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Biomedical subjects

Masami Ikeda

Publications and source records attributed to Masami Ikeda.

11 recordsLinked to original sources

ConPred II: a consensus prediction method for obtaining transmembrane topology models with high reliability.

ConPred II (http://bioinfo.si.hirosaki-u.ac.jp/~ConPred2/) is a server for the prediction of transmembrane (TM) topology [i.e. the number of TM segments (TMSs), TMS positions and N-tail location] based on a consensus approach by combining the results of several proposed methods. The ConPred II system is constructed from ConPred_elite and ConPred_all (previously named ConPred), proposed earlier by our group. The prediction accuracy of ConPred_elite is almost 100%, which is achieved by sacrificing the prediction coverage (20-30%). ConPred_all predicts TM topologies for all the input sequences with accuracies improved by up to 11% over individual proposed methods. In the ConPred II system, the TM topology prediction of input TM protein sequences is executed following a two-step process: (i) input sequences are first run through the ConPred_elite program; (ii) sequences for which ConPred_elite does not give the TM topology are delivered to the ConPred_all program for TM topology prediction. Users can get access to the ConPred II system automatically by submitting sequences to the server. The ConPred II server will return the predicted TM topology models and graphical representations of their contents (hydropathy plots, helical wheel diagrams of predicted TMSs and snake-like diagrams).

Algorithms↗

ConPred_elite: a highly reliable approach to transmembrane topology predication.

The function of transmembrane (TM) proteins is closely correlated to their TM topology; large quantities of highly reliable TM topology data are becoming increasingly required. We present a new consensus approach for TM topology prediction (ConPred_elite) that can predict the whole topology with accuracies of 0.98 for prokaryotic and 0.95 for eukaryotic proteins on a dataset of experimentally-characterized TM topologies. The predicted yield on the dataset is 30.4% for prokaryotic and 21.5% for eukaryotic proteins. Applying ConPred_elite to predicted TM proteins extracted from 29 prokaryotic and 10 eukaryotic proteomes, we obtained 3871 and 7271 highly reliable TM topologies (yields, 19.8 and 13.3%), respectively. The predicted TM topology data may contribute to further research into a comprehensive functional classification and identification of TM proteins based on information of the topology.

Archaeal Proteins↗

Proteome-wide classification and identification of mammalian-type GPCRs by binary topology pattern.

G protein-coupled receptors (GPCRs), a large eukaryotic protein family, have proved difficult to comprehensively detect and functionally identify by homology searches and domain detection, because they are highly divergent and their sequences share strikingly little similarity. Transmembrane (TM) topology pattern analysis has been used to classify TM proteins, and such patterns are conserved within GPCRs of similar function. Here, we developed a stepwise binary topology pattern (BTP) method for GPCR classification and identification and used it to identify and classify mammalian-type GPCRs in the genomes of 10 different eukaryotic species. A binary topology pattern was obtained for each functional class or group by assigning binary loop threshold lengths of "0" (short loop) or "1" (long loop). The GPCR-classification ability of the BTP method had quite high accuracies for classifying GPCR functions at the class level (Classes A, B, C, Frizzled/Smoothened, Non-GPCR, based on the GPCRDB classification scheme), with many classes being classified with 100% accuracy. Sufficiently high accuracies were also maintained at the functional group level, 0.945 over 15 functional groups. Proteome-wide mammalian-type GPCR searches in 10 eukaryotic genomes (H. sapiens, M. musculus, F. rubripes, C. intestinalis, A. thaliana, D. melanogaster, A. gambiae, C. elegans, P. falciparum, S. cerevisiae) using the BTP method showed much higher classification/identification in non-mammalian genomes than typical BLAST searches, in which a higher number of sequences were classified as Non-GPCR. This stepwise BTP method should prove useful for the identification and functional classification of GPCRs from the genomes of a wide range of species.

Animals↗

[Human efficiency for symmetry detection on 3D bumpy surfaces].

