COBRA-seq: Sensitive and Quantitative Methylome Profiling

We describe two versions of COBRA-seq: First, Genome-Wide COBRA (GW-COBRA) that uses PCR to exponentially amplify the sequencing library fragments after linker ligation. Second, Linear Amplification COBRA (LA-COBRA) that relies on T7 RNA polymerase-mediated transcription yielding many RNA transcripts of the library fragments generated in a linear manner which are subsequently converted to cDNA. The COBRA-seq library protocol is largely adapted to provide robust coverage of the human genome, however, all of the steps are applicable to both model and non-model organisms.