Evidence map›Paper›PMID 41703322›Full record

ArticleNature cancer2026

M-PACT leverages cell-free DNA methylomes to achieve robust classification of pediatric brain tumors.

Kyle S Smith, Tom T Fischer, Katie Han, Anna Kostecka, Hong Lin, Daniel Senfter, Taha Soliman, Natalia Stepien, Stefanie Volz, Nathalie Schwarz and 22 more

Abstract read
In one paragraph

Article in Nature cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the 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.

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

8 citing papers in PubMed.

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

32 authors.

Kyle S Smith *Center of Excellence in Neuro-Oncology Sciences (CENOS), St. Jude Children's Research Hospital, Memphis, TN, USA.
Tom T Fischer *Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany.ORCID http://orcid.org/0000-0002-2138-9102
Katie Han *Center of Excellence in Neuro-Oncology Sciences (CENOS), St. Jude Children's Research Hospital, Memphis, TN, USA.
Anna KosteckaCenter of Excellence in Neuro-Oncology Sciences (CENOS), St. Jude Children's Research Hospital, Memphis, TN, USA.
Hong LinCenter of Excellence in Neuro-Oncology Sciences (CENOS), St. Jude Children's Research Hospital, Memphis, TN, USA.
Daniel SenfterDepartment of Pediatrics and Adolescent Medicine, Comprehensive Center for Pediatrics and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
Taha SolimanCenter of Excellence in Neuro-Oncology Sciences (CENOS), St. Jude Children's Research Hospital, Memphis, TN, USA.ORCID http://orcid.org/0000-0003-3185-3092
Natalia StepienDepartment of Pediatrics and Adolescent Medicine, Comprehensive Center for Pediatrics and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
Stefanie VolzHopp Children's Cancer Center (KiTZ), Heidelberg, Germany.
Nathalie SchwarzHopp Children's Cancer Center (KiTZ), Heidelberg, Germany.
Tatjana WedigHopp Children's Cancer Center (KiTZ), Heidelberg, Germany.
Sibylle MadlenerDepartment of Pediatrics and Adolescent Medicine, Comprehensive Center for Pediatrics and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.ORCID http://orcid.org/0000-0001-7099-9997
Christine HaberlerDepartment of Neurology, Division of Neuropathology and Neurochemistry, Medical University of Vienna, Vienna, Austria.ORCID http://orcid.org/0000-0003-1016-0545
Sandeep K DhandaDepartment of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA.ORCID http://orcid.org/0000-0003-1381-7434
Santhosh A UpadhyayaDepartment of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Patrick R BlackburnDepartment of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA.ORCID http://orcid.org/0000-0003-0658-1275
Maria T SchmookDivision of Neuroradiology and Musculoskeletal Radiology, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria.
Judith de BontDepartments of Pediatric Oncology/Hematology, Cancer Center Amsterdam, Amsterdam University Medical Centers, Amsterdam, The Netherlands.
Hannu HaapasaloDepartment of Pathology, Fimlab Laboratories Ltd, Tampere, Finland.ORCID http://orcid.org/0000-0003-4389-7391
Justina DargvainieneInstitute of Clinical Chemistry, University Hospital Schleswig-Holstein, Kiel/Lübeck, Kiel, Germany.
Frank LeypoldtInstitute of Clinical Chemistry, University Hospital Schleswig-Holstein, Kiel/Lübeck, Kiel, Germany.
Stefan M PfisterHopp Children's Cancer Center (KiTZ), Heidelberg, Germany.ORCID http://orcid.org/0000-0002-5447-5322
Esther HullemanDepartments of Pediatric Oncology/Hematology, Cancer Center Amsterdam, Amsterdam University Medical Centers, Amsterdam, The Netherlands.ORCID http://orcid.org/0000-0001-9256-947X
Brent A OrrDepartment of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA.ORCID http://orcid.org/0000-0003-0997-4728
Amar GajjarDepartment of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA.ORCID http://orcid.org/0000-0001-5019-0699
Giles W RobinsonDepartment of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA.ORCID http://orcid.org/0000-0001-7441-9486
Joonas HaapasaloDepartment of Pathology, Fimlab Laboratories Ltd, Tampere, Finland.
Kristiina NordforsTampere Center for Child, Adolescent, and Maternal Health Research, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
Johannes GojoDepartment of Pediatrics and Adolescent Medicine, Comprehensive Center for Pediatrics and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.ORCID http://orcid.org/0000-0002-8113-3416
Kristian W PajtlerHopp Children's Cancer Center (KiTZ), Heidelberg, Germany.ORCID http://orcid.org/0000-0002-3562-6121
Kendra K MaassHopp Children's Cancer Center (KiTZ), Heidelberg, Germany.
Paul A NorthcottCenter of Excellence in Neuro-Oncology Sciences (CENOS), St. Jude Children's Research Hospital, Memphis, TN, USA. paul.northcott@stjude.org.ORCID http://orcid.org/0000-0002-1220-5252

Funding

Viral Vector Technology (VVTSR)P30CA021765 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI Shondra Michelle Miller · 1985 to 2026
$166.9M
Brain Tumor Funders' Collaborative (BTFC) BTFC2025-NorthcottNCI NIH HHS P30 CA021765St. Baldrick's Foundation (St. Baldrick's Foundation, Inc) Robert J. Arceci Innovation Award
6 · The paper itself

Abstract

Cerebrospinal fluid (CSF) liquid biopsies serve as a rich source of tumor-derived cell-free DNA (cfDNA) for evaluating persons with central nervous system (CNS) tumors. However, challenges stemming from trace cfDNA yields and low mutational burden have hindered sensitivity, whereas first-generation clinical assays have relied on genetic alterations as biomarkers. Leveraging the diagnostic utility of DNA methylation classification in CNS tumors, we developed M-PACT (methylation-based predictive algorithm for CNS tumors), a robust deep neural network that accurately classifies tumors from subnanogram-input cfDNA methylomes. Across embryonal CNS tumor benchmarking (n = 79) and validation (n = 58) cohorts, M-PACT achieved 92% and 88% accuracy, respectively. We further showcase M-PACT utility in nonembryonal CNS tumors, balanced tumor genomes and nonmalignant CSF. Beyond classification, this workflow enables methylation-based cellular deconvolution and sensitive copy-number variation detection. Altogether, we provide a blueprint for CNS tumor classification from low-input cfDNA methylomes, motivating prospective validation for future clinical implementation.

Indexed as

Biomarkers, TumorBrain NeoplasmsCell-Free Nucleic AcidsDNA MethylationAlgorithmsChildDNA Copy Number VariationsHumansNeural Networks, ComputerBiomarkers, TumorCell-Free Nucleic Acids

Identifiers

PMID41703322
PMCPMC13128451

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.