Biomedical subjects

Laurent Falquet

Publications and source records attributed to Laurent Falquet.

11 recordsLinked to original sources

PubMed2006

PeroxiBase: a class III plant peroxidase database.

Class III plant peroxidases (EC 1.11.1.7), which are encoded by multigenic families in land plants, are involved in several important physiological and developmental processes. Their varied functions are not yet clearly determined, but their characterization will certainly lead to a better understanding of plant growth, differentiation and interaction with the environment, and hence to many exciting applications. Since there is currently no central database for plant peroxidase sequences and many plant sequences are not deposited in the EMBL/GenBank/DDBJ repository or the UniProt KnowledgeBase, this prevents researchers from easily accessing all peroxidase sequences. Furthermore, gene expression data are poorly covered and annotations are inconsistent. In this rapidly moving field, there is a need for continual updating and correction of the peroxidase superfamily in plants. Moreover, consolidating information about peroxidases will allow for comparison of peroxidases between species and thus significantly help making correlations of function, structure or phylogeny. We report a new database (PeroxiBase) accessible through a web server with specific tools dedicated to facilitate query, classification and submission of peroxidase sequences. Recent developments in the field of plant peroxidase are also mentioned.

Databases, Genetic↗

PubMed2006

Hunting for insect-specific protein domains.

Automatically finding new protein domains is a challenge when using the complete collection of known proteins (i.e., UniProt). By limiting the taxonomic range to class insecta, including two full proteomes (A. gambiae and D. melanogaster), we reduced the size of the search space in the hope of finding taxon-specific domains. The MKDOM2 program (http://prodes.toulouse.inra.fr/prodom/xdom/mkdom2.html) was used to cluster the insect proteins into potential domains that were analyzed manually in a second step. We analyzed 219 potential domains, of which 2 were insect-specific. We show that it is possible to find new domains or to extend known domains using a semi-automated method; however the goal to detect class-specific domains was only partially achieved in the sense that the new domains we found were not all insect-specific domains. The files used as input and the resulting output files, as well as extensive descriptions of the domains, are available as supplementary data from http://bioinf.ibun.unal.edu.co/insecta/.

Animals↗

PubMed2005

On ubiquitin ligases and cancer.

Protein kinase genes account for almost 10% of all currently known cancer genes, highlighting the role of signal transduction in oncogenesis. A reexamination of the literature and available databases shows that E3 ubiquitin ligases are also key mediators of tumorigenesis. Altogether kinase and E3 genes represent more than 15% of the known cancer genes, underlining the importance of phosphorylation and ubiquitylation signaling pathways in cancer formation. Considering the recent literature reporting correlations between alterations in ubiquitylation processes and oncogenesis, this percentage is likely to increase even further in the future. Finally, E3 genes could serve as baits for the identification of additional cancer genes (e.g. their interacting partners). In contrast, deubiquitinases, like phosphatases, are not overrepresented among cancer genes. The same holds for E1 and E2 genes. Thus, kinase and E3 genes represent primary targets as cancer susceptibility genes for mutation screening and for the design of novel therapies.

Genes, Neoplasm↗

PubMed2005

The Saccharomyces cerevisiae YLL012/YEH1, YLR020/YEH2, and TGL1 genes encode a novel family of membrane-anchored lipases that are required for steryl ester hydrolysis.

