PacBio’s Sequel system is based on the same SMRT technology behind the RS II, with a number of improvements. Although we’ve gone over SMRT sequencing chemistry and yield in depth in another blog post, here’s an overview: Single Molecule Real Time (SMRT) sequencing relies on a couple of key innovations. The first of these is a novel approach to phospho-labeling nucleotides. PacBio label their nucleotides on the terminal phosphate that is cleaved during the synthesis reaction. What remains is a completely “natural” DNA double helix. In order to observe this reaction, and actually, perform the base-calling, the polymerase is confined to a nanophotonic chamber - dubbed the Zero-Mode Waveguide (ZMW). This 70nM chamber can observe and quantify the excitation of the phosphate during incorporation. The sequence can consequently be read due to each of the four nucleotides having a distinct fluorescent label.
 Hashmi, Uzair, et al. "Plant exomics: concepts, applications, and methodologies in crop improvement." Plant signaling & behavior 10.1 (2015): e976152.
 Wenger, Aaron, et al. "Structural variant detection with low-coverage PacBio sequencing." Nature 517.7536: 608-611.
 Davis, Brigid M., Michael C. Chao, and Matthew K. Waldor. "Entering the era of bacterial epigenomics with single molecule real-time DNA sequencing." Current opinion in microbiology 16.2 (2013): 192-198.
Ashby, Meredith, et al. "Simplified sequencing of full-length isoforms in cancer on the PacBio Sequel System." (2017): 2442-2442.
Tedersoo, Leho, Ave Tooming‐Klunderud, and Sten Anslan. "PacBio metabarcoding of Fungi and other eukaryotes: errors, biases and perspectives." New Phytologist 217.3 (2018): 1370-1385.
Rhoads, Anthony, and Kin Fai Au. "PacBio sequencing and its applications." Genomics, proteomics & Bioinformatics 13.5 (2015): 278-289.