New Publication from Drs. He, Lupien and Pugh
MBP researchers Dr. Hansen He, Dr. Mathieu Lupien and Dr. Trevor Pugh have co-authored a new Nature Cancer paper entitled 'A pan-cancer compendium of 1,294 plasma cell-free DNA methylomes and fragmentomes enabling multicancer detection'.
The paper includes collaboration from fellow MBP scientists Dr. Scott Bratman, Dr. Daniel DeCarvalho, Dr. Michael Hoffman, Dr. Benjamin Lok and Dr. Faiyaz Notta.
Article Abstract
Cell-free DNA analysis via methylation and fragmentation profiling hasadvanced minimally invasive cancer detection; however, broader applicationhas been limited by small cohorts and inconsistent data processing. Herewe collated 1,074 cfMeDIP-seq profiles across 9 studies, comprising cancersamples from 11 cancer types, carriers of Li-Fraumeni syndrome and healthycontrols. We developed a uniform computational workflow to mitigatetechnical and biological confounders across cohorts. This analysis identified14,202 pancancer differentially methylated regions for cancer detection,along with cancer-specific markers for subtype monitoring. Fragmentomicprofiling revealed distinguishing differences in 5′ end motifs, fragmentlengths and nucleosome footprints across cancers. Integrating methylomeand fragmentome features enhanced cancer detection and classification.Validation in 220 independent samples, including 3 cancer types absent fromthe primary dataset, confirmed the robustness of our findings. Altogether,this work provides a pancancer cell-free DNA resource of 1,294 samples tosupport future methylome and fragmentome studies.