Section: New Software and Platforms

Platforms and toolboxes

Among others, a goal of the team is to facilitate interplays between tools for biological data analysis and integration. Our tools are based on formal systems. They aim at guiding the user to progressively reduce the space of models (families of sequences of genes or proteins, families of keys actors involved in a system response, dynamical models) which are compatible with both knowledge and experimental observations.

Most of our tools are available both as stand-alone software and through portals such as Mobyle or Galaxy interfaces. Tools are developed in collaboration with the GenOuest resource and data center hosted in the IRISA laboratory, including their computer facilities [more info] .

We present here three toolboxes which each contain complementary tools with respect to their targeted sub-domain of bioinformatics.

Integrative Biology: (constraint-based) toolbox for network filtering

The goal is to offer a toolbox for the reconstruction of networks from genome, literature and large-scale observation data (expression data, metabolomics...) in order to elucidate the main regulators of an observed phenotype. Most of the optimization issues are addressed with Answer Set Programming.

MeMap and MeMerge. We develop a workflow for the Automatic Reconstruction of Metabolic networks (AuReMe). In this workflow, we use heterogeneous sources of data with identifiers from different namespaces. MeMap (Metabolic network Mapping) consists in mapping identifiers from different namespaces to a unified namespace. Then, MeMerge (Metabolic network Merge) merges two metabolic networks previously mapped on the same namespace. [web server] .

meneco [input: draft metabolic network & metabolic profiles. output: metabolic network]. It is a qualitative approach to elaborate the biosynthetic capacities of metabolic networks. In fact, large-scale metabolic networks as well as measured datasets suffer from substantial incompleteness. Moreover, traditional formal approaches to biosynthesis require kinetic information, which is rarely available. Our approach builds upon formal systems for analyzing large-scale metabolic networks. Mapping its principles into Answer Set Programming allows us to address various biologically relevant problems [57] [50] [python package] [web server] .

shogen [input: genome & metabolic network. output : functional regulatory modules]. This software is able to identify genome portions which contain a large density of genes coding for enzymes that regulate successive reactions of metabolic pathways [48] [python package] .

lombarde [input: genome, modules & several gene-expression datasets. output: oriented regulation network]. This tool is useful to enhance key causalities within a regulatory transcriptional network when it is challenged by several environmental perturbations [26] [web server] .

bioquali [input: signed regulation network & one gene-expression dataset. output: consistency-checking and gene-expression prediction]. It is a plugin of the Cytoscape environment. BioQuali analyses regulatory networks and expression datasets by checking a global consistency between the regulatory model and the expression data. It diagnoses a regulatory network searching for the regulations that are not consistent with the expression data, and it outputs a set of genes which predicted expression is decided in order to explain the expression inputed data. It also provides the visualization of this analysis with a friendly environment to encourage users of different disciplines to analyze their regulatory networks [5] [web server] [cytoscape plugin] .

ingranalyze [input: signed regulation network & one gene-expression dataset. output: network repair gene-expression prediction] This tool is an extension to the bioquali tool. It proposes a range of different operations for altering experimental data and/or a biological network in order to re-establish their mutual consistency, an indispensable prerequisite for automated prediction. For accomplishing repair and prediction, we take advantage of the distinguished modeling and reasoning capacities of Answer Set Programming [4] [Python package] [web server] .

Unifier. [input: sbml file with Palsson's metabolites identifiers output: sbml file with standard identifiers for metabolites]. This software is a Decision Support Tool to help biologists to normalize a file, containing Palsson's identifiers to refer to reactions and metabolites, using well known identifiers. Submit a list of Palsson identifiers to retrieve the corresponding database entries. Typically it maps with Metacyc identifiers but it would be used with Kegg or other databases later. A Unifier web service will be soon available.

NetWikiMaker. This tool generates (half) automatically a wiki on our reconstruction workflow. It contains information and data about the network reconstruction process such as different versions of draft metabolic networks files, parameters of tools, log files. It also displays the reactions, genes and metabolites that the workflow has found to be involved in the metabolic network, and provides a powerful search tool.

