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

Area of Science:

• Comparative genomics
• Transcriptomics
• Bioinformatics

Background:

• Mammalian genomics reveals widespread alternative splicing and promoter usage.
• Over 200,000 transcript isoforms exist across nearly 16,000 protein-coding genes between humans and mice.
• Accurate cross-species transcript mapping is crucial for understanding conserved biological functions.

Purpose of the Study:

• To develop a novel method for fine-scale orthology mapping at the exon and transcript level between species.
• To improve the accuracy and comprehensiveness of cross-species transcript mapping compared to existing methods.

Main Methods:

• ExTraMapper leverages sequence conservation between exons of orthologous genes.
• It identifies exon and transcript mappings using only sequence and gene annotation data.
• The method was applied to human-mouse and human-macaque genome comparisons.

Main Results:

• ExTraMapper identified over 350,000 exon mappings and 30,000 transcript mappings between human and mouse.
• The method detected more mappings than previous approaches, including those involving microexons, exon fusions, splits, and losses.
• Reanalysis of RNA-seq data showed improved correlation of transcript-specific expression levels, indicating more accurate mapping.

Conclusions:

• ExTraMapper provides a more accurate and detailed orthology mapping at the exon and transcript level.
• The method enhances the analysis of cross-species transcriptomic data and aids in discovering conserved genomic elements.
• ExTraMapper is broadly applicable to any pair of organisms with orthologous gene pairs.