Category Archives: Genome

Summary

The novel coronavirus uses structures within its RNA to infect cells. Scientists have now identified these configurations, generating the most comprehensive atlas to date of SARS-CoV-2s genome.

HHMI scientists are joining many of their colleagues worldwide in working to combat the new coronavirus. Theyre developing diagnostic testing, understanding the viruss basic biology, modeling the epidemiology, and developing potential therapies or vaccines. Over the next several weeks, we will be sharing stories of some of this work.

Although contained in a long, noodle-like molecule, the new coronaviruss genome looks nothing like wet spaghetti. Instead, it folds into stems, coils, and cloverleafs that evoke molecular origami.

A team led by RNA scientist Anna Marie Pyle has now made the most comprehensive map to date of these genomic structures. In two preprints posted inJuly2020to bioRxiv.org, Pyles team mapped structures across the entire RNA genome of the coronavirus SARS-CoV-2, using living cells and computational analyses.

SARS-CoV-2 relies on its unique RNA structures to infect people and cause the illness COVID-19. But these structures contribution to infection and disease is often underappreciated, even among scientists, says Pyle, a Howard Hughes Medical Institute Investigator at Yale University.

The general wisdom is that if we just focus on the proteins encoded in the viruss genome, well understand how SARS-CoV-2 works, Pyle says. But for these types of viruses, RNA structures in the genome can influence their ability to function as much as encoded proteins.

Researchers can now begin to tease out just how these structures aid the virus information that could ultimately lead to new treatments for COVID-19. Once scientists have identified RNA structures that carry out key tasks, for instance, it may be possible to devise ways to disrupt them and interfere with infection.

Both DNA and its molecular relative RNA store information using a four-letter code. Within human cells, pairs of letters can form bonds spanning two strands of DNA. These strands twist together, forming the familiar double helix. RNA can form helices too, but in viruses such as SARS-CoV-2 and its relatives, it does so when a single molecule folds back on itself.

The result is not only stem-like double helices, but also three- and four-stranded structures, knot-like regions, and multi-stem junctions. Like building blocks, these simple configurations become the basis for even more complex architecture within the genome.

Measuring about 30,000 RNA letters, SARS-CoV-2s genome is unusually long for an RNA virus. Even so, it is still quite stubby compared to the genomes of people, plants, and even bacteria. Contorting its RNA into three-dimensional shapes gives SARS-CoV-2 another set of tools with which to compensate for a limited number of genes. An RNA virus gets the most bang for its buck in terms of how it uses its genome, Pyle says.

Research on other viruses has teased out how they use RNA structures to do their dirty work. The hepatitis C virus, for example, uses a complex configuration of RNA to trick cells into making viral protein, according to Jeffrey Kieft, an RNA structural biologist and virologist at the University of Colorado Anschutz Medical Campus, who was not involved with Pyles teams work. Its kind of amazing, all the different things RNA structures can do in viral infection, he says.

Pyles group set out to decipher the configuration of SARS-CoV-2s genome with two parallel approaches. In one study, they examined the RNAs structure from within the viruss natural environment: infected cells.

It is difficult to access viral RNA within cells, where it mixes with the hosts RNA. However, a quirk of SARS-CoV-2 infection its RNA becomes unusually abundant helped the team create a snapshot of the RNA genomes full structure. This was the first time anyone has captured such a comprehensive picture of a viral genome from within living cells. Previous efforts using HIV- and hepatitis C-infected cells did not produce enough information to create a full inventory of RNA structures.

The coronavirus genome has more structure than any RNA my lab has studied in the past.

Anna Marie Pyle, HHMI Investigator at Yale University

In a related computational study, the team tried to predict how SARS-CoV-2s RNA genome, as well as other pieces of viral RNA made by the cell, might fold and interact with themselves. The two studies have not yet undergone the scientific vetting process known as peer review, but together, they reveal that SARS-CoV-2s genome has a complex, compact architecture. The coronavirus genome has more structure than any RNA my lab has studied in the past, Pyle says.

To study any RNA virus, and SARS-CoV-2 in particular, scientists need a roadmap of its genomic landscape, Kieft says. Dr. Pyle has created a sort of global atlas that is a great starting point for the next round of more targeted experiments, he says. In many ways, it scratches the surface of the richness of RNA structure that probably exists in this virus. I suspect theres going to be a lot of surprises.

The mapping effort also represents a preliminary step toward new drugs that might target the viruss RNA structures. However, that road could be long. Since 2014, when his lab discovered a knot-like structure that viruses like dengue and West Nile use to evade cellular defenses, Kieft has been trying to find a way to neutralize it. He cautions that the research community is not fully geared up to identify RNA structure-disrupting drugs. This strategy just hasnt been studied or pursued in the way that it has for proteins, he says. However, when dealing with a pandemic virus like SARS-CoV-2, initially you try everything.

