Monthly Archives: July 2020

The Victorian health minister, Jenny Mikakos, announced on Friday that early genomic sequencing had pointed to a super spreader of Covid-19 as a source for many new infections across Melbournes north and west.

The revelation comes after the states premier, Daniel Andrews, also credited genomic testing for exposing an infection-control failure in the hotel quarantine program through late May and early June.

While contact tracing detectives were praised for their work during the early months of outbreak, genomic sequencing experts are now playing an increasingly significant part in containing community transmission in what has become Australias largest cluster.

Heres what you need to know about genomic sequencing.

Genomic sequencing analyses the virus sample taken from a diagnosed patient and compares it with other cases.

Prior to Covid-19, genomic sequencing has been used in Australia to trace the source of outbreaks of food-borne bacteria and hospital infections.

After a Covid-19 test (which gathers saliva from the back of the throat and nose) returns a positive result, the swab used goes through several steps to separate the RNA molecules from mucus proteins so they can be captured, then converted into DNA that can be read.

As a virus passes from human to human, the virus changes slightly. While the genome of one Covid-19 patient compared with the person they caught it from will appear almost identical, after the virus has been transmitted onto further people, differences between the strands of the virus they carry become more apparent.

Rory Bowden, the head of the Centre for Genomics at the Walter and Eliza Hall Institute of Medical Research in Melbourne, told the Guardian the information allowed scientists to do detective work to understand patterns of spread of pathogens in populations.

The SARS-CoV-2 genome, at more than 30,000 nucleotides, is long for an RNA virus, so while there were few changes initially, there is room for quite a lot of information about each strains history to accumulate.

He said that by the time the virus arrived in Australia, the different changes, or mutations, of Covid-19 define branches on a tree. Each branch of Covid-19 that exists in Australia could be linked back to China in the original instance, as well as via an outbreak in a foreign country.

Bowden said that when Wuhan experienced the first outbreak, the genomes in the city were mostly identical.

He said genomic testing was particularly informative for tracing the current outbreaks in Victoria, whereas earlier on in the pandemic in Australia, and in overseas countries recording higher daily totals, the methods would not be as useful.

With SARS-CoV-2, there are still not that many variant positions to tell different branches of the tree apart. The thing that helps us is that in Australia, most cases are linked back, through one or a few generations of transmission, to the virus imported from all around the world by returning travellers, Bowden said.

If all we had was community spread from a single source introduction to Victoria, it is unlikely we would be able to tell the different clusters apart.

Benjamin Howden, who leads the public health epidemiology team at Melbourne Universitys Doherty Institute, is currently working with state authorities to use genomic sequencing to track Covid-19 cases.

Howden said that as of Friday, about 80% of Victorias cases had been genomically sequenced.

He said bioinformaticians, who apply information technology to biological and medical research, gathered each patients genome data and compared it against other patients in the state.

A genomic epidemiologist then matched the historical data of each strand recorded to the patient that provided the sample.

Matching the genomic findings to epidemiological information means authorities can tell if a new patient caught a virus from a known source of the virus, and can work to identify the point or person of transmission.

It also means authorities can divert resources more urgently into understanding and containing a case if genomic testing shows someone has caught a strain previously only recorded in a different geographic area.

In the case of the super spreader suggested on Friday, the genomic data of all of the patients infected by them would have very few variations. This is because the transmissions originated from just one person, as opposed to several people passing it along and giving a strain further chances to mutate.

Read more:
Genomic sequencing: what it is and how it's being used against Covid-19 in Victoria - The Guardian

The National Institutes of Health has announced the provision of $75 million in funding over five years for the Electronic Medical Records and Genomics (eMERGE) Genomic Risk Assessment and Management Network, which establish protocols and methodologies for improved genomic risk assessments for diverse populations and to integrate their use in clinical care. The eMERGE Network is supported by the National Human Genome Research Institute (NHGRI), part of NIH.

The funding will build upon the existingeMERGE Networkto support both a coordinating center and clinical sites specifically focused on better understanding disease risk and susceptibility by combining genomic and environmental factors and investigating how future findings can be used to help clinicians and patients manage disease risk.

