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Presents a study which examined the problems encountered by Experimental Medical Care Review Organization (EMCRO) program in the acquisition and use of the medical care using insurance billing claims or medical records in the U.S. Background on the creation of the EMCRO by the Bureau of Health Services Research; Methodology; Results of the study.

ClinVar is a freely available, public archive of human genetic variants and interpretations of their relationships to diseases and other conditions, maintained at the National Institutes of Health (NIH). Submitted interpretations of variants are aggregated and made available on the ClinVar website (https://www.ncbi.nlm.nih.gov/clinvar/), and as downloadable files via FTP and through programmatic tools such as NCBI's E-utilities. The default view on the ClinVar website, the Variation page, was recently redesigned. The new layout includes several new sections that make it easier to find submitted data as well as summary data such as all diseases and citations reported for the variant. The new design also better represents more complex data such as haplotypes and genotypes, as well as variants that are in ClinVar as part of a haplotype or genotype but have no interpretation for the single variant. ClinVar's variant-centric XML had its production release in April 2019. The ClinVar website and E-utilities both have been updated to support the VCV (variation in ClinVar) accession numbers found in the variant-centric XML file. ClinVar's search engine has been fine-tuned for improved retrieval of search results., (Published by Oxford University Press on behalf of Nucleic Acids Research 2019.)

On autopsy, a patient is found to have hypertrophic cardiomyopathy. The patient’s family pursues genetic testing that shows a “likely pathogenic” variant for the condition on the basis of a study in an original research publication. Given the dominant inheritance of the condition and the risk of sudden cardiac death, other family members are tested for the genetic variant to determine their risk. Several family members test negative and are told that they are not at risk for hypertrophic cardiomyopathy and sudden cardiac death, and those who test positive are told that they need to be regularly monitored for cardiomyopathy on echocardiography. Five years later, during a routine clinic visit of one of the genotype-positive family members, the cardiologist queries a database for current knowledge on the genetic variant and discovers that the variant is now interpreted as “likely benign” by another laboratory that uses more recently derived population-frequency data. A newly available testing panel for additional genes that are implicated in hypertrophic cardiomyopathy is initiated on an affected family member, and a different variant is found that is determined to be pathogenic. Family members are retested, and one member who previously tested negative is now found to be positive for this new variant. An immediate clinical workup detects evidence of cardiomyopathy, and an intracardiac defibrillator is implanted to reduce the risk of sudden cardiac death.

The National Center for Biotechnology Information's (NCBI) Gene database (www.ncbi.nlm.nih.gov/gene) integrates gene-specific information from multiple data sources. NCBI Reference Sequence (RefSeq) genomes for viruses, prokaryotes and eukaryotes are the primary foundation for Gene records in that they form the critical association between sequence and a tracked gene upon which additional functional and descriptive content is anchored. Additional content is integrated based on the genomic location and RefSeq transcript and protein sequence data. The content of a Gene record represents the integration of curation and automated processing from RefSeq, collaborating model organism databases, consortia such as Gene Ontology, and other databases within NCBI. Records in Gene are assigned unique, tracked integers as identifiers. The content (citations, nomenclature, genomic location, gene products and their attributes, phenotypes, sequences, interactions, variation details, maps, expression, homologs, protein domains and external databases) is available via interactive browsing through NCBI's Entrez system, via NCBI's Entrez programming utilities (E-Utilities and Entrez Direct) and for bulk transfer by FTP., (Published by Oxford University Press on behalf of Nucleic Acids Research 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Genome-wide association studies, DNA sequencing studies, and other genomic studies are finding an increasing number of genetic variants associated with clinical phenotypes that may be useful in developing diagnostic, preventive, and treatment strategies for individual patients. However, few variants have been integrated into routine clinical practice. The reasons for this are several, but two of the most significant are limited evidence about the clinical implications of the variants and a lack of a comprehensive knowledge base that captures genetic variants, their phenotypic associations, and other pertinent phenotypic information that is openly accessible to clinical groups attempting to interpret sequencing data. As the field of medicine begins to incorporate genome-scale analysis into clinical care, approaches need to be developed for collecting and characterizing data on the clinical implications of variants, developing consensus on their actionability, and making this information available for clinical use. The National Human Genome Research Institute (NHGRI) and the Wellcome Trust thus convened a workshop to consider the processes and resources needed to: (1) identify clinically valid genetic variants; (2) decide whether they are actionable and what the action should be; and (3) provide this information for clinical use. This commentary outlines the key discussion points and recommendations from the workshop., (© 2014 Wiley Periodicals, Inc.)

