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Results: We demonstrate the robustness of our methods to sequencing and assembly errors using extensive experiments on simulated datasets. We then present the results obtained by applying our algorithms to data generated from two bacterial genomes Yersinia aldovae and Yersinia kristensenii. The resulting assemblies contain a single scaffold covering a large fraction of the respective genomes, suggesting that the careful use of optical maps can provide a cost-effective framework for the assembly of genomes.
Availability: The tools described here are available as an open-source package at
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Results: We developed a novel algorithm for predicting functional elements by combining statistical alignment and phylogenetic footprinting (SAPF). SAPF simultaneously performs both alignment and annotation by combining phylogenetic footprinting techniques with an hidden Markov model (HMM) transducer-based multiple alignment model, and can analyze sequence data from multiple sequences. We assessed SAPF's predictive performance on two simulated datasets and three well-annotated cis-regulatory modules from newly sequenced Drosophila genomes. The results demonstrate that removing the traditional dependence on a single alignment can significantly augment the predictive performance, especially when there is uncertainty in the alignment of functional regions.
Availability: SAPF is freely available to download online at
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Supplementary information: Supplementary data are available at Bioinformatics online.
]]>Results: HIV-1 protease sequences from patients subjected to different specific treatments (set 1), and from untreated patients (set 2) were subjected to sequence covariance analysis by evaluating the mutual information (MI) between all residue pairs. Spectral clustering of the resulting covariance matrices disclosed two distinctive clusters of correlated residues: the first, observed in set 1 but absent in set 2, contained residues involved in MDR acquisition; and the second, included those residues differentiated in the various HIV-1 protease subtypes, shortly referred to as the phylogenetic cluster. The MDR cluster occupies sites close to the central symmetry axis of the enzyme, which overlap with the global hinge region identified from coarse-grained normal-mode analysis of the enzyme structure. The phylogenetic cluster, on the other hand, occupies solvent-exposed and highly mobile regions. This study demonstrates (i) the possibility of distinguishing between the correlated substitutions resulting from neutral mutations and those induced by MDR upon appropriate clustering analysis of sequence covariance data and (ii) a connection between global dynamics and functional substitution of amino acids.
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Supplementary information: Supplementary data are available at Bioinformatics online.
]]>Results: We have developed a workflow, named daTAA, for the accurate domain annotation of TAAs. Its core consists of manually curated alignments and of knowledge-based rules that enhance assignments made by sequence similarity. Compared to general domain annotation servers such as PFAM, daTAA captures more domains and provides more sensitive domain detection, as well as integrated and detailed coiled-coil assignments.
Availability: The daTAA server is freely accessible at
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Supplementary information: Supplementary data are available at Bioinformatics online.
]]>Results: Rather than use a priori rules, which can be very subjective, to construct binary profiles from continuous phenotypes, we propose to systematically explore thresholds which can meaningfully separate the phenotype values. We illustrate our method by analyzing optimal growth temperatures, and demonstrate its usefulness by automatically retrieving genes which have been associated with thermophilic growth. We also apply the general approach, for the first time, to optimal growth pH, and make novel predictions. Finally, we show that our method can also be applied to other properties which may not be classically considered as phenotypes. Specifically, we studied correlations between genome size and the distribution of genes.
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Supplementary information: Supplementary data are available at Bioinformatics online.
]]>Results: The best performance which we report on the SCOP PDB-40D benchmark data-set is a 70% accuracy by combining all the available feature groups from global protein characteristics but also including sequence-alignment features. We offer an 8% improvement on the best reported performance that combines multi-class k-nn classifiers while at the same time reducing computational costs and assessing the predictive power of the various available features. Furthermore, we examine the performance of our methodology on the SCOP 1.53 benchmark data-set that simulates remote homology detection and examine the combination of various state-of-the-art string kernels that have recently been proposed.
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Supplementary information: Supplementary data are available at Bioinformatics online.
