Simon Cockell

See more in my Dopplr profile. - Simon Cockell

Nucleic acids research (9 November 2009) The identification of orthologous relationships forms the basis for most comparative genomics studies. Here, we present the second version of the eggNOG database, which contains orthologous groups (OGs) constructed through identification of reciprocal best BLAST matches and triangular linkage clustering. We applied this procedure to 630 complete genomes (529 bacteria, 46 archaea and 55 eukaryotes), which is a 2-fold increase relative to the previous version. The pipeline yielded 224 847 OGs, including 9724 extended versions of the original COG and KOG. We computed OGs for different levels of the tree of life; in addition to the species groups included in our first release (i.e. fungi, metazoa, insects, vertebrates and mammals), we have now constructed OGs for archaea, fishes, rodents and primates. We automatically annotate the non-supervised orthologous groups (NOGs) with functional descriptions, protein domains, and functional categories as... - Simon Cockell

if you can.. send one to mfoolb at gmail dot com thnx - Marco

I'll be there from November 11th until November 12th. See more in my Dopplr profile. - Simon Cockell

Posted via web from Simon's posterous - Simon Cockell from Posterous

Posted via web from Simon's posterous - Simon Cockell from Posterous

I strayed into the comment thread by mistake. #79 is a gem. - Neil Saunders

The best comedy makes you stop and think once in a while - bravo. - Simon Cockell from Bookmarklet

Nature Reviews Drug Discovery, Vol. 3, No. 8. (01 August 2004), pp. 673-683. Biopharmaceutical companies attempting to increase productivity through novel discovery technologies have fallen short of achieving the desired results. Repositioning existing drugs for new indications could deliver the productivity increases that the industry needs while shifting the locus of production to biotechnology companies. More and more companies are scanning the existing pharmacopoeia for repositioning candidates, and the number of repositioning success stories is increasing. Ted Ashburn, Karl Thor - Simon Cockell

Health affairs (Project Hope), Vol. 25, No. 2. (r 2006), pp. 420-428. This paper replicates the drug development cost estimates of Joseph DiMasi and colleagues ("The Price of Innovation"), using their published cost estimates along with information on success rates and durations from a publicly available data set. For drugs entering human clinical trials for the first time between 1989 and 2002, the paper estimated the cost per new drug to be 868 million dollars. However, our estimates vary from around 500 million dollars to more than 2,000 million dollars, depending on the therapy or the developing firm. Christopher Adams, Van Brantner - Simon Cockell

Nucleic acids research, Vol. 37, No. Web Server issue. (1 July 2009), pp. W23-27. BioMart Central Portal (www.biomart.org) offers a one-stop shop solution to access a wide array of biological databases. These include major biomolecular sequence, pathway and annotation databases such as Ensembl, Uniprot, Reactome, HGNC, Wormbase and PRIDE; for a complete list, visit, http://www.biomart.org/biomart.... Moreover, the web server features seamless data federation making cross querying of these data sources in a user friendly and unified way. The web server not only provides access through a web interface (MartView), it also supports programmatic access through a Perl API as well as RESTful and SOAP oriented web services. The website is free and open to all users and there is no login requirement. Syed Haider, Benoit Ballester, Damian Smedley, Junjun Zhang, Peter Rice, Arek Kasprzyk - Simon Cockell

Nucleic acids research, Vol. 36, No. Database issue. (11 January 2008), pp. D480-484. KEGG (http://www.genome.jp/kegg/) is a database of biological systems that integrates genomic, chemical and systemic functional information. KEGG provides a reference knowledge base for linking genomes to life through the process of PATHWAY mapping, which is to map, for example, a genomic or transcriptomic content of genes to KEGG reference pathways to infer systemic behaviors of the cell or the organism. In addition, KEGG provides a reference knowledge base for linking genomes to the environment, such as for the analysis of drug-target relationships, through the process of BRITE mapping. KEGG BRITE is an ontology database representing functional hierarchies of various biological objects, including molecules, cells, organisms, diseases and drugs, as well as relationships among them. KEGG PATHWAY is now supplemented with a new global map of metabolic pathways, which is essentially a combined map of... - Simon Cockell