Sterol homeostasis in eukaryotic cells relies on the reciprocal interconversion of free sterols and steryl esters. The formation of steryl esters is well characterized, but the mechanisms that control steryl ester mobilization upon cellular demand are less well understood. We have identified a family of three lipases of Saccharomyces cerevisiae that are required for efficient steryl ester mobilization. These lipases, encoded by YLL012/YEH1, YLR020/YEH2, and TGL1, are paralogues of the mammalian acid lipase family, which is composed of the lysosomal acid lipase, the gastric lipase, and four novel as yet uncharacterized human open reading frames. Lipase triple-mutant yeast cells are completely blocked in steryl ester hydrolysis but do not affect the mobilization of triacylglycerols, indicating that the three lipases are required for steryl ester mobilization in vivo. Lipase single mutants mobilize steryl esters to various degrees, indicating partial functional redundancy of the three gene products. Lipase double-mutant cells in which the third lipase is expressed from the inducible GAL1 promoter have greatly reduced steady-state levels of steryl esters, indicating that overexpression of any of the three lipases is sufficient for steryl ester mobilization in vivo. The three yeast enzymes constitute a novel class of membrane-anchored lipases that differ in topology and subcellular localization.

Amino Acid Sequence↗

PubMed2004

Transcript profiling suggests that differential metabolic adaptation of mice to a high fat diet is associated with changes in liver to muscle lipid fluxes.

Genetically homogenous C57Bl/6 mice display differential metabolic adaptation when fed a high fat diet for 9 months. Most become obese and diabetic, but a significant fraction remains lean and diabetic or lean and non-diabetic. Here, we performed microarray analysis of "metabolic" transcripts expressed in liver and hindlimb muscles to evaluate: (i) whether expressed transcript patterns could indicate changes in metabolic pathways associated with the different phenotypes, (ii) how these changes differed from the early metabolic adaptation to short term high fat feeding, and (iii) whether gene classifiers could be established that were characteristic of each metabolic phenotype. Our data indicate that obesity/diabetes was associated with preserved hepatic lipogenic gene expression and increased plasma levels of very low density lipoprotein and, in muscle, with an increase in lipoprotein lipase gene expression. This suggests increased muscle fatty acid uptake, which may favor insulin resistance. In contrast, the lean mice showed a strong reduction in the expression of hepatic lipogenic genes, in particular of Scd-1, a gene linked to sensitivity to diet-induced obesity; the lean and non-diabetic mice presented an additional increased expression of eNos in liver. After 1 week of high fat feeding the liver gene expression pattern was distinct from that seen at 9 months in any of the three mouse groups, thus indicating progressive establishment of the different phenotypes. Strikingly, development of the obese phenotype involved re-expression of Scd-1 and other lipogenic genes. Finally, gene classifiers could be established that were characteristic of each metabolic phenotype. Together, these data suggest that epigenetic mechanisms influence gene expression patterns and metabolic fates.

Animals↗

PubMed2004

MyHits: a new interactive resource for protein annotation and domain identification.

The MyHits web server (http://myhits.isb-sib.ch) is a new integrated service dedicated to the annotation of protein sequences and to the analysis of their domains and signatures. Guest users can use the system anonymously, with full access to (i) standard bioinformatics programs (e.g. PSI-BLAST, ClustalW, T-Coffee, Jalview); (ii) a large number of protein sequence databases, including standard (Swiss-Prot, TrEMBL) and locally developed databases (splice variants); (iii) databases of protein motifs (Prosite, Interpro); (iv) a precomputed list of matches ('hits') between the sequence and motif databases. All databases are updated on a weekly basis and the hit list is kept up to date incrementally. The MyHits server also includes a new collection of tools to generate graphical representations of pairwise and multiple sequence alignments including their annotated features. Free registration enables users to upload their own sequences and motifs to private databases. These are then made available through the same web interface and the same set of analytical tools. Registered users can manage their own sequences and annotations using only web tools and freeze their data in their private database for publication purposes.

Computer Graphics↗

PubMed2003

Swiss EMBnet node web server.

EMBnet is a consortium of collaborating bioinformatics groups located mainly within Europe (http://www.embnet.org). Each member country is represented by a 'node', a group responsible for the maintenance of local services for their users (e.g. education, training, software, database distribution, technical support, helpdesk). Among these services a web portal with links and access to locally developed and maintained software is essential and different for each node. Our web portal targets biomedical scientists in Switzerland and elsewhere, offering them access to a collection of important sequence analysis tools mirrored from other sites or developed locally. We describe here the Swiss EMBnet node web site (http://www.ch.embnet.org), which presents a number of original services not available anywhere else.

