Category Archives: Genetic medicine

New York, October 26, 2020 The Ross Prizein Molecular Medicine will be awarded to Adrian R. Krainer, PhD, St. Giles Foundation Professor at Cold Spring Harbor Laboratory, in a virtual ceremony and webinar hosted by the New York Academy of Sciences, Feinstein Institutes for Medical Research, and the journal Molecular Medicine on October 30. The webinar will be held 1 PM to 4:50 PM EDT.

The Feinstein Institutes for Medical Research has selected Dr. Krainer as the eighth recipient of the Ross Prize, which is awarded annually through the Feinstein Institutes peer-reviewed, open-access journal, Molecular Medicine.

The Ross Prize recognizes Dr. Krainer for his pioneering work in introducing anti-sense therapy in clinical use, and for its successful application to spinal muscular atrophy (SMA). The Ross Prize includes a $50,000 award.

After a brief award presentation at the start of the October 30 webinar, Dr. Krainer will discuss his work. This will be followed by a session on topics in the genetics of neurological disorders. Speakers for this session will include: Edward M. Kaye, MD, Stoke Therapeutics; Michelle L. Hastings, PhD, Rosalind Franklin University of Medicine and Science; and Timothy Yu, MD, PhD, Boston Children's Hospital, Harvard Medical School. The webinar will be held 1 PM 4:50 PM EDT.

The Ross Prize is made possible by the generosity of Feinstein Institutes board members Robin and Jack Ross. The Ross Prize recognizes biomedical scientists whose discoveries have transformed the way medicine is practiced. The awardees are midcareer researchers who have made a significant impact in the understanding of human disease pathogenesis and/or treatment. Moreover, it is anticipated that they will continue to make profound advances in the general field of molecular medicine.

The Ross Prize is a worthy tribute to the significance and impact of the fundamental and applied research conducted by my lab and our collaborators, which culminated in a disease-modifying therapy for spinal muscular atrophy, Dr. Krainer said. I greatly admire the seven previous Prize recipients, so I am humbled to join this distinguished group of scientists and clinicians.

Dr Krainer is the eighthrecipient of the Ross Prizein Molecular Medicinebecause his discoveries are revolutionizing treatment of a devastating, crippling pediatric illness, saidKevin J. Tracey, MD, president and CEO of the Feinstein Institutes and editor emeritus ofMolecular Medicine.His work enables children with spinal muscular atrophy to crawl, walk, and live a full life.

Dr. Krainer explained his work in more detail:

"My labs research has a long-standing focus on understanding RNA splicing, a fundamental cellular process. In addition, we are interested in how alterations in this key step in gene expression cause or contribute to disease. This basic research eventually led us to the development of mechanism-based therapies. Our main goals are to continue gaining novel insights into RNA-splicing mechanisms and regulation, and to translate these findings into new drugs or clinically useful methods. These are important goals, because they differ from the traditional path for drug development, and so they have the potential to yield effective solutions to intractable medical problems."

In addition to studying the mechanisms of RNA splicing, Dr. Krainer uses multidisciplinary approaches to examine the ways in which they go awry in disease, and the means by which faulty splicing can be corrected. He co-developed the first FDA-approved therapy for the genetic disorder SMA an illness that has been the leading genetic cause of infant death based on the biological process of RNA splicing. This life-saving drug is also the first approved splicing-corrective therapy.

To learn more about the Ross Prize celebration and symposium, and to register for the event, please visit http://www.nyas.org/RossPrize2020.

Past recipients of the Ross Prize are: Daniel Kastner, MD, PhD, scientific director of the National Institutes of Healths (NIH) National Human Genome Research Institute (NHGRI); Huda Y. Zoghbi, MD, professor, Departments of Pediatrics, Molecular and Human Genetics, Neurology and Neuroscience at Baylor College of Medicine; Jeffrey V.Ravetch, MD, PhD,the Theresa and Eugene M. Lang Professor and head of the Leonard Wagner Laboratory of Molecular Genetics and Immunology at The Rockefeller University; Charles N.Serhan, PhD, DSc, director of the Center for Experimental Therapeutics and Reperfusion Injury at Brigham and Womens Hospital, the SimonGelmanProfessor ofAnaesthesiaat Harvard Medical School and professor at Harvard School of Dental Medicine; Lewis C.Cantley, PhD, the Meyer Director of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medical College andNew York-Presbyterian Hospital; John J. OShea, MD, scientific director at the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); and Dan R. Littman, MD, PhD, the Helen L. and Martin S. Kimmel Professor of Molecular Immunology in theSkirballInstitute ofBiomolecularMedicine at New York University School of Medicine.

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Ross Prize Ceremony and Webinar on the Genetics of Neurological Disorders - The New York Academy of Sciences

Its a day of firsts, with the launch of two new Cambridge, Mass.-based life sciences companies, Be Biopharma, with a focus on B cell malignancies, and AavantiBio, a gene therapy company aimed at treating rare genetic diseases.

AavantiBio launched with a $107 million Series A financing round, which includes not only a $15 million equity investment from Sarepta Therapeutics, but also an experienced executive in Alexander Bo Cumbo to helm the startup. The companys lead asset is a gene therapy treatment for Friedreichs Ataxia (FA), a rare inherited genetic disease that causes cardiac and central nervous system dysfunction.

