Sergey A. Lashin

Orthoscape: a cytoscape application for grouping and visualization KEGG based gene networks by taxonomy and homology principles

BackgroundThere are many available software tools for visualization and analysis of biological networks. Among them, Cytoscape (http://cytoscape.org/) is one of the most comprehensive packages, with many plugins and applications which extends its functionality by providing analysis of protein-protein interaction, gene regulatory and gene co-expression networks, metabolic, signaling, neural as well as ecological-type networks including food webs, communities networks etc. Nevertheless, only three plugins tagged ‘network evolution’ found in Cytoscape official app store and in literature. We have developed a new Cytoscape 3.0 application Orthoscape aimed to facilitate evolutionary analysis of gene networks and visualize the results.ResultsOrthoscape aids in analysis of evolutionary information available for gene sets and networks by highlighting: (1) the orthology relationships between genes; (2) the evolutionary origin of gene network components; (3) the evolutionary pressure mode (diversifying or stabilizing, negative or positive selection) of orthologous groups in general and/or branch-oriented mode. The distinctive feature of Orthoscape is the ability to control all data analysis steps via user-friendly interface.ConclusionOrthoscape allows its users to analyze gene networks or separated gene sets in the context of evolution. At each step of data analysis, Orthoscape also provides for convenient visualization and data manipulation.

Bacteriophages affect evolution of bacterial communities in spatially distributed habitats: a simulation study

BackgroundBacteriophages are known to be one of the driving forces of bacterial evolution. Besides promoting horizontal transfer of genes between cells, they may induce directional selection of cells (for instance, according to more or less resistance to phage infection). Switching between lysogenic and lytic pathways results in various types of (co)evolution in host-phage systems. Spatial (more generally, ecological) organization of the living environment is another factor affecting evolution. In this study, we have simulated and analyzed a series of computer models of microbial communities evolving in spatially distributed environments under the pressure of phage infection.ResultsWe modeled evolving microbial communities living in spatially distributed flowing environments. Non-specific nutrient supplied in the only spatial direction, resulting in its non-uniform distribution in environment. We varied the time and the location of initial phage infestation of cells as well as switched chemotaxis on and off. Simulations were performed with the Haploid evolutionary constructor software (http://evol-constructor.bionet.nsc.ru/).ConclusionSimulations have shown that the spatial location of initial phage invasion may lead to different evolutionary scenarios. Phage infection decreases the speciation rate by more than one order as far as intensified selection blocks the origin of novel viable populations/species, which could carve out potential ecological niches. The dependence of speciation rate on the invasion node location varied on the time of invasion. Speciation rate was found to be lower when the phage invaded fully formed community of sedentary cells (at middle and late times) at the species-rich regions. This is especially noticeable in the case of late-time invasion.Our simulation study has shown that phage infection affects evolution of microbial community slowing down speciation and stabilizing the system as a whole. This influencing varied in its efficiency depending on spatially-ecological factors as well as community state at the moment of phage invasion.

Modeling evolution of spatially distributed bacterial communities: a simulation with the haploid evolutionary constructor

BackgroundMultiscale approaches for integrating submodels of various levels of biological organization into a single model became the major tool of systems biology. In this paper, we have constructed and simulated a set of multiscale models of spatially distributed microbial communities and study an influence of unevenly distributed environmental factors on the genetic diversity and evolution of the community members.ResultsHaploid Evolutionary Constructor software http://evol-constructor.bionet.nsc.ru/ was expanded by adding the tool for the spatial modeling of a microbial community (1D, 2D and 3D versions). A set of the models of spatially distributed communities was built to demonstrate that the spatial distribution of cells affects both intensity of selection and evolution rate.ConclusionIn spatially heterogeneous communities, the change in the direction of the environmental flow might be reflected in local irregular population dynamics, while the genetic structure of populations (frequencies of the alleles) remains stable. Furthermore, in spatially heterogeneous communities, the chemotaxis might dramatically affect the evolution of community members.