About $61 million in total will be awarded over a period of five years to four clinical and six enhanced diversity clinical sites from around the United States (see below for full list). The enhanced diversity clinical sites will recruit a higher percentage of patients from diverse ancestries. $13.4 million will be awarded for an eMERGE Network coordinating center at Vanderbilt University. Funding will go into effect in June 2020.

The goal of the clinical sites is to recruit participants from diverse groups, such as racial or ethnic minority populations, underserved populations, or populations who experience poorer medical outcomes. The sites will then conduct and validate genomic risk-assessment and management methods for a number of common diseases.

Approximately half of the clinical sites will recruit about 10,000 patients, with the aim that 35% or more come from such diverse groups. The other clinical sites, called enhanced diversity clinical sites, will recruit about 15,000 patients, with 75% or more coming from diverse ancestries.

Your browser does not support the video tag.

NHGRI first initiated the eMERGE Network in 2007. Since then, the network has successfully conducted groundbreaking research on how to effectively use electronic health records and large biorepositories for genomics research in order to eventually integrate genomic information into clinical care.

More recent research has highlighted the need to generate datasets from more diverse populations to better understand estimates of disease risk in the general population.

To date, polygenic risk scores, a new approach for assessing disease risk based on DNA variants, have been developed and validated in studies that almost exclusively involved people of European ancestry. It is not clear how well the findings from these initial studies can be used for risk assessment in non-European ancestry populations. In addition, calculating polygenic risk scores usually do not include variables such as age, body-mass index, alcohol use and other clinical data, all of which can affect an individuals risk for certain diseases.

The new sites within the eMERGE Network aim to investigate ways to incorporate additional clinical data into the risk score calculations. Researchers have termed this combined score as genomic risk assessment or integrated risk score.

The new eMERGE Genomic Risk Assessment and Management Network will also develop ways to better incorporate computer-based programs, which analyze electronic health records and provide reminders and prompts to healthcare providers, into clinical practice. This process, called electronic clinical decision support, is meant to help physicians and other healthcare professionals make clinical decisions for their patients.

The sites will use the newly developed protocols to estimate risk for common, complex diseases of public health importance (e.g., coronary heart disease, Alzheimers disease, and diabetes). They will also look to understand how health management recommendations can be introduced to clinicians using electronic health records. In addition, the sites will provide guidance on how to share genomic-based and integrated risk score information electronically using the Fast Healthcare Interoperability Resources (FHIR ) standard, which provides specifications for how to exchange health information electronically.

The eMERGE Network will also leverage the NHGRI Genomic Data Science Analysis, Visualization, Informatics Lab-space (AnVIL) cloud-based resource to develop tools and workflows for generating integrated risk scores, which will be shared with the biomedical research and clinical genomics communities.

The new clinical sites will be led by:

The new enhanced diversity clinical sites will be led by:

See more here:
NIH funds centers to improve the role of genomics in assessing and managing disease risk - National Human Genome Research Institute

A research programme pioneering the use of whole genome sequencing in the NHS has diagnosed hundreds of patients and discovered new genetic causes of disease.

The project, the results of which were published in the journal Nature, offered whole-genome sequencing as a diagnostic test to patients with rare diseases across an integrated health system, a world first in clinical genomics.

Whole genome sequencing is the technology used by the 100,000 Genomes Project, a service set up by the government which aims to introduce routine genetic diagnostic testing in the NHS. The integration of genetic research with NHS diagnostic systems increases the likelihood that a patient will receive a diagnosis and the chance this will be provided within weeks rather than months.

The multi-centre study, led by researchers at the National Institute for Health Research (NIHR) BioResource together with Genomics England, demonstrates how sequencing the whole genomes of large numbers of individuals in a standardised way can improve the diagnosis and treatment of patients with rare diseases.

The researchers, including experts from the University of Bristol, studied the genomes of groups of patients with similar symptoms, affecting different tissues, such as the brain, eyes, kidney, blood, or the immune system. They identified a genetic diagnosis for 60 per cent of individuals in one group of patients with early loss of vision.

