Category Archives: Transhuman News

The Encyclopedia of DNA Elements (ENCODE) Consortium is a universal coordinated effort of research groups funded by the National Human Genome Research Institute (NHGRI). The objective of ENCODE is to make a comprehensive parts list of functional elements in the human genome, including elements that work at the protein and RNA levels, and regulatory elements that control the cells and conditions where a gene is active.

The project will detail how the human genome functions. Recently, the project completed its latest phase- scientists have added millions of candidate DNA switches from the human and mouse genomes. These genomes appear to control when and where genes are turned on, and a new registry that assigns a portion of these DNA switches to useful biological categories.

It also provides the latest visualization tools to help in the use of ENCODEs large datasets.

NHGRI Director Eric Green, M.D., Ph.D. said,A major priority of ENCODE 3 was to develop means to share data from the thousands of ENCODE experiments with the broader research community to help expand our understanding of genome function. ENCODE 3 search and visualization tools make these data accessible, thereby advancing efforts in open science.

To evaluate the potential functions of various DNA locales, ENCODE specialists considered biochemical procedures that are normally connected with the switches that regulate genes. This biochemical methodology is an effective method to investigate the whole genome wholly and quickly.

This strategy assists with finding regions in the DNA that are candidate functional elements DNA regions that are anticipated to be practical components dependent on these biochemical properties. Candidates would then be able to be tested in further experiments to distinguish and portray their useful roles in gene regulation.

Elise Feingold, Ph.D., scientific advisor for strategic implementation in the Division of Genome Sciences at NHGRI and a lead on ENCODE for the institute, said,A key challenge in ENCODE is that different genes and functional regions are active in different cell types. This means that we need to test a large and diverse number of biological samples to work towards a catalog of candidate functional elements in the genome.

During the recently completed third phase of ENCODE, scientists performed almost 6000 experiments in several biological contexts- 4,834 in humans and 1,158 in mice- to enlight details of the genes and their potential regulators in their respective genomes.

Scientists studied developing embryonic mouse tissues to comprehend the timeline of various genomic and biochemical changes that occur during mouse development.

Scientists analyzed how chemical modifications of DNA, proteins that bind to DNA, and RNA (a sister molecule to DNA) interact to regulate genes. Results from ENCODE 3 also help explain how variations in DNA sequences outside of protein-coding regions can influence the expression of genes, even genes located far away from a specific variant itself.

Brenton Graveley, Ph.D., professor and chair of the Department of Genetics and Genome Sciences at UCONN Health, said,The data generated in ENCODE 3 dramatically increase our understanding of the human genome. The project has added tremendous resolution and clarity for previous data types, such as DNA-binding proteins and chromatin marks, and new data types, such as long-range DNA interactions and protein-RNA interactions.

As a new feature, ENCODE 3 scientists created a resource detailing different kinds of DNA regions and their corresponding candidate functions. A web-based tool called SCREEN(link is external) allows users to visualize the data supporting these interpretations.

The projects latest results were published in Nature, accompanied by 13 additional in-depth studies published in other major journals.

Link:
Revealing the intrinsic functioning of human and mouse genomes - Tech Explorist

Health officials and scientists believe genome sequencing of the coronavirus could hold great promise. The technique today helps trace where infections began, and perhaps one day it could help shape the way doctors treat COVID-19 patients.

A new initiative between California and the San Francisco research institution funded by Facebook CEO Mark Zuckerbergs philanthropic organization could bring them one step closer.

The Chan Zuckerberg Biohub will offer free genome sequencing for lab samples that have tested positive for the coronavirus from all California counties, the institution is slated to announce Thursday.

It is one of the largest statewide, coordinated efforts to do genome sequencing for COVID-19, said Dr. Joe DeRisi, co-president of the Chan Zuckerberg Biohub. Genome sequencing helps determine what strain of the virus people have, which helps public health officials trace how transmission occurred and where it came from.

