PubMed Health⌕ Search

Biomedical subjects

Peter Van Loo

Publications and source records attributed to Peter Van Loo.

4 recordsLinked to original sources

Gene prioritization through genomic data fusion.

The identification of genes involved in health and disease remains a challenge. We describe a bioinformatics approach, together with a freely accessible, interactive and flexible software termed Endeavour, to prioritize candidate genes underlying biological processes or diseases, based on their similarity to known genes involved in these phenomena. Unlike previous approaches, ours generates distinct prioritizations for multiple heterogeneous data sources, which are then integrated, or fused, into a global ranking using order statistics. In addition, it offers the flexibility of including additional data sources. Validation of our approach revealed it was able to efficiently prioritize 627 genes in disease data sets and 76 genes in biological pathway sets, identify candidates of 16 mono- or polygenic diseases, and discover regulatory genes of myeloid differentiation. Furthermore, the approach identified a novel gene involved in craniofacial development from a 2-Mb chromosomal region, deleted in some patients with DiGeorge-like birth defects. The approach described here offers an alternative integrative method for gene discovery.

Algorithms↗

TOUCAN 2: the all-inclusive open source workbench for regulatory sequence analysis.

We present the second and improved release of the TOUCAN workbench for cis-regulatory sequence analysis. TOUCAN implements and integrates fast state-of-the-art methods and strategies in gene regulation bioinformatics, including algorithms for comparative genomics and for the detection of cis-regulatory modules. This second release of TOUCAN has become open source and thereby carries the potential to evolve rapidly. The main goal of TOUCAN is to allow a user to come to testable hypotheses regarding the regulation of a gene or of a set of co-regulated genes. TOUCAN can be launched from this location: http://www.esat.kuleuven.ac.be/~saerts/software/toucan.php.

Algorithms↗

A genetic algorithm for the detection of new cis-regulatory modules in sets of coregulated genes.

SUMMARY: The implementation of a genetic algorithm is described that provides a fast method of searching for the optimal combination of transcription factor binding sites in a set of regulatory sequences. AVAILABILITY: The algorithm can be used transparently as a web service from within the Toucan software. Toucan can be accessed at http://www.esat.kuleuven.ac.be/~saerts/software/toucan.php. A standalone version of the software is available upon request.

Algorithms↗

Computational detection of cis -regulatory modules.

MOTIVATION: The transcriptional regulation of a metazoan gene depends on the cooperative action of multiple transcription factors that bind to cis-regulatory modules (CRMs) located in the neighborhood of the gene. By integrating multiple signals, CRMs confer an organism specific spatial and temporal rate of transcription. RESULTS: Based on the hypothesis that genes that are needed in exactly the same conditions might share similar regulatory switches, we have developed a novel methodology to find CRMs in a set of coexpressed or coregulated genes. The ModuleSearcher algorithm finds for a given gene set the best scoring combination of transcription factor binding sites within a sequence window using an A(*)procedure for tree searching. To keep the level of noise low, we use DNA sequences that are most likely to contain functional cis-regulatory information, namely conserved regions between human and mouse orthologous genes. The ModuleScanner performs genomic searches with a predicted CRM or with a user-defined CRM known from the literature to find possible target genes. The validity of a set of putative targets is checked using Gene Ontology annotations. We demonstrate the use and effectiveness of the ModuleSearcher and ModuleScanner algorithms and test their specificity and sensitivity on semi-artificial data. Next, we search for a module in a cluster of gene expression profiles of human cell cycle genes. AVAILABILITY: The ModuleSearcher is available as a web service within the TOUCAN workbench for regulatory sequence analysis, which can be downloaded from http://www.esat.kuleuven.ac.be/~dna/BioI.

Algorithms↗