Principal investigators Andrew Mumford, Professor of Haematology, and Moin Saleem, Professor of Paediatric Renal Medicine, led the set-up of the programme and oversaw regional enrolment in the South West. Professor Mumford provided national oversight for blood related disorders, while Professor Saleem managed inherited kidney diseases.

Professor Mumford and researchers in the School of Cellular and Molecular Medicine collaborated with the Bristol NIHR Biomedical Research Centre and the University of Cambridge to develop ways to improve the genetic identification of blood disorders, contributing significantly to the breakthrough diagnostic potential.

Professor Mumford said: This pioneering study illustrates the power of whole genome sequencing for diagnosis of rare human diseases. The approach developed in this research has paved the way for the flagship 100,000 Genomes Project and the introduction of whole genome sequencing into standard NHS care.

Professor Saleem established the UK National Renal Rare Disease Registry, and the national and international NephroS (Nephrotic Syndrome) groups, based within the UK Renal Registry in Bristol. These provided recruitment, essential genetic data, and DNA collection for the study. Researchers in Bristol provided functional and clinical insights leading to the discovery of causative genes relating to kidney disorders.

Professor Saleem said: Rare diseases in their entirety are common, in that there are more than 7,000 different rare diseases in total affecting about 7 per cent of the population. Most have a genetic cause, so this research for the first time brings the most powerful genetic sequencing capabilities to apply across the whole health service, meaning all patients will now have the best possible chance of finding their individual genetic defect.

In the study, funded mainly by the National Institute for Health Research, the entire genomes of almost 10,000 NHS patients with rare diseases were sequenced and searched for genetic causes of their conditions. Previously unobserved genetic differences causing known rare diseases were identified, in addition to genetic differences causing completely new genetic diseases.

The team identified more than 172 million genetic differences in the genomes of the patients, many of which were previously unknown. Most of these genetic differences have no effect on human health, so the researchers used new statistical methods and powerful supercomputers to search for the differences which cause disease a few hundred needles in the haystack.

Using a new analysis method developed specifically for the project, the team identified 95 genes in which rare genetic differences are statistically very likely to be the cause of rare diseases. Genetic differences in at least 79 of these genes have been shown definitively to cause disease.

The team searched for rare genetic differences in almost all of the 3.2 billion DNA letters that make up the genome of each patient. This contrasts with current clinical genomics tests, which usually examine a small fraction of the letters, where genetic differences are thought most likely to cause disease. By searching the entire genome researchers were able to explore the switches and dimmers of the genome the regulatory elements in DNA that control the activity of the thousands of genes.

The team showed that rare differences in these switches and dimmers, rather than disrupting the gene itself, affect whether or not the gene can be switched on at the correct intensity. Identifying genetic changes in regulatory elements that cause rare disease is not possible with the clinical genomics tests currently used by health services worldwide. It is only possible if the whole of the genetic code is analysed for each patient.

Dr Ernest Turro, from the University of Cambridge and the NIHR BioResource, said: We have shown that sequencing the whole genomes of patients with rare diseases routinely within a health system provides a more rapid and sensitive diagnostic service to patients than the previous fragmentary approach, and, simultaneously, it enhances genetics research for the future benefit of patients still waiting for a diagnosis.

"Thanks to the contributions of hundreds of physicians and researchers across the UK and abroad, we were able to study patients in sufficient numbers to identify the causes of even very rare diseases."

Paper:

Whole-genome sequencing of patients with rare diseases in a national health system, by Ernest Turro et alin Nature.

There are thousands of rare diseases and, together, they affect more than three million people in the UK. To tackle this challenge, the NIHR BioResource created a network of 57 NHS hospitals which focus on the care of patients with rare diseases.

Based on the emerging data from the present NIHR BioResource study and other studies by Genomics England, the UK government previously announced that the NHS will offer whole-genome sequencing analysis for all seriously ill children with a suspected genetic disorder, including those with cancer. The sequencing of whole genomes will expand to one million genomes per year by 2024.