AavantiBios gene therapy builds on the work of its co-founders, renowned gene therapy researchers Barry Byrne and Manuela Corti, who have researched FA and other genetic disorders. In addition to the foundational work of Byrne and Corti, the startup will also benefit from strategic partnerships with the University of Floridas renowned Powell Gene Therapy Center and the MDA Care Center at UF Health where Byrne and Corti maintain their research and clinical practices.

Cumbo, who spent eight years at Sarepta as chief commercial officer, will serve as the first chief executive officer of AavantiBio. He said his time at Sarepta has been incredibly rewarding as that company emerged as a pioneer in treating Duchenne muscular dystrophy and limb-girdle muscular dystrophy patients and ultimately transformed into a genetic medicine leader.

It has been a privilege to contribute to this growth and play a role in serving these communities. As I look ahead to the bright future of AavantiBio and the exciting opportunity to lead this innovative company, this same dedication to serving unmet patient needs and to leveraging deep scientific expertise will be core to our mission. I am also thrilled to continue to collaborate with the talented team at Sarepta, said Cumbo, who will continue to serve as an adviser to Sarepta through the end of 2020.

Sarepta CEO Doug Ingram praised Cumbos work over the past eight years and said he built a first-in-class rare disease commercial organization. As a partner with AavantiBio, Ingram said he looks forward to a continued relationship with Cumbo and AavantiBios efforts to advance therapies for FA and other rare diseases.

In addition to Sarepta, AavantiBios Series A was supported by Perceptive Advisors, Bain Capital Life Sciences and RA Capital Management.

Be Biopharma launched with a $52 million Series A financing round. The company will use the funds to engineer B cells to treat a range of diseases. B cells are prolific protein producers that can be collected from peripheral blood, have a programmable lifetime that could last decades, can target specific tissues, and have broad, customizable functionality.

The company intends to build on the work of co-founders David Rawlings and Richard James conducted at Seattle Childrens Research Institute. Rawlings said the goal is to build new class of engineered B cell medicines that will provide direct control over the power of humoral immunity and transform the prognosis for patients who currently have limited treatment options.

Be Biopharma is helmed by David Steinberg, a co-founder of the company and a partner at Longwood Fund, one of the supporters of the Series A.

Be Bio is capitalizing on the unique attributes of B cells to create a new category of medicine that is distinct from traditional cell or gene therapy. B cells can be engineered to express a wide variety of proteins, have the potential to generate durable responses, and can be dose-titrated and administered multiple times without the need for toxic preconditioning, Steinberg said in a statement. Moreover, the varied functions of B cells suggest that B cell medicines can address a range of conditions including autoimmune diseases, cancer, and monogenic disorders, as well as enhance the immune response to infectious pathogens. We believe Be Bio is at the forefront of a new approach to fighting disease.

In addition to Longwood Fund, the Series A financing round was supported by investment leaders Atlas Venture and RA Capital Management. Alta Partners and Takeda Ventures also supported the financing round.

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Be Biopharma, AavantiBio Launch With Millions in Financing to Support Therapeutic Goals - BioSpace

Yale Daily News

Advocating for the transition of medicine away from race-based practices and toward a more race-conscious approach, Yale Medical School MD-PhD student Jessica Cerdea GRD 21, Yale Emergency Medicine physician Jennifer Tsai and Howard University PhD student Marie Plaisime recently co-authored an editorial for The Lancet, a peer-reviewed medical journal, this month about reforming medical education for future doctors.

The editorial characterizes the current practice of medicine as race-based, stating that physicians often infer that race has inherent biological significance, whereas in actuality race is merely a social construct. The authors say the future of medicine should move from this race-based approach to a race-conscious approach, with the end goal being a reduction in health inequities across racial lines. They advocated for emphasizing institutional inequities in healthcare during medical education, which they said would raise the cultural competency of future physicians.

Race-based medicine uses and treats race as an essential biological variable that has utility in medical education and clinical practice, Cerdea said. Race-conscious medicine understands that race is a social and power construct that changes for political utility over time, and that it is a poor proxy for human genetic variation. Instead, the more salient variable when it comes to differences in human groups that have been socially categorized in this way is the experience of racism and racialization This idea that there are biological differences between racial groups comes from colonization. This is how white supremacy operates.

The editorial was published in The Lancet after the prominent medical journal released a statement supporting the Black Lives Matter movement and its continuing commitment to advancing racial equality. This editorial was also published following a summer of racial unrest and protests around the country that advocated for putting an end to police brutality against Black Americans. The timing of the publication was significant to the authors.

Certainly we were motivated by the very apparent murders of George Floyd, Ahmaud Arbery and Breonna Taylor, among others, Tsai said. But also because this is a very long-standing problem that I think all three of us have been working on, thinking about and advocating against beforehand.

The article presented a wide range of examples in which race heavily influences physicians medical assessment of patients, such as the Atherosclerotic Cardiovascular Disease risk calculator equation. This online tool determines a given patients risk of having a cardiovascular event within ten years, Cerdea said. These calculations involve categorizing the patient as either Black or not Black. If the patient is Black, the predicted risk is significantly increased, and the patient is more likely to start taking a certain medication earlier than patients of other racial groups.

The prescription dosage for certain drugs can also vary based on racial groups. According to Cerdea, medical practitioners consider East Asian people to have different metabolisms, which means that a drug like Eltrombopag, a bone marrow stimulant, is started at half the normal dose for these people. This type of race-based medicine is condemned in the article.