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Citation

Rafael de Cesaris Araujo Tavares et al. The global and local distribution of RNA structure throughout the SARS-CoV-2 genome. Posted on bioRxiv.org on July 7, 2020. doi: 10.1101/2020.07.06.190660

Nicholas C. Huston et al. Comprehensive in-vivo secondary structure of the SARS-CoV-2 genome reveals novel regulatory motifs and mechanisms. Posted on bioRxiv.org on July 7, 2020. doi: 10.1101/2020.07.10.197079

Excerpt from:
Mapping the 3-D Geometry of SARS-CoV-2's Genome - Howard Hughes Medical Institute

News Release

Monday, August 31, 2020

The finding marks a new effort in conserving an ancient dog breed, with potential to inform human vocalization processes

In a study published in PNAS, researchers used conservation biology and genomics to discover that the New Guinea singing dog, thought to be extinct for 50 years, still thrives. Scientists found that the ancestral dog population still stealthily wanders in the Highlands of New Guinea. This finding opens new doors for protecting a remarkable creature that can teach biologists about human vocal learning. The New Guinea singing dog can also be utilized as a valuable and unique animal model for studying how human vocal disorders arise and finding potential treatment opportunities. The study was performed by researchers at the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health, Cenderawasih University in Indonesia, and other academic centers.

The New Guinea singing dog was first studied in 1897, and became known for their unique and characteristic vocalization, able to make pleasing and harmonic sounds with tonal quality. Only 200300 captive New Guinea singing dogs exist in conservation centers, with none seen in the wild since the 1970s.

"The New Guinea singing dog that we know of today is a breed that was basically created by people," said Elaine Ostrander, Ph.D., NIH Distinguished Investigator and senior author of the paper. "Eight were brought to the United States from the Highlands of New Guinea and bred with each other to create this group."

According to Dr. Ostrander, a large amount of inbreeding within captive New Guinea singing dogs changed their genomic makeup by reducing the variation in the group's DNA. Such inbreeding is why the captive New Guinea singing dogs have most likely lost a large number of genomic variants that existed in their wild counterparts. This lack of genomic variation threatens the survival of captive New Guinea singing dogs. Their origins, until recently, had remained a mystery.

Another New Guinea dog breed found in the wild, called the Highland Wild Dog, has a strikingly similar physical appearance to the New Guinea singing dogs. Considered to be the rarest and most ancient dog-like animal in existence, Highland Wild Dogs are even older than the New Guinea singing dogs.

Researchers previously hypothesized that the Highland Wild Dog might be the predecessor to captive New Guinea singing dogs, but the reclusive nature of the Highland Wild Dog and lack of genomic information made it difficult to test the theory.

In 2016, in collaboration with the University of Papua, the New Guinea Highland Wild Dog Foundation led an expedition to Puncak Jaya, a mountain summit in Papua, Indonesia. They reported 15 Highland Wild Dogs near the Grasberg Mine, the largest gold mine in the world.

A follow-up field study in 2018 allowed researchers to collect blood samples from three Highland Wild Dogs in their natural environment as well as demographic, physiological and behavioral data.

NHGRI staff scientist Heidi Parker, Ph.D., led the genomic analyses, comparing the DNA from captive New Guinea singing dogs and Highland Wild Dogs.

"We found that New Guinea singing dogs and the Highland Wild Dogs have very similar genome sequences, much closer to each other than to any other canid known. In the tree of life, this makes them much more related to each other than modern breeds such as German shepherd or bassett hound," Dr. Parker said.

According to the researchers, the New Guinea singing dogs and the Highland Wild Dogs do not have identical genomes because of their physical separation for several decades and due to the inbreeding among captive New Guinea singing dogs not because they are different breeds.

In fact, the researchers suggest that the vast genomic similarities between the New Guinea singing dogs and the Highland Wild Dogs indicate that Highland Wild Dogs are the wild and original New Guinea singing dog population. Hence, despite different names, they are, in essence, the same breed, proving that the original New Guinea singing dog population are not extinct in the wild.

The researchers believe that because the Highland Wild Dogs contain genome sequences that were lost in the captive New Guinea singing dogs, breeding some of the Highland Wild Dogs with the New Guinea singing dogs in conservation centers will help generate a true New Guinea singing dogs population. In doing so, conservation biologists may be able to help preserve the original breed by expanding the numbers of New Guinea singing dogs.

"This kind of work is only possible because of NHGRI's commitment to promoting comparative genomics, which allows researchers to compare the genome sequences of the Highland Wild Dog to that of a dozen other canid species," Dr. Ostrander said.

Although New Guinea singing dogs and Highland Wild Dogs are a part of the dog species Canis lupus familiaris, researchers found that each contain genomic variants across their genomes that do not exist in other dogs that we know today.

"By getting to know these ancient, proto-dogs more, we will learn new facts about modern dog breeds and the history of dog domestication," Dr. Ostrander said. "After all, so much of what we learn about dogs reflects back on humans."

The researchers also aim to study New Guinea singing dogs in greater detail to learn more about the genomics underlying vocalization (a field that, to date, heavily relies on birdsong data). Since humans are biologically closer to dogs than birds, researchers hope to study New Guinea singing dogs to gain a more accurate insight into how vocalization and its deficits occur, and the genomic underpinnings that could lead to future treatments for human patients.

NHGRI is one of the 27 institutes and centers at the National Institutes of Health. The NHGRI Extramural Research Program supports grants for research, and training and career development at sites nationwide. Additional information about NHGRI can be found at https://www.genome.gov/.

