Paraphase Enables Researchers to Analyze Genes
That are Critically Relevant but Hard to Genotype
MENLO
PARK, Calif., March 14,
2023 /PRNewswire/ -- PacBio (NASDAQ: PACB), a
leading developer of highly accurate sequencing solutions, today
announced a new informatics method that genotypes gene paralogs and
pseudogenes with high accuracy. The new computational tool, named
"Paraphase," enables variant calling, copy number analysis and
phasing by identifying the full gene sequence of each of the
haplotypes for all genes and pseudogenes of the same gene family.
Many medically relevant genes fall into segmental duplications and
thus have highly similar gene family members or pseudogenes. The
sequence similarity often leads to error prone read alignment and
variant calling.
"Through the use of Paraphase, we are able to identify the full
sequence of each copy of a gene and, importantly, identify the
number of functional and non-functional copies of a gene," said
Mike Eberle, Vice President of
Computational Biology at PacBio. "This will allow researchers to
conduct more accurate carrier analyses and provide a framework for
studying the underlying genetics of these complex genomic regions.
We believe that applying this method to larger, diverse, population
data will ultimately enable researchers to better understand
medically important problems, such as silent carriers for spinal
muscular atrophy."
Paraphase has been used on several medically relevant genes with
highly similar paralogs or pseudogenes, including,
CYP21A2 (21-hydroxylase-deficient congenital adrenal
hyperplasia), TNXB (Ehlers-Danlos syndrome), STRC
(hereditary hearing loss and deafness) and SMN1 and 2
(spinal muscular atrophy). SMN1 is >99.9 percent similar
in sequence to its paralog, SMN2, and both genes have
variable copy numbers across populations. Mutations in SMN1
cause spinal muscular atrophy (SMA), a leading cause of early
infant death.
High throughput detailed sequence analysis of complete genes is
challenging using existing technologies, and identifying silent
carriers (having two copies of SMN1 on one chromosome and
zero copies on the other, accounting for 27 percent of carriers in
African populations) is impossible without pedigree information. In
a recent peer-reviewed publication, Paraphase was able to detect
these pathogenic variants for SMA. The study also identified
major SMN1 and SMN2 sequence
haplogroups and characterized their co-segregation through
pedigree-based analyses. In addition, the authors identified a pair
of haplotypes that can serve as a genetic marker for alleles
carrying two copies of SMN1 in African populations,
demonstrating the potential of haplotype-based screening of silent
carriers.
"The fact that HiFi sequencing not only allows access to the
most difficult regions of the human genome, but also enables
calling of all known variant types, such as SNVs, Indels, and SVs
including CNVs, plus phasing of these loci, keeps a great promise
for applications in rare disease research," said Alexander
Hoischen, Ph.D., Associate Professor for Genomic Technologies and
Immuno-Genomics at Radboud University Medical Centre.
Paraphase is being extended into a genome-wide generalized
paralog caller as more highly homologous genes are included.
Paraphase works on whole-genome sequencing and hybrid capture-based
enrichment data. It can also be adapted to work with amplicon
sequencing data, when the full regions of interest are captured or
amplified.
About PacBio
Pacific Biosciences of California, Inc. (NASDAQ: PACB) is a premier
life science technology company that is designing, developing, and
manufacturing advanced sequencing solutions to help scientists and
clinical researchers resolve genetically complex problems. Our
products and technology under development stem from two highly
differentiated core technologies focused on accuracy, quality, and
completeness which include our existing HiFi long-read sequencing
and our emerging SBB® short-read sequencing technologies. Our
products address solutions across a broad set of research
applications, including human germline sequencing, plant and animal
sciences, infectious disease and microbiology, oncology, and other
emerging applications. For more information, please visit
www.pacb.com and follow @PacBio.
PacBio products are provided for Research Use
Only. Not for use in diagnostic procedures.
Forward Looking Statements
This press release may contain "forward-looking statements"
within the meaning of Section 21E of the Securities Exchange Act of
1934, as amended, and the U.S. Private Securities Litigation Reform
Act of 1995. All statements other than statements of historical
fact are forward-looking statements, including statements relating
to the uses, accuracy, coverage, advantages, quality or performance
of, or benefits or expected benefits of using, PacBio products or
technologies, including Paraphse, and other future events. Readers
are cautioned not to place undue reliance on these forward-looking
statements and any such forward-looking statements are qualified in
their entirety by reference to the following cautionary statements.
All forward-looking statements speak only as of the date of this
press release and are based on current expectations, and involve a
number of assumptions, risks and uncertainties that could cause the
actual results to differ materially from such forward-looking
statements, including, challenges inherent in developing,
manufacturing, launching, marketing and selling new products;
potential product performance and quality issues; rapidly changing
technologies and extensive competition in genomic sequencing;
customers and prospective customers curtailing or suspending
activities utilizing PacBio's products; and third-party claims
alleging infringement of patents and proprietary rights or seeking
to invalidate PacBio's patents or proprietary rights. Readers are
strongly encouraged to read the full cautionary statements
contained in PacBio's filings with the Securities and Exchange
Commission, including the risks set forth in PacBio's Forms 8-K,
10-K, and 10-Q. PacBio disclaims any obligation to update or revise
any forward-looking statements.
Contacts
Investors:
Todd Friedman
ir@pacificbiosciences.com
Media:
Lizelda Lopez
pr@pacificbiosciences.com
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SOURCE Pacific Biosciences of California, Inc.