MOTIVATION: Splice variation plays important roles in evolution and cancer. Different splice variants of a gene may be characteristic of particular cellular processes, subcellular locations or organs. Although several genomic projects have identified splice variants, there have been no large-scale computational studies of the relationship between number of splice variants and biological function. The Gene Ontology (GO) and tools for leveraging GO, such as GoMiner, now make such a study feasible. RESULTS: We partitioned genes into two groups: those with numbers of splice variants b (b=1,..., 10). Then we used GoMiner to determine whether any GO categories are enriched in genes with particular numbers of splice variants. Since there was no a priori 'appropriate' partition boundary, we studied those 'robust' categories whose enrichment did not depend on the selection of a particular partition boundary. Furthermore, because the distribution of splice variant number was a snapshot taken at a particular point in time, we confirmed that those observations were stable across successive builds of GenBank. A small number of categories were found for genes in the lower partitions. A larger number of categories were found for genes in the higher partitions. Those categories were largely associated with cell death and signal transduction. Apoptotic genes tended to have a large repertoire of splice variants, and genes with splice variants exhibited a distinctive 'apoptotic island' in clustered image maps (CIMs). AVAILABILITY: Supplementary tables and figures are available at URL http://discover.nci.nih.gov/OG/supplementaryMaterials.html. The Safari browser appears to perform better than Firefox for these particular items.

BACKGROUND: There are many fewer genes in the human genome than there are expressed transcripts. Alternative splicing is the reason. Alternatively spliced transcripts are often specific to tissue type, developmental stage, environmental condition, or disease state. Accurate analysis of microarray expression data and design of new arrays for alternative splicing require assessment of probes at the sequence and exon levels. DESCRIPTION: SpliceMiner is a web interface for querying Evidence Viewer Database (EVDB). EVDB is a comprehensive, non-redundant compendium of splice variant data for human genes. We constructed EVDB as a queryable implementation of the NCBI Evidence Viewer (EV). EVDB is based on data obtained from NCBI Entrez Gene and EV. The automated EVDB build process uses only complete coding sequences, which may or may not include partial or complete 5' and 3' UTRs, and filters redundant splice variants. Unlike EV, which supports only one-at-a-time queries, SpliceMiner supports high-throughput batch queries and provides results in an easily parsable format. SpliceMiner maps probes to splice variants, effectively delineating the variants identified by a probe. CONCLUSION: EVDB can be queried by gene symbol, genomic coordinates, or probe sequence via a user-friendly web-based tool we call SpliceMiner (http://discover.nci.nih.gov/spliceminer). The EVDB/SpliceMiner combination provides an interface with human splice variant information and, going beyond the very valuable NCBI Evidence Viewer, supports fluent, high-throughput analysis. Integration of EVDB information into microarray analysis and design pipelines has the potential to improve the analysis and bioinformatic interpretation of gene expression data, for both batch and interactive processing. For example, whenever a gene expression value is recognized as important or appears anomalous in a microarray experiment, the interactive mode of SpliceMiner can be used quickly and easily to check for possible splice variant issues.

Many wonderful algorithms are published each month in Bioinformatics and other computational biology journals.Most of these algorithms are made freely available to the rest of the bioinformatics community.However, there is a growing trend to make new software available only through a HTML interface on the World-Wide Web, or via a closed, proprietary binary distribution.This trend will ultimately inhibit the growth of our discipline.As a community, we need to dedicate ourselves to the free and open exchange of algorithms and software.Our journals recognize the need for freely exchanged ideas: Bioinformatics requires that software be available for two years.However, the mechanism of making programs available to the rest of the community is not specified.The choice is rightly left up to the researcher.But some choices are better than others, and it is important to be sure that we make the choice that will best advance our community as well as our careers.The most forthright approach to sharing software is through the use of Open Source.

MOTIVATION: The construction of physical maps based on bacterial clones [e.g. bacterial artificial chromosomes (BACs)] is valuable for a number of molecular genetics applications, including the high-resolution mapping of genomic regions of interest and the identification of clones suitable for systematic sequencing. A common approach for large-scale screening of bacterial clone libraries involves the hybridization of high-density arrays of immobilized, lysed colonies with collections of DNA probes. The use of a multiplex hybridization screening strategy, whereby pooled probes are analysed en masse, simplifies the effort by reducing the total number of parallel experiments required. However, this approach generates large amounts of hybridization-based data that must be carefully analysed, assimilated, and disambiguated in a careful but efficient manner. RESULTS: To facilitate the screening of high-density clone arrays by a multiplex hybridization approach, we have written a program called ComboScreen. This program provides an organizational framework and analytical tools required for the high-throughput hybridization screening of clone arrays with pools of probes. We have used this program extensively for constructing mouse sequence-ready BAC contig maps.

Database federation enables biological researchers to utilize resources more effectively, creating an environment in which the researcher can query multiple data sources without spending time learning new query mechanisms or issuing redundant queries which need to be integrated. Several mechanisms exist to federate databases. The ENQUire system is a network database federation system which uses a World-Wide-Web (WWW) interface to connect the users to various databases. Generic queries entered via a query generator form are sent in parallel to multiple databases, and the results are presented to the user in a unified format. All forms building, query generation, and results translation is done on the fly, and individual database translation modules can be added dynamically. ENQUire is a flexible answer to the problems of database federation on the WWW.