The Biohub had already been doing genome sequencing on samples from many California county public health departments on a smaller scale since March. Now, it is formally partnering with the state Department of Public Health to expand the work.

Sequencing is not necessary for all samples, but can be useful to determine the source of an outbreak in some settings or to rule out a suspected pattern of transmission. For example, if sequencing found that similar strains of the virus are rampant at two different nursing homes, and the two facilities share staff, that may indicate a staffer brought the virus from one home to the other. Or if one factory employee has a strain that is similar to that of a coworker, it may indicate the virus spread at work; but if strains found in one workplace are vastly different, it indicates the employees likely got sick from interactions outside of work.

Where its the most helpful is understanding the number of circulating strains in a given community, to understand if theres been a new introduction of a strain to a particular geographic area or facility, DeRisi said. That establishes whether youre looking at ongoing, in-community transmission, or whether theres been an outside introduction that was unbeknownst to you.

Sequencing involves putting a sample that has tested positive for the coronavirus into a lab machine that analyzes the viral genetic material and identifies where mutations occur.

A strain is a group of viruses with similar mutations. SARS-CoV-2, the virus that causes COVID-19, has 30,000 letters of RNA, genetic material that includes instructions on how to make new copies of the virus. When the virus spreads from cell to cell and person to person, it passes on small changes, or mutations, in the viral information. Some of those mutations are then passed on to the next person. A strain is a product of a long chain of transmission, and the cumulative changes that occurred over time.

The Biohub will not sequence every single sample. But it will sequence samples when the work can help answer critical questions about some outbreaks and how they started. Biohub has sequenced about 1,600 samples from nursing homes, packing plants and prisons from 20 California counties. It is sequencing samples from San Quentin State Prison to determine whether the outbreak there came in from one source and then spread, or if it came in from multiple sources carrying different strains.

Sequencing has helped scientists determine that the East Coast has largely been hit with a European strain of the virus, while California has been hit by many strains, including from Europe and China.

One of the potential promises of genome sequencing is that it could eventually help scientists learn whether certain strains of the coronavirus are resistant to certain drugs. That could help doctors pick which drugs, or cocktail of drugs, to administer to patients. With HIV, for instance, sequencing helped researchers glean that some strains of the virus respond well to certain drugs while other strains are resistant to the same drugs.

Ultimately, we might be able to use this data for things like susceptibility to drugs or a vaccine, said Dr. Robert Siegel, a Stanford infectious disease expert. Were not there yet.

It is too early with the coronavirus to know whether some strains are resistant to drugs. There have not been many drugs that have successfully treated COVID-19. But a few, including remdesivir, appear to help some very sick patients.

Imagine that you took all the patients on remdesivir, and you had good clinical data on them, and it turns out some people responded to remdesivir and some didnt, Siegel said. Its possible that is either a function of the viral strain or of the genetic makeup of the host, or a combination of the two. Or it could be luck. ... If we started seeing remdesivir resistance, almost certainly wed be able to tell what mutations gave rise to remdesivir resistance.

It costs about $15 to $20 to sequence each sample, DeRisi said.

The sequencing will be done at a lab at the Biohub, which is financed by the philanthropic organization Chan Zuckerberg Initiative in San Franciscos Mission Bay. The initiative was created in 2015 by Zuckerberg and his wife Dr. Priscilla Chan, who pledged $600 million over 10 years to help advance medical research.

The initiative has also committed $13.6 million to fund large, long-term COVID-19 studies in the Bay Area and a $4 million UCSF lab to process coronavirus tests.

Catherine Ho is a San Francisco Chronicle staff writer. Email: cho@sfchronicle.com Twitter: @Cat_Ho

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California and Zuckerberg lab team up to map coronavirus genome, one of the largest efforts to discover how it spreads - San Francisco Chronicle

Less than a year after launch, Omega Therapeutics is getting an $85 million (PDF) cash boost. It will push a pipeline of treatments toward the clinic as well as bankroll the identification of new targets for genomic medicines.

