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Detection and analysis of spliced chimeric mRNAs in sequence databanks
Antonello Romani1, Emanuela Guerra, Marco Trerotola
1Department of Experimental Medicine, Section of Molecular Pathology and Immunology, University of Parma, Italy.
Nucleic Acids Research
|February 13, 2003
Summary
A new computational method, In Silico Trans-splicing Retrieval System (ISTReS), efficiently identifies chimeric mRNAs. This system aids in discovering novel gene fusions and understanding transcript origins, revealing approximately 1% of database transcripts are canonically spliced chimeras.
Area of Science:
- Bioinformatics
- Molecular Biology
- Genomics
Background:
- Chimeric mRNAs can arise from various genetic events, including chromosomal translocations and trans-splicing.
- Identifying these chimeric transcripts is crucial for understanding gene regulation and disease mechanisms.
- Existing methods may struggle to accurately distinguish true chimeric transcripts from artifacts.
Purpose of the Study:
- To develop and validate a computational procedure for identifying heterologous, spliced mRNAs.
- To assess the frequency and characteristics of chimeric transcripts in public databases.
- To discover novel chimeric mRNAs with potential biological significance.
Main Methods:
- Development of the In Silico Trans-splicing Retrieval System (ISTReS) using a parsing algorithm.
- Screening of cDNA versus genome BLAST outputs with stringent filtering criteria (e.g., BLAST scores, match length, exon-exon junctions, sense/sense orientation).
- Validation using known translocation-derived fusion transcripts and analysis of public databases (HGI, RefSeq, UNIGENE).
Main Results:
- ISTReS successfully identified bona fide chromosomal translocation-derived fusion transcripts.
- The system demonstrated the artefactual origin of certain previously reported chimeric antisense transcripts.
- Analysis revealed approximately 1% of transcripts in the UNIGENE database are chimeric, with a similar frequency of canonically spliced chimeras in the RefSeq databank.
- Novel chimeric mRNAs, including FOP-Rho GAP and methionyl tRNA synthetase-advillin, were identified.
Conclusions:
- ISTReS is an efficient tool for identifying chimeric mRNAs derived from heterologous gene splicing.
- Sequence and structure-based strategies are feasible for discovering chimeric mRNA candidates.
- The findings highlight the prevalence of canonically spliced chimeras in biological databases and their potential implications.