Category Archives: Transhuman News

By Allison Proffitt

January 15, 2021 | In his first J.P. Morgan Healthcare Conference presentation on behalf of Pacific Biosciences yesterday, Christian Henry, PacBios August-announced CEO, laid out a route to the clinic for PacBios HiFi sequencing reads, and set a 2021 goal of expansion across the business: improving commercial footprint, driving product development pipelines, and establishing market leadership in whole-genome clinical sequencing.

Perhaps most importantlywere really trying to improve and drive our collaborations with key opinion leaders so we can bring whole genome sequencing into the clinic, Henry said in yesterdays presentation. Its very clear that whole genome sequencing using HiFi chemistry improves diagnostic yield, and were working hard to make sure that we can have those proof statements as we start to scale up.

Invitae Partnership: Clinical Whole Genomes

Key to that effort is the PacBio-Invitae partnership that the two companies announced on Wednesday, the day between the two company presentations. The multi-year collaboration aims to develop a production-scale high-throughput clinical whole-genome sequencing platform leveraging HiFi chemistry. This is perhaps one of the most exciting collaborations weve entered into as a company, Henry said.

We anticipate developing a sequencer with a scale thats unprecedented for long reads and will enable us to deliver a medically-relevant genome at prices substantially lower than $1,000. We believe that will help open adoption in routine medical care, and we also think that will give Invitae the opportunity to dramatically scale their whole genome testing capabilities.

The partnership launches immediately, Henry said, and he expects to develop the sequencer over the next few years with substantial funding from Invitae, and then to transition into a supply agreement. Hopefully, he said, Invitae will move many of their different assays onto the platform so they can offer whole genome sequencing capability at prices that are affordable.

Invitae shares the same vision as PacBio, Henry said: Whole genome sequencing in clinical applications is the path forward. For PacBio, this could be our killer application. Were uniquely positioned; our technology is uniquely capable.

Henry emphasized messaging around the value of the genome, not just price. What were bringing to the table is really a clinical-grade genome that others cant provide. The value of that genome will be different, I believe, than others in the market Im confident that we can deliver a product at high value at a competitive value proposition. Yet when asked if payers are ready to pay widely for whole-genome sequencing, Henry conceded that it still comes down to price.

Expanded Development Pipelines

The planned Invitae platform, however, is not PacBios single focus. This is whats so exciting! Henry said. We need to develop a multi-product portfolio so we can provide the right product to the right customer in multiple parts of the market. This Invitae program will leverage our core technology, of course, and Im sure well get benefits in both directions, but this is a completely separate product than other products we already had in development. Theres no plan at this point to slow any of that down.

He outlined all the areas in which PacBio is working to accelerate development in service of whole genome sequencing workflows. We need to improve our platform so we can create the scale required to create this notion of the Genome as a Platformsolving different disease conditions across different parts of ones life, Henry said, echoing terminology Sean George used in his Tuesday presentation for Invitae. We believe the whole genome will be critical to healthcare much like medical imaging is today.

Thus PacBio is working to increase automation and reduce sample input in the library prep stage so that more sample types can be used. In the core sequencing technology, PacBio is seeking wide-scale improvements in sample loading, platform density, and faster polymerases, all while maintaining the exquisite accuracy that is one of the key aspects of our technology that differentiates us from others. Finally, Henry identified many opportunities to improve data analytics including improvements to raw base calling, simplifying the workflow, refining secondary analysis, reducing costs, and implementing reporting in the cloud.

Youll see us, over the next several years, work in all these different areas to hopefully enable this concept of Genome as a Platform, he said.

Commercial Expansion: Doubled Footprint

But until then, Henry also said the company plans to pursue an aggressive commercial expansion, more than doubling the commercial footprint, adding commercial expertise to the executive team, and increasing the companys digital presence.

Henry predicted the Sequel IIe to be the primary platform the company is shipping in the foreseeable future. The Sequel IIe started shipping in November 2020, offering on-instrument data processing while also being cloud enabled. The company boasts 90% storage reduction and 70-85% reduction in data analysis and a compute savings of $700 per genome. The platform opened doors to new customers, Henry said, who didnt have the compute infrastructure or budgets for prior generations of PacBio sequencers.