About the National Institutes of Health (NIH):NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

NIHTurning Discovery Into Health

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Scientists use genomics to discover an ancient dog species that may teach us about human vocalization - National Institutes of Health

Over the past few years, Professor Zhang Yongzhen has made it his business to sequence thousands of previously unknown viruses. But he knew straight away that this one was particularly nasty. It was about 1:30 p.m. on Jan. 3 that a metal box arrived at the drab, beige buildings that house the Shanghai Public Health Clinical Center. Inside was a test tube packed in dry ice that contained swabs from a patient suffering from a peculiar pneumonia sweeping Chinas central city of Wuhan. But little did Zhang know that that box would also unleash a vicious squall of blame and geopolitical acrimony worthy of Pandora herself. Now, he is seeking to set the record straight.

Zhang and his team set to work, analyzing the samples using the latest high-throughput sequencing technology for RNA, the viral genetic building blocks, which function similar to how DNA works in humans. By 2 a.m. on Jan. 5, after toiling through two nights straight, they had mapped the first complete genome of the virus that has now sickened 23 million and killed 810,000 across the globe: SARS-CoV-2. It took us less than 40 hours, so very, very fast, Zhang tells TIME in an exclusive interview. Then I realized that this virus is closely related to SARS, probably 80%. So certainly, it was very dangerous.

The events that followed Zhangs discovery have since become swathed in controversy. Crises beget scapegoats and the coronavirus is no different. The floundering U.S. response to the pandemic has prompted a wave of racially tinged soundbites, such as China virus and Kung Flu, as President Donald Trumps Administration seeks to divert blame onto the nation where the pathogen was first identified. The outbreak of COVID angered many people in the Administration and presented an election issue for President Trump, Ambassador Jeffrey Bader, formerly President Obamas chief adviser on Asia, said at a recent meeting of the Foreign Correspondents Club of China.

Read more: Inside the Global Quest to Trace the Origins of COVID-19and Predict Where It Will Go Next

Upon first obtaining the genome, Zhang says he immediately called Dr. Zhao Su, head of respiratory medicine at Wuhan Central Hospital, to request the clinical data of the relevant patient. I couldnt say it was more dangerous than SARS, but I told him it was certainly more dangerous than influenza or Avian flu H5N1, says Zhang. He then contacted Chinas Ministry of Health and traveled to Wuhan, where he spoke to top public health officials over dinner Jan. 8. I had two judgements: first that it was a SARS-like virus; second, that the virus transmits by the respiratory tract. And so, I had two suggestions: that we should take some emergency public measures to protect against this disease; also, clinics should develop antiviral treatments.

Afterward, Zhang returned to Shanghai and prepared to travel to Beijing for more meetings. On the morning of Jan. 11, he was on the runway at Shanghai Hongqiao Airport when he received a phone call from a colleague, Professor Edward Holmes at the University of Sydney. A few minutes later, Zhang was strapped in for takeoff and still on the phonethen Holmes asked permission to release the genome publicly. I asked Eddie to give me one minute to think, Zhang recalls. Then I said ok. For the next two hours, Zhang was cocooned from the world at 35,000 feet, but Holmes post on the website Virological.org sent shockwaves through the global scientific community.

By the time Zhang touched down in Beijing, his discovery was headline news. Officials swooped on his laboratory to demand an explanation. Maybe they couldnt understand how we obtained the genome sequence so fast, says Zhang. Maybe they didnt fully believe our genome. So, I think its normal for the authorities to check our lab, our protocols.

Read more: China Says Its Beating Coronavirus. But Can We Believe Its Numbers?

Critics of Chinas response have latched onto the Jan. 11 date of publication as evidence of a cover-up: why, they ask, didnt Zhang publish it on Jan. 5, when he first finished the sequencing? Also, Zhangs lab was probed by Chinese authorities for rectification, an obscure term to imply some malfeasance. To many observers, it seemed that furious officials scrambling to snuff out evidence of the outbreak were punishing Zhang simply for sharing the SARS-CoV-2 genomeand in the meanwhile, slowing down the release of this key information.

Yet Zhang denies reports in Western media that his laboratory suffered any prolonged closure, and instead says it was working furiously during the early days of the outbreak. From late January to April, we screened more than 30,000 viral samples, says Fan Wu, a researcher who assisted Zhang with the first SARS-CoV-2 sequencing.

And, in fact, Zhang insists he first uploaded the genome to the U.S. National Center for Biotechnology Information (NCBI) on Jan. 5an assertion corroborated by the submission date listed on the U.S government institutions Genbank. When we posted the genome on Jan. 5, the United States certainly knew about this virus, he says. But it can take days or even weeks for the NCBI to look at a submission, and given the gravity of the situation and buoyed by the urging of colleagues, Zhang chose to expedite its release to the public, by publishing it online. (Approached by TIME, Holmes deferred to Zhangs version of events.) Its a decision that facilitated the swift development of testing kits, as well as the early discussion of antivirals and possible vaccines.

Read more: We Will Share Our Vaccine with the World. Inside the Chinese Biotech Firm Leading the Fight Against COVID-19

Zhang, 55, is keen to downplay the bravery of his actions. But the stakes of doing what is right over what one is told are rendered far higher in authoritarian systems like Chinas. Several whistleblower doctors were detained early in the pandemic. According to a Jan. 3 order seen by respected Beijing-based finance magazine Caixin, Chinas National Health Commission, the nations top health authority, forbade the publishing of any information regarding the Wuhan disease, while labs were told to destroy or transfer all viral samples to designated testing institutions. Caixin also reports that other labs had processed genome sequences before Zhang obtained his sample. None were published.

