A cornerstone of biotechnology is the use microorganisms for efficient production chemicals and elimination harmful waste. Pseudomonas putida an archetype such microbes due to its metabolic versatility, stress resistance, amenability genetic modifications, vast potential environmental industrial applications. To address both elucidation wiring in P. uses biocatalysis, particular non-growth-related biochemicals, we developed present here a genome-scale constraint-based model metabolism...

ABSTRACT Pseudomonas aeruginosa is a major life-threatening opportunistic pathogen that commonly infects immunocompromised patients. This bacterium owes its success as largely to metabolic versatility and flexibility. A thorough understanding of P. 's metabolism thus pivotal for the design effective intervention strategies. Here we aim provide, through systems analysis, basis characterization genome-scale properties this pathogen's versatile network. To end, reconstructed network PAO1....

Abstract Culturing microorganisms is a critical step in understanding and utilizing microbial life. Here we map the landscape of existing culture media by extracting natural-language recipes into Known Media Database (KOMODO), which includes >18,000 strain–media combinations, >3300 variants compound concentrations (the entire collection Leibniz Institute DSMZ repository). Using KOMODO, show that although are usually tuned for individual strains using biologically common salts, trace...

In the past decade, over 50 genome-scale metabolic reconstructions have been built for a variety of single- and multi- cellular organisms. These enabled host computational methods to be leveraged systems-analysis metabolism, leading greater understanding observed phenotypes. sparsely applied comparisons between multiple organisms, however, due mainly existence differences that are inherited from respective reconstruction processes organisms compared. To circumvent this obstacle, we developed...

Abstract Background Optimization theory has been applied to complex biological systems interrogate network properties and develop refine metabolic engineering strategies. For example, methods are emerging engineer cells optimally produce byproducts of commercial value, such as bioethanol, well molecular compounds for disease therapy. Flux balance analysis (FBA) is an optimization framework that aids in this interrogation by generating predictions optimal flux distributions cellular networks....

System-level modeling is beginning to be used decipher high throughput data in the context of disease. In this study, we present an integration expression microarray with a genome-scale metabolic reconstruction Pseudomonas aeruginosa chronic cystic fibrosis (CF) lung infection. A P. metabolism was tailored represent states two clonally related lineages isolated from lungs CF patient at different points over 44-month time course, giving mechanistic glimpse into how bacterial adapts lung....

Glycans form the primary nutritional source for microbes in human gut, and understanding their metabolism is a critical yet understudied aspect of microbiome research. Here, we present novel computational pipeline modeling glycan degradation (GlyDeR) which predicts potency 10,000 reference glycans based on either genomic or metagenomic data. We first validated GlyDeR by comparing profiles genomes Human Microbiome Project against KEGG reaction annotations. Next, applied to analysis mammalian...

Background Widespread availability of rapid diagnostic testing for respiratory viruses allows more in‐depth studies human parainfluenza (HPIV). Objectives This study aimed to assess seasonality HPIV types 1‐4, clinical outcomes by type, and risk factors illness severity. Patients/Methods retrospective was performed from January 2013 December 2015 in children adults with HPIV, detected multiplex reverse transcription polymerase chain reaction, participating a community surveillance acute...

Abstract Background The epidemiology, clinical features, and resource utilization of respiratory syncytial virus (RSV) cases in the community hospital are not fully characterized. Methods We identified individuals all ages with laboratory‐confirmed RSV from two sources, a cohort undergoing surveillance for acute infections (ARIs) hospitalized patients same geographic area New York City between 2013 15. (antibiotic/steroid/ribavirin usage, chest X‐rays, respiratory‐support (continuous...

Understanding microbial nutritional requirements is a key challenge in microbiology. Here we leverage the recent availability of thousands automatically generated genome-scale metabolic models to develop predictor minimal medium requirements, which apply species study relationship between their and ecological genomic traits. We first show that are more similar among co-habit many niches. then reveal three fundamental characteristics fastidiousness (i.e., complex specific requirements): (1)...

Recent insights suggest that non-specific and/or promiscuous enzymes are common and active across life. Understanding the role of such is an important open question in biology. Here we develop a genome-wide method, PROPER, uses permissive PSI-BLAST approach to predict activities metabolic genes. Enzyme promiscuity typically studied experimentally using multicopy suppression, which over-expression 'replacer' gene rescues lethality caused by inactivation 'target' gene. We use PROPER...

Abstract Background Tissue morphogenesis is a complex process whereby tissue structures self-assemble by the aggregate behaviors of independently acting cells responding to both intracellular and extracellular cues in their environment. During embryonic development, particularly important for organizing into tissues, although key regulatory events this are well studied isolation, number systems-level questions remain unanswered. This due, part, lack integrative tools that enable coupling...

Although the burden of influenza is well characterized, community-onset non-influenza respiratory viruses has not been systematically assessed. Understanding severity and seasonality viruses, including human coronaviruses, will provide a better understanding overall disease from that could inform resource utilization for hospitals highlight value preventative strategies, vaccines.

OBJECTIVE: To characterize postpartum hemorrhage trends and outcomes using bioinformatics electronic health record data. METHODS: This retrospective analysis included all women who delivered in a four-hospital system from July 2014 to 2017 during implementation of bundle. Data on billing codes, uterotonics, transfusion, intrauterine tamponade device placement, hysterectomy were analyzed. A framework four levels based interventions was created this informatics Levels analyzed relation...

Altered cellular metabolism is an important characteristic and driver of cancer. Surprisingly, however, we find here that aggregating individual gene expression using canonical metabolic pathways fails to enhance the classification noncancerous vs. cancerous tissues prediction cancer patient survival. This supports notion alterations in rewire through unconventional pathways. Here present MCF (Metabolic classifier feature generator), which incorporates measurements into a human network infer...

Using eight newly generated models relevant to addiction, Alzheimer's disease, cancer, diabetes, HIV, heart malaria, and tuberculosis, we show that systems analysis of small (4–25 species), bounded protein signaling modules rapidly generates new quantitative knowledge from published experimental research. For example, our tumor sclerosis complex (TSC) inhibitors may be more effective than the rapamycin (mTOR) currently used treat HIV infection could effectively blocked by increasing...

GENERAL COMMENTARY article Front. Physiol., 23 January 2015Sec. Computational Physiology and Medicine Volume 5 - 2014 | https://doi.org/10.3389/fphys.2014.00527

Growth rate has long been considered one of the most valuable phenotypes that can be measured in cells. Aside from being highly accessible and informative laboratory cultures, maximal growth is often a prime determinant cellular fitness, predicting underlie fitness key to both understanding manipulating life. Despite this, current methods for microbial typically focus on yields [e.g., predictions biomass yield using GEnome-scale metabolic Models (GEMs)] or notably require many empirical...

Genetic robustness is a hallmark of cells, occurring through many mechanisms and at levels. Essential genes lack the common mechanism genetic redundancy (i.e., existing alongside other with same function), thus appear first glance to leave cells highly vulnerable or environmental perturbations. Here we explore hypothesis that might protect against essential gene loss occur various cellular levels aside from level gene. Using Escherichia coli Saccharomyces cerevisiae as models, find are...

Objective: Measurement of obstetric hemorrhage-related morbidity is important for quality assurance purposes but presents logistical challenges in large populations. Billing codes are typically used to track severe maternal may be suboptimal validity. The objective this study was evaluate the validity billing code diagnoses compared data obtained from electronic medical record.Study design: Deliveries occurring between July 2014 and 2017 three hospitals within a single system were analyzed....