Databases, Protein↗

PubMed2003

The InterPro Database, 2003 brings increased coverage and new features.

InterPro, an integrated documentation resource of protein families, domains and functional sites, was created in 1999 as a means of amalgamating the major protein signature databases into one comprehensive resource. PROSITE, Pfam, PRINTS, ProDom, SMART and TIGRFAMs have been manually integrated and curated and are available in InterPro for text- and sequence-based searching. The results are provided in a single format that rationalises the results that would be obtained by searching the member databases individually. The latest release of InterPro contains 5629 entries describing 4280 families, 1239 domains, 95 repeats and 15 post-translational modifications. Currently, the combined signatures in InterPro cover more than 74% of all proteins in SWISS-PROT and TrEMBL, an increase of nearly 15% since the inception of InterPro. New features of the database include improved searching capabilities and enhanced graphical user interfaces for visualisation of the data. The database is available via a webserver (http://www.ebi.ac.uk/interpro) and anonymous FTP (ftp://ftp.ebi.ac.uk/pub/databases/interpro).

Animals↗

PubMed2002

The PROSITE database, its status in 2002.

PROSITE [Bairoch and Bucher (1994) Nucleic Acids Res., 22, 3583-3589; Hofmann et al. (1999) Nucleic Acids Res., 27, 215-219] is a method of identifying the functions of uncharacterized proteins translated from genomic or cDNA sequences. The PROSITE database (http://www.expasy.org/prosite/) consists of biologically significant patterns and profiles designed in such a way that with appropriate computational tools it can rapidly and reliably help to determine to which known family of proteins (if any) a new sequence belongs, or which known domain(s) it contains.

Amino Acid Motifs↗

PubMed2002

InterPro: an integrated documentation resource for protein families, domains and functional sites.

The exponential increase in the submission of nucleotide sequences to the nucleotide sequence database by genome sequencing centres has resulted in a need for rapid, automatic methods for classification of the resulting protein sequences. There are several signature and sequence cluster-based methods for protein classification, each resource having distinct areas of optimum application owing to the differences in the underlying analysis methods. In recognition of this, InterPro was developed as an integrated documentation resource for protein families, domains and functional sites, to rationalise the complementary efforts of the individual protein signature database projects. The member databases - PRINTS, PROSITE, Pfam, ProDom, SMART and TIGRFAMs - form the InterPro core. Related signatures from each member database are unified into single InterPro entries. Each InterPro entry includes a unique accession number, functional descriptions and literature references, and links are made back to the relevant member database(s). Release 4.0 of InterPro (November 2001) contains 4,691 entries, representing 3,532 families, 1,068 domains, 74 repeats and 15 sites of post-translational modification (PTMs) encoded by different regular expressions, profiles, fingerprints and hidden Markov models (HMMs). Each InterPro entry lists all the matches against SWISS-PROT and TrEMBL (2,141,621 InterPro hits from 586,124 SWISS-PROT and TrEMBL protein sequences). The database is freely accessible for text- and sequence-based searches.

Algorithms↗

PubMed2002

PROSITE: a documented database using patterns and profiles as motif descriptors.

Among the various databases dedicated to the identification of protein families and domains, PROSITE is the first one created and has continuously evolved since. PROSITE currently consists of a large collection of biologically meaningful motifs that are described as patterns or profiles, and linked to documentation briefly describing the protein family or domain they are designed to detect. The close relationship of PROSITE with the SWISS-PROT protein database allows the evaluation of the sensitivity and specificity of the PROSITE motifs and their periodic reviewing. In return, PROSITE is used to help annotate SWISS-PROT entries. The main characteristics and the techniques of family and domain identification used by PROSITE are reviewed in this paper.

Amino Acid Motifs↗