laboratory Medicine, School of Medicine, University of California San Francisco, San Francisco, CA 94143, United States.
Brooke E HowittDepartment of Pathology, School of Medicine, Stanford University, Stanford, CA 94305, United States.
Brittany HolmesDepartment of Pathology, School of Medicine, Stanford University, Stanford, CA 94305, United States.
Alarice Cheng-Yi LoweDepartment of Pathology, School of Medicine, Stanford University, Stanford, CA 94305, United States.
Wei GuDepartment of Pathology, School of Medicine, Stanford University, Stanford, CA 94305, United States.ORCID 0000-0002-2480-6645

Funding

Noninvasive Risk Stratification of Prostate Cancer Using Cell-Free Nucleic AcidsK08CA230156 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GU, WEI · 2018 to 2022
$1.4M
Burroughs-Wellcome CAMS AwardDOD HT94252310894NCI NIH HHS K08 CA230156NIH HHS CA230156
6 · The paper itself

Abstract

Epigenetic profiling is an emerging clinical tool for tumor profiling and liquid biopsies. Here, we developed Fragment Ligation EXclusive methylation sequencing (FLEXseq), a genome-wide methylation profiler that enriches and sequences the DNA fragments flanking CCGG motifs to cover a broad range of regulatory regions. FLEXseq strongly correlates with whole genome bisulfite sequencing (WGBS; Pearson's r = 0.97) yet requires only three- to seven-fold less sequencing depth than whole genome approaches to cover cell type-specific markers and 4- to 20-fold less sequencing to cover key regulatory regions like promoters. DNA dilutions down to 250 pg decreased CpG coverage, but bias in methylation remained low (Pearson's r ≥ 0.90). To demonstrate the broad applicability of FLEXseq, including highly fragmented DNA found in clinical specimens, we verified its usage across cells, body fluids, and formalin-fixed paraffin-embedded (FFPE) tissues. Across 106 cerebrospinal fluids, a specimen type challenged by low-input and fragmented DNA, FLEXseq enabled cell type deconvolution to distinguish between different tumor types and negative controls with an accuracy of 97%. FLEXseq offers a cost-efficient, single-nucleotide resolution approach to profile the methylome even with fragmented, low-input DNA.

Indexed as

DNADNA MethylationEpigenomeSequence Analysis, DNACpG IslandsHigh-Throughput Nucleotide SequencingHumansNeoplasmsDNA

Identifiers

PMID42130071
PMCPMC13171454

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.