Whole-genome sequencing will be phased in nationally for the diagnosis of rare diseases as the standard of care, ensuring equivalent care across the country.

View post:
July: Genome sequencing rare diseases | News and features - University of Bristol

For the nascent brain of a human embryo to develop into the complex organ that controls human consciousness, a finely tuned sequence of genetic events has to take place; hundreds of genes are activated and deactivated in a precise symphony. Mutations in these genes disrupt the molecular instruments of the symphony and, if they occur in genes that are important for brain development, can result in neurological diseases such as autism and epilepsy. Researchers have long struggled to understand how mutations in regulatory regions of the genome--the conductors, rather than the instruments--can also make this process go awry.

Now, researchers at Gladstone Institutes and UC San Francisco (UCSF) Weill Institute for Neurosciences have created a comprehensive region-specific atlas of the regulatory regions of the genome linked to human embryonic brain development.

"This gives us a searchable, data-rich atlas of part of the developing human brain," said Katie Pollard, PhD, director of the Gladstone Institute of Data Science and Biotechnology. "This is a valuable tool for probing the underlying biology of neurodevelopmental disorders."

Pollard and UCSF professor of psychiatry John Rubenstein are the senior authors of the new study, published online in the journalCell.

Only about two percent of the human genome encodes actual genes. Much of the rest of the genome contains regulatory elements, the conductors that control when and where those genes are activated. Genes important for specific aspects of liver function, for example, don't need to be turned on in brain cells, so different regulatory elements are needed to control gene expression in those tissues.

When researchers analyze the DNA of people with neurodevelopmental disorders, they often uncover dozens, if not hundreds, of natural variations in DNA sequences. However, only a minority of those variants may be related to the disorder itself, and pinning down which are important is difficult.

"Much of the genome is still this vast and mysterious place because we don't know which parts of the genome play roles in which tissues," said Eirene Markenscoff-Papadimitriou, PhD, a postdoctoral researcher at the UCSF Weill Institute for Neurosciences and co-first author of the paper.

In the new study, the researchers studied cells from a section of the developing human brain called the telencephalon. This region contains structures responsible for sensory processing, voluntary movement, language, and communication.

The team took advantage of the fact that inside cells, the genome is tightly wound into a dense structure known as chromatin. This three-dimensional structure reveals the important parts of the genome in any given cell by exposing the stretches of regulatory DNA needed for the cell to function. Using a technology called ATAC-seq, the team cut up exposed DNA in embryonic brain cells. By analyzing where these cuts are made, they were able to surmise what parts of the genome are exposed and might contain important regulatory regions.

Their initial experiments revealed more than 103,000 regions of open chromatin in the developing brain cells. To narrow down that list, the researchers turned to a machine-learning approach. They wrote a computer program that uses information already known about regulatory DNA to help pick out patterns specific to brain cells.

"We wanted to whittle this initial list down to a smaller set that was the most likely to be important to regulating brain development," said Gladstone Research Scientist Sean Whalen, PhD, co-first author of the new paper.

If a regulatory region was similar to one known to only be active in limbs or lungs, for instance, the machine-learning program concluded that it wasn't a brain-specific enhancer. In the end, the group came up with a set of about 19,000 regulatory regions of the genome expected to play a role in brain development.

To show the utility of the new dataset, the researchers looked more closely at two sections of the genome that appeared in the new atlas that had also been previously implicated in autism and epilepsy. The DNA sequences, they showed, did indeed act as enhancers in brain cells--they had the ability to turn on genes.

"We can now use this approach to ask how all sorts of other mutations affect the non-coding genome," said Markenscoff-Papadimitriou. "This atlas points us in the direction of specific brain regions that are affected by genetic mutations."

If a research team finds hundreds of genetic variants associated with a neurodevelopmental disease, for instance, they can now use the atlas to cross-check which variants are part of the 19,000 regions identified as critical to brain development. That can help them home in on which variants are worth follow-up studies, rather than spending months testing genetic variants that end up to be unrelated to disease.

