A Half Billion for Genomics
By Kyser Lough August 7, 2017
From 1990 to 2013, thousands of scientists from around the world mapped the genes that make up human DNA. The Human Genome Project, as it was called, was an historic achievement.
It was also an achievement, by design, that created a vast new array of questions in its wake. What do all these genes do? How do they work together? What are the patterns? And most practically, how can we use our knowledge of the human genome to improve human health and life?
Since that time, we’ve started answering those questions. Now, thanks to a half-billion-dollar federal award, Texas researchers will play a key role in adding critical details to what we know about the human genome. Their work will provide insight into the development of complex diseases and help build a knowledge base to improve treatments.
The University of Texas Health Science Center at Houston (UTHealth) has joined two related centers to participate in a $500 million program of the National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine (TOPMed) program. The collaboration is one of four in the country that is being funded, by TOPMed, to use whole genome and other biological data to better understand heart, lung, blood and sleep disorders.
UTHealth’s component is led by Eric Boerwinkle, Ph.D., Dean of the UTHealth School of Public Health and Associate Director of the Human Genome Sequencing Center at Baylor College of Medicine. The project focuses on two key areas that intersect with the broader field of genomics: methylation of DNA and metabolomics.
Methylation is one of the ways in which the expression of DNA is controlled within our cells. When a methyl group attaches to a DNA molecule, it can turn genes on or off, determining what proteins are produced and ultimately what’s happening in the cell. It’s a fundamental way in which our bodies adapt to their environment, and respond to behaviors such as excessive alcohol consumption and tobacco use. When it comes to disease, researchers are especially interested in how environmental risk factors produce methylation, and how this can increase risk of disease.
Boerwinkle gives the example of a set of identical twins, where one is a smoker and one is not. Although their DNA is the same, the two are at radically different risk for certain diseases. The tobacco use, and lack of use, cause their DNA to express itself in different ways.
“As you go through life, your DNA sequence doesn’t change but your life exposure changes how those genes are expressed,” said Boerwinkle. “So your risk of disease can change based on how certain environmental factors affect gene expression. In this sense, DNA is more of a guidebook and not necessarily a blueprint.”
Metabolomics involves the study of small molecules, called metabolites, that are the products of various genetic and genomic processes within the cell. The hope is that by better understanding metabolites, Boerwinkle and his colleagues can identify metabolic biomarkers—signposts—that can be used to identify disease risk earlier, both in individuals and at the population level. It may also point toward interventions that could improve and save lives.
“The goal is to be able to ascertain environmental risk. Ultimately, it can be used to reduce or prevent risk based on what we know, or even understand why two people may respond differently to a drug or why one person with diabetes carries on a normal life and another is unable to,” Boerwinkle said.
Two key components made the grant, and the research itself, possible. First, collaboration. UTHealth is partnering with both the Human Genome Sequencing Center at Baylor College of Medicine (HGSC) and the Alkek Center for Metagenomics and Microbiome Research (CMMR) at Baylor. It took time to build the partnership, infrastructure and trust to make it possible, but without that hard work, says Boerwinkle, the project wouldn’t have been funded.
The second key component is technology. UTHealth and Baylor would be unable to process and analyze the massive amounts of data were it not for significant general advances in lab and cloud computing technologies. Each institution brings important technology to the collaboration, which will make it possible both to obtain massive amounts of data, and then to analyze the data efficiently with heavy-duty computers and a cloud-based infrastructure.
The flow of data will begin with the Human Genome Sequencing Center (HGSC) at Baylor, which will receive samples from investigators at the National Heart, Lung, and Blood Institute. The HGSC will perform the whole genome sequencing, as well as some RNA sequencing, and then distribute samples both to UTHealth, for methylation and metabolomics profiling, and to the Alkek Center for metagenomic analysis. The data from all three sources will then be funneled into a data sharing portal and relayed back to TOPMed.
“We as scientists at UTHealth are not just looking at genomics anymore, we’re looking at so much more. This is going to be useful on many levels. We’ll be able to make broad brushstroke recommendations but also more tailored recommendations for subgroups,” Boerwinkle said.