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Multimodal Epigenetic Sequencing Analysis (MESA) of Cell-free DNA for Non-invasive Cancer Detection

ABSTRACT: Multimodal characterization of cell-free DNA (cfDNA) in the blood can enable the sensitive and non-invasive detection of human cancers but remains technically challenging and costly. Here, we developed Multimodal Epigenetic Sequencing Analysis (MESA), a flexible and sensitive method of capturing and integrating multimodal epigenetic information of cfDNA using a single experimental assay, i.e., non-disruptive bisulfite-free methylation sequencing, such as Enzymatic Methyl-seq (EM-seq) and TET-assisted pyridine borane sequencing (TAPS). MESA can simultaneously infer cfDNA methylation, nucleosome occupancy, nucleosome fuzziness, and fragmentation profile for regions surrounding the promoters and polyadenylation sites (PASs). MESAÃ¢Â€Â™s integrated analysis of multimodal epigenetic features significantly improved the performance of cancer detection models compared to the usage of any single modality alone. MESA captures additional and highly complementary epigenetic information from cfDNA without additional experimental assays, highlighting the importance and clinical prospect of using multimodal epigenetic features for non-invasive cancer detection

PROVIDER: EGAS00001006462 | EGA |

REPOSITORIES: EGA

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Multiplex 5mC Marker Barcode Counting (MMBC-seq): A sensitive detection method for cell-free DNA methylation

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Heat selection enables highly scalable methylome profiling in cell-free DNA for noninvasive monitoring of cancer patients [CRC]

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