Based on the ideal observer analysis, we investigated sampling properties of image information used by human visual system, for symmetrical pattern discrimination on 3D bumpy surface. There were three models of ideal observer (IO) to perform the task: 2D-IO using 2D projection image (i.e., retinal image), 2.5D-IO using image transformed to canonical view, and 3D-IO using recovered pattern image of 2D plane. We measured discrimination thresholds on the task for each IO model and subjects, and calculated human statistical efficiency relative to each ideal observer. The results indicated for the detection of a diagonal symmetry in the bumpy surface that human performance was similar to 3D-IO. This implies that human observers use the structure of the bumpy surface to detect the diagonal symmetry.

Adult↗

Genomic analysis of immunity in a Urochordate and the emergence of the vertebrate immune system: "waiting for Godot".

Genome-wide sequence analysis in the invertebrate chordate, Ciona intestinalis, has provided a comprehensive picture of immune-related genes in an organism that occupies a key phylogenetic position in vertebrate evolution. The pivotal genes for adaptive immunity, such as the major histocompatibility complex (MHC) class I and II genes, T-cell receptors, or dimeric immunoglobulin molecules, have not been identified in the Ciona genome. Many genes involved in innate immunity have been identified, including complement components, Toll-like receptors, and the genes involved in intracellular signal transduction of immune responses, and show both expansion and unexpected diversity in comparison with the vertebrates. In addition, a number of genes were identified which predicted integral membrane proteins with extracellular C-type lectin or immunoglobulin domains and intracellular immunoreceptor tyrosine-based inhibitory motifs (ITIMs) and immunoreceptor tyrosine-based activation motifs (ITAMs) (plus their associated signal transduction molecules), suggesting that activating and inhibitory receptors have an MHC-independent function and an early evolutionary origin. A crucial component of vertebrate adaptive immunity is somatic diversification, and the recombination activating genes (RAG) and activation-induced cytidine deaminase (AID) genes responsible for the Generation of diversity are not present in Ciona. However, there are key V regions, the essential feature of an immunoglobulin superfamily VC1-like core, and possible proto-MHC regions scattered throughout the genome waiting for Godot.

Animals↗

Comprehensive analysis of transmembrane topologies in prokaryotic genomes.

We analysed comprehensively transmembrane (TM) topologies of TM proteins of 50 selected prokaryotic genomes, by discriminating between TM and soluble proteins by using SOSUI, then detecting and removing signal peptides by applying 'DetecSig', and finally predicting TM topologies by employing 'ConPred'. Estimated fraction of TM proteins in proteome averaged over the 50 genomes is approximately 22%. About 13% of TM proteins were predicted to have a signal peptide, and the fraction of soluble proteins with signal peptide (secretory proteins) ranges from 8 to 18% for most majority of the genomes. The N(in)-type TM proteins with 2-, 4-, 6- and 12-tms (number of transmembrane segments) are predominant among multi-spanning TM proteins, and correspondingly, significantly higher fractions of N(out)-type TM proteins with 1-, 3-, 5- and 11-tms have a signal peptide. It is also found that the TM proteins with signal peptide tend to have a long N-tail loop. The averaged sequence length of TM proteins increases linearly with the increase of the number of TM segments, with the increasing rate of about 35 residues, suggesting a possibility that TM topologies might have been evolved by the 'internal gene duplication' mechanism. Datasets of TM topologies predicted in this study are available at http://bioinfo.si.hirosaki-u.ac.jp/ approximately TMPinGS/.

Archaea↗

TMPDB: a database of experimentally-characterized transmembrane topologies.

TMPDB is a database of experimentally-characterized transmembrane (TM) topologies. TMPDB release 6.2 contains a total of 302 TM protein sequences, in which 276 are alpha-helical sequences, 17 beta-stranded, and 9 alpha-helical sequences with short pore-forming helices buried in the membrane. The TM topologies in TMPDB were determined experimentally by means of X-ray crystallography, NMR, gene fusion technique, substituted cysteine accessibility method, N-linked glycosylation experiment and other biochemical methods. TMPDB would be useful as a test and/or training dataset in improving the proposed TM topology prediction methods or developing novel methods with higher performance, and as a guide for both the bioinformaticians and biologists to better understand TM proteins. TMPDB and its subsets are freely available at the following web site: http://bioinfo.si.hirosaki-u.ac.jp/~TMPDB/.

