BTW: a web server for Boltzmann time warping of gene expression time series

Dynamic time warping (DTW) is a well-known quadratic time algorithm to determine the smallest distance and optimal alignment between two numerical sequences, possibly of different length. Originally developed for speech recognition, this method has been used in data mining, medicine and bioinformatics. For gene expression time series data, time warping distance is arguably a more flexible tool to determine genes having similar temporal expression, hence possibly related biological function, than either Euclidean distance or correlation coefficient—especially since time warping accommodates sequences of different length. The BTW web server allows a user to upload two tab-separated text files A,B of gene expression data, each possibly having a different number of time intervals of different durations. BTW then computes time warping distance between each gene of A with each gene of B, using a recently developed symmetric algorithm which additionally computes the Boltzmann partition function and outputs Boltzmann pair probabilities. The Boltzmann pair probabilities, not available with any other existent software, suggest possible biological significance of certain positions in an optimal time warping alignment. Availability:

DiANNA 1.1: an extension of the DiANNA web server for ternary cysteine classification

DiANNA is a recent state-of-the-art artificial neural network and web server, which determines the cysteine oxidation state and disulfide connectivity of a protein, given only its amino acid sequence. Version 1.0 of DiANNA uses a feed-forward neural network to determine which cysteines are involved in a disulfide bond, and employs a novel architecture neural network to predict which half-cystines are covalently bound to which other half-cystines. In version 1.1 of DiANNA, described here, we extend functionality by applying a support vector machine with spectrum kernel for the cysteine classification problem—to determine whether a cysteine is reduced (free in sulfhydryl state), half-cystine (involved in a disulfide bond) or bound to a metallic ligand. In the latter case, DiANNA predicts the ligand among iron, zinc, cadmium and carbon. Available at:

DiANNA: a web server for disulfide connectivity prediction

Correctly predicting the disulfide bond topology in a protein is of crucial importance for the understanding of protein function and can be of great help for tertiary prediction methods. The web server outputs the disulfide connectivity prediction given input of a protein sequence. The following procedure is performed. First, PSIPRED is run to predict the protein's secondary structure, then PSIBLAST is run against the non-redundant SwissProt to obtain a multiple alignment of the input sequence. The predicted secondary structure and the profile arising from this alignment are used in the training phase of our neural network. Next, cysteine oxidation state is predicted, then each pair of cysteines in the protein sequence is assigned a likelihood of forming a disulfide bond—this is performed by means of a novel architecture (diresidue neural network). Finally, Rothberg's implementation of Gabow's maximum weighted matching algorithm is applied to diresidue neural network scores in order to produce the final connectivity prediction. Our novel neural network-based approach achieves results that are comparable and in some cases better than the current state-of-the-art methods

Revealing protein-lncRNA interaction

Long non-coding RNAs (lncRNAs) are associated to a plethora of cellular functions, most of which require the interaction with one or more RNA-binding proteins (RBPs); similarly, RBPs are often able to bind a large number of different RNAs. The currently available knowledge is already drawing an intricate network of interactions, whose deregulation is frequently associated to pathological states. Several different techniques were developed in the past years to obtain protein-RNA binding data in a high-throughput fashion. In parallel, in silico inference methods were developed for the accurate computational prediction of the interaction of RBP-lncRNA pairs. The field is growing rapidly, and it is foreseeable that in the near future, the protein-lncRNA interaction network will rise, offering essential clues for a better understanding of lncRNA cellular mechanisms and their disease-associated perturbations

A novel approach to represent and compare RNA secondary structures

Structural information is crucial in ribonucleic acid (RNA) analysis and functional annotation; nevertheless, how to include such structural data is still a debated problem. Dot-bracket notation is the most common and simple representation for RNA secondary structures but its simplicity leads also to ambiguity requiring further processing steps to dissolve. Here we present BEAR (Brand nEw Alphabet for RNA), a new context-aware structural encoding represented by a string of characters. Each character in BEAR encodes for a specific secondary structure element (loop, stem, bulge and internal loop) with specific length. Furthermore, exploiting this informative and yet simple encoding in multiple alignments of related RNAs, we captured how much structural variation is tolerated in RNA families and convert it into transition rates among secondary structure elements. This allowed us to compute a substitution matrix for secondary structure elements called MBR (Matrix of BEAR-encoded RNA secondary structures), of which we tested the ability in aligning RNA secondary structures. We propose BEAR and the MBR as powerful resources for the RNA secondary structure analysis, comparison and classification, motif finding and phylogeny