In addition to maintaining the GenBank® nucleic acid sequence database, the National Center for Biotechnology Information (NCBI) provides analysis and retrieval resources for the data in GenBank and other biological data made available through the NCBI Website. NCBI resources include Entrez, the Entrez Programming Utilities, MyNCBI, PubMed, PubMed Central (PMC), Gene, the NCBI Taxonomy Browser, BLAST, BLAST Link (BLink), Primer-BLAST, COBALT, Splign, RefSeq, UniGene, HomoloGene, ProtEST, dbMHC, dbSNP, dbVar, Epigenomics, Genome and related tools, the Map Viewer, Model Maker, Evidence Viewer, Trace Archive, Sequence Read Archive, BioProject, BioSample, Retroviral Genotyping Tools, HIV-1/Human Protein Interaction Database, Gene Expression Omnibus (GEO), Probe, Online Mendelian Inheritance in Animals (OMIA), the Molecular Modeling Database (MMDB), the Conserved Domain Database (CDD), the Conserved Domain Architecture Retrieval Tool (CDART), Biosystems, Protein Clusters and the PubChem suite of small molecule databases. Augmenting many of the Web applications are custom implementations of the BLAST program optimized to search specialized data sets. All of these resources can be accessed through the NCBI home page at www.ncbi.nlm.nih.gov.

Entrez Gene (http://www.ncbi.nlm.nih.gov/gene) is National Center for Biotechnology Information (NCBI)'s database for gene-specific information. Entrez Gene maintains records from genomes which have been completely sequenced, which have an active research community to submit gene-specific information, or which are scheduled for intense sequence analysis. The content represents the integration of curation and automated processing from NCBI's Reference Sequence project (RefSeq), collaborating model organism databases, consortia such as Gene Ontology and other databases within NCBI. Records in Entrez Gene are assigned unique, stable and tracked integers as identifiers. The content (nomenclature, genomic location, gene products and their attributes, markers, phenotypes and links to citations, sequences, variation details, maps, expression, homologs, protein domains and external databases) is available via interactive browsing through NCBI's Entrez system, via NCBI's Entrez programming utilities (E-Utilities) and for bulk transfer by FTP.

In addition to maintaining the GenBank® nucleic acid sequence database, the National Center for Biotechnology Information (NCBI) provides analysis and retrieval resources for the data in GenBank and other biological data made available through the NCBI Web site. NCBI resources include Entrez, the Entrez Programming Utilities, MyNCBI, PubMed, PubMed Central (PMC), Entrez Gene, the NCBI Taxonomy Browser, BLAST, BLAST Link (BLink), Primer-BLAST, COBALT, Electronic PCR, OrfFinder, Splign, ProSplign, RefSeq, UniGene, HomoloGene, ProtEST, dbMHC, dbSNP, dbVar, Epigenomics, Cancer Chromosomes, Entrez Genomes and related tools, the Map Viewer, Model Maker, Evidence Viewer, Trace Archive, Sequence Read Archive, Retroviral Genotyping Tools, HIV-1/Human Protein Interaction Database, Gene Expression Omnibus (GEO), Entrez Probe, GENSAT, Online Mendelian Inheritance in Man (OMIM), Online Mendelian Inheritance in Animals (OMIA), the Molecular Modeling Database (MMDB), the Conserved Domain Database (CDD), the Conserved Domain Architecture Retrieval Tool (CDART), IBIS, Biosystems, Peptidome, OMSSA, Protein Clusters and the PubChem suite of small molecule databases. Augmenting many of the Web applications are custom implementations of the BLAST program optimized to search specialized data sets. All of these resources can be accessed through the NCBI home page at www.ncbi.nlm.nih.gov.

