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A new advance in alternative splicing databases: from catalogue to detailed analysis of regulation of expression and function of human alternative splicing variants.

de la Grange P, Dutertre M, Correa M, Auboeuf D - BMC Bioinformatics (2007)

Bottom Line: Nevertheless, owing to the diversity of the transcriptome, there is a need for interactive databases that provide information about the potential function of each splicing variant, as well as its expression pattern.Importantly, analyses of all features from transcript metabolism to functional protein domains were integrated in a highly interactive, user-friendly web interface that allows the functional and regulatory features of gene transcripts to be assessed rapidly and accurately.Because gene expression studies are increasingly employed in clinical analyses, our web interface has been designed to be as user-friendly as possible and to be readily searchable and intelligible at a glance by the whole biomedical community.

View Article: PubMed Central - HTML - PubMed

Affiliation: INSERM U685/AVENIR, Centre G. Hayem, Hôpital Saint-Louis, Paris, France. delagrange@stlouis.inserm.fr <delagrange@stlouis.inserm.fr>

ABSTRACT

Background: Most human genes produce several transcripts with different exon contents by using alternative promoters, alternative polyadenylation sites and alternative splice sites. Much effort has been devoted to describing known gene transcripts through the development of numerous databases. Nevertheless, owing to the diversity of the transcriptome, there is a need for interactive databases that provide information about the potential function of each splicing variant, as well as its expression pattern.

Description: After setting up a database in which human and mouse splicing variants were compiled, we developed tools (1) to predict the production of protein isoforms from these transcripts, taking account of the presence of open reading frames and mechanisms that could potentially eliminate transcripts and/or inhibit their translation, i.e. nonsense-mediated mRNA decay and microRNAs; (2) to support studies of the regulation of transcript expression at multiple levels, including transcription and splicing, particularly in terms of tissue specificity; and (3) to assist in experimental analysis of the expression of splicing variants. Importantly, analyses of all features from transcript metabolism to functional protein domains were integrated in a highly interactive, user-friendly web interface that allows the functional and regulatory features of gene transcripts to be assessed rapidly and accurately.

Conclusion: In addition to identifying the transcripts produced by human and mouse genes, fast DB http://www.fast-db.com provides tools for analyzing the putative functions of these transcripts and the regulation of their expression. Therefore, fast DB has achieved an advance in alternative splicing databases by providing resources for the functional interpretation of splicing variants for the human and mouse genomes. Because gene expression studies are increasingly employed in clinical analyses, our web interface has been designed to be as user-friendly as possible and to be readily searchable and intelligible at a glance by the whole biomedical community.

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The fast DB search pages. (A) The fast DB basic search page. (1) Keyword search; (2) Blast search; (3) checkbox to align an input sequence with a graphical representation of the exon/intron gene structure; (4) multiple-queries search: the user can upload a file with a stable gene EnsEMBL ID at each line. (B) The fast DB advanced search page. (1) Minimal and maximal length selection in base pairs; (2) selection of minimal and maximal number of exons; (3) selection of minimal and maximal number of cDNAs; (4) chromosome selection; (5) chromosome strand selection; (6) alternative transcriptional and splicing event selection; (7) NMD pathway targeting prediction selection.
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Figure 1: The fast DB search pages. (A) The fast DB basic search page. (1) Keyword search; (2) Blast search; (3) checkbox to align an input sequence with a graphical representation of the exon/intron gene structure; (4) multiple-queries search: the user can upload a file with a stable gene EnsEMBL ID at each line. (B) The fast DB advanced search page. (1) Minimal and maximal length selection in base pairs; (2) selection of minimal and maximal number of exons; (3) selection of minimal and maximal number of cDNAs; (4) chromosome selection; (5) chromosome strand selection; (6) alternative transcriptional and splicing event selection; (7) NMD pathway targeting prediction selection.

Mentions: Fast DB can be searched using various criteria such as gene, transcript or protein IDs, keywords, and chromosomal location (Figure 1A, item 1). A blast search is available (Figure 1A, item 2), and a list of genes can also be retrieved by uploading a file gathering the stable EnsEMBL ID of these genes (Figure 1A, item 4 and see the fast DB documentation). A list of genes with similar characteristics can also be retrieved using the fast DB advanced search page (Figure 1B). The criteria available for gene selection include gene length (Figure 1B, item 1), number of exons (Figure 1B, item 2), number of transcripts (Figure 1B, item 3), chromosomal location (Figure 1B, items 4 and 5), type of AS event (Figure 1B, item 6), and NMD-targeted transcript prediction (Figure 1B, item 7). After a specific gene is selected, its main page presents its exon/intron structure and general information regarding splicing of its transcripts [4]. From there, three kinds of analyses are available, based on human mRNAs, human mRNAs and ESTs, and mouse mRNAs. After choosing one option, the user can click on the "transcripts view" button. The "transcripts view" page (Figure 2) provides a diagram of the exon/intron structure of the gene (Figure 2, item 1) and the exon content of its transcripts (Figure 2, items 2), with AS events in red (Figure 2, items 3).


