The recent advances made in high throughput genomic sequencing allow researchers to accurately determine the genetic make-up of an individual. Sharing this data across research institutes has proven to be challenging as the amount of data and available bandwidth cause large delays. Here, we present a network of dynamic lightpaths dedicated to the life sciences which connects research groups within the Netherlands to each other, to compute and storage providers and to commercial partners.

SUMMARY: CytoscapeRPC is a plugin for Cytoscape which allows users to create, query and modify Cytoscape networks from any programming language which supports XML-RPC. This enables them to access Cytoscape functionality and visualize their data interactively without leaving the programming environment with which they are familiar. AVAILABILITY: Install through the Cytoscape plugin manager or visit the web page: http://wiki.nbic.nl/index.php/CytoscapeRPC for the user tutorial and download. CONTACT: [email protected]; [email protected].

MOTIVATION: We propose an efficient method to infer combinatorial association logic networks from multiple genome-wide measurements from the same sample. We demonstrate our method on a genetical genomics dataset, in which we search for Boolean combinations of multiple genetic loci that associate with transcript levels. RESULTS: Our method provably finds the global solution and is very efficient with runtimes of up to four orders of magnitude faster than the exhaustive search. This enables permutation procedures for determining accurate false positive rates and allows selection of the most parsimonious model. When applied to transcript levels measured in myeloid cells from 24 genotyped recombinant inbred mouse strains, we discovered that nine gene clusters are putatively modulated by a logical combination of trait loci rather than a single locus. A literature survey supports and further elucidates one of these findings. Due to our approach, optimal solutions for multi-locus logic models and accurate estimates of the associated false discovery rates become feasible. Our algorithm, therefore, offers a valuable alternative to approaches employing complex, albeit suboptimal optimization strategies to identify complex models. AVAILABILITY: The MATLAB code of the prototype implementation is available on: http://bioinformatics.tudelft.nl/ or http://bioinformatics.nki.nl/.

Tumorigenesis is a multi-step process in which normal cells transform into malignant tumors following the accumulation of genetic mutations that enable them to evade the growth control checkpoints that would normally suppress their growth or result in apoptosis. It is therefore important to identify those combinations of mutations that collaborate in cancer development and progression. DNA copy number alterations (CNAs) are one of the ways in which cancer genes are deregulated in tumor cells. We hypothesized that synergistic interactions between cancer genes might be identified by looking for regions of co-occurring gain and/or loss. To this end we developed a scoring framework to separate truly co-occurring aberrations from passenger mutations and dominant single signals present in the data. The resulting regions of high co-occurrence can be investigated for between-region functional interactions. Analysis of high-resolution DNA copy number data from a panel of 95 hematological tumor cell lines correctly identified co-occurring recombinations at the T-cell receptor and immunoglobulin loci in T- and B-cell malignancies, respectively, showing that we can recover truly co-occurring genomic alterations. In addition, our analysis revealed networks of co-occurring genomic losses and gains that are enriched for cancer genes. These networks are also highly enriched for functional relationships between genes. We further examine sub-networks of these networks, core networks, which contain many known cancer genes. The core network for co-occurring DNA losses we find seems to be independent of the canonical cancer genes within the network. Our findings suggest that large-scale, low-intensity copy number alterations may be an important feature of cancer development or maintenance by affecting gene dosage of a large interconnected network of functionally related genes.