Pacific Biosciences Releases Software Upgrade to Support Full-Length
Transcript Sequencing and HLA Haplotype Phasing
MENLO PARK, Calif., March 31, 2014 (GLOBE NEWSWIRE) -- Pacific Biosciences of
California, Inc., (Nasdaq:PACB) provider of the PacBio^® RS II, today
announced the release of a software upgrade for its Single Molecule, Real-Time
(SMRT^®) DNA Sequencing platform. SMRT Analysis 2.2 provides enhanced
functionality to support two additional applications that uniquely benefit
from the company's long-read sequencing technology: Iso-Seq™ full-length
transcript/isoform sequencing, and human leukocyte antigen (HLA) haplotype
The study of mRNA transcript isoforms has been challenging due to the short
read lengths of other sequencing technologies. Long PacBio reads enable
full-length transcript sequencing, as well as the identification of
alternatively spliced forms of a gene. As a result, new genes and isoforms are
accessible for study.
For example, Steve Quakeand Thomas Südhof,Professors at Stanford University
and Investigators with the Howard Hughes Medical Institute, together with
colleagues, used SMRT Sequencing to characterize the genes encoding neurexins,
which are involved in the formation of connections between cells in the human
brain^i. Because of the high number of different splice isoforms, these genes
have been extremely difficult to study and, despite extensive efforts, the
full extent of neurexin alternative splicing remained unclear. Using PacBio
long-read sequencing, the researchers identified hundreds of different
isoforms in the neurexin gene family, highlighting a staggering complexity of
these gene products and providing more insight to the notion that neurexins
function as recognition molecules that contribute to the specification of cell
connections in the brain.
The Iso-Seq application can also be used for transcriptome-wide studies,
improving the ability to annotate genes in reference genomes. Long sequence
reads spanning full-length gene transcripts will eliminate the need for an
RNA-seq assembly step, providing more complete gene models and more
comprehensive annotation of transcribed genes.
Michael Snyder's lab atStanford University demonstrated the utility of PacBio
long-read sequencing for assessing transcribed regions across the human genome
in a paper^ii last October. Dr. Snyder commented: "Full length transcriptome
sequencing allows the analysis of complete transcriptomes including the
deciphering of complex transcripts and thediscovering of new ones. PacBio
sequencing works remarkably well for this."
The second new application is HLA haplotype phasing. The HLA loci are a group
of genes critical to immune system function.In humans, the HLA genes are
extraordinarily polymorphic. Several thousand alleles have been described and
the number of new alleles continues to increase. HLA allele-specific
genotyping is critical for autoimmune disease-association studies, drug
hypersensitivity research and other applications. Accurate phasing of HLA
polymorphisms has previously required several experiments at great expense.
The long reads provided by PacBio sequencing are ideally suited for accurate
allele-level genotyping with unambiguous allele phasing.
PacBio's SMRT Analysis 2.2 generates consensus sequences that can be input
into third-party software for HLA analysis. This data has successfully been
used with the Conexio Genomics (Perth, Australia) Assign MPS sequence analysis
"PacBio's analysis pipeline independently generates the consensus sequence of
each allele in a heterozygous sample, including non-coding regions," said
David Sayer, Chief Executive Officer of Conexio Genomics. "When analyzed in
our sequence analysis software, this data results in a completely phased,
immutable HLA genotype. The analysis is simple and rapid."
"The SMRT Analysis 2.2 upgrade streamlines two important applications that are
uniquely enabled by our robust long-read sequencing technology," said Michael
Hunkapiller, President and CEO of Pacific Biosciences. "We are excited about
the trajectory that has unfolded with each increase in the performance of the
PacBio RS II system, and look forward to seeing what novel insights the
research community will uncover with these new applications."
The new SMRT Analysis software upgrade is available for download from Pacific
Biosciences' DevNet website. To access the software, data, and documentation,
For more information on the new SMRT Analysis software and the PacBio RS II,
please visit www.pacificbiosciences.com.
About the PacBio RS II and SMRT Sequencing
Pacific Biosciences' Single Molecule, Real-Time (SMRT) Sequencing technology
achieves the industry's longest read lengths, highest consensus
accuracy^iii,iv and the least degree of bias.^v These characteristics,
combined with the ability to detect many types of DNA base modifications
(e.g., methylation) as part of the sequencing process, make the PacBio RS II
an essential tool for many scientists for studying genetic and genomic
variation. The PacBio platform is being used as the sequencing solution to
address a growing number of complex medical, agricultural and industrial
About Pacific Biosciences
Pacific Biosciences of California, Inc. (Nasdaq:PACB) offers the PacBio RS II
DNA Sequencing System to help scientists solve genetically complex problems.
Based on its novel Single Molecule, Real-Time (SMRT) technology, the company's
products enable: targeted sequencing to more comprehensively characterize
genetic variations; de novo genome assembly to more fully identify, annotate
and decipher genomic structures; and DNA base modification identification to
help characterize epigenetic regulation and DNA damage. By providing access to
information that was previously inaccessible, Pacific Biosciences enables
scientists to increase their understanding of biological systems.
^i Treutlein et al., "Cartography of neurexin alternative splicing mapped by
single-molecule long-read mRNA sequencing." PNAS, 10.1073/pnas.1403244111
^ii Sharon et al., "A single-molecule long-read survey of the human
transcriptome," Nature Biotechnology 31, 1009–1014 (2013).
^iii Koren et al., "Reducing assembly complexity of microbial genomes with
single-molecule sequencing." Genome Biology, 14:R10.1 (2013).
^iv Chin et al., "Nonhybrid, finished microbial genome assemblies from
long-read SMRT sequencing data." Nature Methods, 10; 563-569 (2013).
^v Ross et al. Characterizing and measuring bias in sequence data. Genome Biol
14: R51 (2013).
CONTACT: For Pacific Biosciences:
For Pacific Biosciences
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