Dataset Information

ExTraMapper: exon- and transcript-level mappings for orthologous gene pairs.

ABSTRACT:

Motivation

Access to large-scale genomics and transcriptomics data from various tissues and cell lines allowed the discovery of wide-spread alternative splicing events and alternative promoter usage in mammalians. Between human and mouse, gene-level orthology is currently present for nearly 16k protein-coding genes spanning a diverse repertoire of over 200k total transcript isoforms.

Results

Here, we describe a novel method, ExTraMapper, which leverages sequence conservation between exons of a pair of organisms and identifies a fine-scale orthology mapping at the exon and then transcript level. ExTraMapper identifies more than 350k exon mappings, as well as 30k transcript mappings between human and mouse using only sequence and gene annotation information. We demonstrate that ExTraMapper identifies a larger number of exon and transcript mappings compared to previous methods. Further, it identifies exon fusions, splits and losses due to splice site mutations, and finds mappings between microexons that are previously missed. By reanalysis of RNA-seq data from 13 matched human and mouse tissues, we show that ExTraMapper improves the correlation of transcript-specific expression levels suggesting a more accurate mapping of human and mouse transcripts. We also applied the method to detect conserved exon and transcript pairs between human and rhesus macaque genomes to highlight the point that ExTraMapper is applicable to any pair of organisms that have orthologous gene pairs.

Availability and implementation

The source code and the results are available at https://github.com/ay-lab/ExTraMapper and http://ay-lab-tools.lji.org/extramapper.

Supplementary information

Supplementary data are available at Bioinformatics online.

SUBMITTER: Chakraborty A

PROVIDER: S-EPMC8545320 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Publications

ExTraMapper: exon- and transcript-level mappings for orthologous gene pairs.

Chakraborty Abhijit A Ay Ferhat F Davuluri Ramana V RV

Bioinformatics (Oxford, England) 20211001 20

<h4>Motivation</h4>Access to large-scale genomics and transcriptomics data from various tissues and cell lines allowed the discovery of wide-spread alternative splicing events and alternative promoter usage in mammalians. Between human and mouse, gene-level orthology is currently present for nearly 16k protein-coding genes spanning a diverse repertoire of over 200k total transcript isoforms.<h4>Results</h4>Here, we describe a novel method, ExTraMapper, which leverages sequence conservation betwe ...[more]

PMID: 34014317

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Project description:BackgroundAntisense oligonucleotides (AOs) can interfere with exon recognition and intron removal during pre-mRNA processing, and induce excision of a targeted exon from the mature gene transcript. AOs have been used in vitro and in vivo to redirect dystrophin pre-mRNA processing in human and animal cells. Targeted exon skipping of selected exons in the dystrophin gene transcript can remove nonsense or frame-shifting mutations that would otherwise have lead to Duchenne Muscular Dystrophy, the most common childhood form of muscle wasting.ResultsAlthough many dystrophin exons can be excised using a single AO, several exons require two motifs to be masked for efficient or specific exon skipping. Some AOs were inactive when applied individually, yet pronounced exon excision was induced in transfected cells when the AOs were used in select combinations, clearly indicating synergistic rather than cumulative effects on splicing. The necessity for AO cocktails to induce efficient exon removal was observed with 2 different chemistries, 2'-O-methyl modified bases on a phosphorothioate backbone and phosphorodiamidate morpholino oligomers. Similarly, other trends in exon skipping, as a consequence of 2'-O-methyl AO action, such as removal of additional flanking exons or variations in exon skipping efficiency with overlapping AOs, were also seen when the corresponding sequences were prepared as phosphorodiamidate morpholino oligomers.ConclusionThe combination of 2 AOs, directed at appropriate motifs in target exons was found to induce very efficient targeted exon skipping during processing of the dystrophin pre-mRNA. This combinatorial effect is clearly synergistic and is not influenced by the chemistry of the AOs used to induce exon excision. A hierarchy in exon skipping efficiency, observed with overlapping AOs composed of 2'-O-methyl modified bases, was also observed when these same sequences were evaluated as phosphorodiamidate morpholino oligomers, indicating design parameters established with one chemistry may be applied to the other.

Dataset Information

ExTraMapper: exon- and transcript-level mappings for orthologous gene pairs.

Motivation

Results

Availability and implementation

Supplementary information

Publications

ExTraMapper: exon- and transcript-level mappings for orthologous gene pairs.

Similar Datasets

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