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

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…

• BT
  Brain Tumor Funders' Collaborative

  Award: BTFC2025-Northcott
• SB
  St. Baldrick's Foundation