In addition to maintaining the GenBank nucleic acid sequence database, the National Center for Biotechnology Information (NCBI) provides analysis and retrieval resources for the data in GenBank and other biological data made available through the NCBI web site. NCBI resources include Entrez, the Entrez Programming Utilities, MyNCBI, PubMed, PubMed Central, Entrez Gene, the NCBI Taxonomy Browser, BLAST, BLAST Link (BLink), Electronic PCR, OrfFinder, Spidey, Splign, Reference Sequence, UniGene, HomoloGene, ProtEST, dbMHC, dbSNP, Cancer Chromosomes, Entrez Genomes and related tools, the Map Viewer, Model Maker, Evidence Viewer, Trace Archive, Sequence Read Archive, Retroviral Genotyping Tools, HIV-1/Human Protein Interaction Database, Gene Expression Omnibus, Entrez Probe, GENSAT, Online Mendelian Inheritance in Man, Online Mendelian Inheritance in Animals, the Molecular Modeling Database, the Conserved Domain Database, the Conserved Domain Architecture Retrieval Tool, Biosystems, Peptidome, Protein Clusters and the PubChem suite of small molecule databases. Augmenting many of the web applications are custom implementations of the BLAST program optimized to search specialized data sets. All these resources can be accessed through the NCBI home page at www.ncbi.nlm.nih.gov.

Since its start, the Mammalian Gene Collection (MGC) has sought to provide at least one full-protein-coding sequence cDNA clone for every human and mouse gene with a RefSeq transcript, and at least 6200 rat genes. The MGC cloning effort initially relied on random expressed sequence tag screening of cDNA libraries. Here, we summarize our recent progress using directed RT-PCR cloning and DNA synthesis. The MGC now contains clones with the entire protein-coding sequence for 92% of human and 89% of mouse genes with curated RefSeq (NM-accession) transcripts, and for 97% of human and 96% of mouse genes with curated RefSeq transcripts that have one or more PubMed publications, in addition to clones for more than 6300 rat genes. These high-quality MGC clones and their sequences are accessible without restriction to researchers worldwide.

In addition to maintaining the GenBank nucleic acid sequence database, the National Center for Biotechnology Information (NCBI) provides analysis and retrieval resources for the data in GenBank and other biological data made available through the NCBI web site. NCBI resources include Entrez, the Entrez Programming Utilities, MyNCBI, PubMed, PubMed Central, Entrez Gene, the NCBI Taxonomy Browser, BLAST, BLAST Link (BLink), Electronic PCR, OrfFinder, Spidey, Splign, RefSeq, UniGene, HomoloGene, ProtEST, dbMHC, dbSNP, Cancer Chromosomes, Entrez Genomes and related tools, the Map Viewer, Model Maker, Evidence Viewer, Clusters of Orthologous Groups (COGs), Retroviral Genotyping Tools, HIV-1/Human Protein Interaction Database, Gene Expression Omnibus (GEO), Entrez Probe, GENSAT, Online Mendelian Inheritance in Man (OMIM), Online Mendelian Inheritance in Animals (OMIA), the Molecular Modeling Database (MMDB), the Conserved Domain Database (CDD), the Conserved Domain Architecture Retrieval Tool (CDART) and the PubChem suite of small molecule databases. Augmenting many of the web applications is custom implementation of the BLAST program optimized to search specialized data sets. All of the resources can be accessed through the NCBI home page at www.ncbi.nlm.nih.gov.

Although many interactions between HIV-1 and human proteins have been reported in the scientific literature, no publicly accessible source for efficiently reviewing this information was available. Therefore, a project was initiated in an attempt to catalogue all published interactions between HIV-1 and human proteins. HIV-related articles in PubMed were used to develop a database containing names, Entrez GeneIDs, and RefSeq protein accession numbers of interacting proteins. Furthermore, brief descriptions of the interactions, PubMed identification numbers of articles describing the interactions, and keywords for searching the interactions were incorporated. Over 100,000 articles were reviewed, resulting in the identification of 1448 human proteins that interact with HIV-1 comprising 2589 unique HIV-1-to-human protein interactions. Preliminary analysis of the extracted data indicates 32% were direct physical interactions (e.g., binding) and 68% were indirect interactions (e.g., upregulation through activation of signaling pathways). Interestingly, 37% of human proteins in the database were found to interact with more than one HIV-1 protein. For example, the signaling protein mitogen-activated protein kinase 1 has a surprising range of interactions with 10 different HIV-1 proteins. Moreover, large numbers of interactions were published for the HIV-1 regulatory protein Tat and envelope proteins: 30% and 33% of total interactions identified, respectively. The database is accessible at http://www.ncbi.nlm.nih.gov/RefSeq/HIVInteractions/ and is cross-linked to other National Center for Biotechnology Information databases and programs via Entrez Gene. This database represents a unique and continuously updated scientific resource for understanding HIV-1 replication and pathogenesis to assist in accelerating the development of effective therapeutic and vaccine interventions.

