Collaborating Authors

Genomes arising


Africans have begun to study their continent's rich human diversity—but what comes after current grants end? In 1987, 10-year-old Segun Fatumo was on the streets of Lagos, Nigeria, hawking palm oil, yams, and pepper each day after school to help put food on the table. In the evenings, he and his family crowded into a two-room dwelling without running water or electricity. He knew nothing of the plan being hatched by U.S. and U.K. geneticists to sequence the human genome. Thirteen years later, when researchers completed the draft sequence of the human genome, Fatumo—then an undergraduate studying computer science—heard all about it. “I knew the project would change our world,” he recalls. What he didn't realize at the time was how it would change his life. Fast forward more than 2 decades. Fatumo is now a computational geneticist in Entebbe, Uganda, with the Medical Research Council/Uganda Virus Research Institute and the London School of Hygiene & Tropical Medicine. Genome data by the terabytes flow through his seven-person lab, which is working to pinpoint genes involved in heart, kidney, and other diseases. All members of his team are African, the data come from African donors, and the ultimate goal is to improve the health of the people of Africa. Until recently, genetic research in Africa was scanty, and most was done by researchers swooping in from afar to gather samples, then leaving to do analyses in well-equipped labs in the United States or Europe. “African genomic study was characterized by ethical dumping, helicopter science, and exploitation,” Fatumo says. Researchers gathered samples with little regard for informed consent and without giving back to the communities they studied, he says. Today, Fatumo and scores of other young Africans are doing a substantial and growing share of this research. “African genomics is a story that's going to be told more and more by Africans,” says Charles Rotimi, a genetic epidemiologist at the U.S. National Human Genome Research Institute (NHGRI). Bolstered by the internationally funded Human Heredity & Health in Africa (H3Africa) Initiative, which sponsored Fatumo as a postdoc, these researchers hope to one day use their data to bring genetically tailored medicine to people who in some places still struggle to get electricity and basic health care. The work is beginning to close a wide gap in who benefits from the human genome revolution. “There's this genomics expansion across the world,” says Neil Hanchard, molecular geneticist at Baylor College of Medicine. “Why should Africa be left behind?” Including African populations is also paving the way for a better understanding of the links between disease and genes in everyone, everywhere, because Africa holds more genomic diversity than any other continent. “The African genome should be used as the reference genome for the entire world,” says Tesfaye Mersha, a geneticist at the University of Cincinnati. But genomic research in Africa has a long way to go. Researchers have only studied between 5000 and 10,000 whole genomes from Africans, compared with as many as 1 million worldwide. Africa has received less than 1% of the global investment in genomics research and clinical studies, Mersha says. What's more, funding for all current projects in H3Africa, a $176 million program supported by the U.S. National Institutes of Health (NIH) and the Wellcome Trust that has jump-started African genomics, is set to end in 2022. Fatumo has corralled another prestigious fellowship, but researchers across the continent are scrambling to make sure the nascent genomics community can survive—and grow. FATUMO DECIDED he wanted to study genetics as a youngster, after a doctor explained sickle cell disease to him. His brother suffered weeklong bouts of pain from the condition. Fatumo learned that his brother had two copies of the responsible gene—and that he himself would be spared because he had just one copy. “The role genes play in disease got me thinking,” he recalls. Sickle cell, which is now being treated through gene therapy, is a classic example of how genetic knowledge can inform medical practice ( Science , 11 December 2020, p. [1254][1]). And it primarily affects people of African descent. Yet most sickle cell studies and medical advances have happened in rich countries. Fatumo wants more Africans doing such research in the future. One of six children, whose father worked as an unskilled tailor and later as a subsistence farmer and bush hunter, Fatumo moved with his family to the outskirts of Lagos when he was 9 years old. He hiked 2 kilometers early every morning to retrieve water from a river, wielded hoe and cutlass to tend crops, trekked to Lagos for school, then topped off the day hawking. He and his parents managed to pay the 105 Nigerian naira (about $1) per year for school, thanks, in part, to Fatumo's hawking profits. Fatumo says poverty fueled in him a fierce determination to do better. “The story of my upbringing is the one that propels anger for success.” Later, he earned a B.S. in computer science at the African University of Science and Technology in Abuja, Nigeria. Because little genetics was being done at African universities, he pursued graduate degrees in computer science at Covenant University in Ota, Nigeria. “I was lucky to study at Covenant where they had some key resources and constant electricity,” he recalls. Even so, his bioinformatics analyses kept crashing the school's computer system. He spent 1 year studying in Heidelberg, Germany, where “the same analysis was completed in less than 30 minutes” with high-performance computers. ![Figure][2] CREDITS: (GRAPHIC) K. FRANKLIN/ SCIENCE ; (DATA) G. SIRUGO ET AL., CELL , 177, 1, 26 (2019) But he was working his way through school at the right time, in the right place. In 2009, the founders of the 6-year-old African Society of Human Genetics met in Cameroon to discuss their vision for an African genome project. “It was a dream we had, but … we didn't know where the funding would come from,” Rotimi says. Francis Collins, who had coordinated the Human Genome Project but was then between jobs, was invited to give the opening talk. He and other participants knew how much