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- Imanishi, T., et al.
(författare)
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Integrative annotation of 21,037 human genes validated by full-length cDNA clones
- 2004
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Ingår i: PLoS biology. - : Public Library of Science (PLoS). - 1544-9173 .- 1545-7885. ; 2:6, s. 856-875
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Tidskriftsartikel (refereegranskat)abstract
- The human genome sequence defines our inherent biological potential; the realization of the biology encoded therein requires knowledge of the function of each gene. Currently, our knowledge in this area is still limited. Several lines of investigation have been used to elucidate the structure and function of the genes in the human genome. Even so, gene prediction remains a difficult task, as the varieties of transcripts of a gene may vary to a great extent. We thus performed an exhaustive integrative characterization of 41,118 full-length cDNAs that capture the gene transcripts as complete functional cassettes, providing an unequivocal report of structural and functional diversity at the gene level. Our international collaboration has validated 21,037 human gene candidates by analysis of high-quality full-length cDNA clones through curation using unified criteria. This led to the identification of 5,155 new gene candidates. It also manifested the most reliable way to control the quality of the cDNA clones. We have developed a human gene database, called the H-Invitational Database (H-InvDB; http://www.h-invitational.jp/). It provides the following: integrative annotation of human genes, description of gene structures, details of novel alternative splicing isoforms, non-protein-coding RNAs, functional domains, subcellular localizations, metabolic pathways, predictions of protein three-dimensional structure, mapping of known single nucleotide polymorphisms (SNPs), identification of polymorphic microsatellite repeats within human genes, and comparative results with mouse full-length cDNAs. The H-InvDB analysis has shown that up to 4% of the human genome sequence (National Center for Biotechnology Information build 34 assembly) may contain misassembled or missing regions. We found that 6.5% of the human gene candidates (1,377 loci) did not have a good protein-coding open reading frame, of which 296 loci are strong candidates for non-protein-coding RNA genes. In addition, among 72,027 uniquely mapped SNPs and insertions/deletions localized within human genes, 13,215 nonsynonymous SNPs, 315 nonsense SNPs, and 452 indels occurred in coding regions. Together with 25 polymorphic microsatellite repeats present in coding regions, they may alter protein structure, causing phenotypic effects or resulting in disease. The H-InvDB platform represents a substantial contribution to resources needed for the exploration of human biology and pathology.
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| 3. |
- Alkema, WBL, et al.
(författare)
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Regulog analysis: detection of conserved regulatory networks across bacteria: application to Staphylococcus aureus
- 2004
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Ingår i: Genome research. - : Cold Spring Harbor Laboratory. - 1088-9051. ; 14:7, s. 1362-1373
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Tidskriftsartikel (refereegranskat)abstract
- A transcriptional regulatory network encompasses sets of genes (regulons) whose expression states are directly altered in response to an activating signal, mediated by trans-acting regulatory proteins and cis-acting regulatory sequences. Enumeration of these network components is an essential step toward the creation of a framework for systems-based analysis of biological processes. Profile-based methods for the detection of cis-regulatory elements are often applied to predict regulon members, but they suffer from poor specificity. In this report we describe Regulogger, a novel computational method that uses comparative genomics to eliminate spurious members of predicted gene regulons. Regulogger produces regulogs, sets of coregulated genes for which the regulatory sequence has been conserved across multiple organisms. The quantitative method assigns a confidence score to each predicted regulog member on the basis of the degree of conservation of protein sequence and regulatory mechanisms. When applied to a reference collection of regulons from Escherichia coli, Regulogger increased the specificity of predictions up to 25-fold over methods that use cis-element detection in isolation. The enhanced specificity was observed across a wide range of biologically meaningful parameter combinations, indicating a robust and broad utility for the method. The power of computational pattern discovery methods coupled with Regulogger to unravel transcriptional networks was demonstrated in an analysis of the genome of Staphylococcus aureus. A total of 125 regulogs were found in this organism, including both well-defined functional groups and a subset with unknown functions.