"We think our data will help a lot of other research groups further their work," agreed Whalen. Beyond studying diseases, he says the resource will be useful for basic science on how the brain develops.

Reference: Markenscoff-Papadimitriou, E., Whalen, S., Przytycki, P., Thomas, R., Binyameen, F., Nowakowski, T. J., Kriegstein, A. R., Sanders, S. J., State, M. W., Pollard, K. S., & Rubenstein, J. L. (2020). A Chromatin Accessibility Atlas of the Developing Human Telencephalon. Cell, 0(0). https://doi.org/10.1016/j.cell.2020.06.002

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

Read the original here:
Chromatin Atlas Is a Genomic Map of the Brain's Development - Technology Networks

PepsiCo partnered with the government, academics and other companies to sequence the oat genome in four months, a development the food and beverage giant said may lead to heartier varieties with improved sustainability, taste and nutrition.

The food and beverage company, which uses the grain in its Quaker-branded oatmeal, bars and other products, is releasing the data free for public use because it "serves a broader purpose" to help improve sustainability and the livelihood of farmers who grow the crop, RenLammers, PepsiCo's chief science officer, told Food Dive.

Until now, he said the oat has not been heavily invested in by the food industry because it is not one of the more widely used commodities like corn or wheat. But with more information known about its genetic components, the hope is that it could spur additional use of oats, as well as more research.

"We want to sort of re-energize the conversation and the innovation intensity in this, for what we believe is a very important crop,"Lammerssaid.

The oat has seen its popularity remain largely steady in recent years, with the average person consuming about 4.8 pounds of oat products each year,according to Statista.

But the grain has received more attention recently because it contains a number of attributes popular with consumers. It is rich in anti-oxidants, high in fiber and associated with combating chronic illnesses, such as heart disease.

Oatmeal also is easy to prepare and can be eaten on the go, making it popular with busy consumers looking to fill up with essential nutrients.The global market size for oatmeal, for example,is expected to reach $3.32 billion by 2026, a compound annual growth rate of 4.76%,according to data from Fortune Business Insights.

"We live in a consumer goods world, you want to continue to improve. ... We felt more could be done in the world of oats. We felt there wasn't enough investment and attention going into it."

RenLammers

Chief science officer, PepsiCo

The oat genome is much larger and more complex than other major crops like corn and soy, which historically have had extensive private funding for research, he said.The limited genetic knowledge publicly available about the grain has in turn slowed discovery and breeding of better oat varieties for farmers, the environment and consumers.

"There is a do-good element here in terms of sharing some of your technology,"Lammers noted. "But if you combine it with other layers of advances that we've built over the years, flavoring being one of them, then I think we are still in a very competitive" position.

The genome sequence will help PepsiCo breed oats for a host of sustainability attributes, including increased yields;improved disease resistance;healthier soils that sequester carbon and reduce water run-off; and lower the amount of land and other resources needed to grow oats. Understanding the full genome will also improve the New York company's ability to identify oats rich in fiber and essential nutrients, while creating more flavorful varieties that could widen its appeal with consumers.

"Understanding the complete genome also helps you in targeting these individual qualities, and ultimately benefiting consumers,"Lammers said. "We live in a consumer goods world, you want to continue to improve. ... We felt more could be done in the world of oats. We felt there wasn't enough investment and attention going into it."

To expedite the sequencing of the oat genome, PepsiCo worked with Corteva Agriscience, the University of North Carolina at Charlotte and the University of Saskatchewan, which supplied the oat variety. This is the first time the 122-year-old beverage and snack giant has ever sequenced a specific ingredient. Lammers said while the company is focused on oats for now and doesn't have any immediate plans to work on other commodities, it could consider other ingredients in the future.

"We felt we've always had a good, strong pipeline in our innovation from an oats perspective, but you need to continue to innovate,"Lammers said. "What we hope is we will continue to drive innovation in an important category for us, and an important brand in Quaker Oats."

See the rest here:
PepsiCo partners to sequence the oat genome for the 1st time - Food Dive