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Biomedical subjects

Tiziana Castrignanò

Publications and source records attributed to Tiziana Castrignanò.

7 recordsLinked to original sources

ASPIC: a web resource for alternative splicing prediction and transcript isoforms characterization.

Alternative splicing (AS) is now emerging as a major mechanism contributing to the expansion of the transcriptome and proteome complexity of multicellular organisms. The fact that a single gene locus may give rise to multiple mRNAs and protein isoforms, showing both major and subtle structural variations, is an exceptionally versatile tool in the optimization of the coding capacity of the eukaryotic genome. The huge and continuously increasing number of genome and transcript sequences provides an essential information source for the computational detection of genes AS pattern. However, much of this information is not optimally or comprehensively used in gene annotation by current genome annotation pipelines. We present here a web resource implementing the ASPIC algorithm which we developed previously for the investigation of AS of user submitted genes, based on comparative analysis of available transcript and genome data from a variety of species. The ASPIC web resource provides graphical and tabular views of the splicing patterns of all full-length mRNA isoforms compatible with the detected splice sites of genes under investigation as well as relevant structural and functional annotation. The ASPIC web resource-available at http://www.caspur.it/ASPIC/--is dynamically interconnected with the Ensembl and Unigene databases and also implements an upload facility.

Algorithms↗

The PMDB Protein Model Database.

The Protein Model Database (PMDB) is a public resource aimed at storing manually built 3D models of proteins. The database is designed to provide access to models published in the scientific literature, together with validating experimental data. It is a relational database and it currently contains >74,000 models for approximately 240 proteins. The system is accessible at http://www.caspur.it/PMDB and allows predictors to submit models along with related supporting evidence and users to download them through a simple and intuitive interface. Users can navigate in the database and retrieve models referring to the same target protein or to different regions of the same protein. Each model is assigned a unique identifier that allows interested users to directly access the data.

Databases, Protein↗

GenoMiner: a tool for genome-wide search of coding and non-coding conserved sequence tags.

GenoMiner is a software tool that searches for regions of similarity between user-submitted genome or transcript sequences and user-specified whole genome assemblies. The program then identifies conserved sequence tags (CSTs) in these homologous regions and provides a prediction of their coding or non-coding nature. The analysis is carried out through three steps: (1) definition of sequence regions homologous to the query sequence in the selected target genomes by a fast BLAT alignment; (2) identification of CSTs by a more sensitive BLAST-like alignment between the query and the homologous regions in the target genomes and (3) assessment of the coding or non-coding nature of detected CSTs through the computation of a suitable coding potential score. GenoMiner allows the user to search the query sequence against a number of vertebrate genome assemblies in a single run providing a user-friendly graphical output.

Algorithms↗

CSTminer: a web tool for the identification of coding and noncoding conserved sequence tags through cross-species genome comparison.

The identification and characterization of genome tracts that are highly conserved across species during evolution may contribute significantly to the functional annotation of whole-genome sequences. Indeed, such sequences are likely to correspond to known or unknown coding exons or regulatory motifs. Here, we present a web server implementing a previously developed algorithm that, by comparing user-submitted genome sequences, is able to identify statistically significant conserved blocks and assess their coding or noncoding nature through the measure of a coding potential score. The web tool, available at http://www.caspur.it/CSTminer/, is dynamically interconnected with the Ensembl genome resources and produces a graphical output showing a map of detected conserved sequences and annotated gene features.

Animals↗

Novel cDNAs encoding salivary proteins from the malaria vector Anopheles gambiae.

Several genes encoding salivary components of the mosquito Anopheles gambiae were identified using a selective trapping approach. Among these, five corresponded to genes expressed specifically in female glands and their role may possibly be linked to blood-feeding. Our collection included a fourth member of the D7 protein family and two polypeptides that showed weak similarity to anti-coagulants from distantly related species. Moreover, we identified two additional members of a novel group of proteins that we named glandins. The isolation of tissue-specific genes represents a first step toward a deeper molecular analysis of mosquito salivary secretions.

Amino Acid Sequence↗

Molecular dynamics simulation of the RNA complex of a double-stranded RNA-binding domain reveals dynamic features of the intermolecular interface and its hydration.

The interaction between double-stranded RNA (dsRNA) and the third double-stranded domain (dsRBD) from Drosophila Staufen protein represents a paradigm to understand how the dsRBD protein family, one of the most common RNA-binding protein units, binds dsRNA. The nuclear magnetic resonance (NMR) structure of this complex and the x-ray structure of another family member revealed the stereochemical basis for recognition, but also raised new questions. Although the crystallographic studies revealed a highly ordered interface containing numerous water-mediated contacts, NMR suggested extensive residual motion at the interface. To address how interfacial motion contributes to molecular recognition in the dsRBD-dsRNA system, we conducted a 2-ns molecular dynamics simulation of the complex derived from Staufen protein and of the separate protein and RNA components. The results support the observation that a high degree of conformational flexibility is retained upon complex formation and that this involves interfacial residues that are critical for dsRBD-dsRNA binding. The structural origin of this residual flexibility is revealed by the analysis of the trajectory of motion. Individual basic side chains switch continuously from one RNA polar group to another with a residence time seldom exceeding 100 ps, while retaining favorable interaction with RNA throughout much of the simulation. Short-lived water molecules mediate some of these interactions for a large fraction of the trajectory studied here. This result indicates that water molecules are not statically associated with the interface, but continuously exchange with the bulk solvent on a 1-10-ps time scale. This work provides new insight into dsRBD-dsRNA recognition and builds upon a growing body of evidence, suggesting that short-lived dynamic interactions play important roles in protein-nucleic acid interactions.

Binding Sites↗

[Bioinformatics and GenEnv database in biological risk management].

Identification and molecular typing of environmental isolates by molecular techniques requires knowledge of the genetic characteristics of the microbe species being examined. The introduction of automated sequences has greatly speeded up the entire sequencing process as well as improved the accuracy of the collected information. Bioinformatics tools have become indispensable not only for setting up research studies, but also for storing, organizing and managing enormous quantities of sequencing data. Despite its great advantages, the use of bioinformatics is hindered by difficulties in learning how to use its software tools. The GenEnv database was developed to provide operators involved in biological risk management with a user-friendly tool for sequence analysis. Presently, there are over 20.000 sequence records, and over 9000 bacterial species represented in the database. The initial gene set comprises rDNA16S, rpoB, gyrB. The system allows sequence-driven microbe identification as well as the development of study protocols for research on specific microbe species. Nucleotide sequences are represented graphically. The GenEnv database was designed as a tool for public health operators but also offers wide prospects for scientific research.

Computational Biology↗