MAO: a Multiple Alignment Ontology for nucleic acid and protein sequences

The application of high-throughput techniques such as genomics, proteomics or transcriptomics means that vast amounts of heterogeneous data are now available in the public databases. Bioinformatics is responding to the challenge with new integrated management systems for data collection, validation and analysis. Multiple alignments of genomic and protein sequences provide an ideal environment for the integration of this mass of information. In the context of the sequence family, structural and functional data can be evaluated and propagated from known to unknown sequences. However, effective integration is being hindered by syntactic and semantic differences between the different data resources and the alignment techniques employed. One solution to this problem is the development of an ontology that systematically defines the terms used in a specific domain. Ontologies are used to share data from different resources, to automatically analyse information and to represent domain knowledge for non-experts. Here, we present MAO, a new ontology for multiple alignments of nucleic and protein sequences. MAO is designed to improve interoperation and data sharing between different alignment protocols for the construction of a high quality, reliable multiple alignment in order to facilitate knowledge extraction and the presentation of the most pertinent information to the biologist

Monophyly of lampreys and hagfishes supported by nuclear DNA-coded genes

Abstract. The phylogenetic position of hagfishes in vertebrate evolution is currently controversial. The 18S and 28S rRNA trees support the monophyly of hagfishes and lampreys. In contrast, the mitochondrial DNAs suggest the close association of lampreys and gnathostomes. To clarify this controversial issue, we have conducted cloning and sequencing of the four nuclear DNA-coded single-copy genes encoding the triose phosphate isomerase, calreticulin, and the largest subunit of RNA polymerase II and III. Based on these proteins, together with the Mn superoxide dismutase for which hagfish and lamprey sequences are available in database, phylogenetic trees have been inferred by the maximum likelihood (ML) method of protein phylogeny. It was shown that all the five proteins prefer the monophyletic tree of cyclostomes, and the total log-likelihood of the five proteins significantly supports the cyclostome monophyly at the level of ±1 SE. The ML trees of aldolase family comprising three nonallelic isoforms and the complement component group comprising C3, C4, and C5, both of which diverged during vertebrate evolution by gene duplications, also suggest the cyclostome monophyly

Association between the rs1465040 single-nucleotide polymorphism close to the transient receptor potential subfamily C member 3 (TRPC3) gene and postoperative analgesic requirements

AbstractAn association between postoperative analgesic requirements in subjects who underwent orthognathic surgery and the rs1465040 single-nucleotide polymorphism close to the transient receptor potential subfamily C member 3 (TRPC3) gene was suggested by our previous genome-wide association study. To verify this association, we analyzed the association between the rs1465040 SNP and analgesic requirements, including opioid requirements, after open abdominal surgery. The association between the rs1465040 SNP and postoperative analgesic requirements was confirmed in the open abdominal surgery group (P = 0.036), suggesting that the TRPC3 SNP may contribute to predicting postoperative analgesic requirements

Associations between the orexin (hypocretin) receptor 2 gene polymorphism Val308Ile and nicotine dependence in genome-wide and subsequent association studies

Impact of the HCRTR2 gene risk variant on schizotypal personality traits (mean ± SD). (DOC 54 kb

Improved accuracy of multiple ncRNA alignment by incorporating structural information into a MAFFT-based framework

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusion</p> <p>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.</p

Association between KCNJ6 (GIRK2) Gene Polymorphisms and Postoperative Analgesic Requirements after Major Abdominal Surgery

Opioids are commonly used as effective analgesics for the treatment of acute and chronic pain. However, considerable individual differences have been widely observed in sensitivity to opioid analgesics. We focused on a G-protein-activated inwardly rectifying potassium (GIRK) channel subunit, GIRK2, that is an important molecule in opioid transmission. In our initial polymorphism search, a total of nine single-nucleotide polymorphisms (SNPs) were identified in the whole exon, 5′-flanking, and exon-intron boundary regions of the KCNJ6 gene encoding GIRK2. Among them, G-1250A and A1032G were selected as representative SNPs for further association studies. In an association study of 129 subjects who underwent major open abdominal surgery, the A/A genotype in the A1032G SNP and -1250G/1032A haplotype were significantly associated with increased postoperative analgesic requirements compared with other genotypes and haplotypes. The total dose (mean±SEM) of rescue analgesics converted to equivalent oral morphine doses was 20.45±9.27 mg, 10.84±2.24 mg, and 13.07±2.39 mg for the A/A, A/G, and G/G genotypes in the A1032G SNP, respectively. Additionally, KCNJ6 gene expression levels in the 1032A/A subjects were significantly decreased compared with the 1032A/G and 1032G/G subjects in a real-time quantitative PCR analysis using human brain tissues, suggesting that the 1032A/A subjects required more analgesics because of lower KCNJ6 gene expression levels and consequently insufficient analgesic effects. The results indicate that the A1032G SNP and G-1250A/A1032G haplotype could serve as markers that predict increased analgesic requirements. Our findings will provide valuable information for achieving satisfactory pain control and open new avenues for personalized pain treatment