Andrea Pagnani

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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(More)
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(More)
Several years after sequencing the human genome and the mouse genome, much remains to be discovered about the functions of most human and mouse genes. Computational prediction of gene function promises to help focus limited experimental resources on the most likely hypotheses. Several algorithms using diverse genomic data have been applied to this task in(More)
Competitive endogenous (ce)RNAs cross-regulate each other through sequestration of shared microRNAs and form complex regulatory networks based on their microRNA signature. However, the molecular requirements for ceRNA cross-regulation and the extent of ceRNA networks remain unknown. Here, we present a mathematical mass-action model to determine the optimal(More)
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(More)
We study the graph coloring problem over random graphs of finite average connectivity c. Given a number q of available colors, we find that graphs with low connectivity admit almost always a proper coloring whereas graphs with high connectivity are uncolorable. Depending on q, we find with a one-step replica-symmetry breaking approximation the precise value(More)
We consider the problem of coloring Erdös-Rényi and regular random graphs of finite connectivity using q colors. It has been studied so far using the cavity approach within the so-called one-step replica symmetry breaking (1RSB) ansatz. We derive a general criterion for the validity of this ansatz and, applying it to the ground state, we provide evidence(More)
Signaling and regulatory networks are essential for cells to control processes such as growth, differentiation, and response to stimuli. Although many "omic" data sources are available to probe signaling pathways, these data are typically sparse and noisy. Thus, it has been difficult to use these data to discover the cause of the diseases and to propose new(More)
MicroRNAs (miRNAs) are small RNA molecules, about 22 nucleotide long, which post-transcriptionally regulate their target messenger RNAs (mRNAs). They accomplish key roles in gene regulatory networks, ranging from signaling pathways to tissue morphogenesis, and their aberrant behavior is often associated with the development of various diseases. Recently it(More)
Ten-Eleven Translocation (TETs)proteins mediate the oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). Tet1 is expressed at high levels in mouse embryonic stem cells (ESCs), where it mediates the induction of 5hmC decoration on gene-regulatory elements. While the function of Tet1 is known, the mechanisms of its specificity remain(More)