genomics studies in Africa could contribute to research worldwide. Trace any human's family tree back far enough and the roots wind up in Africa, where our species was born some 300,000 years ago. When some groups left the continent over the past 80,000 years or so and spread across the globe, they carried only a subset of human genomic diversity. As a result, the people of Africa today carry more genetic diversity than those of any other continent. “There are parts of our genome that we cannot study any place beside Africa,” says Rotimi, who directs NHGRI's Center for Research on Genomics and Global Health. Those at the 2009 meeting also recognized that Africans needed to lead the way. “The idea that people outside of Africa are going to be able to decide the priorities … just doesn't work,” Collins says. Local investigators are more likely to understand the culture and constraints and to be trusted by the community, Mersha adds. Some researchers were skeptical about funding African-based research. “People said the money would just disappear,” Collins recalls. But “I was pretty convinced we could step away from the colonial perspective where developed nations make the decisions.” Collins became NIH director in 2009 and helped launch H3Africa in 2011. NIH has committed $150 million to the initiative through 2022, and Wellcome, a U.K. biomedical philanthropy giant, has kicked in another $26 million. The initiative aimed to set up a network of laboratories across the continent to explore the relative roles of environment and genes in diseases that plague Africans, such as HIV/AIDS, trypanosome infections, stroke, diabetes, and heart disease. It also established biorepository and bioinformatics networks. To ensure a lasting legacy, it supports training as well as research. IN 2013 , with H3Africa funding, Fatumo traveled to the Wellcome Sanger Institute in Hinxton, U.K., and the University of Cambridge as a postdoc in genetic epidemiology. At Sanger, he took part in the largest African genomics project to date, a multimillion-dollar effort to analyze genomic data from 14,126 people from five African countries, including newly collected whole genomes from nearly 2000 Ugandans. The international team of researchers found 9.5 million gene variants not previously spotted, underscoring the diversity of African populations and laying the groundwork for future genomic studies. The results, published in Cell in 2019, also included specific variants related to cardiovascular diseases in Africans, such as one previously linked to an inherited blood disorder called alpha thalassemia. That single variant could also shape the diagnosis of a third condition: It alters how sugars bind to red blood cells and so affects the results of the blood glucose test often used to track diabetes. One year later, H3Africa's milestone genome paper came out in Nature . Human geneticist Zané Lombard and bioinformaticist Ananyo Choudhury from the University of the Witwatersrand, along with other African and international colleagues, analyzed 426 genomes, many newly sampled, from 50 populations in 13 countries. They described more than 3 million new human DNA variants, most from previously unsampled populations. The analysis also confirmed the continent's complex migration patterns, tracing the path of Bantu-speaking people as they expanded southward and eastward more than 3000 years ago. That was just one of nearly 300 papers published so far by H3Africa teams, describing results as well as providing curated data sets of African genomes. Those databases will illuminate studies of human variation worldwide, in part because the great genomic diversity in Africans can uncover spurious links to medical conditions, explains Concepcion Nierras, an NIH Common Fund geneticist. For example, in Europeans a rare variant of a gene for a low-density lipoprotein that contributes to high cholesterol seemed to raise the risk of heart disease. But Fatumo and his colleagues found that among Africans, the variant was common even in those who did not have heart disease, suggesting it may not have clinical relevance. The Nature paper uncovered 54 such variants that now need re-evaluation. Scientists say H3Africa has been thoughtful about ethics, vital in a continent with a long history of colonial exploitation and where such concerns remain a flashpoint. For example, until 2019 Sanger was working to develop a DNA chip for scanning African genomes quickly. But whistleblowers said study participants hadn't granted the institute permission to use their DNA in this way. That chip is now not used, although one developed by H3Africa has become a mainstay ( Science , 1 November 2019, p. [555][3]). To guard against exploitation, the project brought on bioethicists to discuss the research with local communities and figure out equitable partnerships, addressing concerns from populations worried about misuse of their data. They are also working to establish standards for effective, ethical informed consent. At Makerere University, orthopedic surgeon and bioethicist Erisa Mwaka Sabakaki and colleagues have reviewed hundreds of informed consent and other documents. Projects sometimes came up with unexpected solutions: For a study involving HIV-infected children, comic books proved a great way to communicate to both adults and children. “There are ongoing and important questions about informed consent, how best to engage communities, benefit sharing, stigma, and many other issues,” says Jantina De Vries, a bioethicist at the University of Cape Town who helped set up H3Africa's policies. “But we've started on a really good trajectory.” H3Africa's biggest achievement may be growing a generation of African genomicists, says Harvard University global public health expert Barry Bloom. The project has trained 137 Ph.D.s and 49 postdocs including Fatumo, as well as hundreds of master's students and undergraduates, and gives an incentive for scientists trained abroad to return to Africa. “If not for H3Africa, maybe I wouldn't be a group leader and principal investigator today,” Fatumo says. These efforts have had spillover effects beyond human genetics. For example, the project helped train Christian Happi, a molecular biologist at Redeemer's