We had founded Omega with a long-term vision to create a controllable epigenomic programming platform, Omega CEO Mahesh Karandetold Fierce Biotech. Rather than switching genes on and off, cutting out disease-causing genes or replacing them with healthy versions, Omegas platform is designed to adjust gene expression to healthy levels.

The companys work is based on neighborhoods of genes and their regulatory elements found in loops of DNA called Insulated Genomic Domains (IGDs). These loops occur because long strands of DNA need to fit into the cells nucleus.

In nature, generally things are not all the way on or all the way off, but rather turned to a very specific range in a healthy setting, Omega Chief Scientific Officer Thomas McCauley, Ph.D., said in a previous interview. Omegas epigenomic controllers are designed to target the right place on specific IGDs to restore gene function at the right level, he said.

Since launch, Omega has been workingto figure out which neighborhoods play a role in different diseases.

RELATED: Flagship unveils 'genome-tuning' biotech Omega Therapeutics

We could have gone in various directions, Karande said. But Omega landed on a handful of areas. Its advancing five programs spanning oncology and inflammation as well as autoimmune, metabolic and raregenetic diseases, the first of which should hit the clinic in 2021.

In addition to tweaking gene expression without making permanent changes to the genome, Omegas approach offers advantages over a small-molecule approach to epigenetics.

There are a number of companies developing small-molecule therapies for epigenetic targets, almost exclusively in cancer, McCauley.

The issue is really specificity, in having those molecules go everywhere in the body as opposed to having them go to specific cell types and specific locations in the genome, McCauley continued, adding that the benefits of such treatments might outweigh the risks in oncology but that this risk-benefit profile may be unacceptable in other diseases.

In its first efforts, Omega is going after targets with links to specific diseases that are well understood, McCauley said. Moving forward, it will take advantage of the lessons it learns to look for new targets.

Were looking for the ability to expand laterally, he added.

One of those lateral expansions could be into COVID-19. Since inflammation plays a big role in COVID-19 infection, Omega could leverage the work its already done in that space to quickly move into drug development against the new coronavirus.

Right now, it's all systems go with its fivepotentially sixprograms. Karande said the company would be "remiss" if it did not ink partnerships.

"We are absolutely open to partnering with people. We have a robust discovery platform that has many, many more targets in the pipeline, so yes, partnering is definitely in the cards for us," he said.

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'Genome-tuning' biotech Omega Therapeutics snags $85M as it aims for the clinic - FierceBiotech

Dr. Andrew Cameron a microbial geneticist with the university of Regina, together with Manitobas Cadham Provincial Laboratory and Saskatchewans Roy Romanow Provincial Laboratory, received funding to lead Genome Prairies COVID-19 Rapid Regional Response (COV3R) project.

The COV3R team also includes members of the Institute for Microbial Systems and Society at the University of Regina where Cameron is co-director, as well as the British Columbia Centre for Disease Control.

Co-infection is a problem because any time your body has to fight multiple infectious diseases, it can compromise the ability of your immune system to protect you, Cameron said,

Genome Prairie provided $240,000 in funding for the project, and the Saskatchewan Health Research Foundation (SHRF) contributed $50,000, while the Centre for Disease Control in B.C., the Roy Romanow Provincial Laboratory in Saskatchewan, and the Cadham Provincial Laboratory in Manitoba provided in-kind support.

Using genome capture, the COV3R initiative aims to tackle the problem of detecting co-infections in humans, and in the process provide powerful new tools for public health.

Co-infection by respiratory pathogens is bad for patients, yet we know very little about co-infection in the context of the COVID-19 pandemic. Integrating the genomic detection of respiratory viruses and bacteria to better understand the severity of COVID-19 infection will directly and immediately improve public health interventions and clinical treatment plans,Cameron explained.

This technique will also give researchers the ability to test for all viral groups, even those scientists dont yet know about.

