Limits...
Splicing factor and exon profiling across human tissues.

de la Grange P, Gratadou L, Delord M, Dutertre M, Auboeuf D - Nucleic Acids Res. (2010)

Bottom Line: It has been shown that alternative splicing is especially prevalent in brain and testis when compared to other tissues.To test whether there is a specific propensity of these tissues to generate splicing variants, we used a single source of high-density microarray data to perform both splicing factor and exon expression profiling across 11 normal human tissues.In addition to providing a unique resource on expression profiling of alternative splicing variants and splicing factors across human tissues, this study demonstrates that the higher prevalence of alternative splicing in a subset of tissues originates from the larger number of genes, including splicing factors, being expressed than in other tissues.

View Article: PubMed Central - PubMed

Affiliation: GenoSplice technology, Centre Hayem, Hôpital Saint-Louis, 1 avenue Claude Vellefaux, 75010, Paris, France. didier.auboeuf@inserm.fr

ABSTRACT
It has been shown that alternative splicing is especially prevalent in brain and testis when compared to other tissues. To test whether there is a specific propensity of these tissues to generate splicing variants, we used a single source of high-density microarray data to perform both splicing factor and exon expression profiling across 11 normal human tissues. Paired comparisons between tissues and an original exon-based statistical group analysis demonstrated after extensive RT-PCR validation that the cerebellum, testis, and spleen had the largest proportion of differentially expressed alternative exons. Variations at the exon level correlated with a larger number of splicing factors being expressed at a high level in the cerebellum, testis and spleen than in other tissues. However, this splicing factor expression profile was similar to a more global gene expression pattern as a larger number of genes had a high expression level in the cerebellum, testis and spleen. In addition to providing a unique resource on expression profiling of alternative splicing variants and splicing factors across human tissues, this study demonstrates that the higher prevalence of alternative splicing in a subset of tissues originates from the larger number of genes, including splicing factors, being expressed than in other tissues.

Show MeSH

Related in: MedlinePlus

Identification of differentially expressed exons by group comparison. (A) Number of differentially expressed exons and number of corresponding genes identified by a group comparison. Tissue ranking was done depending on the number of differentially expressed exons associated with each tissue. (B) Proportion of differentially expressed exons identified for each tissue. The number of differentially expressed exons associated with each tissue was divided by the total number of differentially expressed exons identified by a group comparison. (C) Non-supervised hierarchical clustering of gene-normalized exon intensities. Differentially regulated exons across 11 tissues were hierarchically clustered based on their gene-normalized exon intensity. Color scale representing gene-normalized exon intensity is shown below the clustergram. (D) Proportion of ‘splicing index’ fold-changes that were up or down in the tissue group comparison. ‘Splicing index’ values corresponding to the exons identified in the statistical group comparison for each individual tissue were either up (preferentially included) or down (preferentially excluded).
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2875023&req=5

Figure 2: Identification of differentially expressed exons by group comparison. (A) Number of differentially expressed exons and number of corresponding genes identified by a group comparison. Tissue ranking was done depending on the number of differentially expressed exons associated with each tissue. (B) Proportion of differentially expressed exons identified for each tissue. The number of differentially expressed exons associated with each tissue was divided by the total number of differentially expressed exons identified by a group comparison. (C) Non-supervised hierarchical clustering of gene-normalized exon intensities. Differentially regulated exons across 11 tissues were hierarchically clustered based on their gene-normalized exon intensity. Color scale representing gene-normalized exon intensity is shown below the clustergram. (D) Proportion of ‘splicing index’ fold-changes that were up or down in the tissue group comparison. ‘Splicing index’ values corresponding to the exons identified in the statistical group comparison for each individual tissue were either up (preferentially included) or down (preferentially excluded).

Mentions: While paired comparisons of tissues identified exons that were differentially expressed between two tissues, they did not allow to determine which tissue or group of tissues specifically expressed a given splicing variant. For that purpose, we compared the exon content of the products of each human gene by considering all the tissues where the gene was expressed in order to identify alternative exons specific to tissues. An exon-based statistical group analysis was performed using the ‘gene-normalized exon intensity’ value that corresponded to the exon expression level relative to the gene expression level as described in ‘Materials and methods’ section and in Supplementary Figure S1. Using this strategy, 1073 unique exons corresponding to 653 unique genes were associated with individual tissues or a group of tissues (including no more than five tissues within a group). Exons found in a group of tissues were then associated with each individual tissue of the group. Between 33 and 349 differentially expressed exons were associated with each tissue as indicated on Figure 2A. The list of the genes containing exons that were differentially expressed in specific tissues is given in Supplementary Table S3, which provides a unique resource of exons being differentially expressed in a tissue-specific manner.Figure 2.


