A5082126398- Microbial Metabolic Engineering and Bioproduction
- Bioinformatics and Genomic Networks
- Metabolomics and Mass Spectrometry Studies
- Gene Regulatory Network Analysis
- Bacterial Genetics and Biotechnology
- Tuberculosis Research and Epidemiology
- RNA and protein synthesis mechanisms
- Mycobacterium research and diagnosis
- Evolution and Genetic Dynamics
- Protein Structure and Dynamics
- Adipose Tissue and Metabolism
- Biofuel production and bioconversion
- Gut microbiota and health
- Erythrocyte Function and Pathophysiology
- Drug Transport and Resistance Mechanisms
- Cholesterol and Lipid Metabolism
- Diet and metabolism studies
- Peroxisome Proliferator-Activated Receptors
- CRISPR and Genetic Engineering
- Blood transfusion and management
- Computational Drug Discovery Methods
- Health, Environment, Cognitive Aging
- SARS-CoV-2 and COVID-19 Research
- Genomics and Phylogenetic Studies
- Advanced Proteomics Techniques and Applications
ProNAi Therapeutics (United States)
2023-2024
University of California, San Diego
2015-2024
Buck Institute for Research on Aging
2023-2024
The University of Texas at Dallas
2023
La Jolla Bioengineering Institute
2016-2022
Institute for Systems Biology
2018-2021
Seattle University
2021
InSysBio (Russia)
2019-2020
Abstract The BiGG Models knowledge base (http://bigg.ucsd.edu) is a centralized repository for high-quality genome-scale metabolic models. For the past 12 years, website has allowed users to browse and search Within this update, we detail new content features in repository, continuing original effort connect each model genome annotations external databases as well standardization of reactions metabolites. We describe addition 31 models that expand portion phylogenetic tree covered by Models....
Increasing evidence suggests Alzheimer's disease (AD) pathophysiology is influenced by primary and secondary bile acids, the end product of cholesterol metabolism. We analyze 2,114 post-mortem brain transcriptomes identify genes in alternative acid synthesis pathway to be expressed brain. A targeted metabolomic analysis acids measured from samples 111 individuals supports these results. Our metabolic network that taurine transport, synthesis, metabolism differ AD cognitively normal...
Mycobacterium tuberculosis is a serious human pathogen threat exhibiting complex evolution of antimicrobial resistance (AMR). Accordingly, the many publicly available datasets describing its AMR characteristics demand disparate data-type analyses. Here, we develop reference strain-agnostic computational platform that uses machine learning approaches, complemented by both genetic interaction analysis and 3D structural mutation-mapping, to identify signatures 13 antibiotics. This applied 1595...
Abstract The increasing availability of metabolomics data necessitates novel methods for deeper analysis and interpretation. We present a flux balance method that allows the computation dynamic intracellular metabolic changes at cellular scale through integration time-course absolute quantitative metabolomics. This approach, termed “unsteady-state analysis” (uFBA), is applied to four systems: three one steady-state as negative control. uFBA FBA predictions are contrasted, found be more...
Abstract Salmonella strains are traditionally classified into serovars based on their surface antigens. While increasing availability of whole-genome sequences has allowed for more detailed subtyping strains, links between genotype, serovar, and host remain elusive. Here we reconstruct genome-scale metabolic models 410 spanning 64 serovars. Model-predicted growth capabilities in over 530 different environments demonstrate that: (1) the accessory network includes alternative carbon...
Significance While the transcriptional regulatory network (TRN) of Escherichia coli has expanded considerably in recent years through new chromatin immunoprecipitation (ChIP) data, an open question remains: Does global TRN, reconstructed by combining ChIP data for individual transcriptions factors, consistently explain observed differential gene expression? We have a high-confidence determined its consistency with transcriptomics and predictive capabilities across multiple conditions,...
Catalysis using iron-sulfur clusters and transition metals can be traced back to the last universal common ancestor. The damage metalloproteins caused by reactive oxygen species (ROS) prevent cell growth survival when unmanaged, thus eliciting an essential stress response that is fundamental in biology. Here we develop a computable multiscale description of ROS Escherichia coli, called OxidizeME. We use OxidizeME explain four key responses oxidative stress: 1) ROS-induced auxotrophy for...