The company has shipped several of the Sequel IIe platforms since launch and reported a combined install base of Sequel II and Sequel IIe at 203 platforms.

2020 did bring some nice deployments of the Sequel II system. Henry highlighted that LabCorp is using the Sequel II in its work to characterize SARS-CoV-2 and was recently awarded a CDC contract to provide genomic sequencing of samples of SARS-CoV-2, the virus that causes COVID-19, Henry reported. And the Wellcome Sanger Institute increased its Sequel II investment to support its Darwin Tree of Life project, sequencing all eukaryotes in Britain and Ireland.

See the article here:
PacBio: Year of Expansion, Whole-Genome Clinical Goals - Bio-IT World

This article was originally published here

Mol Cell. 2021 Jan 1:S1097-2765(20)30962-X. doi: 10.1016/j.molcel.2020.12.041. Online ahead of print.

ABSTRACT

Severe-acute-respiratory-syndrome-related coronavirus 2 (SARS-CoV-2) is the positive-sense RNA virus that causes coronavirus disease 2019 (COVID-19). The genome of SARS-CoV-2 is unique among viral RNAs in its vast potential to form RNA structures, yet as much as 97% of its 30 kilobases have not been structurally explored. Here, we apply a novel long amplicon strategy to determine the secondary structure of the SARS-CoV-2 RNA genome at single-nucleotide resolution in infected cells. Our in-depth structural analysis reveals networks of well-folded RNA structures throughout Orf1ab and reveals aspects of SARS-CoV-2 genome architecture that distinguish it from other RNA viruses. Evolutionary analysis shows that several features of the SARS-CoV-2 genomic structure are conserved across -coronaviruses, and we pinpoint regions of well-folded RNA structure that merit downstream functional analysis. The native, secondary structure of SARS-CoV-2 presented here is a roadmap that will facilitate focused studies on the viral life cycle, facilitate primer design, and guide the identification of RNA drug targets against COVID-19.

PMID:33444546 | DOI:10.1016/j.molcel.2020.12.041

See the article here:
Comprehensive in vivo secondary structure of the SARS-CoV-2 genome reveals novel regulatory motifs and mechanisms - DocWire News

SAN DIEGO, Jan. 11, 2021 (GLOBE NEWSWIRE) -- Bionano Genomics, Inc. (Nasdaq: BNGO), announced today the first publication from the COVID-19 Host Genome Structural Variant Consortium. The study found that optical genome mapping (OGM) with Bionanos Saphyr System identified structural variants (SVs) that affect genes in pathways that control immune and inflammatory response, viral reproduction and mucosal function. The authors believe these SVs may provide key insights into the pathogenesis of COVID-19 and outcomes in patients who become severely ill.

The consortium was formed by Dr. Ravindra Kolhe from Augusta University with the goal of identifying large SVs that factor into the clinical course and outcomes of patients who contract COVID-19. Unlike other analyses of the host genome which are usually limited to genome-wide association studies or exome/genome sequencing and aim to detect single basepair changes, the consortium focuses on finding larger variants in patients genomes because they are believed to have a greater potential to impact genes. The consortium has selected OGM with the Saphyr System for genome analysis owing to Saphyrs documented performance as the leading platform for detecting these large SVs. The current study received contributions from scientists at Augusta University, the University of California San Diego, Radboud University Medical Center, The Rockefeller University, University of Texas M.D. Anderson Cancer Center, Columbia University Medical Center, Virginia Commonwealth University, New York Genome Center, Harvard Medical School, and Bionano Genomics.

The study reports the analysis of the genomes of 37 patients who were admitted to the ICU at Augusta University with severe COVID-19 disease. 30 patients needed mechanical ventilation with a mean intubation duration of 12 days. Of the 37 patients, 25 recovered and 12 died. The SVs revealed by Saphyr were confirmed with other technologies such as quantitative PCR.

One of the most compelling findings among the SVs identified was the duplication of the STK26 gene,a key element of the Toll-Like Receptor signaling pathway which controls the cells response to viral infection. In the follow-on analysis of the expression of the STK26 gene in patients with the duplication, the study found significant upregulation ofSTK26in all severely ill patients tested but not in asymptomatic COVID-19 patients, implying the duplication to be a potential novel, prognostic biomarker for the severe immune response seen in severely ill patients.

