DNA analysis servers: plot.it,bend.it,model.it and IS

The WWW servers at http://www.icgeb.trieste.it/dna/ are dedicated to the analysis of user-submitted DNA sequences; plot.it creates parametric plots of 45 physicochemical, as well as statistical, parameters; bend.it calculates DNA curvature according to various methods. Both programs provide 1D as well as 2D plots that allow localisation of peculiar segments within the query. The server model.it creates 3D models of canonical or bent DNA starting from sequence data and presents the results in the form of a standard PDB file, directly viewable on the user's PC using any molecule manipulation program. The recently established introns server allows statistical evaluation of introns in various taxonomic groups and the comparison of taxonomic groups in terms of length, base composition, intron type etc. The options include the analysis of splice sites and a probability test for exon-shuffling.     

The SBASE protein domain library, Release 4.0: a collection of annotated protein sequence segments.

SBASE 4.0 is the fourth release of SBASE, a collection of annotated protein domain sequences that represent various structural, functional, ligand binding and topogenic segments of proteins. SBASE was designed to facilitate the detection of functional homologies and can be searched with standard database search tools, such as FASTA and BLAST3. The present release contains 61 137 entries provided with standardized names and cross-referenced to all major protein, nucleic acid and sequence pattern collections. The entries are clustered into 13 155 groups in order to facilitate detection of distant similarities. SBASE 4.0 is freely available by anonymous ftp file transfer from ftp.icgeb.trieste.it. Individual records can be retrieved with the gopher server at icgeb.trieste.it and with a World Wide Web server at http://www.icgeb.trieste.it. Automated searching of SBASE with BLAST can be carried out with the electronic mail server sbase@icgeb.trieste.it, which now also provides a graphic representation of the homologies. A related mail server, domain@hubi.abc.hu, assigns SBASE domain homologies on the basis of SWISS-PROT searches.     

The domain-server: direct prediction of protein domain-homologies from BLAST search.

RESULTS: A WWW server for protein domain homology prediction, based on BLAST search and a simple data-mining algorithm (Hegyi,H. and Pongor,S. (1993) Comput. Appl. Biosci., 9, 371-372), was constructed providing a tabulated list and a graphic plot of similarities. AVAILABILITY: http://www.icgeb.trieste.it/domain. Mirror site is available at http://sbase.abc.hu/domain. A standalone programme will be available on request. SUPPLEMENTARY INFORMATION: A series of help files is available at the above addresses.     

The SBASE protein domain library, release 3.0: a collection of annotated protein sequence segments.

SBASE 3.0 is the third release of SBASE, a collection of annotated protein domain sequences. SBASE entries represent various structural, functional, ligand-binding and topogenic segments of proteins as defined by their publishing authors. SBASE can be used for establishing domain homologies using different database-search tools such as FASTA [Lipman and Pearson (1985) Science, 227, 1436-1441], and BLAST3 [Altschul and Lipman (1990) Proc. Natl. Acad. Sci. USA, 87, 5509-5513] which is especially useful in the case of loosely defined domain types for which efficient consensus patterns can not be established. The present release contains 41,749 entries provided with standardized names and cross-referenced to the major protein and nucleic acid databanks as well as to the PROSITE catalogue of protein sequence patterns. The entries are clustered into 2285 groups using the BLAST algorithm for computing similarity measures. SBASE 3.0 is freely available on request to the authors or by anonymous 'ftp' file transfer from < ftp.icgeb.trieste.it >. Individual records can be retrieved with the gopher server at < icgeb.trieste.it > and with a www-server at < http:@www.icgeb.trieste.it >. Automated searching of SBASE by BLAST can be carried out with the electronic mail server < sbase@icgeb.trieste.it >. Another mail server < domain@hubi.abc.hu > assigns SBASE domain homologies on the basis of SWISS-PROT searches. A comparison of pertinent search strategies is presented.     