]]>Result: We have developed Membrane Insertion (MINS), a novel sequence-based computational method for predicting the membrane insertion free energies of protein sequences. A benchmark test gives a correlation coefficient of 0.74 between predicted and observed free energies for 357 known cases, which corresponds to a mean unsigned error of 0.41 kcal/mol. These results are significantly better than those obtained by traditional hydropathy analysis. Moreover, the ability of MINS to reasonably predict membrane insertion free energies of protein sequences allows for effective identification of transmembrane (TM) segments. Subsequently, MINS was applied to predict the membrane insertion free energies of 316 TM segments found in known structures. An in-depth analysis of the predicted free energies reveals a number of interesting findings about the biogenesis and structural stability of HMPs.
Availability: A web server for MINS is available at
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Supplementary information: Supplementary data are available at Bioinformatic online.
]]>Results: The experiments showed that finiteness of both probe and target molecules should be considered to explain the hybridization behavior. In this article, we present an extension of the Langmuir model that reproduces the experimental results consistently. In this model, we introduced the effects of secondary structure formation, and dissociation of the probe–target duplex during washing after hybridization. The results will provide useful methods for the understanding and analysis of microarray experiments.
Availability: The method was implemented for the R software and can be downloaded from our website (
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Supplementary information: Supplementary data are available at Bioinformatics online.
]]>Results: A novel algorithm for the inference of biomolecular interaction networks from temporal expression data is presented. Linear time-varying models, which can represent a much wider class of time-series data than linear time-invariant models, are employed in the algorithm. From time-series expression profiles, the model parameters are identified by solving a non-linear optimization problem. In order to systematically reduce the set of possible solutions for the optimization problem, a filtering process is performed using a phase-portrait analysis with random numerical perturbations. The proposed approach has the advantages of not requiring the system to be in a stable steady state, of using time-series profiles which have been generated by a single experiment, and of allowing non-linear network interactions to be identified. The ability of the proposed algorithm to correctly infer network interactions is illustrated by its application to three examples: a non-linear model for cAMP oscillations in Dictyostelium discoideum, the cell-cycle data for Saccharomyces cerevisiae and a large-scale non-linear model of a group of synchronized Dictyostelium cells.
Availability: The software used in this article is available from
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Supplementary information: Supplementary data are available at Bioinformatics online.
]]>Results: We propose a peak bagging method for single MS-based protein identification. It combines results from multiple PMF algorithms, where each PMF algorithm takes a random peak subset as input. Evaluation with a set of real MALDI-TOF MS spectra shows that the new peak bagging method provides consistent improvements over the single PMF algorithm.
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Results: ASPicDB is a database designed to provide access to reliable annotations of the alternative splicing pattern of human genes and to the functional annotation of predicted splicing isoforms. Splice-site detection and full-length transcript modeling have been carried out by a genome-wide application of the ASPic algorithm, based on the multiple alignments of gene-related transcripts (typically a Unigene cluster) to the genomic sequence, a strategy that greatly improves prediction accuracy compared to methods based on independent and progressive alignments.
Enhanced query and download facilities for annotations and sequences allow users to select and extract specific sets of data related to genes, transcripts and introns fulfilling a combination of user-defined criteria. Several tabular and graphical views of the results are presented, providing a comprehensive assessment of the functional implication of alternative splicing in the gene set under investigation.
ASPicDB, which is regularly updated on a monthly basis, also includes information on tissue-specific splicing patterns of normal and cancer cells, based on available EST sequences and their library source annotation.
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Supplementary information: Supplementary data are available at Bioinformatics online.
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Availability: CompariMotif can be run online at
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Supplementary information: Further details are available at
Availability: MTMDAT can be downloaded from the following page:
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Availability:
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Supplementary information: Supplementary data are available on Bioinformatics online.
]]>We created design rules for predicting the likelihood of a non-specific effect and present a web server that allows the user to check the specificity of a given siRNA in a flexible manner using a combination of methods. The server finds potential off-target matches in the corresponding RefSeq database and ranks them according to a scoring system based on experimental studies of specificity.
Availability: The server is available at
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Supplementary information: Supplementary analysis and figures are available at Bioinformatics online.
]]>Availability: RENCO is a C++ command line program, available at
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Supplementary information: Supplementary data are available at Bioinformatics online.
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