Biomedical subjects

Vicente Arnau

Publications and source records attributed to Vicente Arnau.

3 recordsLinked to original sources

PubMed2006

UVPAR: fast detection of functional shifts in duplicate genes.

BACKGROUND: The imprint of natural selection on gene sequences is often difficult to detect. A plethora of methods have been devised to detect genetic changes due to selective processes. However, many of those methods depend heavily on underlying assumptions regarding the mode of change of DNA sequences and often require sophisticated mathematical treatments that made them computationally slow. The development of fast and effective methods to detect modifications in the selective constraints of genes is therefore of great interest. RESULTS: We describe UVPAR, a program designed to quickly test for changes in the functional constraints of duplicate genes. Starting with alignments of the proteins encoded by couples of duplicate genes in two different species, UVPAR detects the regions in which modifications of the functional constraints in the paralogs occurred since both species diverged. Sequences can be analyzed with UVPAR in just a few minutes on a standard PC computer. To demonstrate the power of the program, we first show how the results obtained with UVPAR compare to those based on other approaches, using data for vertebrate Hox genes. We then describe a comprehensive study of the RBR family of ubiquitin ligases in which we have performed 529 analyses involving 14 duplicate genes in seven model species. A significant increase in the number of functional shifts was observed for the species Danio rerio and for the gene Ariadne-2. CONCLUSION: These results show that UVPAR can be used to generate sensitive analyses to detect changes in the selection constraints acting on paralogs. The high speed of the program allows its application to genome-scale analyses.

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PubMed2006

Comparative genomics and protein domain graph analyses link ubiquitination and RNA metabolism.

The human gene parkin, known to cause familial Parkinson disease, as well as several other genes, likely involved in other neurodegenerative diseases or in cancer, encode proteins of the RBR family of ubiquitin ligases. Here, we describe the structural diversity of the RBR family in order to infer their functional roles. Of particular interest is a relationship detected between RBR-mediated ubiquitination and RNA metabolism: a few RBR proteins contain RNA binding domains and DEAH-box RNA helicase domains. Global protein domain graph analyses demonstrate that this connection is not RBR-specific, but instead many other proteins contain both ubiquitination and RNA-related domains. These proteins are present in animals, plants and fungi, suggesting that the link between these two cellular processes is ancient. Our results show that global bioinformatic approaches, involving comparative genomics and domain network analyses, may unearth novel functional relationships involving well-known and thoroughly studied groups of proteins.

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PubMed2004

Iterative cluster analysis of protein interaction data.

MOTIVATION: Generation of fast tools of hierarchical clustering to be applied when distances among elements of a set are constrained, causing frequent distance ties, as happens in protein interaction data. RESULTS: We present in this work the program UVCLUSTER, that iteratively explores distance datasets using hierarchical clustering. Once the user selects a group of proteins, UVCLUSTER converts the set of primary distances among them (i.e. the minimum number of steps, or interactions, required to connect two proteins) into secondary distances that measure the strength of the connection between each pair of proteins when the interactions for all the proteins in the group are considered. We show that this novel strategy has advantages over conventional clustering methods to explore protein-protein interaction data. UVCLUSTER easily incorporates the information of the largest available interaction datasets to generate comprehensive primary distance tables. The versatility, simplicity of use and high speed of UVCLUSTER on standard personal computers suggest that it can be a benchmark analytical tool for interactome data analysis. AVAILABILITY: The program is available upon request from the authors, free for academic users. Additional information available at http://www.uv.es/genomica/UVCLUSTER.

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