Its difficult to know what conclusions to draw. Dr. Dale Fisher, head of infectious diseases at Singapores National University Hospital, says he doesnt think that any delay by the Chinese authorities was malicious. It was more like appropriate verification, he says. Fisher traveled to China as part of a World Health Organization (WHO) delegation in early February and says outbreak settings are always confusing and chaotic with people unsure what to believe. To actually have the whole genome sequence by early January was outstanding compared to outbreaks of the past.

Of course, Zhangs fears based on the viral genome were just one evidence strut to inform Chinas decision-making process, alongside public health data and clinical reports about specific cases. Despite mounting evidence of human-to-human transmission, including doctors falling ill, it was only on Jan. 20 that China officially confirmed community transmission. Two days later, Wuhans 11 million residents were placed on a bruising lockdown that would last for 76 days. Even while the WHO publicly praised China for transparency, internal documents seen by the Associated Press suggest health officials were privately frustrated by the slow release of information. One joint study by scientists in China, the U.K. and U.S. suggests there would have been 95% fewer cases in China had lockdown measures been introduced three weeks earlier. Two weeks earlier, 86% fewer; one week, 66% fewer.

Read more: I Told Myself to Stay Calm. As Wuhans Lockdown Ends, A Doctor Recalls Fighting Coronavirus on the Front Line

Yet there was some historical basis for skepticism about the severity of the emerging viral disease. After all, the last global pandemicthe swine flu outbreak of 2009was far less deadly than initially feared, mainly because many older people had some immunity to the virus, leading to criticism that the WHO was overly hasty and even overly dramatic in declaring a pandemic when the virology didnt warrant it. In China, even though we had a very bad experience with SARS and other diseases, in the beginning nobodynot even experts from Chinas CDC and the Ministry of Healthpredicted the disease could be quite so bad, says Zhang.

Donald Trump disagrees. He has repeatedly claimed that swifter action by China could have stopped the pandemic in its tracks. The virus came from China, Trump said Aug. 10. Its Chinas fault. Beijing concedes that mistakes were made at the outset, though insists that blame lies solely with bungling local officials (who have since been punished for those failures), while the central governments response was exemplary. This is, of course, its own politically motivated oversimplification. On both sides, wild accusations have eclipsed reason as Sino-U.S. relations spiral to an unprecedented nadir. While U.S. officials have suggested that COVD-19 originated in a Wuhan laboratory, their Chinese counterparts have propagated conspiracy theories that the U.S. military is responsible. Its not a good thing for China and the U.S. to be involved in this struggle, says Zhang. If we cant work together, we cant solve anything.

Read more: The Coronavirus Outbreak Could Derail Xi Jinpings Dreams of a Chinese Century

Some facts are undeniable. The first U.S. case was confirmed on Jan. 21a man in his 30s who had just returned from Wuhan to his hometown in Washington State. Japan confirmed its first coronavirus case one day later, and reported the worlds highest infection number early in the outbreak, before getting a handle on the situation. Today, the U.S. has 16,407 cases per million population compared with 462 in Japan. Across the world, authoritarian and democratic nations have both handled the crisis well and poorly.

For its part, the global scientific community has risen to the challenge, working across national boundaries to advance understanding of the disease, including priceless collaborations between Chinese and Western virologists. Previously, the best described epidemic in terms of viral genetics was the 2014 West African Ebola outbreak. Then, about 1,600 genomes were mapped over three years, providing insights into how viruses move between locations and accumulate genetic differences as they do. But for SARS-CoV-2, following Zhangs initial genome, scientists mapped about 20,000 within three months. Genomic surveillance enables scientists to trace the speed and character of genetic changes, with ramifications for infection rates and the production of vaccines and antivirals. Very large-scale genomic screening can evaluate whether any resistance mutations have occurred and, if they do, how those spread through time, says Oliver Prybus, professor of evolution and infectious disease at Oxford University.

For Zhang, focus must now be on understanding how pathogens and the environment interact. Over the past century, an inordinate number of new viral diseases have emerged in China, including the 1956 Asian Flu, 2002 SARS and 2013 H7N9. Zhang attributes this to Chinas diverse ecology and enormous population. Moreover, as Chinas economy boomed its people have begun traveling far and wide in search of work, education and opportunities. According to the World Bank, almost 200 million people moved to urban areas in East Asia during the first decade of the 21st century. In China, 61% of the population lived in urban areas in 2020 compared with just 18% in 1978. This brings unknown pathogens and people without natural defenses into close proximity. People and pathogens must be in contact [for outbreaks], says Zhang. If no contact, no disease.

As urbanization intensifies, outbreaks of pathogenic diseases will only become more common. Mitigation, says Zhang, comes from deeper understanding of viruses, so that we can accurately map and predict which are likely to spill over into human populations. Just as satellites have made forecasting weather patterns unerringly reliable, Zhang believes science holds the key to predicting viral outbreaks with similar accuracy as with which we now anticipate typhoons and tornadoes. If we dont learn lessons from this disease, says Zhang, humankind will suffer another.

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Write to Charlie Campbell at charlie.campbell@time.com.