Sequence‐dependent modelling of local DNA bending phenomena: curvature prediction and vibrational analysis

Bending is a local conformational micropolymorphism of DNA in which the original B-DNA structure is only distorted but not extensively modified. Bending can be predicted by simple static geometry models as well as by a recently developed elastic model that incorporate sequence dependent anisotropic bendability (SDAB). The SDAB model qualitatively explains phenomena including affinity of protein binding, kinking, as well as sequence-dependent vibrational properties of DNA. The vibrational properties of DNA segments can be studied by finite element analysis of a model subjected to an initial bending moment. The frequency spectrum is obtained by applying Fourier analysis to the displacement values in the time domain. This analysis shows that the spectrum of the bending vibrations quite sensitively depends on the sequence, for example the spectrum of a curved sequence is characteristically different from the spectrum of straight sequence motifs of identical basepair composition. Curvature distributions are genome-specific, and pronounced differences are found between protein-coding and regulatory regions, respectively, that is, sites of extreme curvature and/or bendability are less frequent in protein-coding regions. A WWW server is set up for the prediction of curvature and generation of 3D models from DNA sequences (http://www.icgeb.trieste.it/dna).This revised version was published online in October 2005 with corrections to the Cover Date.     

The SBASE protein domain library, release 5.0: a collection of annotated protein sequence segments.

SBASE 5.0 is the fifth release of SBASE, a collection of annotated protein domain sequences that represent various structural, functional, ligand-binding and topogenic segments of proteins. SBASE was designed to facilitate the detection of functional homologies and can be searched with standard database-search programs. The present release contains over 79863 entries provided with standardized names and is cross-referenced to all major sequence databases and sequence pattern collections. The information is assigned to individual domains rather than to entire protein sequences, thus SBASE contains substantially more cross-references and links than do the protein sequence databases. The entries are clustered into >16 000 groups in order to facilitate the detection of distant similarities. SBASE 5.0 is freely available by anonymous 'ftp' file transfer from <ftp.icgeb.trieste.it >. Automated searching of SBASE with BLAST can be carried out with the WWW-server <http://www.icgeb.trieste.it/sbase/ >. and with the electronic mail server <sbase@icgeb.trieste.it >which now also provides a graphic representation of the homologies. A related WWW-server <http://www.abc.hu/blast.html > and e-mail server <domain@hubi.abc.hu > predicts SBASE domain homologies on the basis of SWISS-PROT searches.     

The SBASE protein domain library, release 7.0: a collection of annotated protein sequence segments

SBASE 7.0 is the seventh release of the SBASE protein domain library sequences that contains 237 937 annotated structural, functional, ligand-binding and topogenic segments of proteins, cross-referenced to all major sequence databases and sequence pattern collections. The entries are clustered into over 1811 groups and are provided with two WWW-based search facilities for on-line use. SBASE 7.0 is freely available by anonymous 'ftp' file transfer from ftp.icgeb. trieste.it. Automated searching of SBASE with BLAST can be carried out with the WWW servers http://www.icgeb.trieste.it/sbase/and http://sbase.abc.hu/sbase/     

IS: a web-site for intron statistics

SUMMARY: A web server has been established for the statistical evaluation of introns in various taxonomic groups and the comparison of taxonomic groups in terms of intron type, length, base composition, etc. The options include the graphic analysis of splice sites and a probability test for exon-shuffling within the selected group. AVAILABILITY: introns.abc.hu, http://www.icgeb.trieste.it/introns     

ToolShop: prerelease inspections for protein structure prediction servers.

The ToolShop server offers a possibility to compare a protein tertiary structure prediction server with other popular servers before releasing it to the public. The comparison is conducted on a set of 203 proteins and the collected models are compared with over 20 other programs using various assessment procedures. The evaluation lasts circa one week. AVAILABILITY: The ToolShop server is available at http://BioInfo.PL/ToolShop/. The administrator should be contacted to couple the tested server to the evaluation suite. CONTACT: leszek@bioinfo.pl SUPPLEMENTARY INFORMATION: The evaluation procedures are similar to those implemented in the continuous online server evaluation program, LiveBench. Additional information is available from its homepage (http://BioInfo.PL/LiveBench/).     