Abstract Transcriptional regulation enables cells to respond environmental changes. Of the estimated 304 candidate transcription factors (TFs) in Escherichia coli K-12 MG1655, 185 have been experimentally identified, but ChIP methods used fully characterize only a few dozen. Identifying these remaining TFs is key improving our knowledge of E. transcriptional regulatory network (TRN). Here, we developed an integrated workflow for computational prediction and comprehensive experimental...
The efficacy of antibiotics against M. tuberculosis has been shown to be influenced by experimental media conditions. Investigations growth in physiological conditions have described an environment that is different from common vitro media. Thus, elucidating the interplay between available nutrient sources and antibiotic clear medical relevance. While genome-scale reconstructions enabled ability interrogate differences for past 10 years, recent diverged each other without standardization. A...
Whole-cell (WC) modeling is a promising tool for biological research, bioengineering, and medicine. However, substantial work remains to create accurate comprehensive models of complex cells.We organized the 2015 Whole-Cell Modeling Summer School teach WC evaluate need new standards software by recoding recently published model in Systems Biology Markup Language.Our analysis revealed several challenges representing using current standards.We, therefore, propose standards, software,...
Commentary26 August 2020Open Access Community standards to facilitate development and address challenges in metabolic modeling Maureen A Carey orcid.org/0000-0003-2890-5445 Division of Infectious Diseases International Health, Department Medicine, University Virginia, Charlottesville, VA, USA Search for more papers by this author Andreas Dräger orcid.org/0000-0002-1240-5553 Computational Systems Biology Infection Antimicrobial-Resistant Pathogens, Institute Biomedical Informatics (IBMI),...
Bacteria regulate gene expression to adapt changing environments through transcriptional regulatory networks (TRNs). Although extensively studied, no TRN is fully characterized since the identity and activity of all regulators comprising a are not known. Here, we experimentally evaluate 40 uncharacterized proteins in Escherichia coli K-12 MG1655, which were computationally predicted be transcription factors (TFs). First, used multiplexed chromatin immunoprecipitation method combined with...
Introduction A digital twin is a virtual representation of patient's disease, facilitating real-time monitoring, analysis, and simulation. This enables the prediction disease progression, optimization care delivery, improvement outcomes. Methods Here, we introduce framework for type 2 diabetes (T2D) that integrates machine learning with multiomic data, knowledge graphs, mechanistic models. By analyzing substantial clinical dataset, constructed predictive models to forecast progression....
Understanding the complex interactions of protein posttranslational modifications (PTMs) represents a major challenge in metabolic engineering, synthetic biology, and biomedical sciences. Here, we present workflow that integrates multiplex automated genome editing (MAGE), genome-scale modeling, atomistic molecular dynamics to study effects PTMs on enzymes microbial fitness. This incorporates complementary approaches across scientific disciplines; provides insight into how influence cellular...
Mathematical models of metabolic networks utilize simulation to study system-level mechanisms and functions. Various approaches have been used model the steady state behavior using genome-scale reconstructions, but formulating dynamic from such reconstructions continues be a key challenge. Here, we present Mass Action Stoichiometric Simulation Python (MASSpy) package, an open-source computational framework for modeling metabolism. MASSpy utilizes mass action kinetics detailed chemical build...
Significance Defining a core functional proteome supporting the living process has importance for both developing fundamental understanding of cell functions and synthetic biology applications. Comparative genomics been primary approach to achieve such definition. Here, we use genome-scale models define that computationally supports basic cellular function. This metabolism protein expression, defined through systems methods, is validated characterized by using multiple disparate data types.
Mycobacterium tuberculosis (MTB) displays the remarkable ability to transition in and out of dormancy, a hallmark pathogen's capacity evade immune system exploit susceptible individuals. Uncovering gene regulatory programs that underlie phenotypic shifts MTB during disease latency reactivation has posed challenge. We develop an experimental precisely control dissolved oxygen levels cultures order capture transcriptional events unfold as transitions into hypoxia-induced dormancy. Using...