Animals↗

Reconstruction after distal gastrectomy by interposition of a double-jejunal pouch using a triangulating stapling technique.

Sustaining good nutrition and preventing postgastrectomy syndrome are important for increasing the quality of life after distal gastrectomy. Many surgeons have proposed surgical methods designed to enhance long-term patient quality of life. An immediate, safe method based on current physiologic reconstructive principles shown to reduce postoperative patient complaints is presented. A reconstructive method using a modified interpositioned double-jejunal pouch after distal gastrectomy in 18 cancer patients was reviewed. This method uses a triangulating stapling technique with wide end-to-side anastomosis between the residual stomach and the pouch. In all patients, the anastomosis site was without leakage or stenosis, and there were no episodes of severe reflux esophagitis, residual gastritis, or dumping syndrome. The mean pooling rate was 44.2%, and emptying half-time was 73.0 minutes. After 2 years the body weight was 91.3% of the preoperative weight, the food volume was 89.2% of normal intake, and meal frequency was 3.0 per day. This method of reconstruction is useful for immediate and safe creation of a wide anastomosis between the residual stomach and the double-jejunal pouch after distal gastrectomy and in the prevention of esophagitis and residual gastritis.

Adult↗

Ile-Leu substitution (I415L) in germline E-cadherin gene (CDH1) in Japanese familial gastric cancer.

BACKGROUND: Germline mutation in the cell adhesion molecule E-cadherin is known to be associated with the development of undifferentiated or diffuse-type familial gastric cancers, but the prevalence of this contribution seems to be low in Japanese familial cases, so far. METHODS: We screened all exons of the E-cadherin gene for mutations in 101 Japanese patients having an intense family history of gastric cancers. RESULTS: An abnormal band pattern was found in exon 9 in three patients (Y6, B21, B37) from two families by PCR-SSCP. DNA sequencing analysis of these three patients revealed isoleucine-leucine substitution at codon 415 in exon 9. B21 and B37 are siblings and the other three brothers died of gastric cancer and another brother (B36) has not been affected by gastric cancer to date. This case (B36) did not have this alteration in the exon 9 of E-cadherin. CONCLUSION: Although the mechanistic basis is not clear, our findings may provide a possibility that this additional missense mutation in germline E-cadherin gene may contribute to gastric cancer predisposition.

Cadherins↗

Transmembrane topology prediction methods: a re-assessment and improvement by a consensus method using a dataset of experimentally-characterized transmembrane topologies.

We selected 10 transmembrane (TM) prediction methods (KKD, TMpred, TopPred II, DAS, TMAP, MEMSAT 2, SOSUI, PRED-TMR2, TMHMM 2.0 and HMMTOP 2.0) and re-assessed its prediction performance using a reliable dataset with 122 entries of experimentally-characterized TM topologies. Then, we improved prediction performance by a consensus prediction method. Prediction performance during re-assessment and consensus prediction were based on four attributes: (i) the number of transmembrane segments (TMSs), (ii) the number of TMSs plus TMS-position, (iii) N-tail location and (iv) TM topology. We noted that hidden Markov model-based methods dominate over other methods by individual prediction performance for all four attributes. In addition, all top-performing methods generally were model-based. Among prokaryotic sequences, HMMTOP 2.0 solely topped among other methods with prediction accuracies ranging from 64% to 86% across all attributes. However, among eukaryotic sequences, prediction performance for all the attributes was relatively poor compared with prokaryotic ones. On the other hand, our results showed that our proposed consensus prediction method significantly improved prediction performance by, at least, an additional nine percentage points particularly among prokaryotic sequences for the number of TMS (84%), number of TMS and position (80%), and TM topology attributes (74%). Although our consensus prediction method improved also the prediction performance among eukaryotic sequences, the obtained accuracies for all attributes were relatively lower than that obtained by prokaryotic counterparts particularly for TM topology.

Cell Membrane↗