PubServer: literature searches by homology.

PubServer, available at http://pubserver.burnham.org/, is a tool to automatically collect, filter and analyze publications associated with groups of homologous proteins. Protein entries in databases such as Entrez Protein database at NCBI contain information about publications associated with a given protein. The scope of these publications varies a lot: they include studies focused on biochemical functions of individual proteins, but also reports from genome sequencing projects that introduce tens of thousands of proteins. Collecting and analyzing publications related to sets of homologous proteins help in functional annotation of novel protein families and in improving annotations of well-studied protein families or individual genes. However, performing such collection and analysis manually is a tedious and time-consuming process. PubServer automatically collects identifiers of homologous proteins using PSI-Blast, retrieves literature references from corresponding database entries and filters out publications unlikely to contain useful information about individual proteins. It also prepares simple vocabulary statistics from titles, abstracts and MeSH terms to identify the most frequently occurring keywords, which may help to quickly identify common themes in these publications. The filtering criteria applied to collected publications are user-adjustable. The results of the server are presented as an interactive page that allows re-filtering and different presentations of the output

Community Classification of the Protein Universe

Protein family databases are an important resource for biologists seeking to characterise the function of proteins, the structure of their domains, and their localisation within the cell. Operating a protein family database requires the identification of families, and the curation of literature related to the family. This labour is currently performed by skilled professional curators, whose abilities are a scarce resource. In this thesis, I have developed methods to enable some of this labour to be performed by the community of protein sequence similarity search users. In the first chapter, I review the history of protein sequence and protein family databases, and how the abstract concept of a protein family is expressed as a computational model. I review in greater detail the protein family database Pfam, and the software package hmmer, which uses hidden Markov models to search protein sequence databases. In the second chapter, I explore how the quality of computational models for a protein family can be measured, and how these measurements might be used to assess the quality of community-sourced protein family models. I then investigate how a protein sequence similarity search can be rapidly analysed for overlap with existing protein families in Pfam, using locality sensitive hashing. In the third chapter, I discuss the use of literature search in protein family database curation, and the existing literature resources used by protein family database curators. I then develop a system for performing literature search based on protein families, exploiting the manually annotated links between literature and proteins found in the Swiss-Prot subset of the UniProt protein database. In the fourth chapter, I develop a web application for analysing the results of protein sequence similarity searches, using the methods discussed in the second chapter, and for performing literature search based on the results of protein sequence similarity search, using the methods discussed in the third chapter. In the fifth chapter, I develop a web application which applies the methods developed in the third chapter to the task of curation of the protein classification resource, InterPro.My fellowship was funded by the European Molecular Biology Laboratory's International PhD Programm

GeneReporter--sequence-based document retrieval and annotation.

GeneReporter is a web tool that reports functional information and relevant literature on a protein-coding sequence of interest. Its purpose is to support both manual genome annotation and document retrieval. PubMed references corresponding to a sequence are detected by the extraction of query words from UniProt entries of homologous sequences. Data on protein families, domains, potential cofactors, structure, function, cellular localization, metabolic contribution and corresponding DNA binding sites complement the information on a given gene product of interest

Antioxidant and DPPH-Scavenging Activities of Compounds and Ethanolic Extract of the Leaf and Twigs of Caesalpinia bonduc L. Roxb.

Antioxidant effects of ethanolic extract of Caesalpinia bonduc and its isolated bioactive compounds were evaluated in vitro. The compounds included two new cassanediterpenes, 1α,7α-diacetoxy-5α,6β-dihydroxyl-cass-14(15)-epoxy-16,12-olide (1)and 12α-ethoxyl-1α,14β-diacetoxy-2α,5α-dihydroxyl cass-13(15)-en-16,12-olide(2); and others, bonducellin (3), 7,4’-dihydroxy-3,11-dehydrohomoisoflavanone (4), daucosterol (5), luteolin (6), quercetin-3-methyl ether (7) and kaempferol-3-O-α-L-rhamnopyranosyl-(1Ç2)-β-D-xylopyranoside (8). The antioxidant properties of the extract and compounds were assessed by the measurement of the total phenolic content, ascorbic acid content, total antioxidant capacity and 1-1-diphenyl-2-picryl hydrazyl (DPPH) and hydrogen peroxide radicals scavenging activities.Compounds 3, 6, 7 and ethanolic extract had DPPH scavenging activities with IC50 values of 186, 75, 17 and 102 μg/ml respectively when compared to vitamin C with 15 μg/ml. On the other hand, no significant results were obtained for hydrogen peroxide radical. In addition, compound 7 has the highest phenolic content of 0.81±0.01 mg/ml of gallic acid equivalent while compound 8 showed the highest total antioxidant capacity with 254.31±3.54 and 199.82±2.78 μg/ml gallic and ascorbic acid equivalent respectively. Compound 4 and ethanolic extract showed a high ascorbic acid content of 2.26±0.01 and 6.78±0.03 mg/ml respectively.The results obtained showed the antioxidant activity of the ethanolic extract of C. bonduc and deduced that this activity was mediated by its isolated bioactive compounds