MAMMOTh: A new database for curated mathematical models of biomolecular systems

MOTIVATION Living systems have a complex hierarchical organization that can be viewed as a set of dynamically interacting subsystems. Thus, to simulate the internal nature and dynamics of the entire biological system, we should use the iterative way for a model reconstruction, which is a consistent composition and combination of its elementary subsystems. In accordance with this bottom-up approach, we have developed the MAthematical Models of bioMOlecular sysTems (MAMMOTh) tool that consists of the database containing manually curated MAMMOTh fitted to the experimental data and a software tool that provides their further integration. RESULTS The MAMMOTh database entries are organized as building blocks in a way that the model parts can be used in different combinations to describe systems with higher organizational level (metabolic pathways and/or transcription regulatory networks). The tool supports export of a single model or their combinations in SBML or Mathematica standards. The database currently contains 110 mathematical sub-models for Escherichia coli elementary subsystems (enzymatic reactions and gene expression regulatory processes) that can be combined in at least 5100 complex/sophisticated models concerning more complex biological processes as de novo nucleotide biosynthesis, aerobic/anaerobic respiration and nitrate/nitrite utilization in E. coli. All models are functionally interconnected and sufficiently complement public model resources. AVAILABILITY http://mammoth.biomodelsgroup.ru.

PGMiner reloaded, fully automated proteogenomic annotation tool linking genomes to proteomes

Abstract Improvements in genome sequencing technology increased the availability of full genomes and transcriptomes of many organisms. However, the major benefit of massive parallel sequencing is to better understand the organization and function of genes which then lead to understanding of phenotypes. In order to interpret genomic data with automated gene annotation studies, several tools are currently available. Even though the accuracy of computational gene annotation is increasing, a combination of multiple lines of experimental evidences should be gathered. Mass spectrometry allows the identification and sequencing of proteins as major gene products; and it is only these proteins that conclusively show whether a part of a genome is a coding region or not to result in phenotypes. Therefore, in the field of proteogenomics, the validation of computational methods is done by exploiting mass spectrometric data. As a result, identification of novel protein coding regions, validation of current gene models, and determination of upstream and downstream regions of genes can be achieved. In this paper, we present new functionality for our proteogenomic tool, PGMiner which performs all proteogenomic steps like acquisition of mass spectrometric data, peptide identification against preprocessed sequence databases, assignment of statistical confidence to identified peptides, mapping confident peptides to gene models, and result visualization. The extensions cover determining proteotypic peptides and thus unambiguous protein identification. Furthermore, peptides conflicting with gene models can now automatically assessed within the context of predicted alternative open reading frames.

AltORFev facilitates the prediction of alternative open reading frames in eukaryotic mRNAs

Motivation: Protein synthesis is not a straight forward process and one gene locus can produce many isoforms, for example, by starting mRNA translation from alternative start sites. altORF evaluator (altORFev) predicts alternative open reading frames within eukaryotic mRNA translated by a linear scanning mechanism and its modifications (leaky scanning and reinitiation). The program reveals the efficiently translated altORFs recognized by the majority of 40S ribosomal subunits landing on the 5′‐end of an mRNA. This information aids to reveal the functions of eukaryotic genes connected to synthesis of either unknown isoforms of annotated proteins or new unrelated polypeptides. Availability and Implementation: altORFev is available at http://www.bionet.nsc.ru/AUGWeb/and has been developed in Java 1.8 using the BioJava library; and the Vaadin framework to produce the web service. Contact: ak@bionet.nsc.ru

The Animal Domestication Experiment as a Model of the Evolutionary Process: A New Insight into Evolution Under Selection Targeting Regulatory Systems

The paper considers the main results of the long-lasting experimental domestication of animals—foxes, minks and brown rats. The following important conclusions have been made. Fundamental to the domestication process is the intensive selection of animals for human-tolerant behavior and the capability to adapt to the emerging social structure “human—domestication object”. Intensive selection for behavior and, therefore, for the central regulatory systems, which control the functioning of the entire organism, leads to large amounts of variability in the population under domestication. Stress caused by rapid environmental changes, with its neurohormonal mechanisms of regulation of genetic processes, has an important role in the induction of variability. These considerations prompted Dmitry Belyaev, mutational variability is rendered neutral. Under directional (and destabilizing) selection, hidden mutational variability becomes exposed. If the regulatory circuits with negative feedback are lost, hidden genotypic variability becomes exposed and individuals with major phenotypic aberrations occur.