In addition to maintaining the GenBank(R) nucleic acid sequence database, the National Center for Biotechnology Information (NCBI) provides analysis and retrieval resources for the data in GenBank and other biological data available through NCBI's web site. NCBI resources include Entrez, the Entrez Programming Utilities, My NCBI, PubMed, PubMed Central, Entrez Gene, the NCBI Taxonomy Browser, BLAST, BLAST Link, Electronic PCR, OrfFinder, Spidey, Splign, RefSeq, UniGene, HomoloGene, ProtEST, dbMHC, dbSNP, Cancer Chromosomes, Entrez Genome, Genome Project and related tools, the Trace, Assembly, and Short Read Archives, the Map Viewer, Model Maker, Evidence Viewer, Clusters of Orthologous Groups, Influenza Viral Resources, HIV-1/Human Protein Interaction Database, Gene Expression Omnibus, Entrez Probe, GENSAT, Database of Genotype and Phenotype, Online Mendelian Inheritance in Man, Online Mendelian Inheritance in Animals, the Molecular Modeling Database, the Conserved Domain Database, the Conserved Domain Architecture Retrieval Tool and the PubChem suite of small molecule databases. Augmenting the web applications are custom implementations of the BLAST program optimized to search specialized data sets. These resources can be accessed through the NCBI home page at www.ncbi.nlm.nih.gov.

NCBI's reference sequence (RefSeq) database (http://www.ncbi.nlm.nih.gov/RefSeq/) is a curated non-redundant collection of sequences representing genomes, transcripts and proteins. The database includes 3774 organisms spanning prokaryotes, eukaryotes and viruses, and has records for 2,879,860 proteins (RefSeq release 19). RefSeq records integrate information from multiple sources, when additional data are available from those sources and therefore represent a current description of the sequence and its features. Annotations include coding regions, conserved domains, tRNAs, sequence tagged sites (STS), variation, references, gene and protein product names, and database cross-references. Sequence is reviewed and features are added using a combined approach of collaboration and other input from the scientific community, prediction, propagation from GenBank and curation by NCBI staff. The format of all RefSeq records is validated, and an increasing number of tests are being applied to evaluate the quality of sequence and annotation, especially in the context of complete genomic sequence.

Entrez Gene (www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene) is NCBI's database for gene-specific information. Entrez Gene includes records from genomes that have been completely sequenced, that have an active research community to contribute gene-specific information or that are scheduled for intense sequence analysis. The content of Entrez Gene represents the result of both curation and automated integration of data from NCBI's Reference Sequence project (RefSeq), from collaborating model organism databases and from other databases within NCBI. Records in Entrez Gene are assigned unique, stable and tracked integers as identifiers. The content (nomenclature, map location, gene products and their attributes, markers, phenotypes and links to citations, sequences, variation details, maps, expression, homologs, protein domains and external databases) is provided via interactive browsing through NCBI's Entrez system, via NCBI's Entrez programing utilities (E-Utilities), and for bulk transfer by ftp.

