Biomedical subjects

Vincent Schächter

Publications and source records attributed to Vincent Schächter.

8 recordsLinked to original sources

PubMed2006

Global trends of whole-genome duplications revealed by the ciliate Paramecium tetraurelia.

The duplication of entire genomes has long been recognized as having great potential for evolutionary novelties, but the mechanisms underlying their resolution through gene loss are poorly understood. Here we show that in the unicellular eukaryote Paramecium tetraurelia, a ciliate, most of the nearly 40,000 genes arose through at least three successive whole-genome duplications. Phylogenetic analysis indicates that the most recent duplication coincides with an explosion of speciation events that gave rise to the P. aurelia complex of 15 sibling species. We observed that gene loss occurs over a long timescale, not as an initial massive event. Genes from the same metabolic pathway or protein complex have common patterns of gene loss, and highly expressed genes are over-retained after all duplications. The conclusion of this analysis is that many genes are maintained after whole-genome duplication not because of functional innovation but because of gene dosage constraints.

Animals↗

PubMed2006

Model of interactions in biology and application to heterogeneous network in yeast.

A major challenge for bioinformatics and theoretical biology is to build and analyse a unified model of biological knowledge resulting from high-throughput experiment data. Former work analyzed heterogeneous data (protein-protein interactions, genetic regulation, metabolism, synexpression) by modelling them by graphs. These models are unable to represent the qualitative dynamics of the reactions or to model the n-ary interactions. Here, MIB, the Model of Interactions in Biology, a bipartite model of biological networks, is introduced, and its use for topological analysis of the heterogeneous network is presented. Heterogeneous loops and links between synexpression pattern and underlying molecular mechanisms are proposed.

Biology↗

PubMed2006

ASEtrap: a biological method for speeding up the exploration of spliceomes.

Alternative splicing (AS) of pre-messenger RNA is a major mechanism for generating protein diversity from a limited number of genes in higher eukaryotes, and it constitutes a central mode of genetic regulation. Thus, efficient methods are needed to systematically identify new AS events at a genomic scale across different tissues, stages of development, and physiological or pathological conditions in order to better understand gene expression. To fulfill this goal, we have designed the ASEtrap, which is a cloning procedure for producing AS libraries that is based on a single-stranded trap consisting of an ssDNA-binding protein. In this paper, we have applied our approach to the construction of an AS library and a Control library from human placenta. By analyzing 9226 and 9999 sequences of the AS and Control libraries, respectively, we show that internal AS events (events that can be identified by the sole resources provided by either the AS or the Control library) and the discovery rate of new AS events measured at early stages of sequencing were nine to 10 times higher in the former than in the latter. Moreover, by performing a search for new AS events within a group of 162 known drug target genes, we identified six new events in six genes, and we observed that they all were discovered exclusively through the AS library. Thus, it appears that ASEtrap has the potential to greatly facilitate the determination of the total complement of splice variants expressed in human, as well as other organisms.

Alternative Splicing↗

PubMed2006

The adaptive filter of the yeast galactose pathway.

In the yeast Saccharomyces cerevisiae, the interplay between galactose, Gal3p, Gal80p and Gal4p determines the transcriptional status of the genes required for galactose utilization. After an increase in galactose concentration, galactose molecules bind onto Gal3p. This event leads via Gal80p to the activation of Gal4p, which then induces GAL3 and GAL80 gene transcription. Here we propose a qualitative dynamical model, whereby these molecular interaction events represent the first two stages of a functional feedback loop that closes with the capture of activated Gal4p by newly synthesized Gal3p and Gal80p, decreasing transcriptional activation and creating again the protein complex that can bind incoming galactose molecules. Based on the differential time-scales of faster protein interactions versus slower biosynthetic steps, this feedback loop functions as a derivative filter where galactose is the input step signal, and released Gal4p is the output derivative signal. One advantage of such a derivative filter is that GAL genes are expressed in proportion to cellular requirements. Furthermore, this filter adaptively protects the cellular receptors from saturation by galactose, allowing cells to remain sensitive to variations in galactose concentrations rather than to absolute concentrations. Finally, this feedback loop, by allowing phosphorylation of some active Gal4p, may be essential to initiate the subsequent long-term response.

Feedback, Physiological↗

PubMed2004

Numerous novel annotations of the human genome sequence supported by a 5'-end-enriched cDNA collection.

A collection of 90,000 human cDNA clones generated to increase the fraction of "full-length" cDNAs available was analyzed by sequence alignment on the human genome assembly. Five hundred fifty-two gene models not found in LocusLink, with coding regions of at least 300 bp, were defined by using this collection. Exon composition proposed for novel genes showed an average of 4.7 exons per gene. In 20% of the cases, at least half of the exons predicted for new genes coincided with evolutionary conserved regions defined by sequence comparisons with the pufferfish Tetraodon nigroviridis. Among this subset, CpG islands were observed at the 5' end of 75%. In-frame stop codons upstream of the initiator ATG were present in 49% of the new genes, and 16% contained a coding region comprising at least 50% of the cDNA sequence. This cDNA resource also provided candidate small protein-coding genes, usually not included in genome annotations. In addition, analysis of a sample from this cDNA collection indicates that approximately 380 gene models described in LocusLink could be extended at their 5' end by at least one new exon. Finally, this cDNA resource provided an experimental support for annotations based exclusively on predictions, thus representing a resource substantially improving the human genome annotation.

5' Untranslated Regions↗

PubMed2004

Whole genome sequence comparisons and "full-length" cDNA sequences: a combined approach to evaluate and improve Arabidopsis genome annotation.

To evaluate the existing annotation of the Arabidopsis genome further, we generated a collection of evolutionary conserved regions (ecores) between Arabidopsis and rice. The ecore analysis provides evidence that the gene catalog of Arabidopsis is not yet complete, and that a number of these annotations require re-examination. To improve the Arabidopsis genome annotation further, we used a novel "full-length" enriched cDNA collection prepared from several tissues. An additional 1931 genes were covered by new "full-length" cDNA sequences, raising the number of annotated genes with a corresponding "full-length" cDNA sequence to about 14,000. Detailed comparisons between these "full-length" cDNA sequences and annotated genes show that this resource is very helpful in determining the correct structure of genes, in particular, those not yet supported by "full-length" cDNAs. In addition, a total of 326 genomic regions not included previously in the Arabidopsis genome annotation were detected by this cDNA resource, providing clues for new gene discovery. Because, as expected, the two data sets only partially overlap, their combination produces very useful information for improving the Arabidopsis genome annotation.

Arabidopsis↗

PubMed2002

Protein-interaction networks: from experiments to analysis.

Functional proteomics approaches aim to characterize comprehensively the function of gene products, and provide a first-level understanding of cellular mechanisms. Here, we review recent techniques for the construction and prediction of large-scale protein-interaction networks, with a particular emphasis on computational processing steps and comparative assessment of the reliability and completeness of the various approaches. We also discuss the use of protein-interaction network information in functional annotation and in the generation of higher-level biological hypotheses on pathways.

Computational Biology↗

PubMed2002

Bioinformatics of large-scale protein interaction networks.

We survey recent techniques for construction and prediction of large-scale protein interaction networks, focusing on computational processing steps. Special emphasis is placed on critical assessment of data completeness and reliability of the various approaches. Once built, protein interaction networks can be used for functional annotation or to generate higher-level biological hypotheses on pathways.

Bacterial Proteins↗