You cant know someones pharmacokinetics, or the way that they metabolize a drug, by looking at them, or by their race, Cerdea said. Thats the problem with race-based medicine.

The Lancet piece includes different policy recommendations for researchers, clinicians and practitioners. According to Plaisime, It was crafted with care towards its intended audience of physicians, picking and choosing words that would be most accessible. The most important step in moving forward, Tsai said, is to change the curriculum of medical schools to be more race-conscious.

The authors also wrote this editorial from the perspective of their own experiences as women of color within the American healthcare system. Cerdea is Italian and Chilean with Indigenous Mapuche ancestry, Plaisime is Haitian American and Tsai is Taiwanese American.

As a Black woman, for sure there have definitely been times where Ive been treated differently based on how I appeared in the clinical room, how I was spoken to, Plaisime said. Also being the daughter of Haitian immigrants, I know first-hand what its like to have your accent judged. Not just one isolated event that kind of sparked this, its my story, and I want to make sure that all people receive equitable care.

The authors also emphasized that even research studies are subjected to racialization, despite undergoing objective screening processes instituted by peer-reviewed journals. Although race has no inherent biological significance, countless epidemiological studies include race as a critical variable when mapping out the prevalence of certain diseases.

In their article, the authors urged clinical research journals to include instructions in their publication guidelines that denounce the use of race as a proxy for biological variables such as genetics, pharmacokinetics and metabolism.

Prestigious publications continue to allow research that [uses] problematic versions of race in their research, Tsai said. They still allow that to be published, which means this kind of data and this kind of thinking is continually generated and perpetuated.

Plaisime, who is a medical sociologist studying the impacts of race and racism in clinical decision-making processes, explained that biologizing race is harmful. Prior to this collaboration, she had published a piece about the implications of using race in medicine.

She emphasized the need for using evidence-based treatments that do not rely solely on race as a factor of consideration, as this can often be detrimental to members of racial minority groups.

The different biomarkers and tools they use arent necessarily based on science, but more on racist assumptions, Plaisime said. My work was based on how that kind of training impacts later on how patients receive care, and how medical students are trained.

Cerdea and Plaisime are both Robert Wood Johnson Foundation Health Policy Research Scholars, and Tsai is completing her residency at the Yale New Haven Hospital.

Anjali Mangla | anjali.mangla@yale.edu

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Members of medical community call for shift from race-based to race-conscious medicine - Yale Daily News

Newswise PITTSBURGH, Oct. 26, 2020 James J. Collins, Ph.D., an innovator in synthetic biology whose ideas have contributed to novel diagnostics and treatments targeting infections and complex diseases, has been awarded the 2020 Dickson Prize in Medicine, the University of Pittsburgh School of Medicines highest honor.

The prize is given annually to an American biomedical researcher who has made significant, progressive contributions to medicine. The award consists of a specially commissioned medal, a $50,000 honorarium and an invitation to present the keynote lecture during the Universitys annual campus-wide showcase of scientific research. Due to the COVID-19 pandemic, both the annual showcase and Collins lecture have been postponed until 2021 at a date to be determined.

Dr. Collins is defining whats possible in the disciplines of synthetic and systems biology. His highly creative work applying engineering design principles to molecular biology has generated numerous new diagnostics and therapeutics with wide application to medicine, said Anantha Shekhar, M.D., Ph.D., Pitts senior vice chancellor for the health sciences and John and Gertrude Petersen Dean of Medicine. It is our honor to recognize him with the School of Medicines most prestigious award.

Im grateful to work with outstanding lab members and collaborators whose dedication and insight have been critical to what weve achieved, said Collins, who is the Termeer Professor of Medical Engineering and Science in the Department of Biological Engineering at Massachusetts Institute of Technology and is affiliated faculty with the Broad Institute of MIT and Harvard University, and the Wyss Institute at Harvard. I am thrilled and honored to receive the Dickson Prize in Medicine.

A seminal 2000 publication describing the successful creation of a stable, synthetic gene circuit in Escherichia coli bacteria has been cited more than 4,000 times and marked the arrival of an important new discipline in biomedicine. Collins later demonstrated that synthetic gene networks could be linked with a cells genetic circuitry as a regulatory mechanism to create programmable cells for biomedical applications.

More recently, Collins has created engineered microbes and whole-cell biosensors to serve as in vivo diagnostics and therapeutics. One innovative platform that he and colleagues developed embeds freeze-dried, cell-free synthetic gene networks onto paper and other materials with a wide range of potential clinical and research applications.

The resulting materials contain properties of a living cell, are stable at room temperature and can be activated by simply adding water. Collinss work on freeze-dried, cell-free synthetic biology has established a platform for a new class of rapid, programmable in vitro diagnostics for emerging pathogens, including drug-resistant bacteria and viruses. Collins and his team currently are developing a rapid self-activating COVID-19 face mask as a wearable diagnostic.

Collins earned an A.B. in physics at the College of the Holy Cross in Worcester, Mass., before completing a Ph.D. in medical engineering at the University of Oxford with the distinction of Rhodes Scholar. He has received a MacArthur Foundation Genius award, NIH Directors Pioneer Award and Sanofi-Institut Pasteur Award. Collins is an elected member of the National Academy of Sciences, National Academy of Engineering, National Academy of Medicine and the American Academy of Arts and Sciences. He is a charter fellow of the National Academy of Inventors.

