Alternative Splicing

Alternative Splicing (AS) is considered the major mechanism for expanding the set of transcripts expressed in eukaryotic organisms, and challenging computational problems arise from this topic.

Our activity includes the development of efficient algorithms for predicting the gene structure into exons and introns and for assembling the potentially expressed full-length transcripts (isoforms) having in input a set of transcript data (ESTs, mRNAs, RNA-Seq data). In this context the alignment of a transcript sequence to the genome is fundamental to solve the problem of inferring the exon-intron gene structure and assembling the potentially expressed full-length isoforms. Since a given transcript fragment may align on different genomic regions, due to repeated sequences, we have also proposed a method to compute the agreement of a set of alignments with respect to a common gene structure, solving the Minimum Factorization Agreement (MFA) Problem.

Next-Generation Sequencing (NGS) technologies need new methodologies for Alternative Splicing analysis.  We have developed a combinatorial structure giving a compact representation of the isoforms of a gene (called Isoform Graph), and we have investigated  the computational problem of building an isoform graph that is compatible with a set of RNA-Seq reads.


ASPIC (Alternative Splicing PredICtion)



ASGAL (Alternative Splicing Graph ALigner)


Bonizzoni, P., Rizzi, R., Pesole, G. (2005). ASPIC: a novel method to predict the exon-intron structure of a gene that is optimally compatible to a set of transcript sequences. BMC Bionformatics, 6:244.

Bonizzoni, P., Della Vedova. G., Dondi, R., Pirola, Y., Rizzi, R. (2009). Minimum Factorization Agreement of Spliced ESTs. WABI 2009, 1-12.

Martelli, P.L., D’Antonio, M., Bonizzoni, P., Castrignanò, T., D’Erchia, A.M., D’Onorio De Meo, P., Fariselli, P., Finelli, M., Licciulli, F., Mangiulli, M., Mignone, F., Pavesi, G., Picardi, E., Rizzi, R., Rossi, I., Valletti, A., Zauli, A., Zambelli, F., Casadio, R., Pesole, G. (2011). ASPicDB: a database of annotated transcript and protein variants generated by alternative splicing. Nucleic Acids Research 39(Database-Issue): 80-85.

Pirola, Y., Rizzi, R., Picardi, E., Pesole, G., Della Vedova, G., Bonizzoni, P. (2012). PIntron: A fast method for gene structure prediction via maximal pairings of a pattern and a text. BMC Bioinformatics, 13(S-5): S2.

Beretta, S., Bonizzoni, P., Della Vedova, G., Pirola, Y., Rizzi, R. (2014). Modeling Alternative Splicing Variants from RNA-Seq Data with Isoform Graphs. Journal of Computational Biology, 21(1): 16-40.

Beretta, S., Bonizzoni, P., Denti, L., Previtali, M., Rizzi, R. (2017). Mapping RNA-seq Data to a Transcript Graph via Approximate Pattern Matching to a Hypertext. AlCoB: 49-61.