Web-Beagle: a web server for the alignment of RNA secondary structures

Web-Beagle (http://beagle.bio.uniroma2.it) is a web server for the pairwise global or local alignment of RNA secondary structures. The server exploits a new encoding for RNA secondary structure and a substitution matrix of RNA structural elements to perform RNA structural alignments. The web server allows the user to compute up to 10 000 alignments in a single run, taking as input sets of RNA sequences and structures or primary sequences alone. In the latter case, the server computes the secondary structure prediction for the RNAs on-the-fly using RNAfold (free energy minimization). The user can also compare a set of input RNAs to one of five pre-compiled RNA datasets including lncRNAs and 3' UTRs. All types of comparison produce in output the pairwise alignments along with structural similarity and statistical significance measures for each resulting alignment. A graphical color-coded representation of the alignments allows the user to easily identify structural similarities between RNAs. Web-Beagle can be used for finding structurally related regions in two or more RNAs, for the identification of homologous regions or for functional annotation. Benchmark tests show that Web-Beagle has lower computational complexity, running time and better performances than other available methods

DIAL: a web server for the pairwise alignment of two RNA three-dimensional structures using nucleotide, dihedral angle and base-pairing similarities

DIAL (dihedral alignment) is a web server that provides public access to a new dynamic programming algorithm for pairwise 3D structural alignment of RNA. DIAL achieves quadratic time by performing an alignment that accounts for (i) pseudo-dihedral and/or dihedral angle similarity, (ii) nucleotide sequence similarity and (iii) nucleotide base-pairing similarity

webPDBinder: a server for the identification of ligand binding sites on protein structures

The webPDBinder (http://pdbinder.bio.uniroma2.it/PDBinder) is a web server for the identification of small ligand-binding sites in a protein structure. webPDBinder searches a protein structure against a library of known binding sites and a collection of control non-binding pockets. The number of similarities identified with the residues in the two sets is then used to derive a propensity value for each residue of the query protein associated to the likelihood that the residue is part of a ligand binding site. The predicted binding residues can be further refined using conservation scores derived from the multiple alignment of the PFAM protein family. webPDBinder correctly identifies residues belonging to the binding site in 77% of the cases and is able to identify binding pockets starting from holo or apo structures with comparable performances. This is important for all the real world cases where the query protein has been crystallized without a ligand and is also difficult to obtain clear similarities with bound pockets from holo pocket libraries. The input is either a PDB code or a user-submitted structure. The output is a list of predicted binding pocket residues with propensity and conservation values both in text and graphical format

DBATE: database of alternative transcripts expression

The use of high-throughput RNA sequencing technology (RNA-seq) allows whole transcriptome analysis, providing an unbiased and unabridged view of alternative transcript expression. Coupling splicing variant-specific expression with its functional inference is still an open and difficult issue for which we created the DataBase of Alternative Transcripts Expression (DBATE), a web-based repository storing expression values and functional annotation of alternative splicing variants. We processed 13 large RNA-seq panels from human healthy tissues and in disease conditions, reporting expression levels and functional annotations gathered and integrated from different sources for each splicing variant, using a variant-specific annotation transfer pipeline. The possibility to perform complex queries by cross-referencing different functional annotations permits the retrieval of desired subsets of splicing variant expression values that can be visualized in several ways, from simple to more informative. DBATE is intended as a novel tool to help appreciate how, and possibly why, the transcriptome expression is shaped. DATABASE URL: http://bioinformatica.uniroma2.it/DBATE/

Multisensory effects on somatosensation: a trimodal visuo-vestibular-tactile interaction

Vestibular information about self-motion is combined with other sensory signals. Previous research described both visuo-vestibular and vestibular-tactile bilateral interactions, but the simultaneous interaction between all three sensory modalities has not been explored. Here we exploit a previously reported visuo-vestibular integration to investigate multisensory effects on tactile sensitivity in humans. Tactile sensitivity was measured during passive whole body rotations alone or in conjunction with optic flow, creating either purely vestibular or visuo-vestibular sensations of self-motion. Our results demonstrate that tactile sensitivity is modulated by perceived self-motion, as provided by a combined visuo-vestibular percept and not by the visual and vestibular cues independently. We propose a hierarchical multisensory interaction that underpins somatosensory modulation: visual and vestibular cues are first combined to produce a multisensory self-motion percept. Somatosensory processing is then enhanced according to the degree of perceived self-motion