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Biomedical subjects

Hideo Matsuda

Publications and source records attributed to Hideo Matsuda.

6 recordsLinked to original sources

Graph-based clustering for finding distant relationships in a large set of protein sequences.

MOTIVATION: Clustering of protein sequences is widely used for the functional characterization of proteins. However, it is still not easy to cluster distantly-related proteins, which have only regional similarity among their sequences. It is therefore necessary to develop an algorithm for clustering such distantly-related proteins. RESULTS: We have developed a time and space efficient clustering algorithm. It uses a graph representation where its vertices and edges denote proteins and their sequence similarities above a certain cutoff score, respectively. It repeatedly partitions the graph by removing edges that have small weights, which correspond to low sequence similarities. To find the appropriate partitions, we introduce a score combining the normalized cut and a locally minimal cut capacities. Our method is applied to the entire 40,703 human proteins in SWISS-PROT and TrEMBL. The resulting clusters shows a 76% recall (20,529 proteins) of the 26,917 classified by InterPro. It also finds relationships not found by other clustering methods. AVAILABILITY: The complete result of our algorithm for all the human proteins in SWISS-PROT and TrEMBL, and other supplementary information are available at http://motif.ics.es.osaka-u.ac.jp/Ncut-KL/

Algorithms↗

FREP: a database of functional repeats in mouse cDNAs.

The FREP database (http://facts.gsc.riken.go.jp/FREP/) contains 31 396 RepeatMasker-identified non-redundant variant repeat sequences derived from 16,527 mouse cDNAs with protein-coding potential. The repeats were computationally associated with potential effects on transcriptional variation, translation, protein function or involvement in disease to identify Functional REPeats (FREPs). FREPs are defined by the (i) occurrence of exon-exon boundaries in repeats, (ii) presence of polyadenylation sites in 3'UTR-located repeats, (iii) effect on translation, (iv) position in the protein- coding region or protein domains or (v) conditional association with disease MeSH terms. Currently the database contains 9261 (29.5%) inferred FREPs derived from 6861 (41.5%) mouse cDNAs. Integrated evidence of the functional assignments and dynamically generated sequence similarity search results support the exploration and annotation of functional, ancestral or taxon-specific repeats. Keyword and pre-selected feature searches (e.g. coding sequence-repeat or splice site-repeat relations) support intuitive database querying as well as the retrieval of repeat sequences. Integrated sequence search and alignment tools allow the analysis of known or identification of new functional repeat candidates. FREP is a unique resource for illuminating the role of transposons and repetitive sequences in shaping the coding part of the mouse transcriptome and for selecting the appropriate experimental model to study diseases with suspected repeat etiology contributions.

Animals↗

Immunological and endocrinological studies on lymphocyte subpopulation and medical treatment for infertility in patients with endometriosis.

We investigated the relationship between interleukin-6 (IL-6) levels and subset profiles of T lymphocyte (T-cell) and macrophage in peritoneal fluid (PF) with or without endometriosis (EM). IL-6 levels in PF with EM were significantly higher than those without EM. IL-6 producing cells with EM were analyzed in each activated mature T-cell (CD3+CD69+) and macrophage (CD14+) were 0.5 and 3.5%, respectively, whereas it was mostly negative in those without EM. Cytotoxic T-cell (CD8+CD11b-) profiles in PF with EM were also quiet different from those without EM. Cellular immunity in the peripheral blood did not change during the course of IVF-ET cycles, although plasma levels of ovarian steroid hormones significantly increased comparing with that in normal ovarian cycles. Cytotoxic T-cell type 1 (Tc1) profiles might be useful predictive values in the pregnancy outcome for infertile patients with EM.

Ascitic Fluid↗

Mouse proteome analysis.