University in Ede, Nigeria, who runs the African Center of Excellence for Genomics of Infectious Diseases. His team quickly sequenced Nigeria's first Ebola case, identified Lassa fever strains in a 2018 outbreak and—in just 3 days in March 2020—sequenced the first coronavirus genome from an African, showing SARS-CoV-2 had arrived from Europe. “The program's resources have enabled many African countries to respond to other health challenges,” says Clement Adebamowo, a surgical oncologist at the University of Maryland School of Medicine who has been active in African genetics. BUT H3AFRICA'S successes highlight how much more work is needed. Most of the project's genomes are from people of Southern, Central, and West African ancestry (see map, p. 559), and many populations haven't been sampled at all, including those in North Africa. “Our studies combined are just the tip of the iceberg,” says Sarah Tishkoff, a human geneticist at the University of Pennsylvania who has led the way in sampling remote populations. Individual studies highlight how much more researchers need to know to understand the intersection of genes and disease. For example, an H3Africa project called the Collaborative African Genomics Network (CAfGEN) aims to come up with a blood test for HIV-positive newborns to show how quickly their infection could progress to AIDS. Researchers scrutinized the genomes of infected children, hoping to find genetic variants associated with slow HIV progression. Children with such variants could postpone treatment and reduce and delay long-term side effects. But so far, the team has found just one piece of DNA, involved in the immune system, that varies significantly among the children. And candidate variants that popped up in a study of Botswanan children failed to appear in Ugandan children, underscoring the diversity of African genomes. “The African genome is much more complex than we anticipated,” says CAfGEN trainee Lesedi Williams, now a genomicist at the University of Botswana, Gaborone. “The sad reality is that genomics data from Africa [are] still too few,” says geneticist Aimé Lumaka of the University of Liège and the University of Kinshasa. So the medical significance of many variants in people of African descent is unknown. Tishkoff and others are broadening their samples; this year she hopes to publish on 180 more African genomes, while Choudhury and his H3Africa colleagues are coming up with new places to sample, including Mauritius, Réunion, and other islands. More mundane challenges also loom. “Our supply chains, financial systems, and infrastructure need strengthening,” says Iruka Okeke, who studies pathogen genomes at the University of Ibadan. The continent is short of both sequencing capacity and computers powerful enough to analyze giant data sets. These impediments can lead H3Africa investigators to delay making data publicly available in order to do their own analyses, a practice that can create its own problems, says Steven Salzberg, a computational biologist at Johns Hopkins University. “As long as each group keeps its data private, the next group that wants to study these populations has to start over and sequence a new cohort,” he says. ![Figure][2] GRAPHIC: K. FRANKLIN/ SCIENCE With funding scarce, some H3Africa trainees are leaving human genetics for fields where research is cheaper. One CAfGEN trainee, Gerald Mboowa at Makerere University, has shifted away from human genomes—which cost $1000 per sequence—to those of bacteria, which are a mere $90. He recently received a $100,000 Grand Challenges Africa grant funded by the Bill & Melinda Gates Foundation to track drug-resistant bacteria in hospitals. Others, noting that direct health benefits from genes are often a long way off, wonder whether H3Africa money would be better spent on more immediate public health needs such as antismoking and healthy eating campaigns. “In 2011 we didn't know” whether H3Africa was the best way to spend international resources in Africa, says Richard Cooper, an emeritus epidemiologist at Loyola University Chicago who helped get the project off the ground. “Unfortunately I [now] think the answer is in the negative,” because genomics has yet to lead to many concrete boosts in health. Fatumo is satisfied that his own work is of immediate benefit. As his organization gathered blood samples in rural Uganda, it discovered and treated diseases participants hadn't been aware of, including hepatitis and hypertension. But a big challenge looms in 2022, when NIH Common Fund support ends. That loss could “be a major blow to everything that's been built up,” says Stefan Jansen, a psychologist at the University of Rwanda involved with an H3Africa project on posttraumatic stress disorder. Some support will come from another NIH program, Harnessing Data Science for Health Discovery and Innovation in Africa (DS-I Africa), which is slated to spend $62 million over the next 6 years. And an African genomics startup called 54Gene has gotten $15 million in international backing for a multimillion-dollar facility in Nigeria. But most H3Africa-supported researchers have had little luck finding funding within Africa. It's “really, really challenging getting African funding from private companies or African governments,” Rotimi says. Some of Africa's genomics researchers will manage to win new support from abroad, as Mboowa has done. Fatumo was recently awarded a highly competitive Wellcome International Intermediate Fellowship and now has $1.2 million over the next 5 years plus other support to explore genomic variants linked to chronic kidney disease; he hopes to develop risk scores based on patients' genetic makeup. He has also teamed up with a South African colleague and applied to become a DS-I Africa research hub. If successful, they will get $1.3 million per year for 5 years to use existing African genetic data to find and validate new drug targets. Fatumo and others hope their generation's accomplishments will lay the foundation for an even stronger research network. “It is a great time for all of us doing genomics in Africa,” Okeke says. “The discovery potential is very high, and the impact that our work could have on health could be huge.” [1]: [2]: pending:yes [3]:

