Publications by Elisa Ficarra

The new protocol for sequencing the messenger RNA in a cell, named RNA-seq produce millions of short sequence fragments. Next Generation Sequencing technology allows more accurate analysis but increase needs in term of computational resources. This paper describes the optimization of a RNA-seq analysis pipeline devoted to splicing variants detection, aimed at reducing computation time and providing a multi-user/multisample environment. This work brings two main contributions. First, we optimized a well-known algorithm called TopHat by parallelizing some sequential mapping steps. Second, we designed and implemented a hybrid virtual GRID infrastructure allowing to efficiently execute multiple instances of TopHat running on different samples or on behalf of different users, thus optimizing the overall execution time and enabling a flexible multi-user environment.

TopHat is a fast splice junction mapper for Next Generation Sequencing analysis, a technology for functional genomic research. Next Generation Sequencing technology allows more accurate analysis increasing data to elaborate, this opens to new challenges in terms of development of tools and computational infrastructures. We present a solution that cover aspects both software and hardware, the first one, after a reverse engineering phase, provides an improvement of algorithm of TopHat making it parallelizable, the second aspect is an implementation of an hybrid infrastructure: grid and virtual grid computing. Moreover the system allows to have a multi sample environment and is able to process automatically totally transparent to user.

Many essential cell processes, such as the conformation of embedded proteins, membrane permeability, interaction with drugs and signalling, are directly connected to the molecular dynamics of cell membranes. The importance of this biology has led to an intensifying demand for hardware and software optimized models and tools, implemented on commodity high performance low-cost hardware, in order to provide the scientific community with virtual low cost laboratories. In the light of these considerations, we implemented an accelerated version of a molecular dynamics coarse-grain lipid bilayers simulator on commodity Graphic Processing Units (GPU) architectures. The characteristics of this molecular dynamics model, such as new force fields for pair potentials that include an unconventional representation for water and charges, were particularly challenging. We introduced new algorithms and data structures required by coarse-grain models compared to atomistic ones, for the modelling of the integration timestep, neighbour list generation, and nonbonded force interactions. We characterized the impact on performance of biological systems of differing complexity in terms of size, particle type and timestep. We also compared the simulations of many particle-type systems against single particle-type systems, to evaluate the overhead of additional structures needed to model more complex molecules. Moreover, we performed a detailed analysis on the profiling of the simulation code and its execution flows due to the computation of the non-bonded forces. Finally, we characterized the acceleration and accuracy of the simulations on three GPUs having different computation capabilities and parallelism, achieving one order of magnitude faster simulation execution times.

Nowadays, a considerable amount of genetic and biomedical studies are mostly diffused on the Web and freely available. This exciting capability, if from one side opens the way to new scenarios of cooperating research, on the other side makes the knowledge retrieval and extraction an extremely time consuming operation. In this context, the development of new tools and algorithms to automatically support the scientist activity to achieve a reliable interpretation of the complex interactions among biological entities is mandatory. In this paper we present a new methodology aimed at quantifying the biological degree of correlation among biomedical terms present in literature. The proposed method overcomes the limitation of current tools based on public literature information only, by exploiting the trustworthy information provided by biological pathways databases. We demonstrate how to integrate trusted pathway information in a semantic correlation extraction chain based on UMLS Metathesaurus and relying on PubMed as literature database. The effectiveness of the obtained results remarks the importance of automatically quantifying the degree of correlation among biomedical terms in order to helpfully support the scientist research activity.

This study presents a fully automated membrane segmentation technique for immunohistochemical tissue images with membrane staining, which is a critical task in computerized immunohistochemistry (IHC). Membrane segmentation is particularly tricky in immunohistochemical tissue images because the cellular membranes are visible only in the stained tracts of the cell, while the unstained tracts are not visible. Our automated method provides accurate segmentation of the cellular membranes in the stained tracts and reconstructs the approximate location of the unstained tracts using nuclear membranes as a spatial reference. Accurate cell-by-cell membrane segmentation allows per cell morphological analysis and quantification of the target membrane proteins that is fundamental in several medical applications such as cancer characterization and classification, personalized therapy design, and for any other applications requiring cell morphology characterization. Experimental results on real datasets from different anatomical locations demonstrate the wide applicability and high accuracy of our approach in the context of IHC analysis.

In this paper we present a methodology to evaluate the binding free energy of a miRNA-mRNA complex through Molecular Dynamics-Thermodynamic Integration simulations. We applied our method on the C-elegans let-7 miRNA:lin-41 mRNA complex, known to be a validate miRNA:mRNA interaction, in order to evaluate the energetic stability of the structure. The methodology has been designed to face the various challenges of nucleic acid simulations and binding free energy computations and to allow an optimal trade-off between accuracy and computational cost.

The increasing pace of biotechnological advances produced an unprecedented amount of both experimental data and biological information mostly diffused on the web. However, the heterogeneity of the data organization and the different knowledge representations open the ways to new challenges in the integration and the extraction of biological information fundamental for correctly interpreter experimental results. In the present work we introduce a new methodology for quantitatively scoring the degree of biological correlation among biological terms occurring in biomedical abstracts. The proposed flow is based on the latent semantic analysis of biomedical literature coupled with the UMLS Metathesarurs and PubMed literature information. The results demonstrate that the structured and consolidated knowledge in the UMLS and pathway database efficiently improves the accuracy of the latent semantic analysis of biomedical literature. © Springer-Verlag Berlin Heidelberg 2013.