METHODS OF ASSESSING EPIGENETIC REGULATION OF GENOME FUNCTION VIA DNA METHYLATION STATUS AND SYSTEMS AND KITS THEREFOR

摘要

Systems, kits and methods are disclosed for assessing epigenetic regulation of genome function via deoxyribonucleic acid (DNA) methylation status. The systems, kits and methods rely on a covert then capture concept in which unmethylated cytosine residues in a nucleic acid sequence are first converted to uracil residues and then captured for subsequent analysis. The systems, kits and method use a solution-phase capture probe pool having a mixture of at least three (3) types of capture probes. One type is “wobble” probes, in which some cytosine residues in a nucleic acid sequence are randomly assumed to be unmethylated and thus converted to uracil residues, while other cytosine residues are assumed to be methylated and thus conserved as cytosine residues. Moreover, each type of probe can include a mixture of probes that bind/hybridize to one or the other strand of a nucleic acid sequence of interest, thereby improving sequencing depth and reliability.