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Zhang Yongzhen Speaks Out About Controversies Around His Work - TIME

In a study published in PNAS, researchers used conservation biology and genomics to discover that the New Guinea singing dog, thought to be extinct for 50 years, still thrives. Scientists found that the ancestral dog population still stealthily wanders in the Highlands of New Guinea. This finding opens new doors for protecting a remarkable creature that can teach biologists about human vocal learning. The New Guinea singing dog can also be utilized as a valuable and unique animal model for studying how human vocal disorders arise and finding potential treatment opportunities. The study was performed by researchers at the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health, Cenderawasih University in Indonesia, and other academic centers.

A female New Guinea singing dog sings at the San Diego zoo. Credit: San Diego Zoo

The New Guinea singing dog was first studied in 1897, and became known for their unique and characteristic vocalization, able to make pleasing and harmonic sounds with tonal quality. Only 200-300 captive New Guinea singing dogs exist in conservation centers, with none seen in the wild since the 1970s.

"The New Guinea singing dog that we know of today is a breed that was basically created by people," said Elaine Ostrander, Ph.D., NIH Distinguished Investigator and senior author of the paper. "Eight were brought to the United States from the Highlands of New Guinea and bred with each other to create this group."

According to Dr. Ostrander, a large amount of inbreeding within captive New Guinea singing dogs changed their genomic makeup by reducing the variation in the group's DNA. Such inbreeding is why the captive New Guinea singing dogs have most likely lost a large number of genomic variants that existed in their wild counterparts.This lack of genomic variation threatens the survival of captive New Guinea singing dogs. Their origins, until recently, had remained a mystery.

Another New Guinea dog breed found in the wild, called the Highland Wild Dog, has a strikingly similar physical appearance to the New Guinea singing dogs. Considered to be the rarest and most ancient dog-like animal in existence, Highland Wild Dogs are even older than the New Guinea singing dogs.

Researchers previously hypothesized that the Highland Wild Dog might be the predecessor to captive New Guinea singing dogs, but the reclusive nature of the Highland Wild Dog and lack of genomic information made it difficult to test the theory.

In 2016, in collaboration with the University of Papua, the New Guinea Highland Wild Dog Foundation led an expedition to Puncak Jaya, a mountain summit in Papua, Indonesia. They reported 15 Highland Wild Dogs near the Grasberg Mine, the largest gold mine in the world.

A follow-up field study in 2018 allowed researchers to collect blood samples from three Highland Wild Dogs in their natural environment as well as demographic, physiological and behavioral data.

NHGRI staff scientist Heidi Parker, Ph.D., led the genomic analyses, comparing the DNA from captive New Guinea singing dogs and Highland Wild Dogs.

"We found that New Guinea singing dogs and the Highland Wild Dogs have very similar genome sequences, much closer to each other than to any other canid known. In the tree of life, this makes them much more related to each other than modern breeds such as German shepherd or bassett hound," Dr. Parker said.

According to the researchers, the New Guinea singing dogs and the Highland Wild Dogs do not have identical genomes because of their physical separation for several decades and due to the inbreeding among captive New Guinea singing dogsnot because they are different breeds.

In fact, the researchers suggest that the vast genomic similarities between the New Guinea singing dogs and the Highland Wild Dogs indicate that Highland Wild Dogs are the wild and original New Guinea singing dog population. Hence, despite different names, they are, in essence, the same breed, proving that the original New Guinea singing dog population are not extinct in the wild.

The researchers believe that because the Highland Wild Dogs contain genome sequences that were lost in the captive New Guinea singing dogs, breeding some of the Highland Wild Dogs with the New Guinea singing dogs in conservation centers will help generate a true New Guinea singing dogs population.In doing so, conservation biologists may be able to help preserve the original breed by expanding the numbers of New Guinea singing dogs.

"This kind of work is only possible because of NHGRI's commitment to promoting comparative genomics, which allows researchers to compare the genome sequences of the Highland Wild Dog to that of a dozen other canid species," Dr. Ostrander said.

Although New Guinea singing dogs and Highland Wild Dogs are a part of the dog speciesCanis lupus familiaris, researchers found that each contain genomic variants across their genomes that do not exist in other dogs that we know today.

"By getting to know these ancient, proto-dogs more, we will learn new facts about modern dog breeds and the history of dog domestication," Dr. Ostrander said. "After all, so much of what we learn about dogs reflects back on humans."

The researchers also aim to study New Guinea singing dogs in greater detail to learn more about the genomics underlying vocalization (a field that, to date, heavily relies on birdsong data). Since humans are biologically closer to dogs than birds, researchers hope to study New Guinea singing dogs to gain a more accurate insight into how vocalization and its deficits occur, and the genomic underpinnings that could lead to future treatments for human patients.

Read more:
Scientists use genomics to discover ancient dog species that may teach us about human vocalization - National Human Genome Research Institute

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Global Single-Cell Genome Sequencing Technology Market 2020 Analysis, Types, Applications, Forecast and COVID-19 Impact Analysis 2025 - Scientect

The COVID-19 pandemic has dramatically demonstrated humankinds vulnerability towards infectious diseases especially with the lack of a vaccine or drug to treat the infections.