In addition to maintaining the GenBank nucleic acid sequence database, the National Center for Biotechnology Information (NCBI) provides analysis and retrieval resources for the data in GenBank and other biological data made available through NCBI's Web site. NCBI resources include Entrez, the Entrez Programming Utilities, My NCBI, PubMed, PubMed Central, Entrez Gene, the NCBI Taxonomy Browser, BLAST, BLAST Link(BLink), Electronic PCR, OrfFinder, Spidey, Splign, RefSeq, UniGene, HomoloGene, ProtEST, dbMHC, dbSNP, Cancer Chromosomes, Entrez Genome, Genome Project and related tools, the Trace and Assembly Archives, the Map Viewer, Model Maker, Evidence Viewer, Clusters of Orthologous Groups (COGs), Viral Genotyping Tools, Influenza Viral Resources, HIV-1/Human Protein Interaction Database, Gene Expression Omnibus (GEO), Entrez Probe, GENSAT, Online Mendelian Inheritance in Man (OMIM), Online Mendelian Inheritance in Animals (OMIA), the Molecular Modeling Database (MMDB), the Conserved Domain Database (CDD), the Conserved Domain Architecture Retrieval Tool (CDART) and the PubChem suite of small molecule databases. Augmenting many of the Web applications are custom implementations of the BLAST program optimized to search specialized data sets. These resources can be accessed through the NCBI home page at www.ncbi.nlm.nih.gov.

In addition to maintaining the GenBank nucleic acid sequence database, the National Center for Biotechnology Information (NCBI) provides analysis and retrieval resources for the data in GenBank and other biological data made available through NCBI's Web site. NCBI resources include Entrez, the Entrez Programming Utilities, MyNCBI, PubMed, PubMed Central, Entrez Gene, the NCBI Taxonomy Browser, BLAST, BLAST Link (BLink), Electronic PCR, OrfFinder, Spidey, Splign, RefSeq, UniGene, HomoloGene, ProtEST, dbMHC, dbSNP, Cancer Chromosomes, Entrez Genomes and related tools, the Map Viewer, Model Maker, Evidence Viewer, Clusters of Orthologous Groups, Retroviral Genotyping Tools, HIV-1, Human Protein Interaction Database, SAGEmap, Gene Expression Omnibus, Entrez Probe, GENSAT, Online Mendelian Inheritance in Man, Online Mendelian Inheritance in Animals, the Molecular Modeling Database, the Conserved Domain Database, the Conserved Domain Architecture Retrieval Tool and the PubChem suite of small molecule databases. Augmenting many of the Web applications are custom implementations of the BLAST program optimized to search specialized datasets. All of the resources can be accessed through the NCBI home page at: http://www.ncbi.nlm.nih.gov.

In addition to maintaining the GenBank nucleic acid sequence database, the National Center for Biotechnology Information (NCBI) provides data retrieval systems and computational resources for the analysis of data in GenBank and other biological data made available through NCBI's website. NCBI resources include Entrez, Entrez Programming Utilities, PubMed, PubMed Central, Entrez Gene, the NCBI Taxonomy Browser, BLAST, BLAST Link (BLink), Electronic PCR, OrfFinder, Spidey, RefSeq, UniGene, HomoloGene, ProtEST, dbMHC, dbSNP, Cancer Chromosomes, Entrez Genomes and related tools, the Map Viewer, Model Maker, Evidence Viewer, Clusters of Orthologous Groups (COGs), Retroviral Genotyping Tools, HIV-1/Human Protein Interaction Database, SAGEmap, Gene Expression Omnibus (GEO), Online Mendelian Inheritance in Man (OMIM), the Molecular Modeling Database (MMDB), the Conserved Domain Database (CDD) and the Conserved Domain Architecture Retrieval Tool (CDART). Augmenting many of the Web applications are custom implementations of the BLAST program optimized to search specialized datasets. All of the resources can be accessed through the NCBI home page at http://www.ncbi.nlm.nih.gov.

Entrez Gene (www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene) is NCBI's database for gene-specific information. It does not include all known or predicted genes; instead Entrez Gene focuses on the genomes that have been completely sequenced, that have an active research community to contribute gene-specific information, or that are scheduled for intense sequence analysis. The content of Entrez Gene represents the result of curation and automated integration of data from NCBI's Reference Sequence project (RefSeq), from collaborating model organism databases, and from many other databases available from NCBI. Records are assigned unique, stable and tracked integers as identifiers. The content (nomenclature, map location, gene products and their attributes, markers, phenotypes, and links to citations, sequences, variation details, maps, expression, homologs, protein domains and external databases) is updated as new information becomes available. Entrez Gene is a step forward from NCBI's LocusLink, with both a major increase in taxonomic scope and improved access through the many tools associated with NCBI Entrez.

