MOTIVATION: Modeling of signaling pathways is an important step towards the understanding and the treatment of diseases such as cancers, HIV or auto-immune diseases. MaBoSS is a software that allows to simulate populations of cells and to model stochastically the intracellular mechanisms that are deregulated in diseases. MaBoSS provides an output of a Boolean model in the form of time-dependent probabilities, for all biological entities (genes, proteins, phenotypes, etc.) of the model. RESULTS: We present a new version of MaBoSS (2.0), including an updated version of the core software and an environment. With this environment, the needs for modeling signaling pathways are facilitated, including model construction, visualization, simulations of mutations, drug treatments and sensitivity analyses. It offers a framework for automated production of theoretical predictions. AVAILABILITY AND IMPLEMENTATION: MaBoSS software can be found at https://maboss.curie.fr , including tutorials on existing models and examples of models. CONTACT: [email protected] or [email protected]. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

BACKGROUND: Detecting and quantifying isoforms from RNA-seq data is an important but challenging task. The problem is often ill-posed, particularly at low coverage. One promising direction is to exploit several samples simultaneously. RESULTS: We propose a new method for solving the isoform deconvolution problem jointly across several samples. We formulate a convex optimization problem that allows to share information between samples and that we solve efficiently. We demonstrate the benefits of combining several samples on simulated and real data, and show that our approach outperforms pooling strategies and methods based on integer programming. CONCLUSION: Our convex formulation to jointly detect and quantify isoforms from RNA-seq data of multiple related samples is a computationally efficient approach to leverage the hypotheses that some isoforms are likely to be present in several samples. The software and source code are available at http://cbio.ensmp.fr/flipflop.

UNLABELLED: BiNoM (Biological Network Manager) is a new bioinformatics software that significantly facilitates the usage and the analysis of biological networks in standard systems biology formats (SBML, SBGN, BioPAX). BiNoM implements a full-featured BioPAX editor and a method of 'interfaces' for accessing BioPAX content. BiNoM is able to work with huge BioPAX files such as whole pathway databases. In addition, BiNoM allows the analysis of networks created with CellDesigner software and their conversion into BioPAX format. BiNoM comes as a library and as a Cytoscape plugin which adds a rich set of operations to Cytoscape such as path and cycle analysis, clustering sub-networks, decomposition of network into modules, clipboard operations and others. AVAILABILITY: Last version of BiNoM distributed under the LGPL licence together with documentation, source code and API are available at http://bioinfo.curie.fr/projects/binom

MOTIVATION: Microarray-based CGH (Comparative Genomic Hybridization), transcriptome arrays and other large-scale genomic technologies are now routinely used to generate a vast amount of genomic profiles. Exploratory analysis of this data is crucial in helping to understand the data and to help form biological hypotheses. This step requires visualization of the data in a meaningful way to visualize the results and to perform first level analyses. RESULTS: We have developed a graphical user interface for visualization and first level analysis of molecular profiles. It is currently in use at the Institut Curie for cancer research projects involving CGH arrays, transcriptome arrays, SNP (single nucleotide polymorphism) arrays, loss of heterozygosity results (LOH), and Chromatin ImmunoPrecipitation arrays (ChIP chips). The interface offers the possibility of studying these different types of information in a consistent way. Several views are proposed, such as the classical CGH karyotype view or genome-wide multi-tumor comparison. Many functionalities for analyzing CGH data are provided by the interface, including looking for recurrent regions of alterations, confrontation to transcriptome data or clinical information, and clustering. Our tool consists of PHP scripts and of an applet written in Java. It can be run on public datasets at http://bioinfo.curie.fr/vamp AVAILABILITY: The VAMP software (Visualization and Analysis of array-CGH,transcriptome and other Molecular Profiles) is available upon request. It can be tested on public datasets at http://bioinfo.curie.fr/vamp. The documentation is available at http://bioinfo.curie.fr/vamp/doc.

MOTIVATION: The identification of recurrent genomic alterations can provide insight into the initiation and progression of genetic diseases, such as cancer. Array-CGH can identify chromosomal regions that have been gained or lost, with a resolution of approximately 1 mb, for the cutting-edge techniques. The extraction of discrete profiles from raw array-CGH data has been studied extensively, but subsequent steps in the analysis require flexible, efficient algorithms, particularly if the number of available profiles exceeds a few tens or the number of array probes exceeds a few thousands. RESULTS: We propose two algorithms for computing minimal and minimal constrained regions of gain and loss from discretized CGH profiles. The second of these algorithms can handle additional constraints describing relevant regions of copy number change. We have validated these algorithms on two public array-CGH datasets. AVAILABILITY: From the authors, upon request. CONTACT: [email protected] SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

The need to distribute objects on the Internet and to offer views from databases has found a solution with the advent of CORBA. Most database management systems now offer CORBA interfaces which are generally simple mapping of the database schema to the CORBA world. This approach does not address all the problems of database interoperation because (i) such a view is static (ii) its semantic is completely bound to the semantic of the schema and it is not possible to re-model it (iii) only one view per database can be offered (iv) access may be limited to reading and no mechanism is given to write in the database through the view. To solve these problems, we have designed a language, the Interface Mapping Definition Language (IMDL) and some tools, grouped in the Interface Mapping Service (IMS). IMDL is used to define CORBA views from OODBMS, while IMS generates an IDL construct and a full CORBA implementation from an IMDL construct and a database schema.

This paper introduces the EYEDB object oriented database management system (OODBMS). EYEDB implements all the standard features of OODBMS, is language oriented, provides a generic object model and a support for data distribution using CORBA. It can deal with very large databases, and is both efficient and scalable. It is used in the genome project where a huge amount of data have to be managed and intricate data structures needs to be modeled. Online information and a trial version of EYEDB can be obtained from http://www.sysra.com/eyedb.

MOTIVATION: Links between biological objects are frequently used by researchers in biology. However, many of the links found in public databases are insufficiently documented and difficult to retrieve. Virgil introduces the idea of a rich link, i.e. the link itself and the related pieces of information. Virgil was developed to collect, manage and distribute such links. RESULTS: At the moment, Virgil is a prototype database that contains rich links between GDB genes and Genbank sequences. The Virgil data model is rich enough to describe comprehensively a link between two biological objects. Two different means to access the information were developed: a schema-driven Web interface and a CORBA server. AVAILABILITY: http://www.infobiogen. fr/services/virgil/home.html CONTACT: [email protected]