White Paper - Detecting DNA Base Modifications Using SMRT Sequencing

Traditionally, it has been a challenge to study the wide variety of base modifications that are seen in nature. Most high-throughput techniques focus only on cytosine methylation and involve both bisulfite sequencing to convert unmethylated cytosine nucleotides to uracil nucleotides, and comparison of sequence reads from bisulfite-treated and untreated samples. SMRT sequencing, in contrast, does not require base conversion within the source material in order to detect base modifications. Instead, the kinetics of base addition is measured during the normal course of sequencing. These kinetic measurements present characteristic patterns in response to a wide variety of base modifications – researchers at PacBio have been able to observe unique kinetic characteristics for over 25 base modifications.