Publisher Health

Baboons (Papio) are found across the continent of Africa, from the west to the east and all the way south. They have doglike noses, impressive teeth and thick fur that ranges widely in color between the six species, which are olive, yellow, chacma, Kinda, Guinea and hamadryas. Their habitats vary from savannas and bushlands to tropical forests and mountains. Chacma baboons, the largest at up to 100 pounds, are even found in the Kalahari Desert, while the neighboring Kinda baboons, the smallest at around 30 pounds, stay near water. Most live in large troops with dozens or hundreds of members. While most baboons are polygynandrous, with males and females mating with multiple partners, hamadryas baboons, also called sacred baboons, live exclusively in units of one male and multiple females.
In a paper published today in the journal Science, “Genome-wide Coancestry Reveals Details of Ancient and Recent Male-driven Reticulation in Baboons,” researchers show surprising amounts of genetic admixture between baboon species, something that also likely occurred in early humans. Mark Batzer, Boyd Professor and the Dr. Mary Lou Applewhite Distinguished Professor of Biological Sciences at LSU; Jessica Storer, PhD, Batzer’s former student at LSU and now research scientist; and LSU research associate Jerilyn Walker all contributed to the research. Together, they analyzed the mobile or “transposable” genetic elements in samples from 225 baboon individuals from 19 geographical sites.
“Everybody believes their genome is perfectly stable, and that’s exactly wrong,” Batzer said. “Well over half of the genome is fluid in nature and moves around in and between individuals, and between generations and populations. This mobile part of the genome, or mobilome, provides important clues as to how different species are related to one another, how they differ and when two individuals share a common ancestor.”
Whole-genomic sequencing has revolutionized the amount and detail of genetic diversity now available to researchers to study. While the LSU researchers previously had looked at a few hundred mobile elements or “jumping genes,” primarily of the Alu and L1 types, they were now able to analyze over 200,000 elements computationally, confirming and expanding on previous studies. The broader research consortium includes more than 30 collaborators around the globe and was led by Jeffrey Rogers, associate professor of molecular and human genetics at Baylor College of Medicine.
“There are questions that were science fiction when I started in the field that are now perfectly approachable,” Batzer said. “We’re also brought back to this fundamental question, ‘What even is a species?’ When I was a young scientist, it meant reproductive isolation; no exchange of genes back and forth, and individuals from different species would form infertile hybrids. Well, that whole concept has evolved, and what we now see are free exchanges of genes back and forth, both in ancient times and more recently. In other words, there hasn’t been a linear trajectory of genetically isolated species that change through time.”
Mobile, transposable elements cause a subset of all genetic mutations known as structural genetic variants, one of the most important types of mutation in the genome. As such, mobile elements are responsible for some genetic diversity, but not all differences. Their activity, or rate of movement, is also variable between species, including at different times. While baboons currently are on “fast forward,” orangutans, for example, are almost on pause. Humans are somewhere in between.

“You can say mobile elements like Alu and L1 are involved in a genetic arms race or competition within the genome,” Batzer said. “The mobile elements attempt to expand in number, while the genome exerts control over that expansion, so the elements don’t ‘overrun’ the genome and cause so much havoc it risks killing the host. Some mobile elements are distant relatives of viruses, so some of the control systems are the same ones that control the spread of viruses.”
Apparent similarities, such as between two individuals of the same species, can disguise surprising amounts of genetic diversity, as one baboon can have almost as much in common — genetically speaking — with a baboon from a different species. The researchers were also able to show, for the very first time in non-human primates, how the yellow baboons in western Tanzania received genetic input from three distinct lineages — yellow, olive and Kinda.
“This was the first time we’ve seen three different species contribute to the genesis of one, and done it in detail,” Batzer said. “These high-resolution data sets allow us to draw much more accurate and detailed conclusions from the observations we make.”
Baboons and humans share about 91 percent of identical DNA. While humans have relatively small amounts of variation from each other, baboons are genetically more diverse. Bigger mobile elements called LINE elements, such as L1, carry around enzymatic machinery that helps them and the smaller Alu elements mobilize and drive change in mammals (L1) and primates (Alu).
Mobile and transposable elements are in themselves diverse and effectively “monkey around” the genomes of all primates, including humans, as well as other species. The processes by which they impact the genome are called insertional mutagenesis, transduction and recombination. Tracking the insertions, which is Batzer’s specialty, offers two advantages in establishing shared or separate ancestry. First, the presence of a mobile element at a particular location in the genome represents identity by descent; the probability of an exact match without shared ancestry is near negligible. Second, it’s possible to trace insertions back to the point where they first appeared, thus establishing the ancestral genetic character state and unambiguously rooting species relationships.
“We now believe mobile elements are one of the single biggest driving forces impacting genomes, and not just among primates, but across many mammals and many non-mammalian systems as well,” Batzer said.
Next, the LSU research team will investigate the mobilization and genomic impact of a recently identified transposable element in South American primates.
LSU does not keep or conduct tests on baboons. All samples for the study were gathered in Africa in accordance with local regulations, including at protected sites.

