No abstract

A rigorous analysis of the Merck-sponsored EST data with respect to known gene sequences increases the utility of the data set and helps refine methods for building a gene index. A highly curated human transcript data base was used as a reference data set of known genes. A detailed analysis of EST sequences derived from known genes was performed to assess the accuracy of EST sequence annotation. The EST data was screened to remove low-quality and low-complexity sequences. A set of high-quality ESTs similar to the transcript data base was identified using BLAST; this subset of ESTs was compared with the set of known genes using the Smith-Waterman algorithm. Error rates of several types were assessed based on a flexible match criterion defining sequence identity. The rate of lane-tracking errors is very low, -0.5%. Insert size data is accurate within -20%. Reversed clone and internal priming error rates are -5% and 2.5%, respectively, contributing to the incorrect identification of reads as 3' ends of genes. Follow-up investigation reveals that a significant number of clones, miscategorized as reversed, represent overlapping genes on the opposite strand of entries in the transcript data base. Relevance of these results to the creation of a high-quality index to the human genome capable of supporting diverse genomic investigations is discussed.

Target Informatics Net (TINet) is a readily extensible data integration system developed at GlaxoSmith- Kline (GSK), based on the Object-Protocol Model (OPM) multidatabase middleware system of Gene Logic Inc. Data sources currently integrated include: the Mouse Genome Database (MGD) and Gene Expression Database (GXD), GenBank, SwissProt, PubMed, GeneCards, the results of runtime BLAST and PROSITE searches, and GSK proprietary relational databases. Special-purpose class methods used to filter and augment query results include regular expression pattern-matching over BLAST HSP alignments and retrieving partial sequences derived from primary structure annotations. All data sources and methods are accessible through an SQL-like query language or a GUI, so that when new investigations arise no additional programming beyond query specification is required. The power and flexibility of this approach are illustrated in such integrated queries as: (1) 'find homologs in genomic sequence to all novel genes cloned and reported in the scientific literature within the past three months that are linked to the MeSH term 'neoplasms"; (2) 'using a neuropeptide precursor query sequence, return only HSPs where the target genomic sequences conserve the G[KR][KR] motif at the appropriate points in the HSP alignment'; and (3) 'of the human genomic sequences annotated with exon boundaries in GenBank, return only those with valid putative donor/acceptor sites and start/stop codons'.

No abstract

Health-care costs are rising dramatically. Errors in medical delivery are associated with an alarming number of preventable, often fatal adverse events. A promising strategy for reversing these trends is to modernize and transform the health-care information exchange (HIE), that is, the mobilization of health-care information electronically across organizations within a region or community. The current HIE is inefficient and error-prone; it is largely paper-based, fragmented, and therefore overly complex, often relying on antiquated IT (information technology). To address these weaknesses, projects are underway to build regional and national HIEs which provide interoperable access to a variety of data sources, by a variety of stakeholders, for a variety of purposes. In this paper we present a technologist's guide to health-care interoperability. We define the stakeholders, roles, and activities that comprise an HIE solution; we describe a spectrum of interoperability approaches and point out their advantages and disadvantages; and we look in some detail at a set of real-world scenarios, discussing the interoperability approaches that best address the needs. These examples are drawn from IBM experience with real-world HIE engagements.