The SBASE protein domain library, release 8.0: a collection of annotated protein sequence segments

SBASE 8.0 is the eighth release of the SBASE library of protein domain sequences that contains 294 898 annotated structural, functional, ligand-binding and topogenic segments of proteins, cross-referenced to most major sequence databases and sequence pattern collections. The entries are clustered into over 2005 statistically validated domain groups (SBASE-A) and 595 non-validated groups (SBASE-B), provided with several WWW-based search and browsing facilities for online use. A domain-search facility was developed, based on non-parametric pattern recognition methods, including artificial neural networks. SBASE 8.0 is freely available by anonymous 'ftp' file transfer from ftp.icgeb.trieste.it. Automated searching of SBASE can be carried out with the WWW servers http://www.icgeb.trieste.it/sbase/ and http://sbase.abc. hu/sbase/.     

iCancer-Pred: A tool for identifying cancer and its type using DNA methylation

DNA methylation is an important epigenetics, which occurs in the early stages of tumor formation. And it also is of great significance to find the relationship between DNA methylation and cancer. This paper proposes a novel model, iCancer-Pred, to identify cancer and classify its types further. The datasets of DNA methylation information of 7 cancer types have been collected from The Cancer Genome Atlas (TCGA). The coefficient of variation firstly is used to reduce the number of features, and then the elastic network is applied to select important features. Finally, a fully connected neural network is constructed with these selected features. In predicting seven types of cancers, iCancer-Pred has achieved an overall accuracy of over 97% accuracy with 5-fold cross-validation. For the convenience of the application, a user-friendly web server: http://bioinfo.jcu.edu.cn/cancer or http://121.36.221.79/cancer/ is available. And the source codes are freely available for download at https://github.com/Huerhu/iCancer-Pred.     

Identification and measurement of neighbor-dependent nucleotide substitution processes

MOTIVATION: Neighbor-dependent substitution processes generated specific pattern of dinucleotide frequencies in the genomes of most organisms. The CpG-methylation-deamination process is, e.g. a prominent process in vertebrates (CpG effect). Such processes, often with unknown mechanistic origins, need to be incorporated into realistic models of nucleotide substitutions. RESULTS: Based on a general framework of nucleotide substitutions we developed a method that is able to identify the most relevant neighbor-dependent substitution processes, estimate their relative frequencies and judge their importance in order to be included into the modeling. Starting from a model for neighbor independent nucleotide substitution we successively added neighbor-dependent substitution processes in the order of their ability to increase the likelihood of the model describing given data. The analysis of neighbor-dependent nucleotide substitutions based on repetitive elements found in the genomes of human, zebrafish and fruit fly is presented. AVAILABILITY: A web server to perform the presented analysis is freely available at: http://evogen.molgen.mpg.de/server/substitution-analysis     

Phylogenetic reconstruction from non-genomic data

MOTIVATION: Recent results related to horizontal gene transfer suggest that phylogenetic reconstruction cannot be determined conclusively from sequence data, resulting in a shift from approaches based on polymorphism information in DNA or protein sequence to studies aimed at understanding the evolution of complete biological processes. The increasing amount of available information on metabolic pathways for several species makes it of greater relevance to understand the similarities and differences among such pathways. These similarities can then be used to infer phylogenetic trees not based exclusively in sequence data, therefore avoiding the previously mentioned problems. RESULTS: In this article, we present a method to assess the structural similarity of metabolic pathways for several organisms. Our algorithms work by using one of the three possible enzyme similarity measures (hierarchical, information content, gene ontology), and one of the two clustering methods (neighbor-joining, unweighted pair group method with arithmetic mean), to produce a phylogenetic tree both in Newick and graphic format. The web server implementing our algorithms is optimized to answer queries in linear time. AVAILABILITY: The software is available for free public use on a web server, at the address http://www.jaist.ac.jp/~clemente/cgi-bin/phylo.pl. It is available on demand in source code form for research use to educational institutions, non-profit research institutes, government research laboratories and individuals, for non-exclusive use, without the right of the licensee to further redistribute the source code.     

