The prescribed output pattern regulates the modular structure of flow networks

Modules are common functional and structural properties of many social, technical and biological networks. Especially for biological systems it is important to understand how modularity is related to function and how modularity evolves. It is known that time-varying or spatially organized goals can lead to modularity in a simulated evolution of signaling networks. Here, we study a minimal model of material flow in networks. We discuss the relation between the shared use of nodes, i.e., the cooperativity of modules, and the orthogonality of a prescribed output pattern. We study the persistence of cooperativity through an evolution of robustness against local damages. We expect the results to be valid for a large class of flow-based biological and technical networks

multiTFA:A python package for multi-variate thermodynamics-based flux analysis

MOTIVATION: We achieve a significant improvement in thermodynamic-based flux analysis (TFA) by introducing multivariate treatment of thermodynamic variables and leveraging component contribution, the state-of-the-art implementation of the group contribution methodology. Overall, the method greatly reduces the uncertainty of thermodynamic variables. RESULTS: We present multiTFA, a Python implementation of our framework. We evaluated our application using the core Escherichia coli model and achieved a median reduction of 6.8 kJ/mol in reaction Gibbs free energy ranges, while three out of 12 reactions in glycolysis changed from reversible to irreversible. AVAILABILITY AND IMPLEMENTATION: Our framework along with documentation is available on https://github.com/biosustain/multitfa. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online

Author Correction: A consensus <i>S. cerevisiae</i> metabolic model Yeast8 and its ecosystem for comprehensively probing cellular metabolism (Nature Communications, (2019), 10, 1, (3586), 10.1038/s41467-019-11581-3)

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Long-Term Effects of a Web-Based Low-FODMAP Diet Versus Probiotic Treatment for Irritable Bowel Syndrome, including Shotgun Analyses of Microbiota:Randomized, Double-Crossover Clinical Trial

BACKGROUND: The long-term management of irritable bowel syndrome (IBS) poses many challenges. In short-term studies, eHealth interventions have been demonstrated to be safe and practical for at-home monitoring of the effects of probiotic treatments and a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs). IBS has been linked to alterations in the microbiota. OBJECTIVE: The aim of this study was to determine whether a web-based low-FODMAP diet (LFD) intervention and probiotic treatment were equally good at reducing IBS symptoms, and whether the response to treatments could be explained by patients’ microbiota. METHODS: Adult IBS patients were enrolled in an open-label, randomized crossover trial (for nonresponders) with 1 year of follow-up using the web application IBS Constant Care (IBS CC). Patients were recruited from the outpatient clinic at the Department of Gastroenterology, North Zealand University Hospital, Denmark. Patients received either VSL#3 for 4 weeks (2 × 450 billion colony-forming units per day) or were placed on an LFD for 4 weeks. Patients responding to the LFD were reintroduced to foods high in FODMAPs, and probiotic responders received treatments whenever they experienced a flare-up of symptoms. Treatment response and symptom flare-ups were defined as a reduction or increase, respectively, of at least 50 points on the IBS Severity Scoring System (IBS-SSS). Web-based ward rounds were performed daily by the study investigator. Fecal microbiota were analyzed by shotgun metagenomic sequencing (at least 10 million 2 × 100 bp paired-end sequencing reads per sample). RESULTS: A total of 34 IBS patients without comorbidities and 6 healthy controls were enrolled in the study. Taken from participating subjects, 180 fecal samples were analyzed for their microbiota composition. Out of 21 IBS patients, 12 (57%) responded to the LFD and 8 (38%) completed the reintroduction of FODMAPs. Out of 21 patients, 13 (62%) responded to their first treatment of VSL#3 and 7 (33%) responded to multiple VSL#3 treatments. A median of 3 (IQR 2.25-3.75) probiotic treatments were needed for sustained symptom control. LFD responders were reintroduced to a median of 14.50 (IQR 7.25-21.75) high-FODMAP items. No significant difference in the median reduction of IBS-SSS for LFD versus probiotic responders was observed, where for LFD it was –126.50 (IQR –196.75 to –76.75) and for VSL#3 it was –130.00 (IQR –211.00 to –70.50; P>.99). Responses to either of the two treatments were not able to be predicted using patients’ microbiota. CONCLUSIONS: The web-based LFD intervention and probiotic treatment were equally efficacious in managing IBS symptoms. The response to treatments could not be explained by the composition of the microbiota. The IBS CC web application was shown to be practical, safe, and useful for clinical decision making in the long-term management of IBS. Although this study was underpowered, findings from this study warrant further research in a larger sample of patients with IBS to confirm these long-term outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT03586622; https://clinicaltrials.gov/ct2/show/NCT0358662