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cfMethyl-seq technology – a novel NGS solution to profile the cfDNA methylome.

cfMethyl-seq Technology

Cell-free DNA (cfDNA) methylation has been demonstrated to be one of the most informative biomarkers for cancer detection. However, Whole-Genome Bisulfite Sequencing (WGBS) of cfDNA is costly.  In collaboration with our founding team at UCLA, we developed the cell-free DNA Methylome Sequencing (cfMethyl-seq) technology for the cost-effective profiling of genome-wide methylation in cfDNA. cfMethyl-seq lowers the cost by sequencing only CpG-rich cfDNA fragments.  cfMethyl-Seq offers a 12.8× enrichment in CpG islands over WGBS. Note that the traditional method, Reduced Representation Bisulfite Sequencing (RRBS), can also enrich CpG-rich regions—but only from intact genomic DNA, not from cfDNA.

Applying cfMethyl-Seq to 408 colon, liver, lung, and stomach cancer patients and controls, at the specificity of 97.9% we achieve a sensitivity of 80.7% in detecting all-stage cancer and a sensitivity of 74.5% in detecting early-stage (I and II) cancers, and an accuracy of 89.1% for locating the Tissue-Of-Origin (TOO) of all-stage cancer and of 85.0% for early-stage cancer.

For details, please refer to the full paper. Stackpole ML. et al., Nature Communications 2022 Sep 29;13:5566.

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