Published23 minutes agoShareclose panelShare pageCopy linkAbout sharingImage source, ReutersBy Oliver SlowBBC NewsWomen in Argentina will no longer require a prescription to obtain emergency contraception. The government said making the morning-after pill more easily available removed an “important barrier” for those seeking terminations.The move was welcomed by feminist groups, who see it as a sign of progress in the Catholic-majority country.However critics said the move displayed a “failure of pregnancy prevention”. The health ministry said the measure would help avoid unintentional pregnancies by overcoming “difficulties of access to health services, contraception supplies, and education” faced by some. “This removes an important barrier to access,” Valeria Isla, director of sexual and reproductive health at the ministry, told Reuters news agency. “People can have this method of contraception as support before an emergency happens.” Vanessa Gagliardi, leader of the feminist group Juntas y a la Izquierda, said the move would help “de-stigmatise” the morning-after pill in a country where seven out of 10 adolescent pregnancies were unplanned, official data show.Argentine pro-life group DerguiXlaVida called the measure worrying, accusing the government of “essentially orienting itself towards promoting abortive measures”. It said the move was recognition of the “failure of pregnancy prevention [and] sex education”. ‘The nurses wanted me to feel guilty about my abortion’It is the latest sign of progress on reproductive rights in Argentina, one of the largest and most influential countries in Latin America, a region where the Catholic Church remains powerful. In 2020, the country legalised abortions up to the 14th week of pregnancy, a move opposed by the Church, which had called on senators to reject the bill. Terminations had previously only been allowed in cases of rape or when the mother’s health was at risk. Emergency contraception pills – commonly known as morning-after pills – taken within 120 hours of unprotected sex prevent pregnancy by blocking the fertilisation of the egg, according to the World Health Organization (WHO), although it is more effective within 12 hours. Emergency contraception – including emergency contraceptive pills and copper-bearing intrauterine devices – can prevent about 95% of pregnancies when taken within five days of intercourse, the WHO says.More on this story’The nurses wanted me to feel guilty about my abortion’Published5 March

To combat outbreaks at restaurants and other dining establishments, policies that support sick workers, including paid leave, may be needed, the agency said in a report this week.People who showed up to their restaurant jobs while sick were linked to 40 percent of food poisoning outbreaks with a known cause from 2017 to 2019, the Centers for Disease Control and Prevention said in a report released on Tuesday.Paid sick leave and other policies that support sick workers could improve food safety outcomes, according to the report, which was based on a review of 800 food poisoning outbreaks, using data provided by 25 state and local health departments.Of the 500 outbreaks where investigators identified at least one cause, 205 involved workers showing up sick, the report said. Other common causes included contaminated raw food items, in 88 cases, and cross-contamination of ingredients, in 68 cases.In 555 of the outbreaks, investigators were able to determine what virus, bacterium, toxin, chemical or parasite was to blame. Most outbreaks were caused by salmonella or norovirus, the report said.To combat these outbreaks, “comprehensive ill worker policies will likely be necessary,” the report said. It highlighted research that showed that expanded paid sick leave reduced how often food service workers showed up at work sick, and noted that paid sick leave regulations were associated with decreased rates of food-borne illness.Daniel Schneider, a professor of social policy at the Harvard Kennedy School, said the report was “sobering,” and highlighted that the United States is the only wealthy country with no federal paid sick leave.“Reports like this show the real urgency of it, not just because it’s in workers’ interests, although it is, but because it is in the public interest,” Professor Schneider said.Of the 725 managers who were interviewed by state and local health departments, 665 said that their business required food workers to tell a supervisor if they were sick, and 620 said that sick employees were either restricted or blocked from working. Fewer than half of the managers — 316 — said their business provided paid sick leave to workers.Professor Schneider is a director of the Shift Project, which collects data about people in the retail and food service industries. He said that workers said they showed up sick because there was nobody able to cover for them, they would feel guilty leaving their co-workers short-handed, they couldn’t afford to miss work or they feared retaliation from management.“Food service workers face really impossible trade-offs around issues like working sick because food service jobs are so low-paid in our economy,” he said.To discourage workers from showing up sick to their jobs at restaurants, catering businesses and food trucks and carts, businesses may need to better enforce existing policies, such as those that prohibit workers from coming in sick; come up with plans to staff a restaurant when someone calls out sick; and adopt “a food safety culture where absenteeism due to illness is not penalized.”While the health departments providing information on outbreaks represented “geographically diverse areas,” the report cautioned that its findings might not be representative of all U.S. outbreaks. It also said that it was based on information that was collected before the coronavirus pandemic and acknowledged evidence that many retail food establishments had since changed at least some of their policies.Each year, 48 million people become sick from a food-borne illness, according to C.D.C. estimates. Of those, 128,000 are hospitalized and 3,000 die.