Dynamics and invariant-based prediction

We develop tools predicting some characteristics of a biological system behavior from incomplete sets of parameters or observations.

cadbiom. Based on Guarded transition semantic, this software provides a formal framework to help the modeling of biological systems such as cell signaling network. It allows investigating synchronization events in biological networks. [software][web server] .

caspo: Cell ASP Optimizer This soft provides an easy to use software for learning Boolean logic models describing the immediate-early response of protein signaling networks. Given a network describing causal interactions, and a phospho-proteomics dataset, caspo is able to searches for optimal Boolean logic models explaining the dataset. Optimality includes both the size of the boolean network and the distance of predictions to real-data observations. It is useful to boolean networks inference, cancer research, drug discovery, and experimental design. It is used in the CellNOpt environment (http://www.cellnopt.org/ ). [python package] [web server] .

nutritionAnalyzer. This tool is dedicated to the computation of allocation for an extremal flux distribution. It allows quantifying the precursor composition of each system output (AIO) and to discuss the biological relevance of a set of flux in a given metabolic network by computing the extremal values of AIO coefficients. This approach enables to discriminate diets without making any assumption on the internal behaviour of the system [14][webserver][software and doc] .

POGG. The POGG software allows scoring the importance and sensibility of regulatory interactions with a biological system with respect to the observation of a time-series quantitative phenotype. This is done by solving nonlinear problems to infer and explore the family of weighted Markov chains having a relevant asymptotic behavior at the population scale. Its possible application fields are systems biology, sensitive interactions, maximal entropy models, natural language processing. It results from our collaboration with the LINA-Nantes [1][matlab package] .

Sequence annotation

We develop tools for discovery and search of complex pattern signatures within biological sequences, with a focus on protein sequences.

Logol Logol is a swiss-army-knife for pattern matching on DNA/RNA/Protein sequences, using a high-level grammar to permit a large expressivity. Allowed patterns can consist in a combination of motifs, structures (stem-loops, repeats), indels etc. It allows pseudo-knot identification, context sensitive grammatical formalism and full genome analysis. Possible fields of application are the detection of mutated binding sites or stem-loop identification (e.g. in CRISPR (http://crispi.genouest.org/ ) [9] ) [software]

Protomata learner This tool is a grammatical inference framework suitable for learning the specific signature of a functional protein family from unaligned sequences by partial and local multiple alignment and automata modeling. It performs a syntactic characterization of proteins by identification of conservation blocks on sequence subsets and modelling of their succession. Possible fields of application are new members discovery or study (for instance, for site-directed mutagenesis) of, possibly non-homologous, functional families and subfamilies such as enzymatic, signaling or transporting proteins [49] [3] [web server]

Integration of toolboxes and platforms in webservices

Most of our software were designed as "bricks" that can combined through workflow application such as Mobyle. It worths considering them into larger dedicated environments to benefit from the expertise of other research groups.

Web servers In collaboration with the GenOuest ressource center, most our tools are made available through several web portals.

• The mobyle@GenOuest portal is the generic web server of our ressource center. It hosts the ingranalysis, meneco, caspo, lombarde and shogun tools [website] .

• The Mobyle@Biotempo server is a mobyle portal for system biology with formal approaches. It hosts the memap, memerge, meneco, ingranalysis, cadbiom and pogg tools [website] .

• The GenOuest galaxy portal now provides access to most tools for integrative biology and sequence annotation (access on demand).

Dr Motif This resource aims at the integration of different software commonly used in pattern discovery and matching. This resource also integrates Dyliss pattern search and discovery software [website] .

ASP4biology and BioASP It is a meta-package to create a powerful environment of biological data integration and analysis in system biology, based on knowledge representation and combinatorial optimization technologies (ASP). It provides a collection of python applications which encapsulates ASP tools and several encodings making them easy to use by non-expert users out-of-the-box. [Python package] [website] .

ASP encodings repository This suite comprises projects related to applications of Answer Set Programming using Potassco systems (the Potsdam Answer Set Solving Collection, bundles tools for Answer Set Programming developed at the University of Potsdam). These are usually a set of encodings possibly including auxiliary software and scripts [respository] .