Double and multiple knockout simulations for genome-scale metabolic network reconstructions

Abstract

BackgroundConstraint-based modeling of genome-scale metabolic network reconstructions has become a widely used approach in computational biology. Flux coupling analysis is a constraint-based method that analyses the impact of single reaction knockouts on other reactions in the network.ResultsWe present an extension of flux coupling analysis for double and multiple gene or reaction knockouts, and develop corresponding algorithms for an in silico simulation. To evaluate our method, we perform a full single and double knockout analysis on a selection of genome-scale metabolic network reconstructions and compare the results.SoftwareA prototype implementation of double knockout simulation is available at http://hoverboard.io/L4FC.

A framework for space-efficient read clustering in metagenomic samples

“…Specifically, we compare bwtCluster to MetaCluster [15], MBBC [11] and BiMeta [14]. Such comparisons are inherently unfair, for a number of reasons.…”

“…reads that share long substrings first, and then further merging such groups by similarity of their k -mer composition vectors (see e.g. [14–16] and references therein). A single metagenomic sample contains tens of gigabases, and to improve accuracy it is becoming more common to cluster the union of multiple samples that are believed to contain shared taxonomic units, as described e.g.…”

“…A pipeline that contains most such primitives is the one described in [15], which we summarize in what follows, pointing the reader to the original paper and to its references for statistical considerations and for criteria used to set the parameters. The same primitives recur in a number of other pipelines [14, 16, 19]. As customary, we call k - mer any string of length k , and we call coverage the average number of reads that contain a position of the genome of a taxonomic unit.…”

Systems approaches in osteoarthritis: Identifying routes to novel diagnostic and therapeutic strategies

“…Large‐scale simulation and perturbation studies using CB analysis should be undertaken. Gene knock‐outs can by simulated in tissue‐specific models to direct further molecular validation of regulatory mechanisms 55. Methods to infer missing or unidentified metabolites in untargeted metabolomic studies, incorporating network techniques, will facilitate a tissue‐specific understanding 56.…”

“…Future strategies for systems orientated studies in osteoarthritis—(A) Coupling constraint‐based, tissue‐specific metabolic models requires the identification of metabolites that are shared across systems,49 for example sub‐chondral bone and cartilage; simulation of single or multiple gene knock‐outs55 has also yet to be explored (B) Most analysis of cellular behavior occurs at the population level and considers average responses. More finely‐grained appreciation of cellular behavior, such as spatially restricted signaling, requires stochastic modelling at a single‐cell (or sub‐cellular) level 26.…”