Proceedings of the National Academy of Sciences of the United States of America, Vol. 101, No. 16. (20 April 2004), pp. 6062-6067. The tissue-specific pattern of mRNA expression can indicate important clues about gene function. High-density oligonucleotide arrays offer the opportunity to examine patterns of gene expression on a genome scale. Toward this end, we have designed custom arrays that interrogate the expression of the vast majority of protein-encoding human and mouse genes and have used them to profile a panel of 79 human and 61 mouse tissues. The resulting data set provides the expression patterns for thousands of predicted genes, as well as known and poorly characterized genes, from mice and humans. We have explored this data set for global trends in gene expression, evaluated commonly used lines of evidence in gene prediction methodologies, and investigated patterns indicative of chromosomal organization of transcription. We describe hundreds of regions of correlated... - Simon Cockell

Nucleic acids research, Vol. 36, No. Database issue. (11 January 2008), pp. D281-288. Pfam is a comprehensive collection of protein domains and families, represented as multiple sequence alignments and as profile hidden Markov models. The current release of Pfam (22.0) contains 9318 protein families. Pfam is now based not only on the UniProtKB sequence database, but also on NCBI GenPept and on sequences from selected metagenomics projects. Pfam is available on the web from the consortium members using a new, consistent and improved website design in the UK (http://pfam.sanger.ac.uk/), the USA (http://pfam.janelia.org/) and Sweden (http://pfam.sbc.su.se/), as well as from mirror sites in France (http://pfam.jouy.inra.fr/) and South Korea (http://pfam.ccbb.re.kr/). Robert Finn, John Tate, Jaina Mistry, Penny Coggill, Stephen John Sammut, Hans-Rudolf Hotz, Goran Ceric, Kristoffer Forslund, Sean Eddy, Erik Sonnhammer, Alex Bateman - Simon Cockell

Journal of molecular biology, Vol. 215, No. 3. (5 October 1990), pp. 403-410. A new approach to rapid sequence comparison, basic local alignment search tool (BLAST), directly approximates alignments that optimize a measure of local similarity, the maximal segment pair (MSP) score. Recent mathematical results on the stochastic properties of MSP scores allow an analysis of the performance of this method as well as the statistical significance of alignments it generates. The basic algorithm is simple and robust; it can be implemented in a number of ways and applied in a variety of contexts including straightforward DNA and protein sequence database searches, motif searches, gene identification searches, and in the analysis of multiple regions of similarity in long DNA sequences. In addition to its flexibility and tractability to mathematical analysis, BLAST is an order of magnitude faster than existing sequence comparison tools of comparable sensitivity. SF Altschul, W Gish, W Miller, EW... - Simon Cockell

Nucleic acids research, Vol. 36, No. Database issue. (11 January 2008), gkm958. DrugBank is a richly annotated resource that combines detailed drug data with comprehensive drug target and drug action information. Since its first release in 2006, DrugBank has been widely used to facilitate in silico drug target discovery, drug design, drug docking or screening, drug metabolism prediction, drug interaction prediction and general pharmaceutical education. The latest version of DrugBank (release 2.0) has been expanded significantly over the previous release. With approximately 4900 drug entries, it now contains 60% more FDA-approved small molecule and biotech drugs including 10% more 'experimental' drugs. Significantly, more protein target data has also been added to the database, with the latest version of DrugBank containing three times as many non-redundant protein or drug target sequences as before (1565 versus 524). Each DrugCard entry now contains more than 100 data fields with half... - Simon Cockell

Science, Vol. 324, No. 5933. (12 June 2009), pp. 1394-1395. 10.1126/science.1169920 Mark Boguski, Kenneth Mandl, Vikas Sukhatme - Simon Cockell

Nature, Vol. advance online publication (1 November 2009) Although drugs are intended to be selective, at least some bind to several physiological targets, explaining side effects and efficacy. Because many drug-target combinations exist, it would be useful to explore possible interactions computationally. Here we compared 3,665 US Food and Drug Administration (FDA)-approved and investigational drugs against hundreds of targets, defining each target by its ligands. Chemical similarities between drugs and ligand sets predicted thousands of unanticipated associations. Thirty were tested experimentally, including the antagonism of the beta(1) receptor by the transporter inhibitor Prozac, the inhibition of the 5-hydroxytryptamine (5-HT) transporter by the ion channel drug Vadilex, and antagonism of the histamine H(4) receptor by the enzyme inhibitor Rescriptor. Overall, 23 new drug-target associations were confirmed, five of which were potent (<100 nM). The physiological relevance of one,... - Simon Cockell

I really should have read this and this before trying to upgrade my Slicehost slice to Ubuntu Karmic last night. Wondered why the darned thing wouldn’t mount the filesystem properly. After half an hour stressing with a read-only filesystem, I finally decided to check out what Slicehost themselves have to say about upgrading Ubuntu. The real [...] - Simon Cockell

