Expression and splicing mediate distinct biological signals
Abstract Background Through alternative splicing, most human genes produce multiple isoforms in a cell-, tissue-, and disease-specific manner. Numerous studies show that alternative splicing is essential for development, diseases, and their treatments. Despite these important examples, the extent an...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-10-01
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| Series: | BMC Biology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12915-023-01724-w |
| _version_ | 1797451475813662720 |
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| author | Søren Helweg Dam Lars Rønn Olsen Kristoffer Vitting-Seerup |
| author_facet | Søren Helweg Dam Lars Rønn Olsen Kristoffer Vitting-Seerup |
| author_sort | Søren Helweg Dam |
| collection | DOAJ |
| description | Abstract Background Through alternative splicing, most human genes produce multiple isoforms in a cell-, tissue-, and disease-specific manner. Numerous studies show that alternative splicing is essential for development, diseases, and their treatments. Despite these important examples, the extent and biological relevance of splicing are currently unknown. Results To solve this problem, we developed pairedGSEA and used it to profile transcriptional changes in 100 representative RNA-seq datasets. Our systematic analysis demonstrates that changes in splicing, on average, contribute to 48.1% of the biological signal in expression analyses. Gene-set enrichment analysis furthermore indicates that expression and splicing both convey shared and distinct biological signals. Conclusions These findings establish alternative splicing as a major regulator of the human condition and suggest that most contemporary RNA-seq studies likely miss out on critical biological insights. We anticipate our results will contribute to the transition from a gene-centric to an isoform-centric research paradigm. |
| first_indexed | 2024-03-09T14:55:12Z |
| format | Article |
| id | doaj.art-672214d891ac4b0d9ea1b70e8924af38 |
| institution | Directory Open Access Journal |
| issn | 1741-7007 |
| language | English |
| last_indexed | 2024-03-09T14:55:12Z |
| publishDate | 2023-10-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Biology |
| spelling | doaj.art-672214d891ac4b0d9ea1b70e8924af382023-11-26T14:14:09ZengBMCBMC Biology1741-70072023-10-0121111010.1186/s12915-023-01724-wExpression and splicing mediate distinct biological signalsSøren Helweg Dam0Lars Rønn Olsen1Kristoffer Vitting-Seerup2Section for Bioinformatics, Department of Health Technology, Technical University of DenmarkSection for Bioinformatics, Department of Health Technology, Technical University of DenmarkSection for Bioinformatics, Department of Health Technology, Technical University of DenmarkAbstract Background Through alternative splicing, most human genes produce multiple isoforms in a cell-, tissue-, and disease-specific manner. Numerous studies show that alternative splicing is essential for development, diseases, and their treatments. Despite these important examples, the extent and biological relevance of splicing are currently unknown. Results To solve this problem, we developed pairedGSEA and used it to profile transcriptional changes in 100 representative RNA-seq datasets. Our systematic analysis demonstrates that changes in splicing, on average, contribute to 48.1% of the biological signal in expression analyses. Gene-set enrichment analysis furthermore indicates that expression and splicing both convey shared and distinct biological signals. Conclusions These findings establish alternative splicing as a major regulator of the human condition and suggest that most contemporary RNA-seq studies likely miss out on critical biological insights. We anticipate our results will contribute to the transition from a gene-centric to an isoform-centric research paradigm.https://doi.org/10.1186/s12915-023-01724-wAlternative splicingIsoformIsoform expressionGene expressionRNA-sequencingRNA-seq |
| spellingShingle | Søren Helweg Dam Lars Rønn Olsen Kristoffer Vitting-Seerup Expression and splicing mediate distinct biological signals BMC Biology Alternative splicing Isoform Isoform expression Gene expression RNA-sequencing RNA-seq |
| title | Expression and splicing mediate distinct biological signals |
| title_full | Expression and splicing mediate distinct biological signals |
| title_fullStr | Expression and splicing mediate distinct biological signals |
| title_full_unstemmed | Expression and splicing mediate distinct biological signals |
| title_short | Expression and splicing mediate distinct biological signals |
| title_sort | expression and splicing mediate distinct biological signals |
| topic | Alternative splicing Isoform Isoform expression Gene expression RNA-sequencing RNA-seq |
| url | https://doi.org/10.1186/s12915-023-01724-w |
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