To read this release online or share it, visit http://www.upmc.com/media/news/102620-Dickson-Prize-2020.

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2020 Dickson Prize in Medicine Awarded to Pioneer Researcher in Synthetic Biology - Newswise

Oct. 26, 2020 16:00 UTC

OAKLAND, Calif.--(BUSINESS WIRE)-- In a step toward the full realization of genomic medicine, Fabric Genomics (Formerly Known As Omicia, Inc.), a leader in AI-based genomic analysis and interpretation, has announced a co-marketing agreement that will provide translational researchers around the world with integrated sample prep to reporting workflows. Combining Roches newly released KAPA HyperExome Probes (RUO) with the Fabric Enterprise bioinformatics and analysis platform will make genetic research faster, less costly and more accurate by providing an end-to-end solution from sample prep through analysis.

Fabric Genomics pioneered AI-driven genomic interpretation, and its Fabric Enterprise software platform for genomic data analysis and reporting is in use by clinical research laboratories, healthcare institutions and country sequencing programs around the world, including Rady Childrens Institute for Genomic Medicine, LabCorp and Genomics England. Last week Fabric Genomics released Fabric GEM, a novel algorithm that quickly identifies the likely genetic cause of rare diseases; the new technology is fully integrated within the Fabric Enterprise platform.

Roches exome sequencing workflow includes the KAPA HyperPrep and HyperPlus library preparation kits and exome probes, which allow users to quickly prepare samples for sequencing while delivering high on-target rates and 98% sensitivity for SNP detection.

In addition to improving turnaround times for genomic sequencing, the combination of these technologies will allow laboratories to increase automation and lower operational costs with improved scalability. Clinical research labs that are expanding assay menus will benefit from reduced costs of development and faster validation.

Clinical research labs have a need to take a collected sample from library prep quickly, all the way through to analysis, and our agreement with Roche demonstrates our commitment to supporting these critical workflows, said Martin Reese, PhD, co-founder and CEO of Fabric Genomics. Using our Fabric Enterprise analysis platform with Roche KAPA HyperExome Probes ensures high coverage of disease-causing genes, which is of the utmost importance in accelerating the identification of rare variants. Combining these technologies into a single workflow will lead to higher quality results and increased reliability of sequencing-based diagnostics in routine care. With widespread adoption of sequencing technology innovation, we can further our shared goal of improving personalized care.

KAPA products are for research use only (RUO). Not for use in diagnostic procedures.

About Fabric Genomics

Headquartered in Oakland, California, Fabric Genomics was founded by industry veterans and innovators with a deep understanding of bioinformatics, large-scale genomics and clinical diagnostics. Fabric Genomics is making genomics-driven precision medicine a reality. The company also provides clinical decision-support software that enables clinical labs, hospital systems and country sequencing programs to gain actionable genomic insights, resulting in faster and more accurate diagnoses and reduced turnaround time. Fabrics end-to-end genomic analysis platform incorporates proven AI algorithms, and has applications in both hereditary disease and oncology.

To learn more, visit https://fabricgenomics.com/roche/ and follow us on Twitter and LinkedIn.

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Fabric Genomics to Co-market Comprehensive Sample-to-Genomic Analysis Sequencing Solutions for Hereditary Genetics - BioSpace

CARLSBAD, Calif., Oct. 22, 2020 /PRNewswire/ -- Ionis Pharmaceuticals, Inc. (NASDAQ: IONS), the leader in antisense therapeutics, today announced that the first patients have been dosed with ION541 (also known as BIIB105), an investigational antisense medicine being developed as a potential therapy to treat most forms of amyotrophic lateral sclerosis (ALS) regardless of family history. This is another milestone in the continuing progress of Ionis' ambitious program to develop novel treatments for ALS. Almost all cases of ALS share the pathological hallmark of TDP-43 protein aggregation in motor neurons. ION541 targets ataxin-2 RNA (ATXN2), which has been shown to prevent or reverse TDP-43 toxicity in preclinical models of ALS.

ALS is a rare, progressive and fatal neurodegenerative disorder that affects approximately 55,000 people globally.i About 90 percent of ALS cases occur in people who have no apparent family history of the disease. People with ALS experience muscle weakness, loss of movement, and difficulty breathing and swallowing, resulting in a severely declining quality of life and potentially death.

"As our third medicine designed to treat different forms of ALS to enter clinical trials, ION541 represents yet another example of the power of Ionis' antisense technology to potentially target root causes of devastating neurodegenerative diseases," said Frank Bennett, Ph.D., Ionis' chief scientific officer and franchise leader for neurological programs. "Initiation of this clinical trial for ION541 marks an important milestone in Ionis' ALS program and reaffirms our commitment to the ALS community."

Ionis received a payment of $10 million from Biogen for initiation of this Phase 1/2 clinical trial of ION541. Biogen is developing ION541 as part of a broad strategic collaboration with Ionis to advance novel antisense therapies for the treatment of neurological disorders.

