Model-driven characterization of functional diversity of Pseudomonas aeruginosa clinical isolates with broadly representative phenotypes
Pseudomonas aeruginosa is a leading cause of infections in immunocompromised individuals and in healthcare settings. This study aims to understand the relationships between phenotypic diversity and the functional metabolic landscape of P. aeruginosa clinical isolates. To better understand the metabolic repertoire of P. aeruginosa in infection, we deeply profiled a representative set from a library […]
Read MoreSystems-ecology designed bacterial consortium protects from severe Clostridioides difficile infection
Fecal Microbiota Transplant (FMT) is an emerging therapy that has had remarkable success in treatment and prevention of recurrent Clostridioides difficile infection (rCDI). FMT has recently been associated with adverse outcomes such as inadvertent transfer of antimicrobial resistance, necessitating development of more targeted bacteriotherapies. To address this challenge, we developed a novel systems biology pipeline […]
Read MoreMetabolic modeling of sex-specific liver tissue suggests mechanism of differences in toxicological responses
Male subjects in animal and human studies are disproportionately used for toxicological testing. This discrepancy is evidenced in clinical medicine where females are more likely than males to experience liver-related adverse events in response to xenobiotics. While previous work has shown gene expression differences between the sexes, there is a lack of systems-level approaches to […]
Read MoreThe blossoming of methods and software in computational biology
PMID:37590323 | DOI:10.1371/journal.pcbi.1011390
Read MoreTranscriptome-guided metabolic network analysis reveals rearrangements of carbon flux distribution in Neisseria gonorrhoeae during neutrophil co-culture
The ability of bacterial pathogens to metabolically adapt to the environmental conditions of their hosts is critical to both colonization and invasive disease. Infection with Neisseria gonorrhoeae (the gonococcus, Gc) is characterized by the influx of neutrophils [polymorphonuclear leukocytes (PMNs)], which fail to clear the bacteria and make antimicrobial products that can exacerbate tissue damage. […]
Read MoreReconstructor: A COBRApy compatible tool for automated genome-scale metabolic network reconstruction with parsimonious flux-based gap-filling
MOTIVATION: Genome-scale metabolic network reconstructions (GENREs) are valuable for understanding cellular metabolism in silico. Several tools exist for automatic GENRE generation. However, these tools frequently (1) do not readily integrate with some of the widely-used suites of packaged methods available for network analysis, (2) lack effective network curation tools, (3) are not sufficiently user-friendly, and […]
Read MoreNetwork analysis of toxin production in Clostridioides difficile identifies key metabolic dependencies
Clostridioides difficile pathogenesis is mediated through its two toxin proteins, TcdA and TcdB, which induce intestinal epithelial cell death and inflammation. It is possible to alter C. difficile toxin production by changing various metabolite concentrations within the extracellular environment. However, it is unknown which intracellular metabolic pathways are involved and how they regulate toxin production. […]
Read MoreMetabolic modeling of sex-specific tissue predicts mechanisms of differences in toxicological responses
Male subjects in animal and human studies are disproportionately used for toxicological testing. This discrepancy is evidenced in clinical medicine where females are more likely than males to experience liver-related adverse events in response to xenobiotics. While previous work has shown gene expression differences between the sexes, there is a lack of systems-level approaches to […]
Read MoreIdentifying metabolic shifts in Crohn’s disease using’ omics-driven contextualized computational metabolic network models
Crohn’s disease (CD) is a chronic inflammatory disease of the gastrointestinal tract. A clear gap in our existing CD diagnostics and current disease management approaches is the lack of highly specific biomarkers that can be used to streamline or personalize disease management. Comprehensive profiling of metabolites holds promise; however, these high-dimensional profiles need to be […]
Read MoreTen simple rules for launching an academic research career
PMID:36520710 | DOI:10.1371/journal.pcbi.1010689
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