Luckily, for many infectious diseases caused by bacterial pathogens, we have efficient drugs antibiotics to treat them. However, for these diseases there is also an alarming trend: Increasing numbers of pathogenic bacteria have acquired antimicrobial resistance, which renders many antibiotics useless and makes formerly easily treatable infections life-threatening or even deadly. Currently, more than 700,000 people die each year due to drug-resistant diseases, including 230,000 people who die from multidrug-resistant tuberculosis, according to the UN.

One important pillar of addressing this severe global challenge is the development of novel antimicrobials. But industrial pipelines are almost empty when it comes to new classes of antibiotics. To understand why, we need to look back.

Historically, most antimicrobials originate from bacterial or fungal microorganisms. Especially in the 1950s and 1960s, the antimicrobial drug discovery field experienced a golden age with many of the current antibiotics being discovered and developed. Starting in the 1970s, however, there was a huge decline in industrial antibiotic development. With many antibiotics running off-patent, the prices for antibiotic therapies dropped significantly, reducing commercial interest in the whole antibiotics development market. Also, there were scientific challenges: In the large-scale screening campaigns of the 1950-70s, most of the low-hanging fruits were picked. New antibiotics were essentially too hard to find and develop compared to the pay-off.

The situation is more or less the same today. But because of antimicrobial resistance and new genome sequencing methods, the field is slowly opening up once more. Instead of solely relying on isolating and characterising the chemicals from bacteria that can grow in a petri dish, researchers turn to Genome Mining. With this approach, identifying so-called biosynthetic gene clusters (BGCs) of potential producing organisms has become feasible. This trend is strongly supported by the parallel development of powerful bioinformatics software that helps scientists in this task. For ten years, scientists of DTU Biosustain have been developing such tools, for example the widely used antiSMASH platform (see box).

Identifying interesting pathways is only the first step: often BGCs encoding a potentially novel compound are not expressed under laboratory conditions; the expression needs triggering. While expression is still a challenge, new CRISPR-based genetic engineering technologies to engineer the producer strains as well as methods to move BGCs from poorly studied organisms into optimized cellular workhorses help us to get back in business, so to speak.

The different technologies developed at DTU Biosustain are integrated into the international project Integration of informatics and metabolic engineering for the discovery of novel antibiotics (iimena), which is funded by a Challenge Grant by the Novo Nordisk Foundation. Scientists from DTU Biosustain work together with the Korea Advanced Institute of Science and Technology (KAIST) and the Fundacin MEDINA Centro de Excelencia en Investigacin de Medicamentos Innovadores en Andaluca. The iimena project integrates BGC discovery with innovative high throughput screening, adaptive laboratory evolution and metabolic engineering technologies. In short: we are using all the newest technologies available to tap into the secret world of active compounds produced by bacteria and fungi to reveal the next generation of antibiotics. And with the access to MEDINAs unique strain collection, we expect to find multiple new antibiotic drug candidates.

Since the project started in late 2017, iimena scientists have contributed to various key technologies, such as the antiSMASH platform (Blin, K., et al., 2019, Nucleic Acids Res. 47:W81-W87, Blin, K., et al., 2019, Nucleic Acids Res. 47:D625-D630), CRISPR-tools (Tong, Y., et al., 2020, Nat. Prot. 15:2470-2502, Tong, Y., et al., 2019, PNAS 116:20366-20375), precursor-biosensors (Yang, D., et al., 2018, PNAS 115:9835-9844), which already now are used by many laboratories world-wide.

The worlds of big data, software, and wet lab biology merge together these days. DTU Biosustain just recently received a 100 million extension grant from the Novo Nordisk Foundation to continue its activities for the next five years. A large proportion of this grant will go into developing software tools for the discovery of sustainable medical compounds, food, and chemicals. iimena speaks directly into this scope, and the synergies are obvious.

The iimena project will run for further 2.5 years and aims in addition to developing core technologies to find five new antibiotic candidates. But it does not stop there: The need for more research and more drug candidates in the antibiotics pipeline is urgent. The problem of antimicrobial resistance does not go away it only gets worse, so we need to act now.

The Open Source genome mining platform antiSMASH is the most widely used bioinformatics software to mine microbial genome sequences for secondary metabolite BGCs. More than 750,000 analysis runs have been computed on the publicly webserver hosted by DTU. antiSMASH is a joint development, currently maintained by T. Weber/K.Blin at DTU Biosustain and M. Medema at Wageningen University, with contributions by dozens of leading scientists working in the field. The software offers an easy access to the genetic potential of microbes to synthesize natural products without requiring dedicated bioinformatics skills. The platform also integrates a database of biosynthetic gene clusters, and the MIBiG repository of experimentally determined and validated gene clusters.

Please note: This is a commercial profile

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Finding new antibiotics: The genome way - Open Access Government

Genome sequencing mapping the genetic sequences of the virus from confirmed COVID-19 cases in a bid to track its spread is now an integral part of New Zealands coronavirus response. It is providing greater certainty in identifying clusters and helps focus the investigations of contact tracers.

In contrast to the first outbreak, during which only 25 of the more than 1,000 positive samples had been genetically sequenced by mid-April, genome sequencing results are now available overnight, and sometimes even on the same day. This allows health authorities to infer a connection between cases or pinpoint potential sources of infection much more promptly than before.

So far, the technique has confirmed Aucklands second wave of cases are all part of the same cluster, except for one case identified on Tuesday who contracted the virus via exposure to a returned traveller from the United States.