More than three years after the start of the pandemic, many Covid survivors continue to struggle. Some, especially those who […]

Published3 hours agoShareclose panelShare pageCopy linkAbout sharingImage source, Health CanadaBy Nadine YousifBBC News, TorontoCanada will soon print warning labels directly on cigarettes in a world-first, the country’s health agency announced.New packaging will feature a warning on each cigarette with phrases like: “Cigarettes cause cancer” and “Poison in every puff”.The regulation will come into effect on 1 August, Health Canada said.It is part of an effort to reduce tobacco use in Canada to less than 5% by 2035. In an announcement on Wednesday, Health Canada said the new regulations “will make it virtually impossible to avoid health warnings” on tobacco products. The health agency anticipates that by April 2025, retailers in Canada will only carry tobacco products that feature the new warning labels directly on the cigarettes. Products that will have labels on tipping paper include individual cigarettes, little cigars, tubes and other tobacco products, Health Canada said.The move follows a 75-day public consultation period that was launched last year.Warning labels are already printed on cigarette package covers. Health Canada said it plans to expand on those by printing additional warning labels inside the packages themselves, and introducing a new external warning messages.In a statement, Canada’s minister of mental health and addictions, Carolyn Bennett, said tobacco use kills around 48,000 Canadians each year. “We are taking action by being the first country in the world to label individual cigarettes with health warning messages,” Ms Bennett said, calling the change a “bold step”. Image source, Health CanadaThe move was applauded by the Canadian Cancer Society, Canada’s Heart and Stroke Foundation and the Canadian Lung Association, who said they hope the measures will deter people, especially youth, from taking up smoking.Cigarette smoking is widely regarded as a risk factor for lung cancer, heart disease and stroke. Canada has required the printing of warning labels on cigarette packages in 1989, though it was behind the UK, which printed warnings as early as 1971. The US was the first nation in the world to require health warnings on cigarette packages, passing its Federal Cigarette Labelling and Advertising Act in 1965.Labels in all three countries have evolved over the years, notably to include sometimes graphic images in addition to text to show the health consequences of smoking. Since the US introduced warning labels, the smoking rate has significantly decreased. Some studies, however, have found that labels are not a deterrent for people who have a high nicotine dependence. According to data from the Center for Disease Control and Prevention, 42% of US adults were smokers in the mid-1960s. In 2021, that number dropped to a historic low of 11%. However, electronic cigarette use appeared to have risen. In Canada, the rate of smokers aged 15 years or older is around 10%, according to a national 2021 Tobacco and Nicotine survey. Like the US, the survey revealed vaping rates to be higher at around 17%.More on this storyWhy US lags behind on graphic cigarette warningsPublished16 August 2019Who are the smokers that haven’t quit?Published24 July 2019Canada mulls putting warnings on each cigarettePublished11 June 2022

