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| 082 | _ | _ | |a 610 |
| 100 | 1 | _ | |a Smith, Kyle S |b 0 |
| 245 | _ | _ | |a M-PACT leverages cell-free DNA methylomes to achieve robust classification of pediatric brain tumors. |
| 260 | _ | _ | |a London |c 2026 |b Nature Research |
| 336 | 7 | _ | |a article |2 DRIVER |
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| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1771505206_3004206 |2 PUB:(DE-HGF) |
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| 500 | _ | _ | |a #EA:B062# / #DKTKZFB26# / #NCTZFB26# / epub |
| 520 | _ | _ | |a 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. |
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| 700 | 1 | _ | |a Fischer, Tom |0 P:(DE-He78)d95caa04c2f0929079004f117746b1e1 |b 1 |e First author |u dkfz |
| 700 | 1 | _ | |a Han, Katie |b 2 |
| 700 | 1 | _ | |a Kostecka, Anna |b 3 |
| 700 | 1 | _ | |a Lin, Hong |b 4 |
| 700 | 1 | _ | |a Senfter, Daniel |b 5 |
| 700 | 1 | _ | |a Soliman, Taha |0 0000-0003-3185-3092 |b 6 |
| 700 | 1 | _ | |a Stepien, Natalia |b 7 |
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| 700 | 1 | _ | |a Madlener, Sibylle |0 0000-0001-7099-9997 |b 11 |
| 700 | 1 | _ | |a Haberler, Christine |0 0000-0003-1016-0545 |b 12 |
| 700 | 1 | _ | |a Dhanda, Sandeep K |0 0000-0003-1381-7434 |b 13 |
| 700 | 1 | _ | |a Upadhyaya, Santhosh A |b 14 |
| 700 | 1 | _ | |a Blackburn, Patrick R |0 0000-0003-0658-1275 |b 15 |
| 700 | 1 | _ | |a Schmook, Maria T |b 16 |
| 700 | 1 | _ | |a de Bont, Judith |b 17 |
| 700 | 1 | _ | |a Haapasalo, Hannu |0 0000-0003-4389-7391 |b 18 |
| 700 | 1 | _ | |a Dargvainiene, Justina |b 19 |
| 700 | 1 | _ | |a Leypoldt, Frank |b 20 |
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| 700 | 1 | _ | |a Hulleman, Esther |0 0000-0001-9256-947X |b 22 |
| 700 | 1 | _ | |a Orr, Brent A |0 0000-0003-0997-4728 |b 23 |
| 700 | 1 | _ | |a Gajjar, Amar |0 0000-0001-5019-0699 |b 24 |
| 700 | 1 | _ | |a Robinson, Giles W |0 0000-0001-7441-9486 |b 25 |
| 700 | 1 | _ | |a Haapasalo, Joonas |b 26 |
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| 700 | 1 | _ | |a Gojo, Johannes |b 28 |
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| 700 | 1 | _ | |a Northcott, Paul A |0 0000-0002-1220-5252 |b 31 |
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