Learn more about the Phase 1/2 trial of ION541 at: https://clinicaltrials.gov/ct2/show/NCT04494256?term=biib105&draw=2&rank=1

Ionis' other leading investigational medicines to treat ALS are tofersen (BIIB067) and IONIS-C9Rx (BIIB078), both partnered with Biogen. Tofersen is designed to reduce the production of superoxide dismutase 1 (SOD1), the cause of a genetic form of ALS, referred to as SOD1-ALS, that results from mutations in the SOD1 gene. SOD1-ALS is the second most common genetic form of ALS, accounting for up to 20 percent of genetic ALS. Tofersen is currently in a Phase 3 clinical trial in SOD1-ALS patients with data expected in 2021. IONIS-C9Rx is designed to selectively reduce the mutant C9ORF72 RNA and associated neurotoxicity. Mutations in the C9orf72 gene account for greater than 30 percent of genetic ALS cases and five to 10 percent of all patients with ALS. It is the most common genetic form of ALS worldwide. IONIS-C9Rx is the first drug to enter clinical development that specifically targets the mutant C9ORF72 RNA and is a potentially first-in-class therapy for patients with C9orf72-ALS, referred to as C9-ALS. IONIS-C9Rx, which earlier this year received Fast Track designation from the U.S. Food and Drug Administration, is currently in a Phase 1/2 trial in C9-ALS patients.

Ionis' Forward-looking Statement

This press release includes forward-looking statements regarding Ionis' business and the therapeutic potential of ION541, tofersen and IONIS-C9Rx. Any statement describing Ionis' goals, expectations, financial or other projections, intentions or beliefs is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties, particularly those inherent in the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such drugs. Ionis' forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements. Although Ionis' forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Ionis. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Ionis' programs are described in additional detail in Ionis' annual report on Form 10-K for the year ended December 31, 2019, and the most recent Form 10-Q quarterly filing, which are on file with the SEC. Copies of these and other documents are available from the Company.

In this press release, unless the context requires otherwise, "Ionis," "Company," "we," "our," and "us" refers to Ionis Pharmaceuticals and its subsidiaries.

Ionis Pharmaceuticals is a trademark of Ionis Pharmaceuticals, Inc.

About Ionis Pharmaceuticals

As the leader in RNA-targeted drug discovery and development, Ionis has created an efficient, broadly applicable, drug discovery platform called antisense technology that can treat diseases where no other therapeutic approaches have proven effective. Our drug discovery platform has served as a springboard for actionable promise and realized hope for patients with unmet needs. We created the first and only approved treatment for all patients, children and adults with spinal muscular atrophy as well as the world's first RNA-targeted therapeutic approved for the treatment of polyneuropathy in adults with hereditary transthyretin amyloidosis. Our sights are set on all the patients we have yet to reach with a pipeline of more than 40 novel medicines designed to potentially treat a broad range of disease, including neurological, cardio-renal, metabolic, infectious, and pulmonary diseases.

To learn more about Ionis visit http://www.ionispharma.com or follow us on twitter @ionispharma.

i G7 countries: Canada, France, Germany, Italy, Japan, the United Kingdom, and the United States.

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SOURCE Ionis Pharmaceuticals, Inc.

Company Codes: NASDAQ-NMS:IONS

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Ionis' third novel antisense medicine for ALS, its first designed to treat a broad ALS population, begins clinical trial - BioSpace

Oct. 27, 2020 12:00 UTC

The only tertiary analysis appliance on the market, CompStor Insight delivers 7x faster annotation in an easy to use solution with integrated workflows, multi-user support, needing no special IT skills

MILPITAS, Calif.--(BUSINESS WIRE)-- OmniTier Inc., an AI and multiomics application company whose bioinformatics solutions help deliver the promise of personalized medicine, debuted the CompStor Insight appliance for tertiary analysis in next-generation sequencing (NGS) applications. In benchmark results, CompStor Insight enables a 7x improvement in gene annotation performance allowing researchers to spend more time developing treatment innovations, and less time on data processing.

OmniTier made the announcement coincident with the ASHG 2020 virtual meeting, where it will showcase CompStor Insight and other members of the CompStor genomics analysis product family.

Our researchers are very busy because we need to analyze and interpret complex variants of many patients, said Kazuhiro Nitta, lecturer at Juntendo Universitys Graduate School of Medicine in Tokyo, and part of the Intractable Disease Research Center. He collaborated with OmniTier on CompStor Insight product development. It was an enjoyable experience to work with the innovative team at OmniTier. With the level of automation and sophisticated filtering that is supported by CompStor Insight, we estimate we could reduce the amount of time for downstream analysis of multi-genomic data sets dramatically.

Personalized medicine initiatives have put the spotlight on tertiary analysis as the most complex step in NGS, where scientists seeking better treatments for cancer or rare diseases investigate variants identified during secondary analysis. Competing open source solutions and internally developed applications in use today for tertiary analysis often exhibit low level of functional automation and require long data ingress-compute-egress cycles delay time to actionable data that does not scale with more server nodes.

CompStor Insight is the first tertiary analysis appliance on the market and enables faster time to results, and low per-subject cost. With an easy set up and straightforward Web browser interface, it provides push-button workflows for annotation, filtering, visualization and querying variant data. Utilizing OmniTiers proprietary MemStac tiered memory technology, CompStor Insight can process up to several thousand genome datasets at speed, enabling faster and more accurate interpretation of data in genome-wide-association studies (GWAS) and rare disease analysis. Because CompStor Insight is designed to interface to a wide range of standard and custom knowledge databases including ClinVar and gnomAD, teams have access to a wide set of reference data at their fingertips. Being a stand-alone appliance, CompStor Insight can store subject data locally in on-premise storage, or leverage cloud storage options.

