Kay Tatsuoka

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MOTIVATION In eukaryotic genomes, histone acetylation and thereafter departure from the chromatin are essential for gene transcription initiation. Because gene transcription is tightly regulated by transcription factors, there are some speculations on the cooperation of histone acetylation and transcription factor binding. However, systematic statistical(More)
We describe a multi-platform ((1)H NMR, LC-MS, microarray) investigation of metabolic disturbances associated with the leptin receptor defective (db/db) mouse model of type 2 diabetes using novel assignment methodologies. For the first time, several urinary metabolites were found to be associated with diabetes and/or diabetes progression and confirmed in(More)
The Critical Path Institute recently established the Predictive Safety Testing Consortium, a collaboration between several companies and the U.S. Food and Drug Administration, aimed at evaluating and qualifying biomarkers for a variety of toxicological endpoints. The Carcinogenicity Working Group of the Predictive Safety Testing Consortium has concentrated(More)
Drug-induced vascular injury is frequently observed in rats but the relevance and translation to humans present a hurdle for drug development. Numerous structurally diverse pharmacologic agents have been shown to induce mesenteric arterial medial necrosis in rats, but no consistent biomarkers have been identified. To address this need, a novel strategy was(More)
Nonclinical studies provide the opportunity to anchor biochemical with morphologic findings; however, liver injury is often complex and heterogeneous, confounding the ability to relate biochemical changes with specific patterns of injury. The aim of the current study was to compare diagnostic performance of hepatobiliary markers for specific manifestations(More)
Assignment of physical meaning to mass spectrometry (MS) data peaks is an important scientific challenge for metabolomics investigators. Improvements in instrumental mass accuracy reduce the number of spurious database matches, however, this alone is insufficient for accurate, unique high-throughput assignment. We present a method for clustering MS(More)
Biomarker discovery through analysis of high-throughput NMR data is a challenging, time-consuming process due to the requirement of sophisticated, dataset specific preprocessing techniques and the inherent complexity of the data. Here, we demonstrate the use of weighted, constrained least-squares for fitting a linear mixture of reference standard data to(More)
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