InFusion: Advancing Discovery of Fusion Genes and Chimeric Transcripts from Deep RNA-Sequencing Data

Abstract

Analysis of fusion transcripts has become increasingly important due to their link with cancer development. Since high-throughput sequencing approaches survey fusion events exhaustively, several computational methods for the detection of gene fusions from RNA-seq data have been developed. This kind of analysis, however, is complicated by native trans-splicing events, the splicing-induced complexity of the transcriptome and biases and artefacts introduced in experiments and data analysis. There are a number of tools available for the detection of fusions from RNA-seq data; however, certain differences in specificity and sensitivity between commonly used approaches have been found. The ability to detect gene fusions of different types, including isoform fusions and fusions involving non-coding regions, has not been thoroughly studied yet. Here, we propose a novel computational toolkit called InFusion for fusion gene detection from RNA-seq data. InFusion introduces several unique features, such as discovery of fusions involving intergenic regions, and detection of anti-sense transcription in chimeric RNAs based on strand-specificity. Our approach demonstrates superior detection accuracy on simulated data and several public RNA-seq datasets. This improved performance was also evident when evaluating data from RNA deep-sequencing of two well-established prostate cancer cell lines. InFusion identified 26 novel fusion events that were validated in vitro, including alternatively spliced gene fusion isoforms and chimeric transcripts that include intergenic regions. The toolkit is freely available to download from http:/bitbucket.org/kokonech/infusion.

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Living Organisms Author Their Read-Write Genomes in Evolution

“…The innovative role of reverse transcribed cDNAs is further enhanced by the well-documented phenomenon of “trans-splicing”, which involves the joining of sequences from two distinct transcripts [ 368 , 369 , 370 , 371 , 372 , 373 , 374 , 375 , 376 , 377 , 378 , 379 ]. Genome insertion of cDNA reverse-transcribed from a trans-spliced RNA molecule generates a novel chimeric domain coding sequence [ 379 , 380 ].…”

Found in Transcription: Gene fusions arise through defects in RNA processing in the absence of chromosomal rearrangements

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