Biomedical subjects

Winston A Hide

Publications and source records attributed to Winston A Hide.

5 recordsLinked to original sources

PubMed2005

Integration of text- and data-mining using ontologies successfully selects disease gene candidates.

Genome-wide techniques such as microarray analysis, Serial Analysis of Gene Expression (SAGE), Massively Parallel Signature Sequencing (MPSS), linkage analysis and association studies are used extensively in the search for genes that cause diseases, and often identify many hundreds of candidate disease genes. Selection of the most probable of these candidate disease genes for further empirical analysis is a significant challenge. Additionally, identifying the genes that cause complex diseases is problematic due to low penetrance of multiple contributing genes. Here, we describe a novel bioinformatic approach that selects candidate disease genes according to their expression profiles. We use the eVOC anatomical ontology to integrate text-mining of biomedical literature and data-mining of available human gene expression data. To demonstrate that our method is successful and widely applicable, we apply it to a database of 417 candidate genes containing 17 known disease genes. We successfully select the known disease gene for 15 out of 17 diseases and reduce the candidate gene set to 63.3% (+/-18.8%) of its original size. This approach facilitates direct association between genomic data describing gene expression and information from biomedical texts describing disease phenotype, and successfully prioritizes candidate genes according to their expression in disease-affected tissues.

Anatomy↗

PubMed2004

FRAGS: estimation of coding sequence substitution rates from fragmentary data.

BACKGROUND: Rates of substitution in protein-coding sequences can provide important insights into evolutionary processes that are of biomedical and theoretical interest. Increased availability of coding sequence data has enabled researchers to estimate more accurately the coding sequence divergence of pairs of organisms. However the use of different data sources, alignment protocols and methods to estimate substitution rates leads to widely varying estimates of key parameters that define the coding sequence divergence of orthologous genes. Although complete genome sequence data are not available for all organisms, fragmentary sequence data can provide accurate estimates of substitution rates provided that an appropriate and consistent methodology is used and that differences in the estimates obtainable from different data sources are taken into account. RESULTS: We have developed FRAGS, an application framework that uses existing, freely available software components to construct in-frame alignments and estimate coding substitution rates from fragmentary sequence data. Coding sequence substitution estimates for human and chimpanzee sequences, generated by FRAGS, reveal that methodological differences can give rise to significantly different estimates of important substitution parameters. The estimated substitution rates were also used to infer upper-bounds on the amount of sequencing error in the datasets that we have analysed. CONCLUSION: We have developed a system that performs robust estimation of substitution rates for orthologous sequences from a pair of organisms. Our system can be used when fragmentary genomic or transcript data is available from one of the organisms and the other is a completely sequenced genome within the Ensembl database. As well as estimating substitution statistics our system enables the user to manage and query alignment and substitution data.

Animals↗

PubMed2004

Positive selection scanning of parasite DNA sequences.

Parasites successfully exist within the host as a result of highly specific genetic adaptations. Therefore, detecting genes that contain relevant adaptive mutations can provide a guide to biological processes that are potentially essential to the parasite. Random genetic mutations that confer selective advantage can act to alter amino acids so as to confer gain of function that has positive impact on the survival of the parasite. Directional selection of advantageous mutations results from an elevated rate of nonsynonymous substitutions in rapidly evolving genes. Genes on which this positive selection operates are considered to have an evolutionary characteristic such that the normalized number of nonsynonymous (dn) substitutions is greater than that of synonymous (ds) substitutions. By searching in a statistically robust way for genes that contain this characteristic, it is possible to apply a stringent method to identify genes that may be under positive selection and thus to identify biological processes involving those genes that are essential to the survival of the parasite. Genes detected typically class into those under host immune surveillance and those intrinsic to pathways essential to survival of the parasite within the host. Depending on their function and location of protein expression, such genes have the potential to provide exceptional vaccine and drug candidates.

Amino Acid Sequence↗

PubMed2003

Integrative analysis of intraerythrocytic differentially expressed transcripts yields novel insights into the biology of Plasmodium falciparum.

BACKGROUND: The intraerythrocytic development of Plasmodium falciparum, the most virulent human malaria parasite involves asexual and gametocyte stages. There has been a significant increase in disparate datasets derived from genomic and post-genomic analysis of the parasite that necessitates delivery of integrated analysis from which biological processes important to the survival of the parasite can be determined. METHODS: In order to resolve genes associated with stage differentially expressed transcripts, we have developed and implemented an integrative approach that combines evidence from P. falciparum expressed sequence tags (ESTs), genomic, microarray, proteomic and gene ontology data. RESULTS: A total of 143 gametocyte-overexpressed and 51 asexual-overexpressed transcripts were identified. A subset of 74 genes associated with these transcripts showed evidence of stage-correlated protein expression, of which 53 have not been experimentally characterised. Our study has revealed (1) possible regulatory mechanisms in malaria parasites' gametocyte maturation, (2) correlation between EST and microarray data for a P. falciparum gene family to present unique EST-derived information, (3) candidate drug and antigenic targets on which computational and experimental studies can be performed, and (4) the need for more empirical studies on gene and protein expression in malaria parasites. CONCLUSION: Applying different domains of data to the same underlying gene set has yielded novel insights into the biology of the parasite and presents an approach to appraise critically the data quality of post-genomic datasets from malaria parasites.

Journal Article↗

PubMed2002

Assessment of the parallelization approach of d2_cluster for high-performance sequence clustering.

The exponential increase in expressed sequence tag (EST) sequence data amplifies the computational cost of clustering sequences such that new algorithms are required to analyze data at a greater rate. We have parallelized d2_cluster on a SGI Origin 2000 multiprocessor and observed a speedup of approximately 100x on 126 processors when processing a 15,876 EST dataset. The parallelized d2_cluster code is obtainable from the SANBI website (http://www.sanbi.ac.za/CODES).

Journal Article↗