Multiple sequence alignment (MSA) is an important step in comparative sequence analyses. Parallelization is a key technique for reducing the time required for large-scale sequence analyses. The three ...calculation stages, all-to-all comparison, progressive alignment and iterative refinement, of the MAFFT MSA program were parallelized using the POSIX Threads library. Two natural parallelization strategies (best-first and simple hill-climbing) were implemented for the iterative refinement stage. Based on comparisons of the objective scores and benchmark scores between the two approaches, we selected a simple hill-climbing approach as the default. Availability: The parallelized version of MAFFT is available at http://mafft.cbrc.jp/alignment/software/. This version currently supports the Linux operating system only. Contact: kazutaka.katoh@aist.go.jp Supplementary information: Supplementary data are available at Bioinformatics online.
Structural alignment of RNAs is becoming important, since the discovery of functional non-coding RNAs (ncRNAs). Recent studies, mainly based on various approximations of the Sankoff algorithm, have ...resulted in considerable improvement in the accuracy of pairwise structural alignment. In contrast, for the cases with more than two sequences, the practical merit of structural alignment remains unclear as compared to traditional sequence-based methods, although the importance of multiple structural alignment is widely recognized.
We took a different approach from a straightforward extension of the Sankoff algorithm to the multiple alignments from the viewpoints of accuracy and time complexity. As a new option of the MAFFT alignment program, we developed a multiple RNA alignment framework, X-INS-i, which builds a multiple alignment with an iterative method incorporating structural information through two components: (1) pairwise structural alignments by an external pairwise alignment method such as SCARNA or LaRA and (2) a new objective function, Four-way Consistency, derived from the base-pairing probability of every sub-aligned group at every multiple alignment stage.
The BRAliBASE benchmark showed that X-INS-i outperforms other methods currently available in the sum-of-pairs score (SPS) criterion. As a basis for predicting common secondary structure, the accuracy of the present method is comparable to or rather higher than those of the current leading methods such as RNA Sampler. The X-INS-i framework can be used for building a multiple RNA alignment from any combination of algorithms for pairwise RNA alignment and base-pairing probability. The source code is available at the webpage found in the Availability and requirements section.
Background:A thorough understanding of the anatomy of the aortic valve is necessary for aortic valve-sparing surgery. Normal valvar dimensions and their relationships in the living heart, however, ...have yet to be fully investigated in a 3-dimensional fashion.Methods and Results:In total, 123 consecutive patients (66±12 years, Men 63%) who underwent coronary computed tomographic angiography were enrolled. Mid-diastolic morphology of the aortic roots, including height of the interleaflet triangles, geometric height, free margin length of each leaflet, effective height, and coaptation length were measured using multiplanar reconstruction images. Average height of the interleaflet triangle, geometric height, free margin length, effective height, and the coaptation length were 17.3±1.8, 14.7±1.3, 32.6±3.6, 8.6±1.4, and 3.2±0.8 mm, respectively. The right coronary aortic leaflet displayed the longest free margin length and shortest geometric height. Geometric height, free margin length, and effective height showed positive correlations with aortic root dimensions. Coaptation length, however, remained constant regardless of aortic root dimensions.Conclusions:Diversities, as well as characteristic relationships among each value involving the aortic root, were identified using living-heart datasets. The aortic leaflets demonstrated compensatory elongation along with aortic root dilatation to maintain constant coaptation length. These measurements will serve as the standard value for revealing the underlying mechanism of aortic regurgitation to plan optimal aortic valve-sparing surgery.
Abstract
Aims
Mitral annular disjunction is fibrous separation between the attachment of the posterior mitral leaflet and the basal left ventricular myocardium initially described in dissected ...hearts. Currently, it is commonly evaluated by echocardiography, and potential relationships with mitral valve prolapse and ventricular arrhythmia have been suggested. However, controversy remains as its prevalence and extent have not been fully elucidated in normal living subjects.
Methods and results
Systolic datasets of cardiac computed tomography obtained from 98 patients (mean age, 69.1 ± 12.6 years; 81% men) with structurally normal hearts were assessed retrospectively. Circumferential extent of both mitral leaflets and disjunction was determined by rotating orthogonal multiplanar reconstruction images around the central axis of the mitral valvar orifice. Distribution angle within the circumference of the mitral valvar attachment and maximal height of disjunction were quantified. In total, 96.0% of patients demonstrated disjunction. Average distribution angles of the anterior and posterior mitral leaflets were 91.3 ± 9.4° and 269.8 ± 9.7°, respectively. Average distribution angle of the disjunction was 105.1 ± 49.2°, corresponding to 39.0 ± 18.2% of the entire posterior mitral valvar attachment. Median value of the maximal height of disjunction was 3.0 (1.5–7.0) mm. Distribution prevalence map of the disjunction revealed characteristic double peaks, with frequent sites of the disjunction located at the anterior to antero-lateral and inferior to infero-septal regions.