The retailer, which sees its health care business as a way to drive profits, is trying to retain workers in a competitive labor market.The NewsWalmart, the nation’s largest private employer, said on Wednesday that it was increasing the wages for its 7,700 pharmacists and opticians, as it expands its health business and seeks to retain the workers in a competitive environment.The retailer said the raise would push the average annual salary of its than more 3,700 pharmacists to more than $140,000. Walmart declined to share the current salary rate, saying it was based on location and role.It said opticians could now “expect” to make an average hourly wage of more than $22.50. According to the Bureau of Labor Statistics, the mean annual wage for a pharmacist in the United States is $129,410 and the mean hourly wage for opticians is $21.58.The company also said it was starting a program in which associates who worked in its Vision Center could receive certification and licensing as a way to move into higher-paying positions.“We’ve listened to our associates and taken their feedback about how their work environment needs to improve,” Brian Setzer, Walmart’s executive vice president of health and wellness, said on Wednesday at the retailer’s annual shareholder meeting.Why It Matters: Pay matters in a competitive labor market.This year, Walmart raised wages for workers across its business as a way to compete for talent. Inflation is affecting not only its shoppers, but also its employees. And the job market continues to be robust, giving workers more options. In January, Walmart reduced its pharmacy hours as it grappled with a tight labor market.That same month, the company said it was increasing its minimum wage for store workers to a range of $14 to $19 an hour, up from $12 to $18. Its average wage is still not as high as some competitors, like Costco.Last year, it also raised wages for pharmacy technicians working for Walmart and Sam’s Club to an average of over $20 an hour and promised more frequent raises.For years, Walmart faced pressure from unions, policymakers and activists to increase its pay for workers in its stores. Because of its scale, Walmart’s recent move to boost pay could signal to the rest of the retail industry that companies still need to provide more incentives for workers to stay competitive in the labor market.Background: Walmart sees its health business as a way to drive growth.Walmart opened its first health center in 2019. By providing health care services, the retailer is seeking to gain a deeper foothold in the communities where it operates and grab a bigger share of the billions of dollars Americans spend on medical care each year.It currently has 32 health centers in the United States, with plans to have more than 75 by the end of next year.“Strong growth” in its health and wellness category helped drive an increase in the company’s comparable sales for its most recent quarter, John David Rainey, Walmart’s chief financial officer, said this month.At the same time, there is a shortage of pharmacists across the country. After three years at the front line of helping to battle the coronavirus, a significant number of pharmacy workers burned out and left the industry. In the coming years, the industry is expected to expand more slowly than the national average for other industries, according to a 2021 job outlook report by the Bureau of Labor Statistics. The report said most of the openings would “result from the need to replace workers who transfer to different occupations or exit the labor force.”What’s Next: Expect more Walmart updates.This week, Walmart’s executives, store associates and suppliers are gathered in Bentonville, Ark., for the retailer’s annual shareholder meeting.The company is expected to explain its vision for the year ahead, giving updates about its consumer base, technological innovations and store remodels. Its health business will most likely be a topic of interest for investors and analysts.

Acting as a team, twin stem cells activate the immune system to suppress tumor growth and prolong survival in representative preclinical models.
Overall survival for patients with melanoma that has spread to the brain is only four to six months. Immunotherapies, which harness the power of the immune system to attack cancer cells, have garnered excitement in recent years for their potential to revolutionize the treatment of metastatic melanomas, but results from early clinical studies indicate that the prognosis for most patients remains poor. Now, scientists from Brigham and Women’s Hospital, a founding member of the Mass General Brigham healthcare system, have integrated multiple therapeutic approaches to more effectively target melanoma in the brain. In preclinical studies, the scientists successfully activated immune responses in sophisticated mouse models that mimic human settings. Findings are published in Science Translational Medicine.
“We know that in advanced cancer patients with brain metastases, systemic drugs, given intravenously and orally, do not effectively target brain metastases,” said corresponding author Khalid Shah, MS, PhD, director of the Center for Stem Cell and Translational Immunotherapy (CSTI) and the vice chair of research in the Department of Neurosurgery at the Brigham and faculty at Harvard Medical School and Harvard Stem Cell Institute (HSCI). “We have now developed a new immuno-therapeutic approach that is sustainable and delivered locally to the tumor. We believe that locally delivered immunotherapies represent the future of how we will be treating metastases to the brain.”
The therapy designed by the scientists uses an engineered “twin stem cell model” to maximize an attack on cancer cells that have spread to a part of the brain known as the leptomeninges. One stem cell releases a cancer-killing (oncolytic) virus, a strategy that has previously shown promise in reducing tumor growth. Using stem cells to deliver the virus amplifies the amount of virus that can be released and ensures that the virus will not be degraded by circulating antibodies before it is released on the cancer cells.
However, the oncolytic virus also destroys the very cells that release it, making it an unsustainable therapeutic option on its own. Therefore, the scientists used CRISPR/Cas9 gene editing to a create a second stem cell that cannot be targeted by the oncolytic virus, and which instead releases proteins (immunomodulators) that fortify the immune system to help fight off the cancer.
The twin stem cells can be delivered via intrathecal injection, a technique already used in the treatment of other diseases. Unlike other immunotherapies that have emerged in recent years, it does not need to be repeatedly administered. The authors emphasize that this approach can be used in other cancers with brain metastasis, such as lung and breast cancer, and are working to design similar treatments for these cancers.
Notably, the authors were able to design a preclinical mouse model that faithfully represents a human model of melanoma with leptomeningeal metastasis, which they used to test their therapy. They found that the therapy successfully activated immune responses in their models that mimic human responses, improving the likelihood that the therapy may succeed in a Phase I trial, which the authors are hoping to launch in the near future.
“A number of biological therapies that look promising often fail in Phase I or Phase II clinical trials, in part because the preclinical models do not authentically replicate clinical settings,” Shah said. “We realized that if we did not fix this piece of the puzzle, we would always be playing catch-up. I don’t think we have been at a point in the last 20 years where we have been as close to curing metastases in the brain as we are now.”

