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Brian P Brunk

Publications and source records attributed to Brian P Brunk.

5 recordsLinked to original sources

Integrating computationally assembled mouse transcript sequences with the Mouse Genome Informatics (MGI) database.

Databases of experimentally generated and computationally derived transcript sequences are valuable resources for genome analysis and annotation. The utility of such databases is enhanced when the sequences they contain are integrated with such biological information as genomic location, gene function, gene expression and phenotypic variation. We present the analysis and results of a semi-automated process of connecting transcript assemblies with highly curated biological information for mouse genes that is available through the Mouse Genome Informatics (MGI) database.

Animals↗

Gene discovery in the apicomplexa as revealed by EST sequencing and assembly of a comparative gene database.

Large-scale EST sequencing projects for several important parasites within the phylum Apicomplexa were undertaken for the purpose of gene discovery. Included were several parasites of medical importance (Plasmodium falciparum, Toxoplasma gondii) and others of veterinary importance (Eimeria tenella, Sarcocystis neurona, and Neospora caninum). A total of 55192 ESTs, deposited into dbEST/GenBank, were included in the analyses. The resulting sequences have been clustered into nonredundant gene assemblies and deposited into a relational database that supports a variety of sequence and text searches. This database has been used to compare the gene assemblies using BLAST similarity comparisons to the public protein databases to identify putative genes. Of these new entries, approximately 15%-20% represent putative homologs with a conservative cutoff of p < 10(-9), thus identifying many conserved genes that are likely to share common functions with other well-studied organisms. Gene assemblies were also used to identify strain polymorphisms, examine stage-specific expression, and identify gene families. An interesting class of genes that are confined to members of this phylum and not shared by plants, animals, or fungi, was identified. These genes likely mediate the novel biological features of members of the Apicomplexa and hence offer great potential for biological investigation and as possible therapeutic targets.

Animals↗

A molecular profile of a hematopoietic stem cell niche.

The hematopoietic microenvironment provides a complex molecular milieu that regulates the self-renewal and differentiation activities of stem cells. We have characterized a stem cell supportive stromal cell line, AFT024, that was derived from murine fetal liver. Highly purified in vivo transplantable mouse stem cells are maintained in AFT024 cultures at input levels, whereas other primitive progenitors are expanded. In addition, human stem cells are very effectively supported by AFT024. We suggest that the AFT024 cell line represents a component of an in vivo stem cell niche. To determine the molecular signals elaborated in this niche, we undertook a functional genomics approach that combines extensive sequence mining of a subtracted cDNA library, high-density array hybridization and in-depth bioinformatic analyses. The data have been assembled into a biological process oriented database, and represent a molecular profile of a candidate stem cell niche.

Amino Acid Sequence↗

Predicting gene ontology functions from ProDom and CDD protein domains.

A heuristic algorithm for associating Gene Ontology (GO) defined molecular functions to protein domains as listed in the ProDom and CDD databases is described. The algorithm generates rules for function-domain associations based on the intersection of functions assigned to gene products by the GO consortium that contain ProDom and/or CDD domains at varying levels of sequence similarity. The hierarchical nature of GO molecular functions is incorporated into rule generation. Manual review of a subset of the rules generated indicates an accuracy rate of 87% for ProDom rules and 84% for CDD rules. The utility of these associations is that novel sequences can be assigned a putative function if sufficient similarity exists to a ProDom or CDD domain for which one or more GO functions has been associated. Although functional assignments are increasingly being made for gene products from model organisms, it is likely that the needs of investigators will continue to outpace the efforts of curators, particularly for nonmodel organisms. A comparison with other methods in terms of coverage and agreement was performed, indicating the utility of the approach. The domain-function associations and function assignments are available from our website http://www.cbil.upenn.edu/GO.

Algorithms↗