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000309923 1001_ $$aSmith, Kyle S$$b0
000309923 245__ $$aM-PACT leverages cell-free DNA methylomes to achieve robust classification of pediatric brain tumors.
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000309923 520__ $$aCerebrospinal 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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000309923 7001_ $$aHan, Katie$$b2
000309923 7001_ $$aKostecka, Anna$$b3
000309923 7001_ $$aLin, Hong$$b4
000309923 7001_ $$aSenfter, Daniel$$b5
000309923 7001_ $$00000-0003-3185-3092$$aSoliman, Taha$$b6
000309923 7001_ $$aStepien, Natalia$$b7
000309923 7001_ $$0P:(DE-He78)8477f8350b8bfb2a9af7e0be9e272c07$$aVolz, Stefanie$$b8$$udkfz
000309923 7001_ $$0P:(DE-He78)ea34e980776660c55815059cb8015f59$$aSchwarz, Nathalie$$b9$$udkfz
000309923 7001_ $$0P:(DE-He78)73c8cbd36c9b5a386838ad737a401dac$$aWedig, Tatjana$$b10$$udkfz
000309923 7001_ $$00000-0001-7099-9997$$aMadlener, Sibylle$$b11
000309923 7001_ $$00000-0003-1016-0545$$aHaberler, Christine$$b12
000309923 7001_ $$00000-0003-1381-7434$$aDhanda, Sandeep K$$b13
000309923 7001_ $$aUpadhyaya, Santhosh A$$b14
000309923 7001_ $$00000-0003-0658-1275$$aBlackburn, Patrick R$$b15
000309923 7001_ $$aSchmook, Maria T$$b16
000309923 7001_ $$ade Bont, Judith$$b17
000309923 7001_ $$00000-0003-4389-7391$$aHaapasalo, Hannu$$b18
000309923 7001_ $$aDargvainiene, Justina$$b19
000309923 7001_ $$aLeypoldt, Frank$$b20
000309923 7001_ $$0P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9$$aPfister, Stefan$$b21$$udkfz
000309923 7001_ $$00000-0001-9256-947X$$aHulleman, Esther$$b22
000309923 7001_ $$00000-0003-0997-4728$$aOrr, Brent A$$b23
000309923 7001_ $$00000-0001-5019-0699$$aGajjar, Amar$$b24
000309923 7001_ $$00000-0001-7441-9486$$aRobinson, Giles W$$b25
000309923 7001_ $$aHaapasalo, Joonas$$b26
000309923 7001_ $$aNordfors, Kristiina$$b27
000309923 7001_ $$aGojo, Johannes$$b28
000309923 7001_ $$0P:(DE-He78)a7c1bbac024fa232d9c6b78443328d9d$$aPajtler, Kristian$$b29$$udkfz
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000309923 7001_ $$00000-0002-1220-5252$$aNorthcott, Paul A$$b31
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