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Posters
IonTracker™ - Automatic Organization of GC/MS and LC/MS Data into Chemical Libraries
Tom Barrett and Stan Young
Metabolon, Inc., 800 Capitola Drive, Suite 1, Durham, NC 27713
Summary: One of the fundamental challenges of metabolomics is to reduce a complex set of individual ions (m/z, RT, intensity values) into a smaller set of chemical library entries representing the distinct chemicals found in the samples being analyzed. IonTracker™ addresses this problem by utilizing data from multiple samples rather than one. It exploits the fact that biological samples are diverse and that chemicals are largely covariant with each other when viewed over multiple samples.
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Correlation between In Vitro and In Vivo Effects of HIV Protease Inhibitors on the Hepatocyte and Adipocyte Metabolome
A. Bellamine1, C. Elosua1,C. Cao1, M. Noor1,A. Berger2, D. Alexander2, and O. Flint1
1Research and Development, Bristol-Myers Squibb, Princeton, NJ USA
2Metabolon, Inc., Research Triangle, NC USA
Summary: The use of protease inhibitors (PIs) in HAART has been associated with metabolic side effects including disturbance of glucose homeostasis and dyslipidemia. To better understand the mechanisms underlying these changes, we compared the endogenous metabolite profiles (metabolome) of hepatocytes and adipocytes treated with atazanavir (ATV) or lopinavir (LPV), and compared them to the plasma metabolome of HIV patients treated with these PIs.
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Metabolomics Analysis of Plasma and Urine in Rats Treated with Fenofibrate
Tetsuya Ohta1, Naoya Masutomi1, Naohisa Tsutsui1, Matthew Mitchell2, Michael Milburn2, John Ryals2, Lining Guo2
1Mitsubishi Pharma Corporation, 1-1-1, Kazusa-Kamatari, Kisarazu, Chiba 292-0818, Japan
2Metabolon, Inc., 800 Capitola Drive, Suite 1, Durham, NC 27709 USA
Summary: Fenofibrate, a peroxisome proliferator-activated receptor-α-agonist, is widely used to treat dyslipidemia. It is also a known rat carcinogen. In order to better understand the mechanisms of drug action and toxicity, a metabolomic analysis was performed to study Fenofibrate effects in rats.
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Metabolomics Analysis of a Population of Human Plasma to Determine Compounds Differentiated as a Result of Gender, Age and Race
Anne M. Evans1, Matt Mitchell1, Eric Milgram1, Alvin Berger1, Kay Lawton1, Richard Hanson2, Satish Kalhan3, and Mike Milburn1
1Metabolon, Inc., Research Triangle Park, NC USA
2Dept Biochem, Case Western Reserve Univ Sc Medicine, Cleveland, OH USA
3Cleveland Clinic Foundation, Cleveland, OH USA
Summary: A globally unbiased metabolomics analysis of plasma from 269 individuals was performed to identify compounds that were a result of differences due to age, gender and race. Over 150 compounds were found to be statistically different with respect to age and 46 were statistically differentiated by race. These results illustrate the importance of taking gender, race and/or age into account in biomarker discovery studies.
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A Comparative Metabolomic Analysis of PPAR Activators for Evaluating Drug On- and Off- Target Effects
Alvin Berger and Mike Milburn
Metabolon, Inc. Research Triangle Park, NC USA
Summary: Effective and reliable selection of lead candidates early in drug discovery is dependent upon established in vitro models predictive of on- and off- target effects. Application of metabolomic analysis to lysates of drug exposed cultured cells provides a novel and comprehensive analysis of changes in their biochemical profile.
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Metabolomics for Biomarker Discovery in Prostate Cancer
Bruce McCreedy1, Alvin Berger1, Arul Chinnaiyan2
1Metabolon, Inc., Research Triangle Park, NC USA
2University of Michigan, Ann Arbor, Michigan 48109 USA
Summary: Biomarkers for predicting whether a subject with elevated PSA should be monitored or have a prostate biopsy would drastically reduce the number of unnecessary prostate biopsies performed each year. The results of this biomarker discovery study will be used to design a targeted method for evaluation of early detection of prostate cancer and prediction of aggressive versus indolent tumors.
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VPHIL: Software for Performing Compound Identification QC on Large Metabolomic Datasets
Corey DeHaven and Tom Barrett
Metabolon, Inc. Research Triangle Park, NC USA
Summary: VPHIL provides analysts many options for quickly performing rapid quality control of metabolomic data. The ability to analyze and perform QC on large-scale, multi-sample metabolomics data on an industrial scale is an important step in the evolution of the technology as a whole.
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Identification of Metabolic Biomarkers for Amyotrophic Lateral Sclerosis
K.A. Lawton1, L.A. Paige1, M. Mitchell1, R. Kaddurah-Daouk3, R. H. Brown2, M. Milburn1, M.E. Cudkowicz2
1Metabolon, Inc., Research Triangle Park, NC USA
2Massachusetts General Hospital, Alzheimer’s Disease Research Unit, Charlestown, MA USA 02129
3Duke University Medical Center, Durham, NC 27710
Summary: To discover metabolic biomarkers that will provide diagnostic and therapeutic benefits for Amyotrophic Lateral Sclerosis (ALS), metabolomic analysis was carried out on over 350 plasma samples collected from ALS patients and heavily controlled subjects. Compounds that show statistically significant changes in ALS compared to the healthy controls were discovered; these compounds are disease biomarker candidates.
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HIV Protease Inhibitors and the Hepatic Metabolome
Oliver P. Flint1, Caroline Elosua1, Rex A. Parker1, Mustafa Noor1, Carol Hamilton2
1Pharmaceutical Research Institute, Bristol-Myers Squibb Company, Princeton, NJ, USA
2Metabolon, Inc., Research Triangle Park, NC USA
Summary: In order to further understand the implications of differential effects of HIV protease inhibitors on the overall cellular metabolic state, a metabolomic analysis was completed of HepG2 hepatomas exposed to five different protease inhibitors in vitro.
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Miscellaneous
Interview with Ernie Hood, Host, Radio In Vivo (mp3 file 23.7 mb)
Science radio program on WCOM-FM 103.5, Carrboro, NC.
Interview with Mike Milburn, Ph.D., Chief Scientific Officer and Mr. Tim Germann, VP, Sales.
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