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Record W4415147988 · doi:10.1038/s41467-025-64153-z

Analysis of cfDNA fragmentomics metrics and commercial targeted sequencing panels

2025· article· en· W4415147988 on OpenAlexaff
Kyle T. Helzer, Marina N. Sharifi, Jamie M. Sperger, Matthew R. Chrostek, Matthew L. Bootsma, Shannon R. Reese, Amy K. Taylor, Hannah M. Krause, Jennifer L. Schehr, Nan Sethakorn, David Kosoff, Christos E. Kyriakopoulos, Michael Bassetti, Grace C. Blitzer, John M. Floberg, Martin Sjöström, Andrew J. Armstrong, Himisha Beltran, Rana R. McKay, Felix Y. Feng, Ruth O’Regan, Kari B. Wisinski, Hamid Emamekhoo, Alexander W. Wyatt, Joshua M. Lang, Shuang G. Zhao

Bibliographic record

VenueNature Communications · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCancer Genomics and Diagnostics
Canadian institutionsCanada's Michael Smith Genome Sciences CentreUniversity of British Columbia
FundersSchool of Medicine and Public Health, University of Wisconsin-MadisonNational Cancer InstituteNational Institutes of HealthU.S. Department of Health and Human ServicesProstate Cancer FoundationNational Institute of General Medical SciencesMovember FoundationUniversity of Wisconsin Carbone Cancer CenterU.S. Department of Defense
KeywordsDNA sequencingExonGenomeCancer genome sequencingGenomicsEpigeneticsDeep sequencingGene

Abstract

fetched live from OpenAlex

Fragmentomics based analysis of cell-free DNA (cfDNA) has recently emerged as a method to infer epigenetic and transcriptional data. Many of these reports analyze whole genome sequencing (WGS) which is not readily available clinically. Targeted exon panels are used for clinical cfDNA variant calling. In this report, we conduct an investigation of multiple published fragmentomics methods for WGS, but on cancer exon panels. We find that strategies utilizing normalized depth metrics, as well as all exons present on the panel, generally allow for better prediction of cancer phenotypes across a range of tumor fractions, though other metrics work particularly well in specific applications. Additionally, genes from commercial clinical targeted sequencing panels could be similarly employed for cancer phenotyping with a minimal decrease in performance despite their smaller genomic coverage. These results suggest that fragmentomics-based analysis of cfDNA can utilize targeted sequencing panels and does not necessarily require additional WGS.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.003
metaresearch head score (Gemma)0.011
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.018

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0030.011
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0020.002
Science and technology studies0.0000.000
Scholarly communication0.0010.001
Open science0.0010.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.017
GPT teacher head0.308
Teacher spread0.291 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations6
Published2025
Admission routes1
Has abstractyes

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Same venueNature CommunicationsSame topicCancer Genomics and DiagnosticsFrench-language works237,207