But despite our rapidly improving knowledge, we still dont know how and where the current outbreak started.

Genome Sequencing Proves Useful to Understand the Cluster

There are now 87 confirmed cases in the new Auckland cluster. All are in quarantine, along with some of their close contacts.

The sequencing technology has shown its value in three distinct ways since this new outbreak was confirmed last week.

First, it identified a new case without links to the current community cluster. A maintenance worker at the Rydges Hotel managed isolation facility tested positive on Sunday. By Tuesday, sequencing results showed this case was not part of the wider cluster, but rather that the genetic sequences matched those from a US returnee who had stayed at the Rydges before testing positive and being moved into quarantine.

Without rapid genome sequencing, contact tracers would have spent considerable effort looking for a link to the known cluster. Instead, their work is now focused on finding out how the worker got infected and whether there are any intermediate cases.

Second, genome sequencing has also shown that all other cases so far are part of a single cluster. This was mostly expected based on established physical links, but the genetic confirmation is nevertheless valuable.

Contact tracing casts a broad net. If a known case has visited a school, church or large workplace, many hundreds of people may need to be tested. Genomic evidence can tell us whether any of those contacts who subsequently test positive are indeed part of the same cluster, or whether they were infected elsewhere. When we look back at the first wave of infections, several of the cases that were assigned to the same cluster were shown not to be genetically related after all, showing contact tracing alone is not fail-safe.

Third, there were a few cases for which contact tracing produced only uncertain links between people, but sequencing confirmed they were part of the same cluster.

Looking for a Source

So far, genomics has given us a lot of valuable information about New Zealands current round of infections. But it hasnt established the ultimate source of this second-wave outbreak. However, it has yielded some clues.

It indicates the current cluster comes from the so-called B.1.1.1 lineage, most frequently documented in the UK but more recently found in Europe, Australia and South Africa. This lineage has been seen once before in New Zealand, in a pair of cases in mid-April who were in managed isolation in Auckland.

This points to two possible scenarios. Either the second wave is due to a recent border incursion from a country where this viral lineage has been transmitted. Or, alternatively, it is the result of ongoing transmission in New Zealand starting from the pair identified in April.

Lets tackle each in turn, starting with the recent border incursion theory.

The virus can be transmitted in managed isolation facilities, as the recent Rydges hotel case underlines. Around 40% of cases found in managed facilities have no available genome sequence because the sample contains too little viral material. This usually indicates a low viral load (and low level of infectiousness), but it does not rule out transmission. The source may be among one of these cases.

Neither can we rule out the possibility that a case in managed isolation or elsewhere at the border was not detected. Even testing twice (currently on days three and 12 of quarantine) is expected to miss at least 4% of cases, based on a false negative rate that is at best 20%. This high false negative rate is one reason to insist on 14 days of isolation.

Next, lets look at the possibility of ongoing transmission in NZ since the first outbreak. With a close genomic match found, we cant completely dismiss this possibility. But the theory also depends on some unlikely assumptions: that the infection leaked from managed isolation, was transmitted undetected for about 15 generations until finally being found, and mutated fairly slowly over that period.

This sounds very unlike the virulent, fast-spreading virus we think we know, although its also true the initial stages of growth of an outbreak can be slow.

Ideally, we would accurately calculate the likelihood of each scenario. But even so, recent transmission across the border is clearly more likely, given the presence of this strain around the world and the absence of any intermediate cases to link NZs first and second waves.

Even trying to determine the country of origin is hard. Many lineages, including B.1.1.1, have a wide global spread. We can understand the extent of the spread using GISAID, the global database in which viral genomes are shared. But with different countries having radically different sequencing efforts (of the 81,000 genomes on GISAID, 35,000 are from the UK alone), finding a link to a country could merely indicate that country has done lots of sequencing. An approach that combines genomic data with data on all international arrivals could be more fruitful.

Whatever the source, we can take heart in New Zealands response to this first known community transmission since the original epidemic. New systems to understand the epidemic have swung into action and quickly proved their worth.

Sequencing of viral genomes has become part of the pipeline to aid contact tracing. The resulting sequences will be useful to science well beyond the immediate response, as we seek to develop a deeper understanding of this virus, and epidemics more generally.

David Welch, Senior lecturer

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Image: Reuters

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What Genome Sequencing Can Tell Us About Auckland Coronavirus Outbreak - The National Interest

LONDON--(BUSINESS WIRE)--Technavio has been monitoring the human microbiome therapeutics market and it is poised to grow by USD 276.93 mn during 2020-2024, progressing at a CAGR of almost 15% during the forecast period. The report offers an up-to-date analysis regarding the current market scenario, latest trends and drivers, and the overall market environment.

Although the COVID-19 pandemic continues to transform the growth of various industries, the immediate impact of the outbreak is varied. While a few industries will register a drop in demand, numerous others will continue to remain unscathed and show promising growth opportunities. Technavios in-depth research has all your needs covered as our research reports include all foreseeable market scenarios, including pre- & post-COVID-19 analysis. Download a Free Sample Report on COVID-19 Impacts

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The market is concentrated, and the degree of concentration will accelerate during the forecast period. Bristol-Myers Squibb Co., Dow Inc., ENTEROME SA, Ferring Pharmaceuticals AS, Johnson & Johnson, Kaleido Biosciences Inc., PureTech Health Plc, Second Genome Therapeutics, Seres Therapeutics Inc., and Takeda Pharmaceutical Co. Ltd. are some of the major market participants. The growing prevalence of chronic diseases will offer immense growth opportunities. To make most of the opportunities, market vendors should focus more on the growth prospects in the fast-growing segments, while maintaining their positions in the slow-growing segments.

