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Raffaella Rizzi

Publications and source records attributed to Raffaella Rizzi.

4 recordsLinked to original sources

ASPIC: a web resource for alternative splicing prediction and transcript isoforms characterization.

Alternative splicing (AS) is now emerging as a major mechanism contributing to the expansion of the transcriptome and proteome complexity of multicellular organisms. The fact that a single gene locus may give rise to multiple mRNAs and protein isoforms, showing both major and subtle structural variations, is an exceptionally versatile tool in the optimization of the coding capacity of the eukaryotic genome. The huge and continuously increasing number of genome and transcript sequences provides an essential information source for the computational detection of genes AS pattern. However, much of this information is not optimally or comprehensively used in gene annotation by current genome annotation pipelines. We present here a web resource implementing the ASPIC algorithm which we developed previously for the investigation of AS of user submitted genes, based on comparative analysis of available transcript and genome data from a variety of species. The ASPIC web resource provides graphical and tabular views of the splicing patterns of all full-length mRNA isoforms compatible with the detected splice sites of genes under investigation as well as relevant structural and functional annotation. The ASPIC web resource-available at http://www.caspur.it/ASPIC/--is dynamically interconnected with the Ensembl and Unigene databases and also implements an upload facility.

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Computational methods for alternative splicing prediction.

The fact that a large majority of mammalian genes are subject to alternative splicing indicates that this phenomenon represents a major mechanism for increasing proteome complexity. Here, we provide an overview of current methods for the computational prediction of alternative splicing based on the alignment of genome and transcript sequences. Specific features and limitations of different approaches and software are discussed, particularly those affecting prediction accuracy and assembly of alternative transcripts.

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ASPIC: a novel method to predict the exon-intron structure of a gene that is optimally compatible to a set of transcript sequences.

BACKGROUND: Currently available methods to predict splice sites are mainly based on the independent and progressive alignment of transcript data (mostly ESTs) to the genomic sequence. Apart from often being computationally expensive, this approach is vulnerable to several problems--hence the need to develop novel strategies. RESULTS: We propose a method, based on a novel multiple genome-EST alignment algorithm, for the detection of splice sites. To avoid limitations of splice sites prediction (mainly, over-predictions) due to independent single EST alignments to the genomic sequence our approach performs a multiple alignment of transcript data to the genomic sequence based on the combined analysis of all available data. We recast the problem of predicting constitutive and alternative splicing as an optimization problem, where the optimal multiple transcript alignment minimizes the number of exons and hence of splice site observations. We have implemented a splice site predictor based on this algorithm in the software tool ASPIC (Alternative Splicing PredICtion). It is distinguished from other methods based on BLAST-like tools by the incorporation of entirely new ad hoc procedures for accurate and computationally efficient transcript alignment and adopts dynamic programming for the refinement of intron boundaries. ASPIC also provides the minimal set of non-mergeable transcript isoforms compatible with the detected splicing events. The ASPIC web resource is dynamically interconnected with the Ensembl and Unigene databases and also implements an upload facility. CONCLUSION: Extensive bench marking shows that ASPIC outperforms other existing methods in the detection of novel splicing isoforms and in the minimization of over-predictions. ASPIC also requires a lower computation time for processing a single gene and an EST cluster. The ASPIC web resource is available at http://aspic.algo.disco.unimib.it/aspic-devel/.

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