We are pursuing the dream of eternal life. We fast to stay healthy. And each year, we spend billions of kroner on treatment to make sure we stay alive. But some people turn 100 years old all by themselves. Why is that?
Researchers from the Novo Nordisk Foundation Center for Protein Research at the University of Copenhagen have set out to find the answer.
Studying 176 healthy Japanese centenarians, the researchers learned that the combination of intestinal bacteria and bacterial viruses of these people is quite unique.
“We are always eager to find out why some people live extremely long lives. Previous research has shown that the intestinal bacteria of old Japanese citizens produce brand new molecules that make them resistant to pathogenic — that is, disease-promoting — microorganisms. And if their intestines are better protected against infection, well, then that is probably one of the things that cause them to live longer than others,” says Postdoc Joachim Johansen, who is first author of the new study.
Among other things, the new study shows that specific viruses in the intestines can have a beneficial effect on the intestinal flora and thus on our health.
“Our intestines contain billions of viruses living of and inside bacteria, and they could not care less about human cells; instead, they infect the bacterial cells. And seeing as there are hundreds of different types of bacteria in our intestines, there are also lots of bacterial viruses,” says Associate Professor Simon Rasmussen, last author of the new study.

Joachim Johansen adds that aside from the important, new, protective bacterial viruses, the researchers also found that the intestinal flora of the Japanese centenarians is extremely interesting.
“We found great biological diversity in both bacteria and bacterial viruses in the centenarians. High microbial diversity is usually associated with a healthy gut microbiome. And we expect people with a healthy gut microbiome to be better protected against aging related diseases,” says Joachim Johansen.
Once we know what the intestinal flora of centenarians looks like, we can get closer to understanding how we can increase the life expectancy of other people. Using an algorithm designed by the researchers, they managed to map the intestinal bacteria and bacterial viruses of the centenarians.
“We want to understand the dynamics of the intestinal flora. How do the different kinds of bacteria and viruses interact? How can we engineer a microbiome that can help us live healthy, long lives? Are some bacteria better than others? Using the algorithm, we are able to describe the balance between viruses and bacteria,” says Simon Rasmussen.
And if the researchers are able to understand the connection between viruses and bacteria in the Japanese centenarians, they may be able to tell what the optimal balance of viruses and bacteria looks like.

Optimising intestinal bacteria
More specifically, the new knowledge on intestinal bacteria may help us understand how we should optimise the bacteria found in the human body to protect it against disease.
“We have learned that if a virus pays a bacterium a visit, it may actually strengthen the bacterium. The viruses we found in the healthy Japanese centenarians contained extra genes that could boost the bacteria. We learned that they were able to boost the transformation of specific molecules in the intestines, which might serve to stabilise the intestinal flora and counteract inflammation,” says Joachim Johansen, and Simon Rasmussen adds:
“If you discover bacteria and viruses that have a positive effect on the human intestinal flora, the obvious next step is to find out whether only some or all of us have them. If we are able to get these bacteria and their viruses to move in with the people who do not have them, more people could benefit from them.”
Even though this requires more research, the new insight is significant, because we are able to modify the intestinal flora.
“Intestinal bacteria are a natural part of the human body and of our natural environment. And the crazy thing is that we can actually change the composition of intestinal bacteria. We cannot change the genes — at least not for a long time to come. If we know why viruses and intestinal bacteria are a good match, it will be a lot easier for us to change something that actually affects our health,” says Simon Rasmussen.