Ravindra Kolhe, MD, PhD, senior author of the study commented: As director of a high-volume testing lab at Augusta University for COVID-19 Ive seen first-hand the pain and devastation this virus can cause in those who get severely ill. The majority of the ICUs across the country are filled with patients fighting for their lives, yet we did not know why some become so severely ill while the same virus causes only mild symptoms in most. Our study shows clearly that many of the severely affected patients carry genetic variants that may cause or at least contribute to the severity of their disease by weakening the effectiveness of the immune response, increasing viral replication, or making it easier for the virus to spread between cells in thebody. Importantly, the large genomic variants detected by optical genome mapping in this study are typically missed by the short-read sequencing or SNP-based methods used in other studies, which explains why previous studies havent made the same impact.

Erik Holmlin, PhD, CEO of Bionano Genomics, commented: The COVID-19 pandemic continues without signs of slowing down. This study demonstrates that the wide variation in symptoms exhibited by patients is likely not random for most of them, but instead, at least partially, the result of SVs affecting critical pathways in patients defenses against infection and immune responses to the disease. The results also demonstrate that even when a disease has already been studied extensively with sequencing, OGM with Saphyr has the potential to reveal significant insights not seen without it. While we are devastated by the loss of lives caused by this global pandemic, we are grateful that our genome analysis platform can contribute to a better understanding of the disease and possibly help save lives.

These results will be presented by the authors at Bionanos Next-Generation Cytogenomics Symposium on January 15, register here: http://bit.ly/3pLPT28

The publication is available at:https://www.medrxiv.org/content/10.1101/2021.01.05.21249190v1

About Bionano GenomicsBionano is a genome analysis company providing tools and services based on its Saphyr system to scientists and clinicians conducting genetic research and patient testing, and providing diagnostic testing for those with autism spectrum disorder (ASD) and other neurodevelopmental disabilities through its Lineagen business. Bionanos Saphyr system is a platform for ultra-sensitive and ultra-specific structural variation detection that enables researchers and clinicians to accelerate the search for new diagnostics and therapeutic targets and to streamline the study of changes in chromosomes, which is known as cytogenetics. The Saphyr system is comprised of an instrument, chip consumables, reagents and a suite of data analysis tools, and genome analysis services to provide access to data generated by the Saphyr system for researchers who prefer not to adopt the Saphyr system in their labs. Lineagen has been providing genetic testing services to families and their healthcare providers for over nine years and has performed over 65,000 tests for those with neurodevelopmental concerns. For more information, visitwww.bionanogenomics.comor http://www.lineagen.com.

Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as may, will, expect, plan, anticipate, estimate, intend and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) convey uncertainty of future events or outcomes and are intended to identify these forward-looking statements. Forward-looking statements include statements regarding our intentions, beliefs, projections, outlook, analyses or current expectations concerning, among other things: potential key insights into the pathogenesis of COVID-19 provided by SVs identified by Saphyr, including the potential of STK26 gene duplication to be a prognostic biomarker for severe immune response seen in severely ill COVID-19 patients; Saphyrs ability to contribute to a better understanding of COVID-19 and help save lives; and timing of the study results to be presented. Each of these forward-looking statements involves risks and uncertainties. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include the risks and uncertainties associated with: the impact of the COVID-19 pandemic on our business and the global economy; general market conditions; changes in the competitive landscape and the introduction of competitive products; changes in our strategic and commercial plans; our ability to obtain sufficient financing to fund our strategic plans and commercialization efforts; the loss of key members of management and our commercial team; and the risks and uncertainties associated withour business and financial condition in general, including the risks and uncertainties described in our filings with the Securities and Exchange Commission, including, without limitation, our Annual Report on Form 10-K for the year ended December 31, 2019 and in other filings subsequently made by us with the Securities and Exchange Commission. All forward-looking statements contained in this press release speak only as of the date on which they were made and are based on management's assumptions and estimates as of such date. We do not undertake any obligation to publicly update any forward-looking statements, whether as a result of the receipt of new information, the occurrence of future events or otherwise.

