Andrea Passerini

DISULFIND: a disulfide bonding state and cysteine connectivity prediction server

DISULFIND is a server for predicting the disulfide bonding state of cysteines and their disulfide connectivity starting from sequence alone. Optionally, disulfide connectivity can be predicted from sequence and a bonding state assignment given as input. The output is a simple visualization of the assigned bonding state (with confidence degrees) and the most likely connectivity patterns. The server is available at .

New results on error correcting output codes of kernel machines

We study the problem of multiclass classification within the framework of error correcting output codes (ECOC) using margin-based binary classifiers. Specifically, we address two important open problems in this context: decoding and model selection. The decoding problem concerns how to map the outputs of the classifiers into class codewords. In this paper we introduce a new decoding function that combines the margins through an estimate of their class conditional probabilities. Concerning model selection, we present new theoretical results bounding the leave-one-out (LOO) error of ECOC of kernel machines, which can be used to tune kernel hyperparameters. We report experiments using support vector machines as the base binary classifiers, showing the advantage of the proposed decoding function over other functions of I he margin commonly used in practice. Moreover, our empirical evaluations on model selection indicate that the bound leads to good estimates of kernel parameters.

Automatic semantics extraction in law documents

Normative texts can be viewed as composed by formal partitions (articles, paragraphs, etc.) or by semantic units containing fragments of a regulation (provisions). Provisions can be described according to a metadata scheme which consists of provision types and their arguments. This semantic annotation of a normative text can make the retrieval of norms easier. The detection and description of the provisions according to the established metadata scheme is an analytic intellectual activity aiming at classifying portions of a normative text into provision types and to extract their arguments. Automatic facilities supporting this intellectual activity are desirable. Particularly, in this paper, two modules able to qualify fragments of a normative text in terms of provision types and to extract their arguments are presented.

Identifying Cysteines and Histidines in Transition-Metal-Binding Sites Using Support Vector Machines and Neural Networks

Accurate predictions of metal‐binding sites in proteins by using sequence as the only source of information can significantly help in the prediction of protein structure and function, genome annotation, and in the experimental determination of protein structure. Here, we introduce a method for identifying histidines and cysteines that participate in binding of several transition metals and iron complexes. The method predicts histidines as being in either of two states (free or metal bound) and cysteines in either of three states (free, metal bound, or in disulfide bridges). The method uses only sequence information by utilizing position‐specific evolutionary profiles as well as more global descriptors such as protein length and amino acid composition. Our solution is based on a two‐stage machine‐learning approach. The first stage consists of a support vector machine trained to locally classify the binding state of single histidines and cysteines. The second stage consists of a bidirectional recurrent neural network trained to refine local predictions by taking into account dependencies among residues within the same protein. A simple finite state automaton is employed as a postprocessing in the second stage in order to enforce an even number of disulfide‐bonded cysteines. We predict histidines and cysteines in transition‐metal‐binding sites at 73% precision and 61% recall. We observe significant differences in performance depending on the ligand (histidine or cysteine) and on the metal bound. We also predict cysteines participating in disulfide bridges at 86% precision and 87% recall. Results are compared to those that would be obtained by using expert information as represented by PROSITE motifs and, for disulfide bonds, to state‐of‐the‐art methods. Proteins 2006.

Brain–Computer Evolutionary Multiobjective Optimization: A Genetic Algorithm Adapting to the Decision Maker

The centrality of the decision maker (DM) is widely recognized in the multiple criteria decision-making community. This translates into emphasis on seamless human-computer interaction, and adaptation of the solution technique to the knowledge which is progressively acquired from the DM. This paper adopts the methodology of reactive search optimization (RSO) for evolutionary interactive multiobjective optimization. RSO follows to the paradigm of “learning while optimizing,” through the use of online machine learning techniques as an integral part of a self-tuning optimization scheme. User judgments of couples of solutions are used to build robust incremental models of the user utility function, with the objective to reduce the cognitive burden required from the DM to identify a satisficing solution. The technique of support vector ranking is used together with a k-fold cross-validation procedure to select the best kernel for the problem at hand, during the utility function training procedure. Experimental results are presented for a series of benchmark problems.

Widespread uncoupling between transcriptome and translatome variations after a stimulus in mammalian cells

BackgroundThe classical view on eukaryotic gene expression proposes the scheme of a forward flow for which fluctuations in mRNA levels upon a stimulus contribute to determine variations in mRNA availability for translation. Here we address this issue by simultaneously profiling with microarrays the total mRNAs (the transcriptome) and the polysome-associated mRNAs (the translatome) after EGF treatment of human cells, and extending the analysis to other 19 different transcriptome/translatome comparisons in mammalian cells following different stimuli or undergoing cell programs.ResultsTriggering of the EGF pathway results in an early induction of transcriptome and translatome changes, but 90% of the significant variation is limited to the translatome and the degree of concordant changes is less than 5%. The survey of other 19 different transcriptome/translatome comparisons shows that extensive uncoupling is a general rule, in terms of both RNA movements and inferred cell activities, with a strong tendency of translation-related genes to be controlled purely at the translational level. By different statistical approaches, we finally provide evidence of the lack of dependence between changes at the transcriptome and translatome levels.ConclusionsWe propose a model of diffused independency between variation in transcript abundances and variation in their engagement on polysomes, which implies the existence of specific mechanisms to couple these two ways of regulating gene expression.