A new study by investigators from Mass General Brigham has linked certain types of gut bacteria to the development of precancerous colon polyps. Their results are published in Cell Host & Microbe.
“Researchers have done a lot of work to understand the relationship between the gut microbiome and cancer. But this new study is about understanding the microbiome’s influence on precancerous polyps,” said co-corresponding author Daniel C. Chung, MD, medical co-director of the Center for Cancer Risk Assessment at the Mass General Cancer Center and a faculty member of the Gastroenterology Division. “Through the microbiome, we potentially have an opportunity to intervene and prevent colorectal cancer from forming.”
Colorectal cancer is the second leading cause of cancer-related death in the U.S., and rates of colorectal cancer are rising among young adults. Nearly all colorectal cancers arise from a precancerous polyp. One of the best ways to reduce the incidence of colorectal cancer is to stop the growth at the polyp stage.
There’s more than one way for a polyp to develop. The two main types of polyps are tubular adenomas and sessile serrated polyps. Risk factors for colorectal cancer and polyps include lifestyle factors like being overweight or obese, low physical activity levels, a diet high in red and processed meats, smoking, and alcohol use. These factors also influence the bacteria that live in our intestines, collectively known as the gut microbiome.
Researchers think these environmental influences could promote polyp growth in one of two ways. Either they change the gut microbiome directly in a way that encourages polyp growth, or they promote polyp growth which in turn influences the gut microbiome by directly affecting the cells lining the intestines.
Earlier, smaller studies trying to link the gut microbiome to polyps have not found a consistent pattern, though they didn’t look at these two types of polyps specifically.
To study the gut microbiome’s link to colon polyps, the researchers took data from 1,200 people getting routine screening colonoscopies. They gathered information on their health, diet, medications, and lifestyle, as well as analyzed stool samples to determine the bacterial makeup of their gut microbiome. The new research is the biggest study from an extensive collaborative research program, the GI Disease and Endoscopy Registry (GIDER) at Massachusetts General Hospital, allowing these researchers to understand gastrointestinal diseases in greater depth than ever. This registry remains active and ongoing data collection will enable longitudinal follow-up.
The new study is the largest of its kind and analyzed the differences in the gut microbial signature of people without colon polyps, with tubular adenomas, or with sessile serrated adenomas. They also correlated this data with the patient’s health and family histories.
Bacterial signatures clustered into three groups based on the type and presence of polyps in the colon. Nineteen bacterial species were significantly different in patients with tubular adenomas than in other populations. In patients with sessile serrated adenomas, eight species were significantly different.
The authors note that the study population was mostly white, limiting generalizability to other racial groups, and that the study cannot establish whether bacterial species or adenoma tissue change first. The next step is for researchers to isolate specific species of bacteria acting in the gut and see if they can verify these functional relationships between the bacterial species and polyp growth with a model in a lab. This information could help develop a probiotic or treatment to lower colorectal cancer risk or as a screening method to assess polyp or colorectal cancer risk.
“The hope is that by changing specific aspects of the diet or the microbiome, we can alter the natural history of these polyps,” Chung said. “Interventions to prevent polyp formation or alter their growth patterns may ultimately prevent colorectal cancer.”