In testing, CompStor Insight delivered a 7x reduction in run time to annotate typical WGS data, compared to Ensembl VEP. For NGS service businesses, where time is money, CompStor accelerates the annotation and filtering functions dramatically, providing an opportunity to grow their revenue and profit easily.

When used with OmniTiers secondary analysis appliance, CompStor Novos, organizations benefit from an end-to-end analytics solution, from sequencer output, advanced variant calling, and fast annotation, to state-of-the-art multisubject tertiary analysis. Pharmaceutical and biotech companies can take advantage of CompStor Insights intuitive GWAS workflows to identify biomarkers for drug development and develop subject selection strategies.

As the cost of gene sequencing decreases, many organizations are looking for faster, easier ways to learn from each patients data, and convert data to knowledge, said Christi Bird, principal consultant and fellow in Frost & Sullivan's Transformational Health Growth consulting team. OmniTier is addressing a key growth market as the bioinformatics industry works to enable the mass adoption of genomic medicine.

Researchers are straining to meet the explosive demand for personalized medicine with analytics that burden them with complexity and delays that impede the ability to turn data into knowledge and then treatments, said Hemant Thapar, CEO and founder of OmniTier. CompStor Insight is enabling the low per subject cost and faster turnaround time to actionable data that is critical to delivering better treatments for hundreds of diseases and genetic conditions.

CompStor Insight appliances will start shipping to pharmaceutical and research organizations in December 2020. For more information or to request pricing please visit http://www.omnitier.com.

About OmniTier Inc.

OmniTier develops AI and multiomics appliances and software for bioinformatics, scientific computing, and web services applications that deliver affordable real-time solutions to enrich everyday living. Its integrated appliance solutions accelerate data-intensive infrastructure applications, including genomic workflows and scientific analysis for machine learning and AI. Founded in February 2015, the company has R&D operations in Milpitas, CA and Rochester, MN.

CompStor Insight is for research purposes only. CompStor, CompStor Insight and MemStac are trademarks of OmniTier, Inc. CompStor Novos is a registered trademark of OmniTier, Inc.

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OmniTier Streamlines Personalized Medicine Workflows with CompStor Insight for Next-Generation Sequencing Tertiary Analysis - BioSpace

This study used powerful genomic tools and supercomputers to analyze massive amounts of genetic data and identify individual strains within single species of the gut microbiome present during an infants first 6 years of life.

Casey Morrow, Ph.D.Since 2017, University of Alabama at Birmingham researchers Casey Morrow, Ph.D., and Hyunmin Koo, Ph.D., have used powerful genomic tools and supercomputers that analyze massive amounts of genetic data to identify individual strains within single species of the gut microbiome.

This microbiome fingerprint method has helped show the maternal sources of microbes for the human infant or mouse pup microbiomes, as well as showing extreme persistence of gut microbial strains in adult human twins who lived apart after cohabitating for decades.

Now Koo and Morrow have turned their microbial strain stability studies to human infants and children, ages shortly after birth (about 6 months) to 6 years. In general, they found that there were individualized patterns of microbial strain specificity as the infant gut microbiomes developed.

The infant gut microbial ecosystem starts with short-term changes in microbial composition that eventually resolve to a stable microbial composition, the focus of the current study. These stable microbe-host interactions are essential for efficient digestion of food, healthy immune development and resistance to colonization with pathogens.

In general, the early gut microbial community is dominated by microbes that can feed on the carbohydrates present in breast milk or formula, such as Bifidobacterium adolescentis, Morrow said. As the infant grows, the transition to solid foods and physical growth result in changes in the spatial structure of the gut, which contributes to the variation in the physical and chemical environment that provides new ecological niche opportunities for growth of microbial strains. This ecosystem transition correlates with the appearance of Bacteroidetes such as Bacteroides vulgatus within the gut microbial community structure.

The UAB researchers applied their microbe fingerprint technique to two metagenomic DNA sequencing data sets, from previously published studies by others, of fecal samples of infants and young children collected as a time series. The first set of 31 infants had samples collected shortly after birth and at 1, 2 and 3 years of age. Fourteen of those children had multiple antibiotic treatments, which can disrupt the gut microbiome; the rest did not have antibiotics. The second data set included nine infants who were sampled from 6 months of age up to 6 years; four of the nine had been given multiple antibiotics.

Of the 17 infants in the first data set who had not received antibiotics during the three years after birth, an infant-specific pattern was seen for stable and unstable microbial strains. Only one infant had no stable strains identified out of the 20 bacterial species analyzed. For the 14 infants who had multiple doses of antibiotics, 10 showed a unique pattern of transient strains that appeared for a short time after multiple antibiotic treatments.

For the second data set, the UAB researchers analyzed the gut microbial strain stability of Bacteroides vulgatus and Bifidobacterium adolescentis for up to six years following birth. They found individual specific patterns of varying dominant microbial strains that were independent of antibiotic exposure and birth mode. Importantly, there was no obvious linkage between strain changes in B. vulgatus and B. adolescentis. For example, one infant given multiple antibiotics had limited change in B. vulgatus strains as B. adolescentis strains changed extensively, while another infant given multiple antibiotics had the opposite pattern of strain changes.

