Entrez: making use of its power.

Entrez 1 is a data retrieval system developed by the National Center for Biotechnology Information (NCBI) that provides integrated access to a wide range of data domains, including literature, nucleotide and protein sequences, complete genomes, three-dimensional structures, and more. Entrez includes powerful search features that retrieve not only the exact search results but also related records within a data domain that might not be retrieved otherwise and associated records across data domains. These features enable us to gather previously disparate pieces of an information puzzle for a topic of interest. Effective and powerful use of Entrez requires an understanding of the available data domains, the variety of data sources and types within each domain, and Entrez's advanced search features. This tutorial uses the human MLH1 gene, implicated in colon cancer, to demonstrate the wide variety of information that we can rapidly gather for a single gene. The numbers noted in the search results will of course change over time as the databases grow. The same techniques shown here can be used for any topic of interest. The search goals are to: • separate the wheat from the chaff – identifying a representative, well-annotated mRNA sequence record; • retrieve associated literature and protein records; • identify conserved domains within the protein; • identify similar proteins; • identify known mutations within the gene or protein; • find a resolved three-dimensional structure for the protein or, in its absence, identify structures with homologous sequence; • view genomic context and download the sequence region. An Entrez data domain usually encompasses data from several different source databases. The goal is to identify a representative, well-annotated mRNA sequence record among the many available in the Entrez Nucleotide data domain. The Entrez Nucleotide domain includes sequence records from the archival GenBank database, the curated Ref Seq 2 database, nucleotide sequences extracted from Protein Data Bank (PDB) 3 records, and a new Third-Party Annotation (TPA) database. As a result, an unrefined search can retrieve records of varying quality (in both sequence and annotation), and there can be a high degree of redundancy in search results, depending upon how many labs have submitted sequence data for a gene or its fragments. For example, an unqualified search of Entrez Nucleotide for colon cancer currently retrieves .10,000 hits. The results include archival and curated records, characterised sequences and