Misdiagnosis is a problem with infectious diseases because of the limited number of signs and symptoms that people experience such as a fever, a sore throat, and a headache. So even in the modern day with all our advanced techniques, we still sometimes attribute disease to the wrong culprit.

Cameron says that genome capture can help in diagnosing infectious diseases by adding a powerful tool for provincial public health testing labs.

Our work with genome capture will directly complement genetic sequencing of 150,000 coronaviruses as part of Genome Canadas Canadian COVID-19 Genomics Network (CanCOGeN) initiative, he said.

We will sequence coronavirus genomes along with co-infecting viruses, then can examine the Manitoba and Saskatchewan coronavirus infections in broader provincial, national, and international contexts through integration with CanCOGeN.

Another key feature of genome capture testing is that it offers the ability to track viruses by their unique genetic makeup. This allows public health officials to compare, for example, coronavirus causing COVID-19 cases in different parts of a province or region with virus strains from elsewhere to find out where the disease is coming from and how its moving through communities.

The COV3R team is also developing a unique tool that efficiently captures genetic material and compares it against all coronaviruses known to infect animals, which will be a valuable asset in the current pandemic and for early detection of coronavirus pathogens in the future.

Whole genome sequencing is revolutionizing epidemiology. This technology has the potential to discover so much. With it, we might find something circulating here that we didnt know we had. No other technology comes close, Cameron said.

The technology will also address the added problem of what the pandemic is doing to testing capacity.

Laboratories, and the experts who run them, are flooded with COVID-19 testing, forcing them to reduce testing for other respiratory pathogens. This means information about other diseases in Canada is being missed at the moment because COVID-19 is the priority, says Cameron. Our project will help to address this gap.

Dr. Gerald Brown, Genome Prairies interim President and CEO, says Genome Prairie is thrilled to be supporting the research teams work.

The COV3R project represents our organizations ability to bring together the best researchers in our Prairie provinces to respond rapidly and effectively to an emerging issue, Brown said.

Dr. Kathleen McNutt, VicePresident (Research) at the University of Regina, says without this work the people of Saskatchewan, Manitoba, and B.C. will likely be hit even harder by the coronavirus, especially in the fall when cold and flu season re-emerges.

Thanks to the support from Genome Prairie and SHRF, the work that Dr. Cameron and the COV3R team are doing is poised to make a dramatic difference in detecting COVID-19, and a multitude of other viruses and bacteria that are yet unknown, McNutt said.

It is not an overstatement to say this research is a matter of life and death.

SHRF CEO Patrick Odnokon says SHRF has been a strong supporter of Cameron and his team since 2013, including earlier work evaluating whole genome sequencing to enhance our understanding of disease transmission.

Dr. Cameron is a perfect example of the expertise that exists in Saskatchewan to seek solutions to health challenges faced by our province and across the globe. The impact of this work will not only benefit public health during the current pandemic, but it will demonstrate what is possible when we nurture and support home-grown talent and collaboration to prepare for potential health crises in the future.

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University of Regina led genome capture project aims to detect COVID-19 or anything else that ails you - Prince Albert Daily Herald

]]]]]]>]]]]>]]> How can genomics help tackle the Covid-19 pandemic? Credit: Shutterstock.

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In 2003, after 13 years of work and more than 2bn spent, scientists involved in the Human Genome Project mapped the first complete genetic code, or genome, of a human being. This was a huge scientific breakthrough and taught genetics researchers a lot about human genes, the genome and how they interact with health and disease.

As further genomics work was undertaken over the next decade or so, it became evident that genome sequences are most useful when combined with other data about the person who donated their sequence, such as physiological measurements and their past medical records of previous illness and prescribed medication.

By joining up these dots, genomic medicine has the potential to improve understanding about the underlying causes of genetic diseases and predict how a person could respond to certain treatments, helping to find personalised approaches for each individual patient, as well as determining what diseases people are at risk of developing in the future.