Researchers from Children’s Hospital of Philadelphia (CHOP), the Alex’s Lemonade Stand Foundation Childhood Cancer Data Lab, the Children’s Brain Tumor Network (CBTN), the Pacific Pediatric Neuro-Oncology Consortium (PNOC), and more than 20 additional institutions have partnered to create a first-of-its-kind open-source, reproducible analysis platform for pediatric brain tumors. With the help of thousands of genomically sequenced samples, researchers have used this platform to identify initial findings about genetic variants associated with poorer outcomes that could help guide future diagnostic and therapeutic advances.
The details of the platform and those initial findings were published online today by the journal Cell Genomics.
Pediatric brain tumors are collectively the leading cause of cancer-related death in children in the United States. However, the severity of pediatric brain tumors varies wildly, with some having an almost universally fatal prognosis while others have relatively strong long-term survival rates, though all brain tumors negatively impact these children and their families to at least some degree. Limited access to tissue samples and patient-derived cell lines has been a significant barrier to understanding the differences between pediatric brain tumors at a molecular level. That long sought-after data could lead to better diagnostic techniques and potential targeted therapies that could treat these deadly tumors.
In 2011, CBTN and PNOC began extracting and preparing what has now become nearly 6,000 tumor samples with over 68,000 sub-samples. More than 1,000 of these tumors were sequenced to form the initial release of the Pediatric Brain Tumor Atlas (PTBA) in 2018, and data were made available without embargo so that researchers could study what variants might be driving certain types of brain tumors. With the help of the Alex’s Lemonade Stand Foundation Childhood Cancer Data Lab, the team of researchers was able to build an open-source version of this atlas, the Open Pediatric Brain Tumor Atlas (OpenPBTA), to analyze these data.
OpenPBTA is accessible to anyone conducting research who is looking for new therapeutic targets or finding new ways to translate research into clinical practice. At the time of this study, OpenPBTA contained genomic and clinical data from more than 1,000 pediatric brain tumors and 22 patient-derived cell lines from the CBTN and PNOC. The OpenPBTA provides an open, real-time framework to genomically characterize pediatric brain tumors. It is the first large-scale, collaborative, open analysis of genomic data and provides a cloud-based resource for researchers looking for more comprehensive data on pediatric brain tumors.
“While there have been many proponents of an open-source model for scientific research, nothing like this existed for pediatric cancer,” said Jo Lynne Rokita, PhD, a Supervisory Bioinformatics Scientist leading OpenPBTA at the Center for Data-Driven Discovery (D3B) at CHOP and one of the study’s corresponding authors. “We designed OpenPBTA so that anyone could access the data, contribute to its analysis, and/or use it in their own research.”
“Collaboration is key to accelerating new cure discovery. OpenPBTA made it possible for experts across the globe to come together and gain a deeper understanding of the leading cause of cancer-related death in children and young adults,” said Jay Scott, Co-Executive Director of Alex’s Lemonade Stand Foundation.
Jaclyn N. Taroni, PhD, another corresponding author on the study and Director of Alex’s Lemonade Stand Foundation Childhood Cancer Data Lab, said, “With our successful launch of OpenPBTA, we’re hoping the research community adapts this model to other pediatric cancers.”
OpenPBTA is already providing researchers with more insight into potential drivers of pediatric brain tumors. In this study, researchers found that the loss of the tumor suppressor gene TP53 is a significant marker for poor overall survival in fast-growing brain and spinal cord tumors called ependymomas and certain diffuse midline gliomas, and dysregulation of the gene was also implicated in hypermutant high-grade gliomas.
“Solving pediatric brain tumors cannot be accomplished by any one institution. The OpenPBTA model of shared, real-time collaboration supported by PNOC and CBTN has not only empowered new discoveries, but also innovative ways of performing the required science on behalf of accelerated, collaborative innovation for children affected by brain tumors,” said Sabine Mueller MD, PhD, MAS, Professor of Neurology, Neurosurgery and Pediatrics at the University of California, San Francisco, and the Lead of PNOC and executive co-chair of CBTN.
This study was supported by the Alex’s Lemonade Stand Foundation (ALSF) Childhood Cancer Data Lab, an ALSF Young Investigator Award, ALSF Catalyst Awards, an ALSF CCDL Postdoctoral Training Grant, Children’s Hospital of Philadelphia Division of Neurosurgery, the Australian Government, Department of Education, the St. Anna Kinderkrebsforschung, Austria, the Mildred Scheel Early Career Center Dresden P2, funded by the German Cancer Aid, and National Institutes of Health (NIH) Grants 3P30 CA016520-44S5, U2C HL138346-03, U24 CA220457-03, K12GM081259, R03-CA23036, and NIH Contract No. HHSN261200800001E. This project was also funded in part with Federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. 75N91019D00024, Task Order No. 75N91020F00003. Additionally, this work was supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics of the National Cancer Institute.