The purpose of the Quantitative Biology Core is to provide investigators with consultative support in biostatistics/computational biology and bioinformatics, and to support web-based dissemination of bioinformatic solutions and database access.
Most specific aims with the projects produce high-dimensional biological and exposure data, and often involve complicated questions addressing the possible interaction of environmental exposures and high-dimensional measures of the genome, proteome, and other high throughput technologies. These high-dimensional data sets are characterized by many thousands of measurements made on each unit (e.g. person, yeast culture, soil community). Core D reflects an evolution in the field of biostatistics and bioinformatics towards developing methodologies that can both find patterns in high dimensional data sets as well as providing proper statistical inference for these patterns. A consensus among our project researches and the methodological experts has formed around a set of core principles regarding optimal estimation and inference in the context of complicated questions and high-dimensional data. Specifically, the consensus favors using (when possible): semi-parametric locally efficient estimation with robust inference and the development of optimal methods used to integrate the statistical results into existing metadata to suggest relevant biological pathways and networks. Applying this approach will enable analyses to incorporate diverse data to query similar patterns/pathways in both related toxins and possible related diseases thus substantially leveraging data generated by the Program. To implement this methodology, the Quantitative Biology Core will provide access to a computational environment that lends itself to the computationally intensive methods developed for data mining and re-sampling based inference. Because of the scale of the data collection as well as the desirability of converging to a general methodology, our Program requires a more centralized system that can both archive data for, provide sharing to this Core, guidance on the access of metadata/annotation and routines for leveraging such data to find overprinting of our results on existing hypothesized regulatory networks. The Core will also develop tools to find and compares pathway, and create and maintain a web-based system that will allow for both efficient sharing of our methodological expertise with the project researchers and ultimately serve as a tool for outreach among the general scientific community.
Despite improvements in technology, the lack of statistical rigor among the proliferating methods used to discover disease etiology and develop effective interventions are producing large numbers of false positive claims. However, by using methods that optimally balance the complexity of models with the need to provide inferences consistent with the amount of data available, one can avoid wild goose chases engendered by false discoveries.
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|Shen, Hua; McHale, Cliona M; Haider, Syed I et al. (2016) Identification of Genes That Modulate Susceptibility to Formaldehyde and Imatinib by Functional Genomic Screening in Human Haploid KBM7 Cells. Toxicol Sci 154:194|
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|Hsu, Ling-I; Briggs, Farren; Shao, Xiaorong et al. (2016) Pathway Analysis of Genome-wide Association Study in Childhood Leukemia among Hispanics. Cancer Epidemiol Biomarkers Prev 25:815-22|
|Carlos-Wallace, Frolayne M; Zhang, Luoping; Smith, Martyn T et al. (2016) Parental, In Utero, and Early-Life Exposure to Benzene and the Risk of Childhood Leukemia: A Meta-Analysis. Am J Epidemiol 183:1-14|
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|Barazesh, James M; Prasse, Carsten; Sedlak, David L (2016) Electrochemical Transformation of Trace Organic Contaminants in the Presence of Halide and Carbonate Ions. Environ Sci Technol 50:10143-52|
|Shen, Hua; McHale, Cliona M; Haider, Syed I et al. (2016) Identification of Genes That Modulate Susceptibility to Formaldehyde and Imatinib by Functional Genomic Screening in Human Haploid KBM7 Cells. Toxicol Sci 151:10-22|
|Hu, Xindi C; Andrews, David Q; Lindstrom, Andrew B et al. (2016) Detection of Poly- and Perfluoroalkyl Substances (PFASs) in U.S. Drinking Water Linked to Industrial Sites, Military Fire Training Areas, and Wastewater Treatment Plants. Environ Sci Technol Lett 3:344-350|
|Bailey, Kathryn A; Smith, Allan H; Tokar, Erik J et al. (2016) Mechanisms Underlying Latent Disease Risk Associated with Early-Life Arsenic Exposure: Current Research Trends and Scientific Gaps. Environ Health Perspect 124:170-5|
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