Hyunmin Koo, Ph.D.The researchers also saw several examples of transient microbial strain change for short periods, without antibiotic treatments, followed by recovery to the dominant strain. Although the driving force for those changes is unknown, there were several instances where an infant-specific complete strain change for B. vulgatus and for B. adolescentis occurred. The metadata for those infants showed no obvious correlation of those changes with sex, country of origin, delivery mode or whether the infant would go on to develop diabetes.

The results of our analysis using both data sets highlight that microbial strain change is inherent in the developing infant gut microbial ecosystem, Koo and Morrow said. Furthermore, the results from our study support the use of the strain-tracking method to monitor the development of a stable and healthy microbial community.

Morrow, Koo and colleagues have used their microbe fingerprint tool in previous strain-tracking studies. In 2017, they found that fecal donor microbes used to treat patients with recurrent Clostridium difficile infections remained in recipients for months or years after fecal transplants. In 2018, they showed that changes in the upper gastrointestinal tract through obesity surgery led to the emergence of new strains of microbes. In 2019, they analyzed the stability of new strains in individuals after antibiotic treatments, and earlier this year, they did the adult twin study, which showed that twins shared a certain strain or strains between each pair for periods of years, and even decades, after they began living apart from each other. Also this year, they showed that an individualized mosaic of microbial strains was transmitted to the infant gut microbiome from a mother giving birth through vaginal delivery, as analyzed in mother-infant pairs, as well as mouse dams and pups.

Co-author with Morrow and Koo in the current study, Strain tracking to identify individualized patterns of microbial strain stability in the developing infant gut ecosystem, published in the journal Frontiers in Pediatrics, is David K. Crossman, Ph.D. Support came from the UAB School of Medicine.

At UAB, Morrow is a professor emeritus in the Department of Cell, Developmental and Integrative Biology, and Koo and Crossman are, respectively, bioinformatician and associate professor in the Department of Genetics.

Original post:
Microbial strains show individualized patterns of stability in the developing infant gut - The Mix

Understanding genetic disease in mixed-breed and purebred dogs and cats can bring about more effective treatments and better client service, says clinical geneticist and general practitioner Dr. Jerold Bell.

If we understand the genetic background of our patients, were better positioned to prevent, to mitigate, or to alter the expression of genetic disease, allowing our patients to be healthier in their lifetimes as well as to breed healthier dogs and cats, Dr. Bell said.

An adjunct professor at the Cummings School of Veterinary Medicine at Tufts University, Dr. Bell spoke about genetic diseases during the AVMA Virtual Convention 2020 this August. In addition to his teaching duties, Dr. Bell works as a solo practitioner, and he sees dogs and cats all day long and sees genetic disease in our patients all day long.

He explained that common genetic disorders are caused by ancient disease liability genes that preceded breed formation. Since these mutations occurred long before the separation of breeds, these diseases are seen across all breeds and in mixed breeds.

The most common hereditary diseases in dogs are allergies, followed by hip and elbow dysplasia; inherited cancers such as lymphoma, hemangiosarcoma, mast cell tumor, and osteosarcoma; patella luxation; nonstruvite bladder stones; hypothyroidism; mitral valve disease; inflammatory bowel disease; diabetes mellitus; retained testicles; and umbilical hernias.

In cats, the most prevalent genetic diseases are inflammatory cystitis, then feline urological syndrome, diabetes mellitus, lymphoplasmocytic gingivostomatitis, nonstruvite bladder stones, allergies, eosinophilic skin disease, and inflammatory bowel disease.

Disease is not a function of homozygosity, which happens when identical DNA sequences for a particular gene are inherited from both biological parents, nor is it a consequence of inbreeding. Rather, Dr. Bell explained, hereditary diseases are a result of the accumulation and propagation of specific disease liability genes. Breed-related deleterious genes accumulate in various ways, including direct selection for disease-associated phenotypes, linkage to selected traits, carriage by popular sires, genetic drift, andmost importantlythe absence of selection against deleterious phenotypes.

If we dont select for healthy parents to produce offspring, then we have no expectation of health in those offspring, Dr. Bell said. Not selecting for health is selecting for disease, and we need to understand that and pass that on to our breeder clients.

On the topic of disease and extreme phenotypes, Dr. Bell said brachycephalic obstructive airway syndrome is frequently diagnosed at veterinary clinics on account of the popularity of certain brachycephalic dog breeds, namely Pugs, French Bulldogs, and Bulldogs. Most breed standards do not call for the expression of extreme phenotypes, he said, nor do they select for the most extreme size or the most extreme brachycephalic trait.

Moderation away from extremes that cause disease should be the guiding principle in breeding, Dr. Bell noted, and in judging dog shows.

Common genetic diseases seen in mixed-breed dogs and cats occur randomly because of dispersed ancient liability genes, according to Dr. Bell. Uncommon and breed-specific recessive or complexly inherited disease is far less likely to occur in mixed-breed individuals.

Dr. Bell said designer-bred dogs and cats often have inherited diseases common in random-bred populations. They can also inherit disease liability genes shared by the parent breeds or parent species. So if youre breeding short-statured breeds together, it wouldnt be surprising to see patellar luxation, or in smaller toy size breeds, to see mitral valve disease, he said.

Hereditary disease manifests as a result of anatomical mismatch between parent breeds. We see a lot of this in dental disease, where we see crowding of teeth and malocclusions and misplaced teeth, Dr. Bell continued. Even in the musculoskeletal, if you breed two breeds with different body types together, we may see degenerative joint disease and poor joints. All of these things, all need to be monitored.

