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Looking Ahead: The 2013 PacBio Technology Roadmap

Wednesday, January 9, 2013

By Jonas Korlach, Chief Scientific Officer

With our minds turning to what 2013 has in store for us,
it’s a good opportunity to look ahead to the advances you can expect in Single
Molecule, Real-Time (SMRT®)
Sequencing. We have many improvements coming to the PacBio® RS and we hope you’ll find them as
exciting as we do.
As many of you know, we released a number of upgrades at
the end of 2012 to improve the PacBio RS
platform, including a new loading system that reduces the amount of sample
required and the new XL chemistry that boosts average read lengths up to 5,000
bases. In 2013, our R&D team is striving to continue optimization of
sequencing performance in three major areas: read length, accuracy, and
throughput. In addition, advances in sample preparation will help widen the
application spaces for SMRT Sequencing. Enhanced data analysis workflows, through
several software upgrades for applications such as de novo assembly and base
modification detection, will make the interpretation of SMRT sequencing data
more efficient.
During the first half of this year, we expect to release
a hardware upgrade that doubles the number of zero-mode waveguides (ZMWs) that
can be interrogated simultaneously, boosting the number to 150,000. That will
immediately offer up to a 2x improvement in throughput compared to previous
long-movie sequencing runs.
Also in the works: we are developing a protective
scaffold between the fluorescent dye and the nucleotide that minimizes
photodamaging effects the dye may exert on the sequencing polymerase. Such
photodamage can reduce read lengths, and our results in R&D from the new,
photo-protected nucleotides are very promising. We believe this advance will allow
average read lengths of 7,000 to 9,000 bases — roughly another doubling of the
read lengths compared to our newly released XL chemistry.
In combination, these improvements should let users
generate 0.5 to 1 gigabases per SMRT Cell, depending on the sequencing mode — a
truly impressive figure, given that just a year ago we released a chemistry
that offered ~100 megabases per SMRT Cell. This tremendous increase in
throughput will make it possible to consider new applications for the PacBio RS, such as routine de novo sequencing of more complex genomes, like human. For
microbial sequencing applications, a new paradigm of ‘one SMRT Cell equals one de novo genome and epigenome’ is within
reach.
I recently discussed this technology roadmap at a
workshop hosted by Stanford University; check out the video for more data.
Finally, I’d like to wish everyone a happy and healthy
new year. May 2013 treat you well!

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