Biomedical subjects

Graham J L Kemp

Publications and source records attributed to Graham J L Kemp.

6 recordsLinked to original sources

PubMed2006

PROPHECY--a yeast phenome database, update 2006.

Connecting genotype to phenotype is fundamental in biomedical research and in our understanding of disease. Phenomics--the large-scale quantitative phenotypic analysis of genotypes on a genome-wide scale--connects automated data generation with the development of novel tools for phenotype data integration, mining and visualization. Our yeast phenomics database PROPHECY is available at http://prophecy.lundberg.gu.se. Via phenotyping of 984 heterozygous diploids for all essential genes the genotypes analysed and presented in PROPHECY have been extended and now include all genes in the yeast genome. Further, phenotypic data from gene overexpression of 574 membrane spanning proteins has recently been included. To facilitate the interpretation of quantitative phenotypic data we have developed a new phenotype display option, the Comparative Growth Curve Display, where growth curve differences for a large number of mutants compared with the wild type are easily revealed. In addition, PROPHECY now offers a more informative and intuitive first-sight display of its phenotypic data via its new summary page. We have also extended the arsenal of data analysis tools to include dynamic visualization of phenotypes along individual chromosomes. PROPHECY is an initiative to enhance the growing field of phenome bioinformatics.

Chromosomes, Fungal↗

PubMed2005

Conformation of the exopolysaccharide of Burkholderia cepacia predicted with molecular mechanics (MM3) using genetic algorithm search.

We present a computational conformational analysis of the exopolysaccharide of Burkholderia cepacia, which is believed to play a role in colonization and persistence of B. cepacia in the lungs of cystic fibrosis patients. The repeating unit of the exopolysaccharide is a heptasaccharide with three branches, which cause significant steric restraints. Conformational searches using glygal, an in-house developed software using genetic algorithm search methods, were performed on fragments as well as on the complete repeating unit with wrap-over residues. The force field used for the calculations was MM3(96). The search showed four favored conformations for an isolated repeating unit. However, for a sequence of several repeating units, the calculations indicate a single, well-defined linear conformation.

Algorithms↗

PubMed2005

The use of a genetic algorithm search for molecular mechanics (MM3)-based conformational analysis of oligosaccharides.

We have implemented a system called glygal that can perform conformational searches on oligosaccharides using several different genetic algorithm (GA) search methods. The searches are performed in the torsion angle conformational space, considering both the primary glycosidic linkages as well as the pendant groups (C-5-C-6 and hydroxyl groups) where energy calculations are performed using the MM3(96) force field. The system includes a graphical user interface for setting calculation parameters and incorporates a 3D molecular viewer. The system was tested using dozens of structures and we present two case studies for two previously investigated O-specific oligosaccharides of the Shigella dysenteriae type 2 and 4. The results obtained using glygal show a significant reduction in the number of structures that need to be sampled in order to find the best conformation, as compared to filtered systematic search.

Algorithms↗

PubMed2005

PROPHECY--a database for high-resolution phenomics.

The rapid recent evolution of the field phenomics--the genome-wide study of gene dispensability by quantitative analysis of phenotypes--has resulted in an increasing demand for new data analysis and visualization tools. Following the introduction of a novel approach for precise, genome-wide quantification of gene dispensability in Saccharomyces cerevisiae we here announce a public resource for mining, filtering and visualizing phenotypic data--the PROPHECY database. PROPHECY is designed to allow easy and flexible access to physiologically relevant quantitative data for the growth behaviour of mutant strains in the yeast deletion collection during conditions of environmental challenges. PROPHECY is publicly accessible at http://prophecy.lundberg.gu.se.

Computer Graphics↗

PubMed2004

Analysis of fish IL-1beta and derived peptide sequences indicates conserved structures with species-specific IL-1 receptor binding: implications for pharmacological design.

A large number of IL-1 protein sequences have become available recently from a range of vertebrate species and especially from bony fish. However, 3D structures are still only known for mammalian IL-1. In this review, we use a multiple sequence alignment of all published non-mammalian vertebrate IL-1beta proteins to locate the structurally important residues critical for maintaining the beta-trefoil fold and we investigate the degree to which functionally important residues involved in receptor binding are conserved across vertebrate species. We find that although there is a high level of variability of positions involved in receptor binding, the mode of binding and overall shape of the ligand-receptor complex is probably maintained. This implies that each species has evolved its own unique interleukin-1 signalling system through ligand-receptor co-evolution. Nonetheless, the IL-1beta processing mechanism in non-mammalian vertebrates remains unclear because, with the exception of three bony fish, all non-mammalian IL-1beta sequences discovered so far lack an ICE (Interleukin Converting Enzyme) cut site. The IL-1 system has become an important drug target because of its significance in inflammatory diseases. Research on peptides derived from IL-1beta has identified peptides that possess agonist activity in humans and in trout, and peptides with antagonist activity. The agonist peptides map to two distinct loop regions of IL-1beta that are known to interact with the flexible domain III of the corresponding receptor. Further analysis of the IL-1 system may prove useful in engineering IL-1 with improved features and in suggesting new avenues for therapeutic intervention.

Amino Acid Sequence↗

PubMed2002

Architecture of a mediator for a bioinformatics database federation.

Developments in our ability to integrate and analyze data held in existing heterogeneous data resources can lead to an increase in our understanding of biological function at all levels. However, supporting ad hoc queries across multiple data resources and correlating data retrieved from these is still difficult. To address this, we are building a mediator based on the functional data model database, P/FDM, which integrates access to heterogeneous distributed biological databases. Our architecture makes use of the existing search capabilities and indexes of the underlying databases, without infringing on their autonomy. Central to our design philosophy is the use of schemas. We have adopted a federated architecture with a five-level schema, arising from the use of the ANSI-SPARC three-level schema to describe both the existing autonomous data resources and the mediator itself. We describe the use of mapping functions and list comprehensions in query splitting, producing execution plans, code generation, and result fusion. We give an example of cross-database querying involving data held locally in P/FDM systems and external data in SRS.

Algorithms↗