Pcons: a neural-network-based consensus predictor that improves fold recognition

During recent years many protein fold recognition methods have been developed, based on different algorithms and using various kinds of information. To examine the performance of these methods several evaluation experiments have been conducted. These include blind tests in CASP/CAFASP, large scale benchmarks, and long-term, continuous assessment with newly solved protein structures. These studies confirm the expectation that for different targets different methods produce the best predictions, and the final prediction accuracy could be improved if the available methods were combined in a perfect manner. In this article a neural-network-based consensus predictor, Pcons, is presented that attempts this task. Pcons attempts to select the best model out of those produced by six prediction servers, each using different methods. Pcons translates the confidence scores reported by each server into uniformly scaled values corresponding to the expected accuracy of each model. The translated scores as well as the similarity between models produced by different servers is used in the final selection. According to the analysis based on two unrelated sets of newly solved proteins, Pcons outperforms any single server by generating approximately 8%-10% more correct predictions. Furthermore, the specificity of Pcons is significantly higher than for any individual server. From analyzing different input data to Pcons it can be shown that the improvement is mainly attributable to measurement of the similarity between the different models. Pcons is freely accessible for the academic community through the protein structure-prediction metaserver at http://bioinfo.pl/meta/.     

A resource for benchmarking the usefulness of protein structure models

ABSTRACT: BACKGROUND: Increasingly, biologists and biochemists use computational tools to design experiments to probe the function of proteins and/or to engineer them for a variety of different purposes. The most effective strategies rely on the knowledge of the three-dimensional structure of the protein of interest. However it is often the case that an experimental structure is not available and that models of different quality are used instead. On the other hand, the relationship between the quality of a model and its appropriate use is not easy to derive in general, and so far it has been analyzed in detail only for specific application RESULTS: This paper describes a database and related software tools that allow testing of a given structure based methods on models of a protein representing different levels of accuracy. The comparison of the results of a computational experiment on the experimental structure and on a set of its decoy models will allow developers and users to assess which is the specific threshold of accuracy required to perform the task effectively. CONCLUSIONS: The ModelDB server automatically builds decoy models of different accuracy for a given protein of known structure and provides a set of useful tools for their analysis. Pre-computed data for a non-redundant set of deposited protein structures are available for analysis and download in the ModelDB database.     

VISTA : visualizing global DNA sequence alignments of arbitrary length

Summary: VISTA is a program for visualizing global DNA sequence alignments of arbitrary length. It has a clean output, allowing for easy identification of similarity, and is easily configurable, enabling the visualization of alignments of various lengths at different levels of resolution. It is currently available on the web, thus allowing for easy access by all researchers. Availability: VISTA server is available on the web at http://www-gsd.lbl.gov/vista. The source code is available upon request. Contact: vista@lbl.gov     

GenNon-h: Generating multiple sequence alignments on nonhomogeneous phylogenetic trees

ABSTRACT: BACKGROUND: A number of software packages are available to generate DNA multiple sequence alignments (MSAs) evolved under continuous-time Markov processes on phylogenetic trees. On the other hand, methods of simulating the DNA MSA directly from the transition matrices do not exist. Moreover, existing software restricts to the time-reversible models and it is not optimized to generate nonhomogeneous data (i.e. placing distinct substitution rates at different lineages). RESULTS: We present the first package designed to generate MSAs evolving under discrete-time Markov processes on phylogenetic trees, directly from probability substitution matrices. Based on the input model and a phylogenetic tree in the Newick format (with branch lengths measured as the expected number of substitutions per site), the algorithm produces DNA alignments of desired length. GenNon-h is publicly available for download. CONCLUSION: The software presented here is an efficient tool to generate DNA MSAs on a given phylogenetic tree. GenNon-h provides the user with the nonstationary or nonhomogeneous phylogenetic data that is well suited for testing complex biological hypotheses, exploring the limits of the reconstruction algorithms and their robustness to such models.