With this in mind, the UK Government created Genomics England to coordinate work in the field. Having a centralised approach also mitigates some security concerns around the storage and use of patients incredibly private health data. The UK is an excellent location to push genomics forward. Not only does the country have a strong genetics heritage two British scientists, James Watson and Francis Crick, discovered the double helix structure of DNA in the 1950s but it has a unique resource in the National Health Service (NHS), one of the worlds largest single-payer healthcare systems in the world.

Initially focused on cancer and rare diseases known to have genetic elements, Genomics England has now diversified to look at how genomics can help track the spread of infectious disease. The organisation has joined a national consortium looking to leverage genomics to better tackle the Covid-19 pandemic. The UK has been hit extremely hard by the pandemic so far according toJohn Hopkins Covid-19 map, the UK has the second-highest number of deaths globally.

Before looking at the latest project, its important to reflect on Genomics Englands foundation and mission.

Genomics England was established in 2013 by the Department of Health and Social Care to deliver the 100,000 Genomes Project, which was launched by former Prime Minister David Cameron in late 2012.

Backed by more than 300m in government funding, the 100,000 Genomes Project aimed to create a foundation for a new era of personalised medicine within the NHS by sequencing 100,000 whole genomes from 70,000 patients with rare diseases and cancers.

To support Genomics England with recruitment for the project, NHS England set up 11 Genomic Medicines Centres (GMCs); now there are 13 in England as well as a few more in Wales, Scotland and Northern Ireland as they got on board with the project in the mid-2010s. The GMCs also helped with finding the clinical information needed to inform better interpretation of each persons genome sequence.

From the outset, Genomics England was very aware that it would need to build its own technology to complete the 100,000 Genomes Project. The company decided the best way to do this was to work with innovators in the genomics and sequencing space.

Genomics Englands first partnership was signed with California-headquartered Illumina to develop a sequencing infrastructure. As part of the deal, Illumina invested 162m in this work in the UK over the next four years.

In addition, as part of its 1bn commitment to the UKs genomics industry, the Wellcome Trust agreed to spend 27m on a world-class sequencing hub just outside Cambridge to house Genomics Englands operations. This gave the 100,000 Genomes Project easy access to world leaders in the genomics space, such as the European Bioinformatics Institute and the Sanger Institute.

Within two years of the launch, ten companies moved to collaborate with Genomics England to support and further accelerate the 100,000 Genomes Project. These companies, which included GSK, AstraZeneca, UCB, AbbVie, Roche and Takeda, established the Genomics Expert Network for Enterprises (GENE) Consortium; Big Pharma had to contribute 250,000 to the project in funding to collaborate. The aim was to carry out a year-long industry trial of select whole-genome sequences to establish how industry could leverage the learnings from the 100,000 Genomes Project into drug discovery and development. This initiative was renamed the Discovery Forum in 2017.

Simultaneously, Genomics England launched its Clinical Interpretation Partnership (GeCIP) to find ways to work with clinicians and researchers to directly bring the benefit of the 100,000 Genomes Project to drive diagnosis.

As part of a pilot scheme under the 100,000 Genomes Project, Newcastle University and Hospitals used whole-genome sequencing to reveal that a patients kidney failure was due to a rare genetic variant; this explains why his father, brother and uncle had all died of the same condition.

This diagnosis using genome sequencing meant that the patient could receive personalised treatment for this specific condition. Also, his family members could be tested to find out if they were affected by the same rare genetic kidney disease, rather than face a lifetime of uncertainty.

Hot on the heels of the first patients diagnosed, two children became the first to be genetically diagnosed through the 100,000 Genomes Project via Great Ormond Street Hospital in London. Both have rare, undiagnosed and unknown medical conditions, but due to whole-genome sequencing doctors now know the genetic changes responsible for their conditions.

NHS chief scientific officer Professor Dame Sue Hill said: This is an excellent example of how whole-genome sequencing can finally provide the answers that families have been seeking out for years. This new insight sets them free to make decisions about the treatment options for their child and how they move forward with future plans for their family.