Splicing factor and exon profiling across human tissues.

de la Grange P, Gratadou L, Delord M, Dutertre M, Auboeuf D - Nucleic Acids Res. (2010)

Identification of differentially expressed exons by group comparison. (A) Number of differentially expressed exons and number of corresponding genes identified by a group comparison. Tissue ranking was done depending on the number of differentially expressed exons associated with each tissue. (B) Proportion of differentially expressed exons identified for each tissue. The number of differentially expressed exons associated with each tissue was divided by the total number of differentially expressed exons identified by a group comparison. (C) Non-supervised hierarchical clustering of gene-normalized exon intensities. Differentially regulated exons across 11 tissues were hierarchically clustered based on their gene-normalized exon intensity. Color scale representing gene-normalized exon intensity is shown below the clustergram. (D) Proportion of ‘splicing index’ fold-changes that were up or down in the tissue group comparison. ‘Splicing index’ values corresponding to the exons identified in the statistical group comparison for each individual tissue were either up (preferentially included) or down (preferentially excluded).
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2875023&req=5

Figure 2: Identification of differentially expressed exons by group comparison. (A) Number of differentially expressed exons and number of corresponding genes identified by a group comparison. Tissue ranking was done depending on the number of differentially expressed exons associated with each tissue. (B) Proportion of differentially expressed exons identified for each tissue. The number of differentially expressed exons associated with each tissue was divided by the total number of differentially expressed exons identified by a group comparison. (C) Non-supervised hierarchical clustering of gene-normalized exon intensities. Differentially regulated exons across 11 tissues were hierarchically clustered based on their gene-normalized exon intensity. Color scale representing gene-normalized exon intensity is shown below the clustergram. (D) Proportion of ‘splicing index’ fold-changes that were up or down in the tissue group comparison. ‘Splicing index’ values corresponding to the exons identified in the statistical group comparison for each individual tissue were either up (preferentially included) or down (preferentially excluded).
Mentions: While paired comparisons of tissues identified exons that were differentially expressed between two tissues, they did not allow to determine which tissue or group of tissues specifically expressed a given splicing variant. For that purpose, we compared the exon content of the products of each human gene by considering all the tissues where the gene was expressed in order to identify alternative exons specific to tissues. An exon-based statistical group analysis was performed using the ‘gene-normalized exon intensity’ value that corresponded to the exon expression level relative to the gene expression level as described in ‘Materials and methods’ section and in Supplementary Figure S1. Using this strategy, 1073 unique exons corresponding to 653 unique genes were associated with individual tissues or a group of tissues (including no more than five tissues within a group). Exons found in a group of tissues were then associated with each individual tissue of the group. Between 33 and 349 differentially expressed exons were associated with each tissue as indicated on Figure 2A. The list of the genes containing exons that were differentially expressed in specific tissues is given in Supplementary Table S3, which provides a unique resource of exons being differentially expressed in a tissue-specific manner.Figure 2.

Bottom Line: It has been shown that alternative splicing is especially prevalent in brain and testis when compared to other tissues.To test whether there is a specific propensity of these tissues to generate splicing variants, we used a single source of high-density microarray data to perform both splicing factor and exon expression profiling across 11 normal human tissues.In addition to providing a unique resource on expression profiling of alternative splicing variants and splicing factors across human tissues, this study demonstrates that the higher prevalence of alternative splicing in a subset of tissues originates from the larger number of genes, including splicing factors, being expressed than in other tissues.

View Article: PubMed Central - PubMed

Affiliation: GenoSplice technology, Centre Hayem, Hôpital Saint-Louis, 1 avenue Claude Vellefaux, 75010, Paris, France. didier.auboeuf@inserm.fr

ABSTRACT
It has been shown that alternative splicing is especially prevalent in brain and testis when compared to other tissues. To test whether there is a specific propensity of these tissues to generate splicing variants, we used a single source of high-density microarray data to perform both splicing factor and exon expression profiling across 11 normal human tissues. Paired comparisons between tissues and an original exon-based statistical group analysis demonstrated after extensive RT-PCR validation that the cerebellum, testis, and spleen had the largest proportion of differentially expressed alternative exons. Variations at the exon level correlated with a larger number of splicing factors being expressed at a high level in the cerebellum, testis and spleen than in other tissues. However, this splicing factor expression profile was similar to a more global gene expression pattern as a larger number of genes had a high expression level in the cerebellum, testis and spleen. In addition to providing a unique resource on expression profiling of alternative splicing variants and splicing factors across human tissues, this study demonstrates that the higher prevalence of alternative splicing in a subset of tissues originates from the larger number of genes, including splicing factors, being expressed than in other tissues.

Show MeSH
Related in: MedlinePlus