Base Modification Detection

Automatically detect DNA base modifications such as methylation on the PacBio RS II

DNA base modifications are important to the understanding of biological processes such as gene expression, host-pathogen interactions, DNA damage, and DNA repair. Traditionally, it has been difficult for scientists to study the more than 20 types of base modifications that occur in nature. Most studies to date have focused solely on cytosine methylation using indirect detection methods. Given the central role of base modifications in a wide variety of natural and disease processes, the ability to detect these changes is key to a more complete understanding of biological function.

Single molecule, real-time (SMRT) Analysis software works by measuring the rate of DNA base incorporation during sequencing. This information, automatically gathered during the sequencing process, is a unique feature of our SMRT technology. Free SMRT Analysis software identifies locations of adenine and cytosine methylation, and reports methyltransferase recognition motifs throughout a bacterial genome.


  • Integrated sequence and chemical modification detection - epigenetic and other base modification data are gathered in the sequencing process, as an integral part of the sequencing workflow
  • Resolve strand-specific modifications - unamplified double-stranded input DNA enables detection of strand-specific modifications such as hemimethylation
  • Hypothesis-free detection - no prior knowledge of the modification is needed, allowing discovery of unknown or unexpected modifications, and those that are undetectable with other sequencing technologies

  • Tutorial - Bacterial Assembly and Methylome Analysis using SMRT Portal (10 min video)
  • Virtual Poster - Detecting Base Modifications with SMRT Sequencing, Jonas Korlach (Pacific Biosciences)
  • Virtual Poster - Detection of Damaged DNA Bases Using SMRT Sequencing, Tyson Clark (Pacific Biosciences)
  • Webinar - Comprehensive methylome analysis of the human gastric pathogen, Helicobacter pylori, Sebastian Suerbaum (Hannover Medical School)
  • Webinar - Dynamic Chromosome Methylation Controls Cell Cycle Progression, Lucy Shapiro (Stanford University)
  • Webinar Epigenetic Analysis of Salmonella and other Bacteria of Public Health Importance, Peter Evans (US FDA, CFSAN)
  • Webinar - Genomics in Food Security: 100k Pathogen Genome Project, Bart Weimer (UC Davis)
  • Webinar - Introduction to Studying Whole Genome Microbial Epigenetics, Jonas Korlach (Pacific Biosciences)
  • Webinar - Large-Scale Analysis of Restriction-Modification in Systems Using SMRT Sequencing, Brian Anton (New England BioLabs)
  • Webinar - Phasevarions - Phase Variation of Type III DNA Methyltransferases Controls Coordinated Switching in Multiple Genes, Michael Jennings (Griffith University)
  • Webinar Studying Whole-Genome Pheumococcal Epigenetics, Garth Ehrlich (Allegheny-Singer Research Institute)
  • Webinar The Methylome and Virulence of Bovine Respiratory Disease Bacterial Pathogens, Greg Harhay (USDA-ARS-USMARC)
  • Webinar - The Role of Adenine Methylation in Determining the Pathogenicity of a Bacteria, Eric Schadt (Mt. Sinai School of Medicine)
  • Brochure: PacBio RS II Sequencing System
  • Case Study: Beyond Four Bases - Epigenetic Modifications Prove Critical to Understanding E. coli Outbreak
  • Primer: The Value of Finished Bacterial Genomes
  • Software: Tools to Perform Bacterial Methylome Motif Analysis
  • Technical Note: Performing Bacterial Methylome Analysis with SMRT Sequencing
  • White Paper: Detecting DNA Base Modifications Using Single Molecule, Real-Time Sequencing
  • Poster: Automated, Non-Hybrid De Novo Genome Assemblies and Epigenomes of Bacterial Pathogens, Tyson Clark (Pacific Biosciences)
  • Poster: Comparative Genomics of Shiga Toxin-Producing E. Coli 0145:H28 Strains Associated with the 2007 Belgium and 2010 US Outbreaks, Kerry Cooper (USDA)
  • Poster: Direct Sequencing and Identification of Damaged DNA Bases, Tyson Clark (Pacific Biosciences)
  • Poster: Exploiting Single Molecule Real-Time DNA Sequencing for Improved Genome Assembly and Methylome Analysis, Tyson Clark (Pacific Biosciences)
  • Poster: Harnessing Kinetic Information on a Single Molecule Real-Time Sequencing, Jonas Korlach (Pacific Biosciences)