CIS Department Talk - Thursday, March 2

The Department of Computer and Information Science & The Society of Computer Science Present

Speaker:	Dr. Bruce Kristal
Topic:	The sera metabolome of dietary restriction - potential biomarkers for long-term disease risk in humans?
Date:	Thursday, March 2, 2006 at 10:00 am
Place:	John Mulcahy Hall 403, Rose Hill Campus

Metabolomics is the systematic and theoretically comprehensive measurement of the small molecule constituents of a biological system or sample, eg, plasma. Our metabolomics work primarily focuses on identifying serum markers for dietary restriction (DR).

Dietary or caloric restriction (DR) is the most potent and reproducible known means of increasing longevity and reducing morbidity in mammals. Exploratory studies previously identified 93 redox-active small molecules from sera (measured by HPLC coupled with coulometric detector arrays) with potential to distinguish dietary groups in both male and female rates. Classification and predictive power were addressed using magavariate data analysis approaches. The compounds weakly distinguished AL and DR samples by Principal Components Analysis (PCA) due to noise resulting from inter-cohort sampling. Soft Independent Modeling of Class Analogy, which builds independent PCA models of each class of interest, distinguished groups with 95% accuracy, but overfit models built on single cohorts. Partial Least Squares Projection to Latent Structures Discriminant Analysis, a projection method optimized for class separation, in contrast, built models with >95% accuracy in distinguishing groups without obvious cohort interference. Data processing choices of transformation, scaling, and winsorizing (outlier removal) each affected strength of the models, and, in some cases, revealed distinct metabolites to be of importance in building these models, often in gender-specific ways. Diets varying in extent and duration of DR were used to develop models for intermediate caloric intakes, which are more relevant for human studies. Partial Least Squares models had r2 values of 0.89 with respect to prediction of caloric intake at the individual level. We have now adapted these markers for use in humans. We will present the models, their ability to distinguish sera based on caloric intake, and the potential for moving these markers to epidemiological studies in human sera.

Bio:

Bruce Kristal received his B.S. in Life Sciences from the Massachusetts Institute of Technology in 1986 and his Ph.D. from Harvard University Graduate School of Arts and Sciences, Division of Medical Sciences, Committee on Virology in 1991. After being a post-doctoral fellow, instructor, and research assistant professor at the University of Texas Health Science Center at San Antonio (1991-1996), he joined the Dementia Research Service of Burke Medical Research Institute in 1996 and subsequently the Departments of Biochemistry (1997) and Neuroscience (1998) at Weill Medical College of Cornell University as an Assistant Professor (Associate Professor in 2004).

Dr. Kristal’s research has been recognized by grant/meeting awards from the National Institutes of Health, American Federation for Aging Research, Will Rogers Society, Oxygen Society, American Institute for Cancer Research, Gordon Research Conference, and the Hereditary Disease Foundation. Dr. Kristal is the first secretary and a member of the Board of Directors of the newly formed Metabolomics Society. He is a Contributing Editor for Science’s Science of Aging Knowledge Environment. He serves as an ad hoc reviewer for NIH and other granting agencies.