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| 5. |
- Kemmer, D., et al.
(författare)
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Exploring the foundation of genomics : a Northern blot reference set for the comparative analysis of transcript profiling technologies
- 2004
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Ingår i: Comparative and functional genomics. - : Hindawi Limited. - 1531-6912 .- 1532-6268. ; 5:8, s. 584-595
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Tidskriftsartikel (refereegranskat)abstract
- In this paper we aim to create a reference data collection of Northern blot results and demonstrate how such a collection can enable a quantitative comparison of modern expression profiling techniques, a central component of functional genomics studies. Historic ally, Northern blots were the de facto standard for determining RNA transcript levels. However, driven by the demand for analysis of large sets of genes in parallel, high-throughput methods, such as microarrays, dominate modern profiling efforts. To facilitate assessment of these methods, in comparison to Northern blots, we created a database of published Northern results obtained with a standardized commercial multiple tissue blot (dbMTN). In order to demonstrate the utility of the dbMTN collection for technology comparison, we also generated expression profiles for genes across a set of human tissues, using multiple profiling techniques. No method produced profiles that were strongly correlated with the Northern blot data. The highest correlations to the Northern blot data were determined with microarrays for the subset of genes observed to be specifically expressed in a single tissue in the Northern analyses. The database and expression profiling data are available via the project website (http://www.cisreg.ca). We believe that emphasis on multitechnique validation of expression profiles is justified, as the correlation results between platforms are not encouraging on the whole. Supplementary material for this article can be found at: http://www.interscience.wiley.com/jpages/1531-6912/suppmat
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| 6. |
- Lenhard, B, et al.
(författare)
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GeneLynx: a gene-centric portal to the human genome
- 2001
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Ingår i: Genome research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 11:12, s. 2151-2157
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Tidskriftsartikel (refereegranskat)abstract
- GeneLynx is a meta-database providing an extensive collection of hyperlinks to human gene-specific information in diverse databases available on the Internet. The GeneLynx project is based on the simple notion that given any gene-specific identifier (accession number, gene name, text, or sequence), scientists should be able to access a single location that provides a set of links to all the publicly available information pertinent to the specified human gene. GeneLynx was implemented as an extensible relational database with an intuitive and user-friendly Web interface. The data are automatically extracted from more than 40 external resources, using appropriate approaches to maximize coverage of the available data. Construction and curation of the system is mediated by a custom set of software tools. An indexing utility is provided to facilitate the establishment of hyperlinks in external databases. A unique feature of the GeneLynx system is a communal curation system for user-aided annotation. GeneLynx can be accessed freely at http://www.genelynx.org.
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| 7. |
- Lenhard, B, et al.
(författare)
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GeneLynx mouse: integrated portal to the mouse genome
- 2003
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Ingår i: Genome research. - : Cold Spring Harbor Laboratory. - 1088-9051. ; 13:6B, s. 1501-1504
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Tidskriftsartikel (refereegranskat)abstract
- GeneLynx Mouse is a meta-database providing an extensive collection of hyperlinks to mouse gene-specific information in diverse databases available via the Internet. The GeneLynx project is based on the simple notion that given any gene-specific identifier (e.g., accession number, gene name, text, or sequence), scientists should be able to access a single location that provides a set of links to all the publicly available information pertinent to the specified gene. The recent climax in the mouse genome and RIKEN cDNA sequencing projects provided the data necessary for the development of a gene-centric mouse information portal based on the GeneLynx ideals. Clusters of RIKEN cDNA sequences were used to define the initial set of mouse genes. Like its human counterpart, GeneLynx Mouse is designed as an extensible relational database with an intuitive and user-friendly Web interface. Data is automatically extracted from diverse resources, using appropriate approaches to maximize the coverage. To promote cross-database interoperability, an indexing utility is provided to facilitate the establishment of hyperlinks in external databases. As a result of the integration of the human and mouse systems, GeneLynx now serves as a powerful comparative genomics data mining resource. GeneLynx Mouse can be freely accessed at http://mouse.genelynx.org.
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