Industry News


Find here a listing of the latest industry news in genomics, genetics, precision medicine, and beyond. Updates are provided on a monthly basis. Sign-Up for our newsletter and never miss out on the latest news and updates. As 2019 came to an end, Veritas Genetics struggled to get funding due to concerns it had previously taken money from China. It was forced to cease US operations and is in talks with potential buyers. The GenomeAsia 100K Project announced its pilot phase with hopes to tackle the underrepresentation of non-Europeans in human genetic studies and enable genetic discoveries across Asia. Veritas Genetics, the start-up that can sequence a human genome for less than $600, ceases US operations and is in talks with potential buyers Veritas Genetics ceases US operations but will continue Veritas Europe and Latin America. It had trouble raising funding due to previous China investments and is looking to be acquired. Illumina loses DNA sequencing patents The European Patent ...

Machine Learning in Genomics – Current Efforts and Future Applications Emerj


Genomics is a branch of molecular biology focused on studying all aspects of a genome, or the complete set of genes within a particular organism. Today, machine learning is playing an integral role in the evolution of the field of genomics. We set out in this article to examine the applications of machine learning in genomics to help business leaders understand current and emerging trends within the field. Before diving into present applications, we'll begin with background facts and terminology about genomics and precision medicine, and a quick summary of the findings of our research on this topic: The ability to sequence DNA provides researchers with the ability to "read" the genetic blueprint that directs all the activities of a living organism. To provide context, the central dogma of biology is summarized as the pathway from DNA to RNA to Protein.

Genetics has learned a ton -- mostly about white people. That's a problem.


In the future, it's possible that when you go in for a physical, your doctor will, along with the usual blood pressure test and bloodwork, analyze your genome for health risks lurking in the code of your DNA. It's possible your genome will suggest you're at high risk of developing heart disease. If you are, your doctor may start you on cholesterol-lowering drugs early or could also, maybe, make predictions about what other medications are most likely to work to prevent the disease. A treatment plan like this -- tailored to an individual's genetic risk -- is one of the great promises of "precision medicine." Whether genomic analysis will ever yield enough useful results to make it possible is a subject of heated debate.

6 expert essays on the future of biotech


What exactly is biotechnology, and how could it change our approach to human health? As the age of big data transforms the potential of this emerging field, members of the World Economic Forum's Global Future Council on Biotechnology tell you everything you need to know. What if your doctor could predict your heart attack before you had it – and prevent it? Or what if we could cure a child's cancer by exploiting the bacteria in their gut? These types of biotechnology solutions aimed at improving human health are already being explored. As more and more data (so called "big data") is available across disparate domains such as electronic health records, genomics, metabolomics, and even life-style information, further insights and opportunities for biotechnology will become apparent. However, to achieve the maximal potential both technical and ethical issues will need to be addressed. As we look to the future, let's first revisit previous examples of where combining data with scientific understanding has led to new health solutions. Biotechnology is a rapidly changing field that continues to transform both in scope and impact. Karl Ereky first coined the term biotechnology in 1919.