CONTACTSCompany Contact:Erik Holmlin, CEOBionano Genomics, Inc.+1 (858) 888-7610eholmlin@bionanogenomics.com

Investor Relations Contact:Ashley R. RobinsonLifeSci Advisors, LLC+1 (617) 430-7577arr@lifesciadvisors.com

Media Contact:Darren Opland, PhDLifeSci Communications+1 (617) 733-7668darren@lifescicomms.com

More:
COVID-19 Host Genome SV Consortium Identifies Structural Variants with Possible Roles in Pathogenesis and Outcomes in Severely Ill COVID-19 Patients...

BOSTON--(BUSINESS WIRE)--Clinicians at Variantyx, a leader in high complexity hereditary disease testing, recently completed analysis of their 2,500th patient genome. The milestone highlights the growing need for whole genome sequencing (WGS)-based tests in patient genetic diagnostics.

Variantyxs Genomic Unity tests pair the patients complete DNA sequence with proprietary data analysis algorithms and phenotype-driven filters to uniquely identify and definitively report on all major types of genetic variation within a single assay. Including genome-wide small sequence changes, structural variants, mitochondrial variants and tandem repeat expansions.

Review of the cases identified many examples of positive test results using Variantyx testing after multiple rounds of failed exome and other NGS tests.

Providing diagnoses for patients using the most comprehensive testing available is a milestone like no other and puts Variantyx at the leading edge of genomic technology. Not only are we identifying results for patients at the end of long diagnostic odysseys of years and sometimes decades, but we are also seeing the real impact of genomes being a first line test in diagnosing patients early and during a time where treatments may still be effective, said Christine Stanley, PhD, FACMG, Chief Director of Clinical Genomics at Variantyx. Our team of MDs, PhDs and Genetic Counselors are honored and humbled to lead the way in using genomes to not only identify single nucleotide variants, but, by using our sophisticated software, to also identify challenging variant types like copy number variants, short tandem repeats, Alu insertions, inversions, single exon deletions and mosaic aneuploidy. By overcoming the limitations of all other platforms used today, were providing much needed answers to patients and their families.

About Variantyx

Variantyx is a CLIA/CAP laboratory providing Genomic Unity, a whole genome sequencing (WGS)-based testing program for diagnosis of rare inherited and neurological disorders. Its single method approach to comprehensive genetic testing identifies multiple variant types within a single patient sample to provide a unified clinical report. For more information, please visit http://www.variantyx.com.

Read this article:
Variantyx Surpasses 2500 Genomes Analyzed, Highlights the Value of Its WGS-Based Testing Methodology - Business Wire

PHOENIX, Jan. 15, 2021 /PRNewswire/ -- Ashion Analytics LLC, a CLIA-certified and CAP-accredited clinical laboratory announced today that they will present data at the 2021 American Society for Clinical Oncology Gastrointestinal (ASCO GI) virtual meeting.

Abstract #109Session Title: Colorectal CancerDate: January 15, 2021; Release Time: 8 am EST

Title: Genomic profiling of gastrointestinal cancers by comprehensive tumor-normal sequencingAuthors: Fadel S. Alyaqoub, Pawan Noel, Szabolcs Szelinger, Thanemozhi G. Natarajan, Susan M. Dombrowski, Audrey A. Ozols, Laurie J. Goodman, Janine LoBello, Thomas Royce, Gargi D. Basu

