The computational analysis of the human genome: Old and new problems

DIKU Talk by Anna Tramontano


The pervasive transcription of the mammalian genomes makes the computational  analysis of their products even more interesting and open to surprises. A large number  of alternative transcriptional start sites, termination and splicing patterns and a complex collection of new antisense, intronic and intergenic transcripts are continuously discovered. As far as alternative transcription is concerned, I will discuss the results of our analysis of the protein coding potential of the alternatively spliced isoforms in human and describe how different computational strategies and their combination can be effectively used as proxies for assessing the likelihood that an isoform observed at the transcriptional level does correspond to a functional protein product (1,2). Our data shows that a large fraction of these transcript do not correspond to functional proteins in the classical sense and this led us to develop new strategies to try and understand their role both as RNA molecules (3) and as putative peptide product (4).

I will also describe how the analysis of long non coding RNAs and of their interaction with microRNAs led us to the discovery of a new regulatory circuitry in which RNAs can crosstalk with each other by competing for shared microRNAs (3). The decoy role of lncRNA opens the road to the prediction and identification of new regulatory networks acting through miRNA competition.

1. Leoni, G., Le Pera, L., Ferre', F., Raimondo, D., Tramontano, A. 2011 Coding potential of the products of alternative splicing in human. Genome Biology 12:R9 doi:10.1186/gb-2011-12-1-r9
2. Floris, M., Raimondo, D., Leoni, G., Orsini, M., Marcaili, P. amd Tramontano, A.(2011) MAISTAS: a tool for automatic structural evaluation of alternative splicing products. Bioinformatics, 79(5) 1513?1524
3. Cesana, M., Cacchiarelli, D., Legnini, I., Santini, T., Sthandier, O., Chinappi, M., Tramontano, A. and Bozzoni, I. A Long Noncoding RNA Controls Muscle Differentiation by Functioning as a Competing Endogenous RNA. (2011) Cell 147, 358?369.
4. Sanchez, C. and Tramontano, A. Detecting Mutually Exclusive Interactions in Protein-Protein Interaction Maps (2012) PLoS ONE 7(6): e38765.


Anna Tramontano was trained as a physicist but she soon became fascinated by thecomplexity of biology and by the promises of computational biology.

After a post-doctoral period at UCSF, she joined the Biocomputing Programme of the EMBL in Heidelberg. In 1990 she moved back to Italy to work in the Merck Research Laboratories near Rome. In 2001, she returned to the academic world as a Chair Professor of Biochemistry in "La Sapienza" University in Rome where she continues to pursue her scientific interests on protein structure prediction and analysis in the Department of Biochemical Sciences.

She is a member of the ERC Scientific Council, of the European Molecular Biology Organization, of the organizing Committee of the Critical Assessment of Techniques for Protein Structure Prediction (CASP) initiative and a member of severaI Advisory Committees. She is Associate Editor of Bioinformatics, PLoS One, Proteins and Current Opinion in Structural Biology.

She was awarded the prize for Natural Sciences of the Italian Government, the Marotta Prize of the Italian National Academy of Science and the Minerva Prize for Scientific Research, the KAUST Investigator Award and has published four books (Bioinformatica - Zanichelli; The ten most wanted solutions in Protein Bioinformatics - CRC Press; Protein Structure Prediction - Wiley; Introduction to Bioinformatics - CRC Press).