Polytechnic University of Turin

About: Polytechnic University of Turin is a education organization based out in Turin, Piemonte, Italy. It is known for research contribution in the topics: Finite element method & Computer science. The organization has 11553 authors who have published 41395 publications receiving 789320 citations. The organization is also known as: POLITO & Politecnico di Torino.

Direct-coupling analysis of residue coevolution captures native contacts across many protein families

Abstract: The similarity in the three-dimensional structures of homologous proteins imposes strong constraints on their sequence variability. It has long been suggested that the resulting correlations among amino acid compositions at different sequence positions can be exploited to infer spatial contacts within the tertiary protein structure. Crucial to this inference is the ability to disentangle direct and indirect correlations, as accomplished by the recently introduced direct-coupling analysis (DCA). Here we develop a computationally efficient implementation of DCA, which allows us to evaluate the accuracy of contact prediction by DCA for a large number of protein domains, based purely on sequence information. DCA is shown to yield a large number of correctly predicted contacts, recapitulating the global structure of the contact map for the majority of the protein domains examined. Furthermore, our analysis captures clear signals beyond intradomain residue contacts, arising, e.g., from alternative protein conformations, ligand-mediated residue couplings, and interdomain interactions in protein oligomers. Our findings suggest that contacts predicted by DCA can be used as a reliable guide to facilitate computational predictions of alternative protein conformations, protein complex formation, and even the de novo prediction of protein domain structures, contingent on the existence of a large number of homologous sequences which are being rapidly made available due to advances in genome sequencing.

Unveiling turbo codes: some results on parallel concatenated coding schemes

Abstract: A parallel concatenated coding scheme consists of two simple constituent systematic encoders linked by an interleaver. The input bits to the first encoder are scrambled by the interleaver before entering the second encoder. The codeword of the parallel concatenated code consists of the input bits to the first encoder followed by the parity check bits of both encoders. This construction can be generalized to any number of constituent codes. Parallel concatenated schemes employing two convolutional codes as constituent codes, in connection with an iterative decoding algorithm of complexity comparable to that of the constituent codes, have been previously shown to yield remarkable coding gains close to theoretical limits. They have been named, and are known as, "turbo codes". We propose a method to evaluate an upper bound to the bit error probability of a parallel concatenated coding scheme averaged over all interleavers of a given length. The analytical bounding technique is then used to shed some light on some crucial questions, which have been floating around in the communications community since the proposal of turbo codes.

Understanding code mobility

Abstract: The technologies, architectures, and methodologies traditionally used to develop distributed applications exhibit a variety of limitations and drawbacks when applied to large scale distributed settings (e.g., the Internet). In particular, they fail in providing the desired degree of configurability, scalability, and customizability. To address these issues, researchers are investigating a variety of innovative approaches. The most promising and intriguing ones are those based on the ability of moving code across the nodes of a network, exploiting the notion of mobile code. As an emerging research field, code mobility is generating a growing body of scientific literature and industrial developments. Nevertheless, the field is still characterized by the lack of a sound and comprehensive body of concepts and terms. As a consequence, it is rather difficult to understand, assess, and compare the existing approaches. In turn, this limits our ability to fully exploit them in practice, and to further promote the research work on mobile code. Indeed, a significant symptom of this situation is the lack of a commonly accepted and sound definition of the term mobile code itself. This paper presents a conceptual framework for understanding code mobility. The framework is centered around a classification that introduces three dimensions: technologies, design paradigms, and applications. The contribution of the paper is two-fold. First, it provides a set of terms and concepts to understand and compare the approaches based on the notion of mobile code. Second, it introduces criteria and guidelines that support the developer in the identification of the classes of applications that can leverage off of mobile code, in the design of these applications, and, finally, in the selection of the most appropriate implementation technologies. The presentation of the classification is intertwined with a review of state-of-the-art in the field. Finally, the use of the classification is exemplified in a case study.

Finding Statistically Significant Communities in Networks

Abstract: Community structure is one of the main structural features of networks, revealing both their internal organization and the similarity of their elementary units. Despite the large variety of methods proposed to detect communities in graphs, there is a big need for multi-purpose techniques, able to handle different types of datasets and the subtleties of community structure. In this paper we present OSLOM (Order Statistics Local Optimization Method), the first method capable to detect clusters in networks accounting for edge directions, edge weights, overlapping communities, hierarchies and community dynamics. It is based on the local optimization of a fitness function expressing the statistical significance of clusters with respect to random fluctuations, which is estimated with tools of Extreme and Order Statistics. OSLOM can be used alone or as a refinement procedure of partitions/covers delivered by other techniques. We have also implemented sequential algorithms combining OSLOM with other fast techniques, so that the community structure of very large networks can be uncovered. Our method has a comparable performance as the best existing algorithms on artificial benchmark graphs. Several applications on real networks are shown as well. OSLOM is implemented in a freely available software (http://www.oslom.org), and we believe it will be a valuable tool in the analysis of networks.

Protein 3D structure computed from evolutionary sequence variation.

Abstract: The evolutionary trajectory of a protein through sequence space is constrained by its function. Collections of sequence homologs record the outcomes of millions of evolutionary experiments in which the protein evolves according to these constraints. Deciphering the evolutionary record held in these sequences and exploiting it for predictive and engineering purposes presents a formidable challenge. The potential benefit of solving this challenge is amplified by the advent of inexpensive high-throughput genomic sequencing. In this paper we ask whether we can infer evolutionary constraints from a set of sequence homologs of a protein. The challenge is to distinguish true co-evolution couplings from the noisy set of observed correlations. We address this challenge using a maximum entropy model of the protein sequence, constrained by the statistics of the multiple sequence alignment, to infer residue pair couplings. Surprisingly, we find that the strength of these inferred couplings is an excellent predictor of residue-residue proximity in folded structures. Indeed, the top-scoring residue couplings are sufficiently accurate and well-distributed to define the 3D protein fold with remarkable accuracy. We quantify this observation by computing, from sequence alone, all-atom 3D structures of fifteen test proteins from different fold classes, ranging in size from 50 to 260 residues., including a G-protein coupled receptor. These blinded inferences are de novo, i.e., they do not use homology modeling or sequence-similar fragments from known structures. The co-evolution signals provide sufficient information to determine accurate 3D protein structure to 2.7–4.8 A Cα-RMSD error relative to the observed structure, over at least two-thirds of the protein (method called EVfold, details at http://EVfold.org). This discovery provides insight into essential interactions constraining protein evolution and will facilitate a comprehensive survey of the universe of protein structures, new strategies in protein and drug design, and the identification of functional genetic variants in normal and disease genomes.