Evidence map›Paper›PMID 41309586›Full record

ArticleNature communications2025

Enabling whole genome sequencing analysis from FFPE specimens in clinical oncology.

Dylan Domenico, Gunes Gundem, Max F Levine, Juan Esteban Arango-Ossa, Pauline Robbe, Georgios Asimomitis, Cassidy Cobbs, Emily Stockfisch, Tara O'Donohue, Charlotte Brierley and 13 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

23 authors.

Dylan DomenicoDepartment of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Gunes GundemDepartment of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID http://orcid.org/0000-0002-0070-9859
Max F LevineDepartment of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID http://orcid.org/0000-0001-5156-9086
Juan Esteban Arango-OssaDepartment of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID http://orcid.org/0000-0003-1109-6178
Pauline RobbeRIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
Georgios AsimomitisDepartment of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID http://orcid.org/0000-0002-9479-5451
Cassidy CobbsIntegrated Genomics Operation Core, Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID http://orcid.org/0000-0003-4465-8894
Emily StockfischDepartment of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Tara O'DonohueDepartment of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Charlotte BrierleyMedical Research Council Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
Janine SenzDepartment of Molecular Oncology, BC Cancer, Vancouver, BC, Canada.
Dawn CochraneDepartment of Molecular Oncology, BC Cancer, Vancouver, BC, Canada.
Neeman MohibullahIntegrated Genomics Operation Core, Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Umesh BhanotDepartment of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID http://orcid.org/0000-0001-6656-1239
Joachim SilberDepartment of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Neerav ShuklaDepartment of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Sohrab P ShahHalvorsen Center for Computational Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID http://orcid.org/0000-0001-6402-523X
Britta WeigeltDepartment of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID http://orcid.org/0000-0001-9927-1270
Oliver ZivanovicGynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Andrew McPhersonHalvorsen Center for Computational Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID http://orcid.org/0000-0002-5654-5101
Anna SchuhOxford Molecular Diagnostics Centre, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0002-3938-8490
Andrew L KungDepartment of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID http://orcid.org/0000-0002-9091-488X
Elli PapaemmanuilDepartment of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA. papaemme@mskcc.org.ORCID http://orcid.org/0000-0003-1709-8983

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4M
NCI NIH HHS P30 CA008748
6 · The paper itself

Abstract

The adoption of whole genome sequencing (WGS) in clinical oncology is challenged by low data quality and increased artifacts in standard-of-care formalin-fixed paraffin-embedded (FFPE) samples. Analysis of 56 fresh frozen (FF) and FFPE matched pairs demonstrates that FFPE processing results in a median 20-fold enrichment in artifactual calls across mutation classes and impairs detection of clinically relevant biomarkers such as homologous recombination deficiency (HRD). We demonstrate that implementation of consensus calling reduces artifactual structural variant (SV) calls by 98% but is not sufficient in mitigating artifactual calls for single nucleotide variants (SNVs) and indels as compared to FF data. We develop FFPErase, a machine learning framework that filters SNV/indel artifacts and delivers clinical grade variant reporting allowing accurate quantification of clinically relevant biomarkers. Comparison of FFPErase WGS calls to clinical reporting by FDA-approved panel tests demonstrates 99% sensitivity and enables reporting of 24% more clinically relevant findings.

Indexed as

Medical OncologyNeoplasmsWhole Genome SequencingArtifactsBiomarkers, TumorFormaldehydeGenome, HumanHumansINDEL MutationMachine LearningMutationParaffin EmbeddingPolymorphism, Single NucleotideTissue FixationBiomarkers, TumorFormaldehyde

Identifiers

PMID41309586
PMCPMC12661053

What OpenQuestion holds

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Registered trials

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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.