Large-scale genomic and trascriptomic analysis in eukaryotic genome projects have produced   surprising results that have strongly challenged the traditional understanding of genes.  In particular, the gene-centricview of molecular biologyhas been changed in favour of considering function products (proteins and ncRNAs) rather than genes. This novel view is a consequence  of some important findings obtained by a widespread use of software tools specifically developed to accomplish the important  task of predicting the gene structure from large-scale gene products. In this talk, we will discuss  this task by presenting some challenging computational problems and  their algorithmic solutions.  We will show that  some open problems involve the  solution of recurrent computational issues related to the use of next generation sequencing data(NGS) such as for example de novo assembly, indexing and graph representation of large collections of strings. 

We present a nucleotide-level model of RNA designed to reproduce structural, mechanical and thermodynamic properties of single-strandedas well as double-stranded RNA. We test the model in a range of nanotechnological and biological settings. Applications explored include the folding thermodynamics of a pseudoknot, the formation of a kissing loop complex, the structure of a hexagonal RNA nanoring, the unzipping of a hairpin motif, and formation of a plectoneme. We further use the model to study the thermodynamics and kinetics of an RNA toehold-mediated strand displacement reaction. Strand displacement is an essential mechanism in active nucleic acid nanotechnology and has also been hypothesized to occur in vivo. Furthermore, recent experiments have demonstrated promising application of RNA strand displacement systems to bionanotechnology. We obtain the rate of displacement reactions as a function of the length of the toehold and temperature and find that the displacement is faster if the toehold is placed at the 5' end of the substrate, thus suggesting a plausible mechanism for improvement of yields of…

The Gowanus Canal in Brooklyn is scheduled to undergo dredging and sub-aquatic capping as part of the US Environmental Protection Agency Superfund Cleanup plan beginning in 2017. Historically a productive estuary, the waterfront was claimed by industrial and cultural needs that dramatically altered the habitat and ecological flow. Beginning when Gowanus Creek was dredged into Gowanus Canal in 1869, and perpetuated until 2013 when the record of decision was reached designating the Gowanus Canal Superfund Site, the canal has collected 150 years of industrial byproducts. To this day raw sewage overflows into the system following each rain event, adding to the unique slurry of hydrocarbons and heavy metals mixed with estuarine silt deposits. Driven by a citizen scientists’ curiosity regarding the extant environment which will be effectively destroyed by cleanup efforts, we have sampled the Canal’s sediment for short-read metagenomic analysis over four seasons of the last year. Functional analysis of these…

We shall explain how to find compressed indexes to represent collections of very repetitive data in genomics (genome populations). We will present a number of results on compression but also on computation over compressed data.  We shall introduce the main conceptual principles that are followed to resolve such questions, becoming of major importance when we deal with more and more genomic data. The seminar will be accessible to a large public comprising experimentalists and theoreticians. 

Dipterans (flies, midges, and mosquitoes) determine segmentation along their main body axis during the blastoderm stage of development. In the initial phase of segmentation, maternal gradients are interpreted by the gap genes, the first set of zygotic genes that divide the embryo in antero-posterior regions (a pattern of stripes). Analysis of spatio-temporal expression and systematic knock-down of the gap genes in the scuttle fly Megaselia abdita reveals quantitative differences in gap gene cross-regulation between this species and Drosophila melanogaster. We have used mathematical modelling and reverse engineering of this gene network to gain insight into the regulatory mechanisms that underlie the observed differences in expression dynamics between the two species. Our models confirm that the qualitative structure of the gap gene network is conserved.  Differences in expression dynamics are fully explained by distinct initial placement of the gap gene expression domains, and quantitative modifications of specific interactions. Our models agree with the…

The development of DNA sequencing technologies allows us to collect large amounts of molecular data about the genome of each individual, and opens the possibility to predict drug response or evaluate the risk of various diseases from one's molecular identity. It also raises statistical and computational challenges, as the quantity of data collected per sample is usually far larger than the number of samples available to estimate predictive models. In this talk I will discuss some of these challenges and describe a few methods to attack them through regularization or change of representation, illustrated on applications in cancer prognosis and drug response prediction from gene expression and somatic mutations

Sexual reproduction is an extraordinarily widespread phenomenon that assures the production of new genetic combinations in nearly all eukaryotic lineages. Although the core features of sexual reproduction (meiosis and syngamy) are highly conserved, the control mechanisms that determine whether an individual is male or female are remarkably labile across eukaryotes. In genetically controlled sexual systems, gender is determined by sex chromosomes, which have emerged independently and repeatedly during evolution. Sex chromosomes have been studied in only a handful of classical model organism, and empirical knowledge on the origin and evolution of the sexes is still surprisingly incomplete. I will present how our group is exploiting the richness of sexual characteristics of the brown algae to gain novel insights into the functional and evolutionary interactions between the sex chromosomes and reproductive/life cycle features.