arXiv subjects

Alessandra Carbone

Publications and source records attributed to Alessandra Carbone.

6 recordsLinked to original sources

arXiv2023

Fast and Functional Structured Data Generators Rooted in Out-of-Equilibrium Physics

In this study, we address the challenge of using energy-based models to produce high-quality, label-specific data in complex structured datasets, such as population genetics, RNA or protein sequences data. Traditional training methods encounter difficulties due to inefficient Markov chain Monte Carlo mixing, which affects the diversity of synthetic data and increases generation times. To address these issues, we use a novel training algorithm that exploits non-equilibrium effects. This approach, applied on the Restricted Boltzmann Machine, improves the model's ability to correctly classify samples and generate high-quality synthetic data in only a few sampling steps. The effectiveness of this method is demonstrated by its successful application to four different types of data: handwritten digits, mutations of human genomes classified by continental origin, functionally characterized sequences of an enzyme protein family, and homologous RNA sequences from specific taxonomies.

cs.LG↗

arXiv2022

Soft disorder modulates the assembly path of protein complexes

The relationship between interactions, flexibility and disorder in proteins has been explored from many angles: folding upon binding, flexibility of the core relative to the periphery, entropy changes, etc. In this work, we provide statistical evidence for the involvement of highly mobile and disordered regions in complex assembly. We ordered the entire set of X-ray crystallographic structures in the PDB into hierarchies of progressive interactions involving identical or very similar protein chains, yielding 40205 hierarchies of complexes with increasing numbers of partners. We then examine them as proxies for the assembly pathways. Using this database, we show that upon oligomerisation, new interfaces tend to be observed at residues that were characterised as softly disordered (flexible, amorphous or missing residues) in the complexes preceding them in the hierarchy. We also rule out the possibility that this correlation is just a surface effect by restricting the analysis to residues on the surface. Interestingly, we find that the location of soft disordered residues in the sequence changes as the number of partners increases. Our results show that there is a general mechanism for protein assembly that involves soft disorder and modulates the way protein complexes are assembled. This work highlights the difficulty of predicting the structure of large protein complexes from sequence and emphasises the importance of linking predictors of disorder to the next generation of predictors of complex structure. Finally, we investigate the relationship between the AF2's confidence metric pLDDT for structure prediction in unbound vs. bound structures, and soft disorder. We show a strong correlation between AF2 low confidence residues and the union of all regions of soft disorder observed in the hierarchy. This paves the way for using the pLDDT metric as a proxy for predicting assembly paths.

cond-mat.soft↗

arXiv2020

The complexity of protein interactions unravelled from structural disorder

The idea that structural disorder might be a novel mechanism of protein interaction is widespread in the Literature, although the number of statistically significant structural studies supporting this is surprisingly low. At variance with previous works, our conclusions rely exclusively on a large-scale analysis of all the 134337 X-ray crystallographic structures of the Protein Data Bank averaged over clusters of almost identical protein sequences. In this work, we explore the complexity of the organization of all the interaction interfaces observed when a protein lies in alternative complexes, showing that interfaces progressively add up in a hierarchical way. We further investigate the connection of this complexity with different measures of structural disorder: the standard missing residues and a new definition, called "soft disorder", that covers all the flexible and structurally amorphous residues of a protein. We show evidences that both the interaction interfaces and the soft disordered regions tend to involve roughly the same amino-acids of the protein, and preliminary results suggesting that soft disorder spots those surface regions where new interfaces are progressively accommodated by complex formation. Our results suggest that disordered regions not only carry crucial information about the location of alternative interfaces within complexes, but also of the order of the assembly. We verify these hypotheses in several examples. We finally compare our measures of disorder with several disorder predictors, showing that these latter are optimized to predict the residues that are missing in all the alternative structures of a protein, and they are not able to catch the progressive evolution of the disordered regions upon complex formation. Yet, the predicted residues, if not missing, tend to be characterized as soft disordered.

cond-mat.dis-nn↗

arXiv1996

Looking from the inside and from the outside

One often sees a sharp distinction in mathematics between descriptions from the outside and from the inside. Think of defining a set in the plane through an algebraic equation, or dynamically as the closure of the orbit of some point under iterations of a given mapping. In logic one sees this dichotomy in the descriptions of sets of tautologies through semantics and proofs. Logic provides several tools for making outer descriptions of mathematical objects. This paper concerns a slightly complicated mixture of themes related to inner descriptions and formal proofs. We use the notion of feasibility to embed mathematical structures into spaces of logical formulas, from which we can obtain new structures through proofs. We present new geometries on finitely generated groups through proofs, and new structure on the rational numbers (or other fields) which is susceptible to dynamical processes, such as the action of $SL(2,Z)$ by projective transformations. We consider the topological notion of {\em Serre fibrations}. This entails more difficulties of formalization, but basic points arise already for {\em torus bundles}, which present exponential distortion through cycling in a nicely geometric way. One of our goals is to bring out mathematical structure related to cuts and cut elimination. Our geometry on groups through proofs is far from the word metric precisely because of the cut rule. We want to explore the idea that in general the existence of short proofs with cuts should be related to internal symmetry or dynamical processes in the underlying mathematical objects. We also want to bring ordinary mathematical proofs closer to proof theory. In this regard the topological example is attractive for presenting realistic difficulties.

math.LO↗

arXiv1996

Making proofs without Modus Ponens: An introduction to the combinatorics and complexity of cut elimination

This paper is intended to provide an introduction to cut elimination which is accessible to a broad mathematical audience. Gentzen's cut elimination theorem is not as well known as it deserves to be, and it is tied to a lot of interesting mathematical structure. In particular we try to indicate some dynamical and combinatorial aspects of cut elimination, as well as its connections to complexity theory. We discuss two concrete examples where one can see the structure of short proofs with cuts, one concerning feasible numbers and the other concerning "bounded mean oscillation" from real analysis.

math.LO↗

arXiv1996

Some Combinatorics behind Proofs

We try to bring to light some combinatorial structure underlying formal proofs in logic. We do this through the study of the Craig Interpolation Theorem which is properly a statement about the structure of formal derivations. We show that there is a generalization of the interpolation theorem to much more naive structures about sets, and then we show how both classical and intuitionistic versions of the statement follow by interpreting properly the set-theoretic language. The theorem we present is a geometrical formulation of the well-known logical statement and gives sufficient conditions for a system of combinatorial nature to enjoy interpolation. Its objects might be graphs just as well as formulas or surfaces. The combinatorial mappings we use correspond whenever interpreted in a logical language to the notion of `logical flow graph' (i.e. a graph tracing the flow of occurrences of formulas in a proof; this notion has been introduced in (Buss, 1991). The idea of using the flow of occurrences to study the structure of proofs was already present in (Girard, 1987) with the concept of `proof net'.)

math.LO↗