A general overview of the protein sequence set for the mouse transcriptome produced during the FANTOM2 sequencing project is presented here. We applied different algorithms to characterize protein sequences derived from a nonredundant representative protein set (RPS) and a variant protein set (VPS) of the mouse transcriptome. The functional characterization and assignment of Gene Ontology terms was done by analysis of the proteome using InterPro. The Superfamily database analyses gave a detailed structural classification according to SCOP and provide additional evidence for the functional characterization of the proteome data. The MDS database analysis revealed new domains which are not presented in existing protein domain databases. Thus the transcriptome gives us a unique source of data for the detection of new functional groups. The data obtained for the RPS and VPS sets facilitated the comparison of different patterns of protein expression. A comparison of other existing mouse and human protein sequence sets (e.g., the International Protein Index) demonstrates the common patterns in mammalian proteomes. The analysis of the membrane organization within the transcriptome of multiple eukaryotes provides valuable statistics about the distribution of secretory and transmembrane proteins

Animals↗

Development and evaluation of an automated annotation pipeline and cDNA annotation system.

Manual curation has long been held to be the "gold standard" for functional annotation of DNA sequence. Our experience with the annotation of more than 20,000 full-length cDNA sequences revealed problems with this approach, including inaccurate and inconsistent assignment of gene names, as well as many good assignments that were difficult to reproduce using only computational methods. For the FANTOM2 annotation of more than 60,000 cDNA clones, we developed a number of methods and tools to circumvent some of these problems, including an automated annotation pipeline that provides high-quality preliminary annotation for each sequence by introducing an "uninformative filter" that eliminates uninformative annotations, controlled vocabularies to accurately reflect both the functional assignments and the evidence supporting them, and a highly refined, Web-based manual annotation tool that allows users to view a wide array of sequence analyses and to assign gene names and putative functions using a consistent nomenclature. The ultimate utility of our approach is reflected in the low rate of reassignment of automated assignments by manual curation. Based on these results, we propose a new standard for large-scale annotation, in which the initial automated annotations are manually investigated and then computational methods are iteratively modified and improved based on the results of manual curation.

Animals↗

Exploration of novel motifs derived from mouse cDNA sequences.

We performed a systematic maximum density subgraph (MDS) detection of conserved sequence regions to discover new, biologically relevant motifs from a set of 21,050 conceptually translated mouse cDNA (FANTOM1) sequences. A total of 3202 candidate sequences, which shared similar regions over >20 amino acid residues, were screened against known conserved regions listed in Pfam, ProDom, and InterPro. The filtering procedure resulted in 139 FANTOM1 sequences belonging to 49 new motif candidates. Using annotations and multiple sequence alignment information, we removed by visual inspection 42 candidates whose members were found to be false positives because of sequence redundancy, alternative splicing, low complexity, transcribed retroviral repeat elements contained in the region of the predicted open reading frame, and reports in the literature. The remaining seven motifs have been expanded by hidden Markov model (HMM) profile searches of SWISS-PROT/TrEMBL from 28 FANTOM1 sequences to 164 members and analyzed in detail on sequence and structure level to elucidate the possible functions of motifs and members. The novel and conserved motif MDS00105 is specific for the mammalian inhibitor of growth (ING) family. Three submotifs MDS00105.1-3 are specific for ING1/ING1L, ING1-homolog, and ING3 subfamilies. The motif MDS00105 together with a PHD finger domain constitutes a module for ING proteins. Structural motif MDS00113 represents a leucine zipper-like motif. Conserved motif MDS00145 is a novel 1-acyl-SN-glycerol-3-phosphate acyltransferase (AGPAT) submotif containing a transmembrane domain that distinguishes AGPAT3 and AGPAT4 from all other acyltransferase domain-containing proteins. Functional motif MDS00148 overlaps with the kazal-type serine protease inhibitor domain but has been detected only in an extracellular loop region of solute carrier 21 (SLC21) (organic anion transporters) family members, which may regulate the specificity of anion uptake. Our motif discovery not only aided in the functional characterization of new mouse orthologs for potential drug targets but also allowed us to predict that at least 16 other new motifs are waiting to be discovered from the current SWISS-PROT/TrEMBL database.

1-Acylglycerol-3-Phosphate O-Acyltransferase↗