Predicting zinc binding at the proteome level

BackgroundMetalloproteins are proteins capable of binding one or more metal ions, which may be required for their biological function, for regulation of their activities or for structural purposes. Metal-binding properties remain difficult to predict as well as to investigate experimentally at the whole-proteome level. Consequently, the current knowledge about metalloproteins is only partial.ResultsThe present work reports on the development of a machine learning method for the prediction of the zinc-binding state of pairs of nearby amino-acids, using predictors based on support vector machines. The predictor was trained using chains containing zinc-binding sites and non-metalloproteins in order to provide positive and negative examples. Results based on strong non-redundancy tests prove that (1) zinc-binding residues can be predicted and (2) modelling the correlation between the binding state of nearby residues significantly improves performance. The trained predictor was then applied to the human proteome. The present results were in good agreement with the outcomes of previous, highly manually curated, efforts for the identification of human zinc-binding proteins. Some unprecedented zinc-binding sites could be identified, and were further validated through structural modelling. The software implementing the predictor is freely available at: http://zincfinder.dsi.unifi.itConclusionThe proposed approach constitutes a highly automated tool for the identification of metalloproteins, which provides results of comparable quality with respect to highly manually refined predictions. The ability to model correlations between pairwise residues allows it to obtain a significant improvement over standard 1D based approaches. In addition, the method permits the identification of unprecedented metal sites, providing important hints for the work of experimentalists.Background Metalloproteins are proteins capable of binding one or more metal ions, which may be required for their biological function, for regulation of their activities or for structural purposes. Metal-binding properties remain difficult to predict as well as to investigate experimentally at the whole-proteome level. Consequently, the current knowledge about metalloproteins is only partial. Results The present work reports on the development of a machine learning method for the prediction of the zinc-binding state of pairs of nearby amino-acids, using predictors based on support vector machines. The predictor was trained using chains containing zinc-binding sites and non-metalloproteins in order to provide positive and negative examples. Results based on strong non-redundancy tests prove that (1) zinc-binding residues can be predicted and (2) modelling the correlation between the binding state of nearby residues significantly improves performance. The trained predictor was then applied to the human proteome. The present results were in good agreement with the outcomes of previous, highly manually curated, efforts for the identification of human zinc-binding proteins. Some unprecedented zinc-binding sites could be identified, and were further validated through structural modelling. The software implementing the predictor is freely available at: Conclusion The proposed approach constitutes a highly automated tool for the identification of metalloproteins, which provides results of comparable quality with respect to highly manually refined predictions. The ability to model correlations between pairwise residues allows it to obtain a significant improvement over standard 1D based approaches. In addition, the method permits the identification of unprecedented metal sites, providing important hints for the work of experimentalists.

MetalDetector : a web server for predicting metal-binding sites and disulfide bridges in proteins from sequence

UNLABELLED The web server MetalDetector classifies histidine residues in proteins into one of two states (free or metal bound) and cysteines into one of three states (free, metal bound or disulfide bridged). A decision tree integrates predictions from two previously developed methods (DISULFIND and Metal Ligand Predictor). Cross-validated performance assessment indicates that our server predicts disulfide bonding state at 88.6% precision and 85.1% recall, while it identifies cysteines and histidines in transition metal-binding sites at 79.9% precision and 76.8% recall, and at 60.8% precision and 40.7% recall, respectively. AVAILABILITY Freely available at http://metaldetector.dsi.unifi.it. SUPPLEMENTARY INFORMATION Details and data can be found at http://metaldetector.dsi.unifi.it/help.php.

Fast learning of relational kernels

We develop a general theoretical framework for statistical logical learning with kernels based on dynamic propositionalization, where structure learning corresponds to inferring a suitable kernel on logical objects, and parameter learning corresponds to function learning in the resulting reproducing kernel Hilbert space. In particular, we study the case where structure learning is performed by a simple FOIL-like algorithm, and propose alternative scoring functions for guiding the search process. We present an empirical evaluation on several data sets in the single-task as well as in the multi-task setting.

MetalDetector v2.0: predicting the geometry of metal binding sites from protein sequence

MetalDetector identifies CYS and HIS involved in transition metal protein binding sites, starting from sequence alone. A major new feature of release 2.0 is the ability to predict which residues are jointly involved in the coordination of the same metal ion. The server is available at http://metaldetector.dsi.unifi.it/v2.0/.