Multimodal analysis of cell-free DNA whole-genome sequencing for pediatric cancers with low mutational burden

Abstract Sequencing of cell-free DNA in the blood cancer patients (liquid biopsy) provides attractive opportunities for early diagnosis, assessment treatment response, and minimally invasive disease monitoring. To unlock liquid biopsy analysis pediatric tumors with few genetic aberrations, we introduce an integrated genetic/epigenetic method demonstrate its utility on 241 deep whole-genome sequencing profiles 95 Ewing sarcoma 31 other sarcomas. Our achieves sensitive detection classification circulating tumor peripheral independent any alterations. Moreover, benchmark different metrics fragmentation analysis, LIQUORICE algorithm detecting based cancer-specific chromatin signatures. Finally, combine several fragmentation-based into machine learning classifier that exploits widespread epigenetic deregulation is tailored to cancers low mutation rates. Clinical associations highlight potential value cfDNA patterns as prognostic biomarkers sarcoma. In summary, our study a comprehensive beyond recurrent it renders benefits more readily accessible childhood cancers.