See the rest here:
Making sense of genetic disease in dogs and cats - American Veterinary Medical Association

The revolution of genetic testing has led to more accurate and widespread assays for patients with cancer; however, as more genetic variants are identified, it has become a greater challenge to determine the optimal treatment for an individual patient, according to GouthamNarla, MD, PhD.

As we sequence more genes, we will have more information, which is a good thing, said Narla. Of course, we will also find more variants that, at this time, we don't know whether they're pathogenic or benign. They get lumped into the uncertain category, which creates uncertainty for patients and for providers, as well.

In an interview withOncLiveduring the 2020 Institutional Perspectives in Cancer (IPC) webinar on Precision Medicine, Narla, an associate professor in the Department of Medicine; chief of the Division of Genetic Medicine, Department of Medicine; and associate director of the Medical Scientist Training Program, University of Michigan, further discussed the utility of genomic testing and updates in next generation sequencing (NGS).

OncLive: Could you discuss the key advances in cancer genetics? What are some of the mechanisms that have driven its development?

Narla: A couple of major advancements we've seen in cancer genetics is the identification of additional disease-causing variants. It used to be when I first trained as a medical geneticist, we really only knew about BRCA1/2 and some of the mismatch repair genes. Now, we know about other genes, including PALB2, and other members and genes in that family. That has expanded the testing opportunities for our patients.

The other aspect that has been very exciting is now some of these gene variants are predictive of response to therapies. We have therapies that can be specifically used and work for patients who harbor some of these germline variants. That has really changed the way in which we have treated patients who carry these variants.

What are some of the recent developments in NGS?

Previously, we were doing single-gene testing, oftentimes by Sanger sequencing. Now, we can do large panels of genes depending upon the company and the panel; these comprise anywhere from 60 to 70 genesin some cases, several thousand genes. It has allowed us to collect vast amounts of sequencing information. Some of it will not be directly actionable now, but it still fuels research opportunities for us at major academic medical centers, and when more knowledge [is] gained, we go back to some of those sequencing results to see if, in fact, there was something that is now actionable based upon new knowledge.

How are we using this information to develop targeting strategies?

A lot of the approaches that we are using now may not involve the directly targeting the defective gene or protein, but they are leveraging knowledge about how that defective gene or protein causes activation of targetable pathways. For example, when it comes to BRCA1 loss, that creates a unique opportunity to use a PARP inhibitor in a synthetic lethal interaction, where those cells become highly dependent upon that enzyme. Then, you can inhibit with small molecules [or perhaps] approved PARP inhibitors, such as olaparib (Lynparza), and others for which there are now [a number of approved drugs that can target] a range of BRCA-deficient metastatic tumors.

How else has genomic testing evolved?

The evolution has been both in the number of individuals that we test, as well as how many genes we test. [For example, we used to] test families in which there are numbers of individuals who have cancer and we had a strong pretest probability that they would have a germline variant. Now, in fact, every patient with metastatic ovarian cancer, regardless of family history, gets tested. This is because we have PARP inhibitors for them. It not only has implications for their family but it also has implications for their treatment choices.

What guidelines have been helpful to your practice as it relates to genomic testing?

There are a number of organizations from the American Cancer Society to National Cancer Institute and the National Comprehensive Cancer Network (NCCN) that have very robust guidelines on who to test. There is also a little bit of subjectivity in making an appraisal with a genetics professional, meaning a genetic counselor or a medical geneticist, because not every family will fit the structure or will even know the entirety of their family history. There is some nuance to this, but there are definitely very established guidelines that exist and that we use when making these types of decisions.

However, the NCCN guidelines are very good and are used by [our institution. Then we apply our own nuances when we see the patient on a case by case basis. But, [in terms of] informing who should be tested and who should not, and which individual in the family should be [tested], the NCCN guidelines are a very good [resource].

What challenges could be addressed with future research?

I would like to see more of an effort to share data across all institutions and testing companies to reclassify these variants. I would like to see more basic science and translational science around what we call variant reclassification, so that we can really make definitive calls about the sequence changes that we see. The more genes we sequence, the more variants we find, and on larger panels, [we can see these uncertain variants in up to] 20% of patients. We're finding something in a gene, but we don't know whether it's good or bad for the patient.

Are there any new capabilities or technologies emerging that you find particularly exciting?

From a technology perspective, the last 10 years in sequencing has been a revolution; the cost of sequencing has come down and the accuracy has gone up. I'm not sure that we're going to see that much more of a revolution in the sequencing technology; it will be more efficient and more cost effective. We're [going to see] the identification of new genes associated with disease [and will therefore] it will be in the variant reclassification space.

What testing or sequencing studies are of particular interest?

One type of study that has read-out recently comprise the effectiveness of immunotherapy in patients who have mismatch repair deficient tumors. That has been really game-changing for those patients. The other major study is the use of PARP inhibitors in BRCA-mutant tumorsoriginally in the second- and third-line settings of ovarian cancer. [PARP inhibitors] have now moved to maintenance [therapy], pancreatic cancer, prostate cancer, and others. That has changed the management of patients with BRCA-positive tumors.

Excerpt from:
Identifying Genetic Variants, Matching With Targeted Therapies Serve as Next Great Challenge With Germline Testing in Oncology - OncLive