The National Center for Biotechnology Information (NCBI) Reference Sequence (RefSeq) database (http://www.ncbi.nlm.nih.gov/RefSeq/) provides a non-redundant collection of sequences representing genomic data, transcripts and proteins. Although the goal is to provide a comprehensive dataset representing the complete sequence information for any given species, the database pragmatically includes sequence data that are currently publicly available in the archival databases. The database incorporates data from over 2400 organisms and includes over one million proteins representing significant taxonomic diversity spanning prokaryotes, eukaryotes and viruses. Nucleotide and protein sequences are explicitly linked, and the sequences are linked to other resources including the NCBI Map Viewer and Gene. Sequences are annotated to include coding regions, conserved domains, variation, references, names, database cross-references, and other features using a combined approach of collaboration and other input from the scientific community, automated annotation, propagation from GenBank and curation by NCBI staff.

The goal of the NCBI Reference Sequence (RefSeq) project is to provide the single best non-redundant and comprehensive collection of naturally occurring biological molecules, representing the central dogma. Nucleotide and protein sequences are explicitly linked on a residue-by-residue basis in this collection. Ideally all molecule types will be available for each well-studied organism, but the initial database collection pragmatically includes only those molecules and organisms that are most readily identified. Thus different amounts of information are available for different organisms at any given time. Furthermore, for some organisms additional intermediate records are provided when the genome sequence is not yet finished. The collection is supplied by NCBI through three distinct pipelines in addition to collaborations with community groups. The collection is curated on an ongoing basis. Additional information about the NCBI RefSeq project is available at http://www.ncbi.nih.gov/RefSeq/.

Thousands of genes have been painstakingly identified and characterized a few genes at a time. Many thousands more are being predicted by large scale cDNA and genomic sequencing projects, with levels of evidence ranging from supporting mRNA sequence and comparative genomics to computing ab initio models. This, coupled with the burgeoning scientific literature, makes it critical to have a comprehensive directory for genes and reference sequences for key genomes. The NCBI provides two resources, LocusLink and RefSeq, to meet these needs. LocusLink organizes information around genes to generate a central hub for accessing gene-specific information for fruit fly, human, mouse, rat and zebrafish. RefSeq provides reference sequence standards for genomes, transcripts and proteins; human, mouse and rat mRNA RefSeqs, and their corresponding proteins, are discussed here. Together, RefSeq and LocusLink provide a non-redundant view of genes and other loci to support research on genes and gene families, variation, gene expression and genome annotation. Additional information about LocusLink and RefSeq is available at http://www.ncbi.nlm.nih.gov/LocusLink/.

The NCBI creates and maintains a set of integrated bibliographic, sequence, map, structure and other database resources to promote the efficient retrieval of information and the discovery of novel relationships. The connections made between elements of these resources permit researchers to start a search from a wide spectrum of entry points. These multiple dimensions of data can be roughly categorized by primary content as text or bibliographic (PubMed, PubMedCentral, OMIM, LocusLink), sequence (GenBank, Reference Sequence Project (RefSeq), dbSNP, MMDB), protein structure (MMDB) or map position (MapView). They can also becategorized by level of expert curation, which may range from validation of submissions from external groups (GenBank, PubMed, PubMedCentral,), to automatic computation (HomoloGene, UniGene), and to highly reviewed and corrected (LocusLink, MMDB, OMIM, RefSeq). Searches can be made by words (in an article title, key words, sequence annotation, database value, author) by sequence (BLAST or e-PCR against multiple sequence databases), or by map coordinates. By computing or curating bi-directional links between related objects, NCBI can represent content on the genetics, molecular biology, and clinical considerations of interest to immunogeneticists. There is also an emerging resource developed by the NCBI in collaboration with the IHWG devoted to the presentation of MHC data (dbMHC). How dbMHC will augment existing resources at the NCBI is described.

The NCBI has introduced two new web resources-LocusLink and RefSeq-that facilitate retrieval of gene-based information and provide reference sequence standards. These resources are designed to provide a non-redundant view of current knowledge about human genes, transcripts and proteins. Additional information about these resources is available on the LocusLink web site at http://www.ncbi.nlm.nih.gov/LocusLink/