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Full-Text Articles in Medicine and Health Sciences
Genome-Scale Metabolic Modeling Reveals Sequential Dysregulation Of Glutathione Metabolism In Livers From Patients With Alcoholic Hepatitis, Alexandra Manchel, Radhakrishnan Mahadevan, Ramon Bataller, Jan B. Hoek, Rajanikanth Vadigepalli
Genome-Scale Metabolic Modeling Reveals Sequential Dysregulation Of Glutathione Metabolism In Livers From Patients With Alcoholic Hepatitis, Alexandra Manchel, Radhakrishnan Mahadevan, Ramon Bataller, Jan B. Hoek, Rajanikanth Vadigepalli
Department of Pathology, Anatomy, and Cell Biology Faculty Papers
Alcoholic hepatitis (AH) is the most severe form of alcoholic liver disease for which there is no efficacious treatment aiding most patients. AH manifests differently in individuals, with some patients showing debilitating symptoms more so than others. Previous studies showed significant metabolic dysregulation associated with AH. Therefore, we sought to analyze how the activity of metabolic pathways differed in the liver of patients with varying degrees of AH severity. We utilized a genome-scale metabolic modeling approach that allowed for integration of a generic human cellular metabolic model with specific RNA-seq data corresponding to healthy and multiple liver disease states to …
Patient-Specific Genome-Scale Metabolic Models For Individualized Predictions Of Liver Disease, Alexandra Manchel, Jan B. Hoek, Ramon Bataller, Radhakrishnan Mahadevan, Rajanikanth Vadigepalli
Patient-Specific Genome-Scale Metabolic Models For Individualized Predictions Of Liver Disease, Alexandra Manchel, Jan B. Hoek, Ramon Bataller, Radhakrishnan Mahadevan, Rajanikanth Vadigepalli
Department of Pathology, Anatomy, and Cell Biology Faculty Papers
The prevalence of liver disease is steadily increasing, coupled with the limited availability of therapeutic treatments. Recent literature points to metabolic reprogramming as a key feature of liver failure. Hence, we sought to uncover the metabolic pathways and mechanisms associated with liver disease and acute liver failure. We generated patient-specific genome scale metabolic models by integrating RNA-seq data from patient liver samples with a generalized human metabolic model. Flux balance analysis simulations showed a distinct separation of non-alcohol associated and alcohol-associated disease states. Our analysis suggests that the alcohol associated liver has an increased flux through nucleotide and glycerophospholipid metabolic …
Making Invisible Rna Visible: Discriminative Sequencing Methods For Rna Molecules With Specific Terminal Formations, Megumi Shigematsu, Yohei Kirino
Making Invisible Rna Visible: Discriminative Sequencing Methods For Rna Molecules With Specific Terminal Formations, Megumi Shigematsu, Yohei Kirino
Computational Medicine Center Faculty Papers
Next generation sequencing of RNA molecules (RNA-seq) has become a common tool to characterize the expression profiles of RNAs and their regulations in normal physiological processes and diseases. Although increasingly accumulating RNA-seq data are widely available through publicly accessible sites, most of the data for short non-coding RNAs (sncRNAs) have been obtained for microRNA (miRNA) analyses by standard RNA-seq, which only capture the sncRNAs with 5′-phosphate (5′-P) and 3′-hydroxyl (3′-OH) ends. The sncRNAs with other terminal formations such as those with a 5′-hydroxyl end (5′-OH), a 3′-phosphate (3′-P) end, or a 2′,3′-cyclic phosphate end (2′,3′-cP) cannot be efficiently amplified and …