Life Sciences Commons^™

Bayesian Analytical Approaches For Metabolomics : A Novel Method For Molecular Structure-Informed Metabolite Interaction Modeling, A Novel Diagnostic Model For Differentiating Myocardial Infarction Type, And Approaches For Compound Identification Given Mass Spectrometry Data., Patrick J. Trainor

Electronic Theses and Dissertations

Metabolomics, the study of small molecules in biological systems, has enjoyed great success in enabling researchers to examine disease-associated metabolic dysregulation and has been utilized for the discovery biomarkers of disease and phenotypic states. In spite of recent technological advances in the analytical platforms utilized in metabolomics and the proliferation of tools for the analysis of metabolomics data, significant challenges in metabolomics data analyses remain. In this dissertation, we present three of these challenges and Bayesian methodological solutions for each. In the first part we develop a new methodology to serve a basis for making higher order inferences in metabolomics, …

Epigenomics And Metabolomics Reveal The Mechanism Of The Apoa2-Saturated Fat Intake Interaction Affecting Obesity, Chao-Qiang Lai, Caren E. Smith, Laurence D. Parnell, Yu-Chi Lee, Dolores Corella, Paul Hopkins, Bertha A. Hidalgo, Stella Aslibekyan, Michael A. Province, Devin Absher, Donna K. Arnett, Katherine L. Tucker, Jose M. Ordovas

Epidemiology and Environmental Health Faculty Publications

Background: The putative functional variant −265T > C (rs5082) within the APOA2 promoter has shown consistent interactions with saturated fatty acid (SFA) intake to influence the risk of obesity.

Objective: The aim of this study was to implement an integrative approach to characterize the molecular basis of this interaction.

Design: We conducted an epigenome-wide scan on 80 participants carrying either the rs5082 CC or TT genotypes and consuming either a low-SFA (< 22 g/d) or high-SFA diet (≥ 22 g/d), matched for age, sex, BMI, and diabetes status in the Boston Puerto Rican Health Study (BPRHS). We then validated the findings in selected participants in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) Study (n = 379) and the Framingham Heart Study (FHS) (n = 243). Transcription and metabolomics analyses were conducted to determine the relation between epigenetic status, APOA2 mRNA expression, …

Acute Loss Of Iron-Sulfur Clusters Results In Metabolic Reprogramming And Generation Of Lipid Droplets In Mammalian Cells, Daniel R. Crooks, Nunziata Maio, Andrew N. Lane, Michal Jarnik, Richard M. Higashi, Ronald G. Haller, Ye Yang, Teresa Whei-Mei Fan, W. Marston Linehan, Tracey A. Rouault

Center for Environmental and Systems Biochemistry Faculty Publications

Iron–sulfur (Fe-S) clusters are ancient cofactors in cells and participate in diverse biochemical functions, including electron transfer and enzymatic catalysis. Although cell lines derived from individuals carrying mutations in the Fe-S cluster biogenesis pathway or siRNA-mediated knockdown of the Fe-S assembly components provide excellent models for investigating Fe-S cluster formation in mammalian cells, these experimental strategies focus on the consequences of prolonged impairment of Fe-S assembly. Here, we constructed and expressed dominant–negative variants of the primary Fe-S biogenesis scaffold protein iron–sulfur cluster assembly enzyme 2 (ISCU2) in human HEK293 cells. This approach enabled us to study the early metabolic reprogramming …