Posted via web from Simon's posterous - Simon Cockell from Posterous

Analytical chemistry (19 October 2009) In order that biological meaning may be derived and testable hypotheses may be built from proteomics experiments, assignments of proteins identified by mass spectrometry or other techniques must be supplemented with additional notation, such as information on known protein functions, protein-protein interactions, or biological pathway associations. Collecting, organizing, and interpreting this data often requires the input of experts in the biological field of study, in addition to the time-consuming search for and compilation of information from online protein databases. Furthermore, visualizing this bulk of information can be challenging due to the limited availability of easy-to-use and freely available tools for this process. In response to these constraints, we have undertaken the design of software to automate annotation and visualization of proteomics data in order to accelerate the pace of research. Here we present the Software Tool for... - Simon Cockell

@SImon, cheers - Frank

J. Bacteriol., Vol. 187, No. 14. (15 July 2005), pp. 4928-4934. Surface proteins of gram-positive bacteria often play a role in adherence of the bacteria to host tissue and are frequently required for virulence. A specific subgroup of extracellular proteins contains the cell wall-sorting motif LPxTG, which is the target for cleavage and covalent coupling to the peptidoglycan by enzymes called sortases. A comprehensive set of putative sortase substrates was identified by in silico analysis of 199 completely sequenced prokaryote genomes. A combination of detection methods was used, including secondary structure prediction, pattern recognition, sequence homology, and genome context information. With the hframe algorithm, putative substrates were identified that could not be detected by other methods due to errors in open reading frame calling, frameshifts, or sequencing errors. In total, 732 putative sortase substrates encoded in 49 prokaryote genomes were identified. We found striking... - Simon Cockell

Biochemistry, Vol. 43, No. 6. (1 February 2004), pp. 1541-1551. The Staphylococcus aureus sortase transpeptidase SrtA isoform is responsible for the covalent attachment of virulence and colonization-associated proteins to the bacterial peptidoglycan. SrtA utilizes two substrates, undecaprenol-pyrophosphoryl-MurNAc(GlcNAc)-Ala-d-isoGlu-Lys(epsilon-Gly5)-d-Ala-d-Ala (branched Lipid II) and secreted proteins containing a highly conserved C-terminal LPXTG sequence. SrtA simultaneously cleaves the ThrGly bond of the LPXTG-containing protein and forms a new amide bond with the nucleophilic amino group of the Gly5 portion of branched Lipid II, anchoring the protein to this key intermediate that is subsequently polymerized into peptidoglycan. Here we describe the development of a general in vitro method for elucidating the substrate specificity of sortase enzymes. In addition, using immunofluorescence, cell adhesion assays, and transmission electron microscopy, we establish links between in... - Simon Cockell

Journal of Biological Chemistry, Vol. 283, No. 21. (23 May 2008), pp. 14762-14771. 10.1074/jbc.M800974200 The transpeptidase sortase A (SrtA) is responsible for anchoring a range of virulence- and colonization-associated proteins to the cell wall. SrtA recognizes substrates that contain a C-terminal LPTG motif. This sequence is cleaved following the threonine, and an amide bond is formed between the threonine and the pentaglycine cross-bridge of branched lipid II. Previous studies have implicated the β6/β7 loop region of SrtA in LPTG recognition but have not systematically characterized this domain. To better understand the individual roles of the residues within this loop, we performed alanine-scanning mutagenesis. Val-168 and Leu-169 were found to be important for substrate recognition, and Glu-171 was also found to be important, consistent with its hypothesized role as a Ca-binding residue. Gly-167 and Asp-170 were dispensable for catalysis, as was Gln-172. The role of Arg-197 in... - Simon Cockell

The guardian have posted satellite trackers to monitor what happens to post during the 48-hour postal workers strike. The map: http://is.gd/4vnyf - Simon Cockell from Bookmarklet

Bioinformatics, Vol. 22, No. 11. (1 June 2006), pp. 1383-1390. Motivation: Assembling the relevant information needed to interpret the output from high-throughput, genome scale, experiments such as gene expression microarrays is challenging. Analysis reveals genes that show statistically significant changes in expression levels, but more information is needed to determine their biological relevance. The challenge is to bring these genes together with biological information distributed across hundreds of databases or buried in the scientific literature (millions of articles). Software tools are needed to automate this task which at present is labor-intensive and requires considerable informatics and biological expertise. Results: This article describes ONDEX and how it can be applied to the task of interpreting gene expression results. ONDEX is a database system that combines the features of semantic database integration and text mining with methods for graph-based analysis. An... - Simon Cockell