Sant'Ambrogio di Torino, Italy
Sant'Ambrogio di Torino, Italy

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PubMed | Civile Mp Arezzo Hospital, The Second University of Naples, Heinrich Heine University Düsseldorf, Wellcome Trust Sanger Institute and 23 more.
Type: Journal Article | Journal: Nature | Year: 2016

Approximately 1.5 billion people worldwide are overweight or affected by obesity, and are at risk of developing type 2 diabetes, cardiovascular disease and related metabolic and inflammatory disturbances. Although the mechanisms linking adiposity to associated clinical conditions are poorly understood, recent studies suggest that adiposity may influence DNA methylation, a key regulator of gene expression and molecular phenotype. Here we use epigenome-wide association to show that body mass index (BMI; a key measure of adiposity) is associated with widespread changes in DNA methylation (187 genetic loci with P<110

Baldassi C.,Polytechnic University of Turin | Baldassi C.,Human Genetics Foundation Turin | Zamparo M.,Polytechnic University of Turin | Zamparo M.,Human Genetics Foundation Turin | And 8 more authors.
PLoS ONE | Year: 2014

In the course of evolution, proteins show a remarkable conservation of their three-dimensional structure and their biological function, leading to strong evolutionary constraints on the sequence variability between homologous proteins. Our method aims at extracting such constraints from rapidly accumulating sequence data, and thereby at inferring protein structure and function from sequence information alone. Recently, global statistical inference methods (e.g. direct-coupling analysis, sparse inverse covariance estimation) have achieved a breakthrough towards this aim, and their predictions have been successfully implemented into tertiary and quaternary protein structure prediction methods. However, due to the discrete nature of the underlying variable (amino-acids), exact inference requires exponential time in the protein length, and efficient approximations are needed for practical applicability. Here we propose a very efficient multivariate Gaussian modeling approach as a variant of direct-coupling analysis: the discrete amino-acid variables are replaced by continuous Gaussian random variables. The resulting statistical inference problem is efficiently and exactly solvable. We show that the quality of inference is comparable or superior to the one achieved by mean-field approximations to inference with discrete variables, as done by direct-coupling analysis. This is true for (i) the prediction of residue-residue contacts in proteins, and (ii) the identification of protein-protein interaction partner in bacterial signal transduction. An implementation of our multivariate Gaussian approach is available at the website © 2014 Baldassi et al.

Pardini B.,Human Genetics Foundation Turin | Rosa F.,Human Genetics Foundation Turin | Barone E.,University of Pisa | Di Gaetano C.,Human Genetics Foundation Turin | And 15 more authors.
Clinical Cancer Research | Year: 2013

Purpose: Colorectal cancer is routinely treated with a 5-fluorouracil (5-FU)-based chemotherapy. 5-FU incorporates into DNA, and the base excision repair (BER) pathway specifically recognizes such damage. We investigated the association of single-nucleotide polymorphisms (SNP) in the 30-untranslated regions (UTR) of BER genes, and potentially affecting the microRNA (miRNA) binding, on the risk of colorectal cancer, its progression, and prognosis. SNPs in miRNA-binding sites may modulate the posttranscriptional regulation of gene expression operated by miRNAs and explain interindividual variability in BER capacity and response to 5-FU. Experimental Design: We tested 12 SNPs in the 30-UTRs of five BER genes for colorectal cancer susceptibility in a case-control study (1,098 cases and 1,459 healthy controls). Subsequently, we analyzed the role of these SNPs on clinical outcomes of patients (866 in the Training set and 232 in the Replication set). Results: SNPs in theSMUG1and NEIL2 genes were associated with overall survival. In particular,SMUG1 rs2233921 TT carriers showed increased survival compared with those with GT/GG genotypes [HR, 0.54; 95% confidence interval (CI), 0.36-0.81; P = 0.003] in the Training set and after pooling results from the Replication set. The association was more significant following stratification for 5-FU-based chemotherapy (P=5.6 × 10-5). A reduced expression of the reporter gene for the T allele of rs2233921 was observed when compared with the common G allele by in vitro assay. None of the genotyped BER polymorphisms were associated with colorectal cancer risk. Conclusions:Weprovidethe first evidence thatvariations inmiRNA-bindingsites inBERgenes30-UTRmay modulate colorectal cancer prognosis and therapy response. © 2013 American Association for Cancer Research.

Tyagi P.,CNR Institute of Neuroscience | Tyagi P.,University of Rome La Sapienza | Pagnani A.,Polytechnic University of Turin | Pagnani A.,Human Genetics Foundation Turin | And 5 more authors.
Journal of Statistical Mechanics: Theory and Experiment | Year: 2015

A statistical inference method is developed and tested for pairwise interacting systems whose degrees of freedom are continuous angular variables, such as planar spins in magnetic systems or wave phases in optics and acoustics. We investigate systems with both deterministic and quenched disordered couplings on two extreme topologies: complete and sparse graphs. To match further applications in optics also complex couplings and external fields are considered and general inference formulas are derived for real and imaginary parts of Hermitian coupling matrices from real and imaginary parts of complex correlation functions. The whole procedure is, eventually, tested on numerically generated correlation functions and local magnetizations by means of Monte Carlo simulations. © 2015 IOP Publishing Ltd and SISSA Medialab srl.

Zamparo M.,Human Genetics Foundation Turin | Zamparo M.,Polytechnic University of Turin | Chianale F.,Human Genetics Foundation Turin | Tebaldi C.,Polytechnic University of Turin | And 4 more authors.
Soft Matter | Year: 2015

We review the molecular and physical aspects of the dynamic localization of signaling molecules on the plasma membranes of living cells. At the nanoscale, clusters of receptors and signaling proteins play an essential role in the processing of extracellular signals. At the microscale, "soft" and highly dynamic signaling domains control the interaction of individual cells with their environment. At the multicellular scale, individual polarity patterns control the forces that shape multicellular aggregates and tissues. © The Royal Society of Chemistry 2015.

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