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Technavio's custom research reports offer detailed insights on the impact of COVID-19 at an industry level, a regional level, and subsequent supply chain operations. This customized report will also help clients keep up with new product launches in direct & indirect COVID-19 related markets, upcoming vaccines and pipeline analysis, and significant developments in vendor operations and government regulations.

Human Microbiome Therapeutics Market 2020-2024: Segmentation

Human Microbiome Therapeutics Market is segmented as below:

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Human Microbiome Therapeutics Market 2020-2024: Scope

Technavio presents a detailed picture of the market by the way of study, synthesis, and summation of data from multiple sources. The human microbiome therapeutics market report covers the following areas:

This study identifies growing investments from venture capitalists as one of the prime reasons driving the human microbiome therapeutics market growth during the next few years.

Technavio suggests three forecast scenarios (optimistic, probable, and pessimistic) considering the impact of COVID-19. Technavios in-depth research has direct and indirect COVID-19 impacted market research reports.

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Human Microbiome Therapeutics Market 2020-2024: Key Highlights

Table of Contents:

Executive Summary

Market Landscape

Market Sizing

Five Forces Analysis

Market Segmentation by Application

Customer landscape

Geographic Landscape

Vendor Landscape

Vendor Analysis

Appendix

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Technavio is a leading global technology research and advisory company. Their research and analysis focuses on emerging market trends and provides actionable insights to help businesses identify market opportunities and develop effective strategies to optimize their market positions. With over 500 specialized analysts, Technavios report library consists of more than 17,000 reports and counting, covering 800 technologies, spanning across 50 countries. Their client base consists of enterprises of all sizes, including more than 100 Fortune 500 companies. This growing client base relies on Technavios comprehensive coverage, extensive research, and actionable market insights to identify opportunities in existing and potential markets and assess their competitive positions within changing market scenarios.

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Impact Analysis of Covid-19

The complete version of the Report will include the impact of the COVID-19, and anticipated change on the future outlook of the industry, by taking into the account the political, economic, social, and technological parameters.

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Single Cell Genome Sequencing Market: Analysis of Prevailing Trends In The Parent Market 2026 - Scientect

Health technology is a rapidly growing industry, and I dont think I need to explain why. Just look around you. Here we are, six months into a pandemic with little improvement in sight. How is there not a reliable treatment for COVID-19 yet? With over 24 million cases worldwide, how will the eventual vaccine be able to effectively immunize the whole world when there are still treatments for diseases from outbreaks past that dont work for many patients?

Our Startup of the Week, 54gene ($54GENE), has some answers. According to 54gene, the African genome is the most genetically diverse than all others in the world combined, yet makes up for only 3% of the data used for research and development of medicines and treatments.

At a BusinessDay panel in March, CEO Abasi Ene-Obong described the problem which 54gene addresses. Twenty-five percent of Africans cannot metabolize [a certain HIV drug], he said. Why is that? Because when that drug is being discovered and being trialed, the drug companies did not look at Africans.

By increasing access to this deep well of information, 54gene hopes to help create better medical solutions.

Thats a pitch that has investors quickly hopping aboard. 54gene is a very young company, only founded in 2019. In that short time, the company raised $4.5 million in a seed round and $15 million in Series A. With a massive pool of data at its fingertips that could have major consequences on global medicine, 54gene is the philosopher in Platos Cave, returned to a small world stuck in its ways armed with a universe of possibilities.

54genes growth shows the scale of the opportunity it has tapped into. In 2020 alone, the Lagos and Washington-based companys workforce has grown by 81 employees - a 225% increase in just six months. 54gene has managed to grow to a size that many startups take years to achieve in a fraction of the time.

54genes timing was impeccable. Breaking into the scene just before COVID-19 became a pandemic, 54gene was prepared with a solution to many of the concerns now facing the medical community. It is already involved in testing services and offers a mountain of data that could help with development of vaccines and treatments, making it easy to see why investors have quickly taken to the young company.

CEO Abasi Ene-Obong is refreshingly honest about the company goals as well. The cliche of the startup that says its making the world a better place is real and rampant, and 54gene sets itself apart by actually offering something that could positively impact the lives of patients across the planet, and by being clear about its goals as a profit-driven company.

I think [people invested in us] because they understood the potential for good. But one of the things Id like to say is that impact investment is not the same as charity, Ene-Obong said. As a company founder and CEO, I want to make money. I want to be profitable. That is one of the metrics Ill judge myself by. But at the same time, I want to do good.

Ene-Obong and 54gene are certainly on their way to accomplishing both. It is one of the fastest-growing health disruptors in the world, and has the potential to make waves across the healthcare industry on a global scale. Years down the road, you may find yourself taking a treatment and experiencing no side effects. It may be thanks to 54gene that you end up giving it little to no thought.

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Startup of the Week: 54gene is bringing medicine out of the dark ages - Thinknum Media