A new advance in alternative splicing databases: from catalogue to detailed analysis of regulation of expression and function of human alternative splicing variants.

de la Grange P, Dutertre M, Correa M, Auboeuf D - BMC Bioinformatics (2007)

The fast DB search pages. (A) The fast DB basic search page. (1) Keyword search; (2) Blast search; (3) checkbox to align an input sequence with a graphical representation of the exon/intron gene structure; (4) multiple-queries search: the user can upload a file with a stable gene EnsEMBL ID at each line. (B) The fast DB advanced search page. (1) Minimal and maximal length selection in base pairs; (2) selection of minimal and maximal number of exons; (3) selection of minimal and maximal number of cDNAs; (4) chromosome selection; (5) chromosome strand selection; (6) alternative transcriptional and splicing event selection; (7) NMD pathway targeting prediction selection.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC1904244&req=5

Figure 1: The fast DB search pages. (A) The fast DB basic search page. (1) Keyword search; (2) Blast search; (3) checkbox to align an input sequence with a graphical representation of the exon/intron gene structure; (4) multiple-queries search: the user can upload a file with a stable gene EnsEMBL ID at each line. (B) The fast DB advanced search page. (1) Minimal and maximal length selection in base pairs; (2) selection of minimal and maximal number of exons; (3) selection of minimal and maximal number of cDNAs; (4) chromosome selection; (5) chromosome strand selection; (6) alternative transcriptional and splicing event selection; (7) NMD pathway targeting prediction selection.
Mentions: Fast DB can be searched using various criteria such as gene, transcript or protein IDs, keywords, and chromosomal location (Figure 1A, item 1). A blast search is available (Figure 1A, item 2), and a list of genes can also be retrieved by uploading a file gathering the stable EnsEMBL ID of these genes (Figure 1A, item 4 and see the fast DB documentation). A list of genes with similar characteristics can also be retrieved using the fast DB advanced search page (Figure 1B). The criteria available for gene selection include gene length (Figure 1B, item 1), number of exons (Figure 1B, item 2), number of transcripts (Figure 1B, item 3), chromosomal location (Figure 1B, items 4 and 5), type of AS event (Figure 1B, item 6), and NMD-targeted transcript prediction (Figure 1B, item 7). After a specific gene is selected, its main page presents its exon/intron structure and general information regarding splicing of its transcripts [4]. From there, three kinds of analyses are available, based on human mRNAs, human mRNAs and ESTs, and mouse mRNAs. After choosing one option, the user can click on the "transcripts view" button. The "transcripts view" page (Figure 2) provides a diagram of the exon/intron structure of the gene (Figure 2, item 1) and the exon content of its transcripts (Figure 2, items 2), with AS events in red (Figure 2, items 3).

Bottom Line: Nevertheless, owing to the diversity of the transcriptome, there is a need for interactive databases that provide information about the potential function of each splicing variant, as well as its expression pattern.Importantly, analyses of all features from transcript metabolism to functional protein domains were integrated in a highly interactive, user-friendly web interface that allows the functional and regulatory features of gene transcripts to be assessed rapidly and accurately.Because gene expression studies are increasingly employed in clinical analyses, our web interface has been designed to be as user-friendly as possible and to be readily searchable and intelligible at a glance by the whole biomedical community.

View Article: PubMed Central - HTML - PubMed

Affiliation: INSERM U685/AVENIR, Centre G. Hayem, Hôpital Saint-Louis, Paris, France. delagrange@stlouis.inserm.fr <delagrange@stlouis.inserm.fr>

ABSTRACT

Background: Most human genes produce several transcripts with different exon contents by using alternative promoters, alternative polyadenylation sites and alternative splice sites. Much effort has been devoted to describing known gene transcripts through the development of numerous databases. Nevertheless, owing to the diversity of the transcriptome, there is a need for interactive databases that provide information about the potential function of each splicing variant, as well as its expression pattern.

Description: After setting up a database in which human and mouse splicing variants were compiled, we developed tools (1) to predict the production of protein isoforms from these transcripts, taking account of the presence of open reading frames and mechanisms that could potentially eliminate transcripts and/or inhibit their translation, i.e. nonsense-mediated mRNA decay and microRNAs; (2) to support studies of the regulation of transcript expression at multiple levels, including transcription and splicing, particularly in terms of tissue specificity; and (3) to assist in experimental analysis of the expression of splicing variants. Importantly, analyses of all features from transcript metabolism to functional protein domains were integrated in a highly interactive, user-friendly web interface that allows the functional and regulatory features of gene transcripts to be assessed rapidly and accurately.

Conclusion: In addition to identifying the transcripts produced by human and mouse genes, fast DB http://www.fast-db.com provides tools for analyzing the putative functions of these transcripts and the regulation of their expression. Therefore, fast DB has achieved an advance in alternative splicing databases by providing resources for the functional interpretation of splicing variants for the human and mouse genomes. Because gene expression studies are increasingly employed in clinical analyses, our web interface has been designed to be as user-friendly as possible and to be readily searchable and intelligible at a glance by the whole biomedical community.

Show MeSH
Related in: MedlinePlus