Conclusion
Mitral annular disjunction is a rather common finding in the normal adult heart with bimodal distribution predominantly observed involving the P1 and P3 scallops of the posterior mitral leaflet.
Conservation and variation scores are used when evaluating sites in a multiple sequence alignment, in order to identify residues critical for structure or function. A variety of scores are available ...today but it is not clear how different scores relate to each other.
We applied 25 conservation and variation scores to alignments from the Catalytic Site Atlas (CSA). We calculated distances among scores based on correlation coefficients, and constructed a dendrogram of the scores by average linking cluster analysis. The cluster analysis showed that most scores fall into one of two groups--substitution matrix based group and frequency based group respectively. We also evaluated the scores' performance in predicting catalytic sites and found that frequency based scores generally perform best.
Conservation and variation scores can be classified into mainly two large groups. When using a score to predict catalytic sites, frequency based scores that also consider a background distribution are most successful.
Intrinsic protein disorder is a widespread phenomenon characterised by a lack of stable three-dimensional structures and is considered to play an important role in protein–protein interactions ...(PPIs). This study examined the genome-wide preference of disorder in PPIs by using exhaustive disorder prediction in human PPIs. We categorised the PPIs into three types (interaction between disordered proteins, interaction between structured proteins, and interaction between a disordered protein and a structured protein) with regard to the flexibility of molecular recognition and compared these three interaction types in an existing human PPI network with those in a randomised network. Although the structured regions were expected to become the identifiers for binding recognition, this comparative analysis revealed unexpected results. The occurrence of interactions between disordered proteins was significantly frequent, and that between a disordered protein and a structured protein was significantly infrequent. We found that this propensity was much stronger in interactions between nonhub proteins. We also analysed the interaction types from a functional standpoint by using GO, which revealed that the interaction between disordered proteins frequently occurred in cellular processes, regulation, and metabolic processes. The number of interactions, especially in metabolic processes between disordered proteins, was 1.8 times as large as that in the randomised network. Another analysis conducted by using KEGG pathways provided results where several signaling pathways and disease-related pathways included many interactions between disordered proteins. All of these analyses suggest that human PPIs preferably occur between disordered proteins and that the flexibility of the interacting protein pairs may play an important role in human PPI networks.
The hepatitis delta virus is a single-stranded circular RNA virus, which is characterized by high self-complementarity. About 70% of the genome sequences can form base-pairs with internal ...nucleotides. There are many studies on the evolution of the hepatitis delta virus. However, the secondary structure has not been taken into account in these studies. In this study, we developed a method to examine the effect of base pairing as a constraint on the nucleotide substitutions during the evolution of the hepatitis delta virus. The method revealed that the base pairing can reduce the evolutionary rate in the non-coding region of the virus. In addition, it is suggested that the non-coding nucleotides without base pairing may be under some constraint, and that the intensity of the constraint is weaker than that by the base pairing but stronger than that on the synonymous site.
Motivation: To construct a multiple sequence alignment (MSA) of a large number (>∼10 000) of sequences, the calculation of a guide tree with a complexity of O(N2) to O(N3), where N is the number of ...sequences, is the most time-consuming process. Results: To overcome this limitation, we have developed an approximate algorithm, PartTree, to construct a guide tree with an average time complexity of O(N log N). The new MSA method with the PartTree algorithm can align ∼60 000 sequences in several minutes on a standard desktop computer. The loss of accuracy in MSA caused by this approximation was estimated to be several percent in benchmark tests using Pfam. Availability: The present algorithm has been implemented in the MAFFT sequence alignment package (). Contact:katoh@bioreg.kyushu-u.ac.jp Supplementary information: Supplementary information is available at Bioinformatics online.
The GGIP web server (https://protein.b.dendai.ac.jp/GGIP/) provides a web application for GPCR-GPCR interaction pair prediction by a support vector machine. The server accepts two sequences in the ...FASTA format. It responds with a prediction that the input GPCR sequence pair either interacts or not. GPCRs predicted to interact with the monomers constituting the pair are also shown when query sequences are human GPCRs. The server is simple to use. A pair of amino acid sequences in the FASTA format is pasted into the text area, a PDB ID for a template structure is selected, and then the 'Execute' button is clicked. The server quickly responds with a prediction result. The major advantage of this server is that it employs the GGIP software, which is presently the only method for predicting GPCR-interaction pairs. Our web server is freely available with no login requirement. In this article, we introduce some application examples of GGIP for disease-associated mutation analysis.
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