One of the biggest challenges facing delivery of the 100,000 Genomes Project early on was to create a bioinformatics pipeline to analyse and interpret the genomics data. To this end, Genomics England decided to expand its sequencing partnership with Illumina to create informatics tools for use at the NHS GMCs and GeCIP.

This was followed later in 2016 by a deal signed with Ohio-based GenomOncology to improve clinical reporting, particularly in clinical trials, for the 100,000 Genomes Project cancer programme.

In early 2018, Genomics England and the Department of Health and Social Care announced 50,000 whole genomes had been sequenced.

This put Genomics England on track to finish recruitment and scale up operations so the full project could be completed on time by the end of 2018.

As the 100,000 Genomes Project came closer to completion, the newly appointed Secretary of State for Health and Social Care Matt Hancock announced a roadmap for honouring its legacy through continuing work on genomics medicine in the NHS.

Hancock committed to sequencing five million whole genomes by 2024 and bringing access to genetic and genomic testing into mainstream clinical practice through theNHS Genomic Medicine Service. Initially it will focus on cancer and rare diseases, like the 100,000 Genomes Project, but it is expected to evolve and expand to other therapeutic areas as the technology becomes more advanced.

At the same time, Genomics England signed a research agreement with life sciences technology vendor IQVIA. This partnership involves the pair running analytics on patient-consented, de-identified data from the 100,000 Genomes Project to drive more efficient drug research and development, particularly in the field of personalised medicine. These insights could be used by IQVIAs life science customers in parallel with their clinical development programmes.

Secretary of State for Health and Social Care Matt Hancock announced in mid-December 2018 that the 100,000 Genome Project had been completed.

Genomics England chair Sir John Chisholm noted: At launch the 100,000 Genomes Project was a bold ambition to corral the UKs renowned skills in genomic science and combine them with the strengths of a truly national health service to propel the UK into a global leadership position in population genomics.

With this announcement, that ambition has been achieved. The results of this will be felt for many generations to come as the benefits of genomic medicine in the UK unfold.

This project led to one in four participants with rare diseases receiving a diagnosis for the first time, while transforming treatment for up to half of cancer patients who participated.

Although launched at the end of 2018, the NHS Genomic Medicine Service was only expected to be operational in mid-2020.

To allow the new service to hit the ground running, Genomics England expanded its sequencing partnership with Illumina to focus on the next 300,000 whole genomes. All clinical samples for the collaboration will be provided through the NHS Genomic Medicine Service.

This follows the late-2018 deal with Congenica to support clinicians to make informed medical decisions based on insights from whole-genome sequencing. Congenica had previously provided similar sequencing services to the 100,000 Genomes Project.

Although Genomics England has primarily focused on cancer and rare diseases, it is clear that insights from genomics also have a role to play in tackling infectious disease.

In the context of the ongoing Covid-19 pandemic, which has killed more than 40,000 people in the UK to date, Genomics England is carrying out a whole-genome study of 35,000 people with either severe, moderate or mild Covid-19 symptoms to try and discover why this viral disease has such a varied impact on patients.

Genomics England will read the data from entire genomes of those who have been most severely impacted by Covid-19 and compare them to those who only experienced mild symptoms; this genomics data will also be enriched by clinical insights into participants.

The company is working with the GenOMICC consortium, Illumina, the NHS and the University of Edinburgh to carry out this study. The project is backed by 28m in funding from UK Research and Innovation, the Department of Health and Social Care and the National Institute for Health Research.

The aim is for this human genomic data to be linked to the virus genome data being sequenced by the COVID-19 Genomics UK Consortium (COG-UK), which is led by the NHS and the Sanger Institute. This would help to improve insights into how the two genomes interact and affect how the patient responds to the infection, which can feed into better knowledge about promising treatments for clinical trials and practice.

Read more:
From rare diseases to Covid-19: charting the history of Genomics England - Pharmaceutical Technology