Genome-Scale Model-Based Identification of Metabolite Indicators for Early Detection of Kidney Toxicity
Toxicol Sci. 2020 Feb 1;173(2):293-312. doi: 10.1093/toxsci/kfz228. ABSTRACT Identifying early indicators of toxicant-induced organ damage is critical to provide effective treatment. To discover such indicators and the underlying mechanisms of toxicity, we used gentamicin as an exemplar kidney toxicant and performed systematic perturbation studies in Sprague Dawley rats. We obtained high-throughput data 7 and 13 […]
Read MoreGenome-Scale Characterization of Toxicity-Induced Metabolic Alterations in Primary Hepatocytes
Toxicol Sci. 2019 Dec 1;172(2):279-291. doi: 10.1093/toxsci/kfz197. ABSTRACT Context-specific GEnome-scale metabolic Network REconstructions (GENREs) provide a means to understand cellular metabolism at a deeper level of physiological detail. Here, we use transcriptomics data from chemically-exposed rat hepatocytes to constrain a GENRE of rat hepatocyte metabolism and predict biomarkers of liver toxicity using the Transcriptionally Inferred […]
Read MoreEvaluating the efficacy of an algae-based treatment to mitigate elicitation of antibiotic resistance
Chemosphere. 2019 Dec;237:124421. doi: 10.1016/j.chemosphere.2019.124421. Epub 2019 Jul 20. ABSTRACT Antibiotics in the effluents of municipal wastewater treatment plants (WWTP) may create selective pressures to induce antibiotic resistance in bacteria downstream. This study evaluates ciprofloxacin (CIP) removal by a freshwater alga, Scenedesmus dimorphus, to assess the efficacy of algae-based tertiary treatment in reducing effluent-induced CIP […]
Read More In Vivo Gene Essentiality and Metabolism in Bordetella pertussis
mSphere. 2019 May 22;4(3):e00694-18. doi: 10.1128/mSphere.00694-18. ABSTRACT Bordetella pertussis is the causative agent of whooping cough, a serious respiratory illness affecting children and adults, associated with prolonged cough and potential mortality. Whooping cough has reemerged in recent years, emphasizing a need for increased knowledge of basic mechanisms of B. pertussis growth and pathogenicity. While previous […]
Read MoreWisdom of crowds in computational biology
PLoS Comput Biol. 2019 May 23;15(5):e1007032. doi: 10.1371/journal.pcbi.1007032. eCollection 2019 May. NO ABSTRACT PMID:31120879 | PMC:PMC6532836 | DOI:10.1371/journal.pcbi.1007032
Read MoreLeveraging the effects of chloroquine on resistant malaria parasites for combination therapies
BMC Bioinformatics. 2019 Apr 15;20(1):186. doi: 10.1186/s12859-019-2756-y. ABSTRACT BACKGROUND: Malaria is a major global health problem, with the Plasmodium falciparum protozoan parasite causing the most severe form of the disease. Prevalence of drug-resistant P. falciparum highlights the need to understand the biology of resistance and to identify novel combination therapies that are effective against resistant […]
Read MoreReconciling high-throughput gene essentiality data with metabolic network reconstructions
PLoS Comput Biol. 2019 Apr 11;15(4):e1006507. doi: 10.1371/journal.pcbi.1006507. eCollection 2019 Apr. ABSTRACT The identification of genes essential for bacterial growth and survival represents a promising strategy for the discovery of antimicrobial targets. Essential genes can be identified on a genome-scale using transposon mutagenesis approaches; however, variability between screens and challenges with interpretation of essentiality data […]
Read MoreMechanistic identification of biofluid metabolite changes as markers of acetaminophen-induced liver toxicity in rats
Toxicol Appl Pharmacol. 2019 Jun 1;372:19-32. doi: 10.1016/j.taap.2019.04.001. Epub 2019 Apr 8. ABSTRACT Acetaminophen (APAP) is the most commonly used analgesic and antipyretic drug in the world. Yet, it poses a major risk of liver injury when taken in excess of the therapeutic dose. Current clinical markers do not detect the early onset of liver […]
Read MoreIntegrated Experimental and Computational Analyses Reveal Differential Metabolic Functionality in Antibiotic-Resistant Pseudomonas aeruginosa
Cell Syst. 2019 Jan 23;8(1):3-14.e3. doi: 10.1016/j.cels.2018.12.002. Epub 2019 Jan 2. ABSTRACT Metabolic adaptations accompanying the development of antibiotic resistance in bacteria remain poorly understood. To study this relationship, we profiled the growth of lab-evolved antibiotic-resistant lineages of the opportunistic pathogen Pseudomonas aeruginosa across 190 unique carbon sources. Our data revealed that the evolution of […]
Read MoreA simplified metabolic network reconstruction to promote understanding and development of flux balance analysis tools
Comput Biol Med. 2019 Feb;105:64-71. doi: 10.1016/j.compbiomed.2018.12.010. Epub 2018 Dec 17. ABSTRACT GEnome-scale Network REconstructions (GENREs) mathematically describe metabolic reactions of an organism or a specific cell type. GENREs can be used with a number of constraint-based reconstruction and analysis (COBRA) methods to make computational predictions on how a system changes in different environments. We […]
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