The Bioinformatics Research Center was pleased to present the 2015 C. Clark Cockerham Guest Lecture, with guest speaker, Dr. Nancy Cox of Vanderbilt University. The title of her lecture was, ““New Kinds of Data Integration: Genome x Transcriptome x Electronic Medical Records”. The Bioinformatics Research Center would like to thank all those who attended and especially Dr. Nancy Cox for her time and efforts.
At the recent annual Symposium on Emerging Technologies in Computational Chemistry, BRC Faculty member, Dr. Denis Fourches won the ACS award for the best presentation. The COMP division (Computers in Chemistry) holds a Symposium on Emerging Technologies in Computational Chemistry at the American Chemical Society Fall National Meeting every year. The objective of the symposium is to stimulate, reward, and publicize methodological advances in computational chemistry. Schrödinger, Inc., sponsors a $1,000 prize for the best talk at the symposium. Pre-selected talks are evaluated at the meeting by a panel of experts based on the quality of the presentation and the impact that the research will have on the future of computational chemistry and allied sciences. More info at http://web2011.acscomp.org/
Recent research conducted by BRC Director Fred Wright and Ivan Rusyn of Texas A&M University (https://news.ncsu.edu/2015/05/wright-chem-sensitivity/) resulted in a treasure trove of data on variation of chemical sensitivities in human cell lines. In collaboration with the National Institute of Environmental Health Sciences and the National Center for Advancing Translational Sciences, the researchers had studied over 1000 cell lines and exposure to 179 chemicals, with the goal of mapping genetic variation in toxicity response. Says Wright “the data are so rich that we really are just scratching the surface.” Expanding the collaboration to include Sage Bionetworks and a crowd-sourcing initiative known as Dream Challenges, the bioinformatics community was enlisted to further mine the data, providing prediction algorithms that can aid future researchers in predicting toxicity based on DNA profiles and chemical structures. An article describing the results of this crowdsourcing effort recently appeared in Nature Biotechnology (http://www.nature.com/nbt/journal/vaop/ncurrent/full/nbt.3299.html).
Image credit: Nature Biotechnology (2015) doi:10.1038/nbt.3299, under Creative Commons License
The Environmental Protection Agency (EPA) has awarded a $6 million grant to fund a multi-institutional collaboration between the Texas A&M College of Veterinary Medicine & Biomedical Sciences and the Bioinformatics Research Center at NCSU. investigating the effects of environmental toxicants on human health with a focus on the potential adverse effects on the heart. The investigators will study the effect of environmental chemicals on cultures of cells that have been coaxed into behaving like heart muscle, even to the point of beating with a regular rhythm. Dr. Fred Wright, the principal investigator for the NCSU site, says “the ability to systematically investigate cardiac toxicity in this manner opens up the study of inter-individual variability in toxicity testing, in a way that was not possible before.” Other investigators at NCSU include Associate Professor David Reif and Research Assistant Professor Yi-Hui Zhou.
Image credit: Cellular Dynamics
New research from North Carolina State University and Reed College shows that when fruit flies are attacked by parasites or bacteria they respond by producing offspring with greater genetic variability. This extra genetic variability may give the offspring an increased chance of survival when faced with the same pathogens. These findings demonstrate that parents may purposefully alter the genotypes of their offspring.
Image credit: Dahlia Nielsen, NCSU
BRC faculty member Yi-Hui Zhou, Research Assistant Professor of Biological Sciences, has received a two-year R21 award from the National Human Genome Research Institute to develop new methods to analyze genome-wide association studies (GWAS). Existing methods for genetic association mapping primarily use parametric statistical assumptions. Explains Dr. Zhou, “standard methods can fail, even for large sample sizes, at the extreme significance thresholds required when testing millions of genetic markers.” An alternative approach uses permutation, a kind of data shuffling that provides accurate results, but is computationally intensive. The grant proposes to develop new mathematical approximations to permutation, in order to provide fast and accurate testing with greatly reduced computational burden.
David Reif was a member of the Working Group that drew experts from 13 countries to a meeting in Lyon, France in order to evaluate the carcinogenicity of the the insecticides gamma-hexachlorocyclohexane (lindane) and dichlorodiphenyltrichloroethane (DDT) and the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D).
It’s 2015, and the link between inherited DNA variation and numerous diseases is well-established. However, an important question remains – how, exactly do these links between genetic variation and disease work? The Genotype-Tissue Expression (GTEx) project, funded by the National Institutes of Health and including a team of researchers from NC State and UNC-Chapel Hill, aims to start answering that question by looking at how genetic variation affects gene expression.
“Important gaps still remain in understanding genetic processes, which vary greatly across the organs and tissues of the human body,” says Fred Wright, professor of statistics and biological sciences at NC State. “We have little understanding of how genetic variants actually cause disease, because we haven’t been able to look at the gene expression part of the equation. GTEx aims to fill the knowledge gap between the DNA you’re born with and actual disease outcomes.”
“You can think of DNA as the controller of a giant genetic switchboard,” explains Wright’s collaborator Andrew Nobel, professor of statistics and operations research at UNC-Chapel Hill. “When DNA switches on a gene, the gene produces proteins with specific functions. In the case of many common diseases, relatively small changes in protein output can have profound effects on disease risk.”
The GTEx project took samples of a large variety of tissues from 175 recently deceased individuals, measuring gene expression in those tissues. First, the researchers established that nearly normal gene activity persists for several hours after death. Then the major task of connecting variation in DNA to expression began. This is where Wright, Nobel and their team came in – to find meaningful correlations among all the “noise.”
“We had data for millions of DNA variants and how each variant was related to gene expression in different tissues,” Wright says. “Since we were looking at multiple tissues, there were gaps and overlaps in the data. We had to come up with a mathematical/statistical model that could assess, for each DNA variant and each gene, the evidence for the variant-gene combination being active for each of the tissues. The data were analyzed all together, but we untangled associations that reflected underlying true biology, versus associations that were happenstance because of sample overlap.”
Initial results were promising. The group found that DNA variants that affect expression tend to do so either in one tissue alone, or in all the examined tissues. Groups within GTEx are now comparing the results of the model to each variant-disease association, helping us further narrow down the genes that the variants affect, and in which tissue. The work may bring us one step closer to personalized therapies for numerous diseases.
The results appear in Science (DOI: 10.1126/science.1262110). NC State co-authors include Yi-Hui Zhou, research assistant professor of biological sciences. Funding was provided by the National Institutes of Mental Health and the NIH Common Fund.
Eric Stone, professor in the Department of Biological Sciences, and Bioinformatics Research Center Professor will receive $200,000 to purchase a NextSeq 500 DNA sequencer that will expedite research projects such as biofuel generation, pollution surveying and remediation, and agricultural crop improvement.