Background: Gastrointestinal cancers (GIC) account for 26% of global cancer incidence and 35% of cancer-related deaths. We investigated the molecular landscape and therapeutic targets across 22 types of GIC using whole exome (WES) and whole transcriptome sequencing (WTS).Methods: GEM ExTra assay was performed on 844 paired samples (ages 18-90 years, median= 61 years). Targeted sequence coverage was 180X for germline DNA and 400X for tumor DNA. Reportable somatic alterations included single base substitutions, indels, Copy Number Alterations, gene fusions, alternate transcripts, as well as tumor mutational burden (TMB) and microsatellite instability (MSI) status. Germline subtraction identified somatic-specific alterations.Results: Analysis of 844 GIC patient samples, including esophageal, gastric cancer (GC), biliary tract (BT), pancreatic cancer (PC), colorectal cancer (CRC), and other cancers. The median number of alterations was 3 per GIC patient. The 5 most common actionable alterations were in APC, KRAS, CDKN2A, ARID1A and PIK3CA. Activation of Wnt signaling was found in 344/844 (40.8%), with the majority being in CRC cases. Alterations in cell cycle genes including TP53, CDKN2A, CDK4/6 and others were noted in 520/844 (61.6%) cases and in 129/844 (15.3%) excluding TP53 alterations, suggesting benefit from CDK4/6 inhibitors. Alterations in DNA damage repair genes were noted in 66/844 (7.9%) cases. Activation of PI3K/PTEN/Akt/mTOR pathway was noted in 183/844 (17%), with the majority harbored in CRC, suggesting benefit from targeting this pathway. ERBB2 amplification and mutations were noted in 41/844 (4.9%) across different GIC tumor types. Alterations in homologous recombination genes predicting platinum and PARP inhibitor response was noted in 167/844 (19.8%) samples distributed across GIC subtypes. KRAS (G12C) mutation was found in 21/324 (6.5%) of the combined PC and CRC tumors, thus allowing patients to enroll in clinical trials with G12C-specific inhibitors. Most cases with MSI- and TMB-high status were identified in GC and CRC tumors and may be predictive of response to immunotherapy. WTS identified actionable fusions, including FGFR1/2/3 and novel NRG1 fusions in BT cancers.Conclusions: Our study revealed actionable targets used in patient selection for precision therapies, in addition to other mutational profiles of clinical significance. Overall, comprehensive genomic profiling enabled detection of established and novel actionable alterations, including fusions, which may have gone undetected using hotspot panels.

"Our study provides a comprehensive analysis of molecular signatures across 22 different gastrointestinal cancers using whole exome and whole transcriptome analysis. Further, the highly sensitive GEM ExTra assay utilizing tumor and matched normal samples maximizes detection of rare actionable alterations therapy providing treatment options for targeted therapy as well as immunotherapy across gastrointestinal cancers," said Gargi D. Basu, Ph.D., Ashion Analytics Senior Director of Clinical Curation.

About Ashion Analytics LLCAshion Analytics LLC is a CLIA-certified and CAP-accredited clinical laboratory that uses advanced genomic technologies to offer a wide range of testing capabilities, including GEM ExTra to assist physicians in providing options for precision cancer treatments. Ashion was developed and launched by the Translational Genomics Research Institute (TGen), an affiliate of City of Hope. TGen is a pioneer in the use of genomics to identify treatment options for cancer patients.

About TGen, an affiliate of City of HopeTranslational Genomics Research Institute (TGen) is a Phoenix, Arizona-based non-profit organization dedicated to conducting groundbreaking research with life-changing results. TGen is affiliated with City of Hope, a world-renowned independent research and treatment center for cancer, diabetes and other life-threatening diseases: http://www.cityofhope.org. This precision medicine affiliation enables both institutes to complement each other in research and patient care, with City of Hope providing a significant clinical setting to advance scientific discoveries made by TGen. TGen is focused on helping patients with neurological disorders, cancer, diabetes and infectious diseases through cutting-edge translational research (the process of rapidly moving research toward patient benefit). TGen physicians and scientists work to unravel the genetic components of both common and complex rare diseases in adults and children. Working with collaborators in the scientific and medical communities worldwide, TGen makes a substantial contribution to help our patients through efficiency and effectiveness of the translational process. For more information, visit: http://www.tgen.org. Follow TGen on Facebook, LinkedIn and Twitter @TGen.

Ashion Analytics ContactGargi D. Basu, Ph.D.Senior Director, Clinical CurationAshion Analytics LLCgbasu@ashion.com480-734-4081www.Ashion.com

TGen Media Contact:Steve YozwiakTGen Senior Science Writer602-343-8704syozwiak@tgen.org

View original content to download multimedia:http://www.prnewswire.com/news-releases/ashion-analytics-to-present-data-on-the-value-of-comprehensive-genomic-profiling-of-gastrointestinal-cancers-by-utilizing-the-gem-extra-test-301209000.html

SOURCE Ashion Analytics

Continued here:
Ashion Analytics to Present Data on the Value of Comprehensive Genomic Profiling of Gastrointestinal Cancers by Utilizing the GEM ExTra Test -...