Logical Operation Based Literature Association with Genes and its application, PosMed.

PosMed prioritizes candidate genes for positional cloning by employing our original database search engine GRASE, which uses an inferential process similar to an artificial neural network comprising documental neurons (or 'documentrons') that represent each document contained in databases such as MEDLINE and OMIM (Yoshida, _et al_. 2009, Makita, _et al_. 2009). PosMed immediately ranks the candidate genes by connecting phenotypic keywords to the genes through connections representing gene–gene interactions other biological relationships, such as metabolite–gene, mutant mouse–gene, drug–gene, disease–gene, and protein–protein interactions, ortholog data, and gene–literature connections.

To make proper relationships between genes and literature, we manually curate queries, which are defined by logical operation rules, against MEDLINE. For example, to detect a set of MEDLINE documents for the AT1G03880 gene in _A. thaliana_, we applied the following logical query: (‘AT1G03880’ OR ‘CRU2’ OR ‘CRB’ OR ‘CRUCIFERIN 2' OR ‘CRUCIFERIN B’) AND (‘Arabidopsis’) NOT (‘chloroplast RNA binding’). Curators refined these queries in mouse, rice and _A. thaliana_. For human and rat genes, we use mouse curation results via ortholog genes in PosMed.

PosMed is available at "http://omicspace.riken.jp/PosMed":http://omicspace.riken.jp/PosMed

References:
Yoshida Y, et al. _Nucleic Acids Res_. 37(Web Server issue):W147-52. 2009. 
Makita Y, et al. _Plant Cell Physiol_. 2009 Jul;50(7):1249-59.
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ECOMICS: A Web-Based Toolkit for Investigating the Biomolecular Web in Ecosystems Using a Trans-omics Approach

Ecosystems can be conceptually thought of as interconnected environmental and metabolic systems, in which small molecules to macro-molecules interact through diverse networks. State-of-the-art technologies in post-genomic science offer ways to inspect and analyze this biomolecular web using omics-based approaches. Exploring useful genes and enzymes, as well as biomass resources responsible for anabolism and catabolism within ecosystems will contribute to a better understanding of environmental functions and their application to biotechnology. Here we present ECOMICS, a suite of web-based tools for ECosystem trans-OMICS investigation that target metagenomic, metatranscriptomic, and meta-metabolomic systems, including biomacromolecular mixtures derived from biomass. ECOMICS is made of four integrated webtools. E-class allows for the sequence-based taxonomic classification of eukaryotic and prokaryotic ribosomal data and the functional classification of selected enzymes. FT2B allows for the digital processing of NMR spectra for downstream metabolic or chemical phenotyping. Bm-Char allows for statistical assignment of specific compounds found in lignocellulose-based biomass, and HetMap is a data matrix generator and correlation calculator that can be applied to trans-omics datasets as analyzed by these and other web tools. This web suite is unique in that it allows for the monitoring of biomass metabolism in a particular environment, i.e., from macromolecular complexes (FT2DB and Bm-Char) to microbial composition and degradation (E-class), and makes possible the understanding of relationships between molecular and microbial elements (HetMap). This website is available to the public domain at: https://database.riken.jp/ecomics/

Crystal structure of o-(p-N,N-dimethylaminobenzoyl)benzoic acid

金沢大学大学院自然科学研究科先端機能物質金沢大学工学

Semantic-JSON: a lightweight web service interface for Semantic Web contents integrating multiple life science databases

Global cloud frameworks for bioinformatics research databases become huge and heterogeneous; solutions face various diametric challenges comprising cross-integration, retrieval, security and openness. To address this, as of March 2011 organizations including RIKEN published 192 mammalian, plant and protein life sciences databases having 8.2 million data records, integrated as Linked Open or Private Data (LOD/LPD) using SciNetS.org, the Scientists' Networking System. The huge quantity of linked data this database integration framework covers is based on the Semantic Web, where researchers collaborate by managing metadata across public and private databases in a secured data space. This outstripped the data query capacity of existing interface tools like SPARQL. Actual research also requires specialized tools for data analysis using raw original data. To solve these challenges, in December 2009 we developed the lightweight Semantic-JSON interface to access each fragment of linked and raw life sciences data securely under the control of programming languages popularly used by bioinformaticians such as Perl and Ruby. Researchers successfully used the interface across 28 million semantic relationships for biological applications including genome design, sequence processing, inference over phenotype databases, full-text search indexing and human-readable contents like ontology and LOD tree viewers. Semantic-JSON services of SciNetS.org are provided at http://semanticjson.org

Involvement of CD11b+ GR-1low cells in autoimmune disorder in MRL-Faslpr mouse

金沢大学医薬保健研究域医学系Objective: Myeloid-derived suppressor cells (MDSCs) have been identified as immunosuppressive cells in tumor-related inflammation. However, the pathogenesis of MDSCs for autoimmune disease has not been investigated as yet. The aim of this study was to address whether MDSCs contribute to autoimmune organ injury in lupus-prone mice. Methods: MDSCs were analyzed by flow cytometric staining of CD11b+ GR-1+ in MRL-Faslpr mice. CD4+ T-cell proliferation assay was performed by coculture with CD11b+ GR-1+ splenocytes. The percentage of immunosuppressive cells was examined during disease progression. Expression of chemokine receptor on immunosuppressive cells was analyzed, and chemotaxis assay was performed. Results: CD11b+ GR-1low cells had a suppressive effect on CD4+ T-cell proliferation, which was restored by an arginase-1 inhibitor. CD11b+ GR-1low cells increased in percentage during disease progression in kidney and blood. The number of migrated CD11b+ GR-1low cells increased in the presence of monocyte chemoattractant protein-1/CCL2. Conclusion: We assessed the involvement of CD11b+ GR-1low cells in autoimmune disorder in MRL-Faslpr mice. These cells regulate immunological responses via CCL2/CCR2 signaling. The regulation of immunosuppressive monocytes may provide novel therapeutic strategy for organ damage in autoimmune diseases. © 2010 Japanese Society of Nephrology.

PosMed: ranking genes and bioresources based on Semantic Web Association Study

ABSTRACT Positional MEDLINE (PosMed; http://biolo

Collagen adhesion gene is associated with blood stream infections caused by methicillin-resistant Staphylococcus aureus

Objectives: Methicillin-resistant Staphylococcus aureus (MRSA) causes hospital- and community-acquired infections. It is not clear whether genetic characteristics of the bacteria contribute to disease pathogenesis in MRSA infection. We hypothesized that whole genome analysis of MRSA strains could reveal the key gene loci and/or the gene mutations that affect clinical manifestations of MRSA infection. Methods: Whole genome sequences (WGS) of MRSA of 154 strains were analyzed with respect to clinical manifestations and data. Further, we evaluated the association between clinical manifestations in MRSA infection and genomic information. Results: WGS revealed gene mutations that correlated with clinical manifestations of MRSA infection. Moreover, 12 mutations were selected as important mutations by Random Forest analysis. Cluster analysis revealed strains associated with a high frequency of bloodstream infection (BSI). Twenty seven out of 34 strains in this cluster caused BSI. These strains were all positive for collagen adhesion gene (cna) and have mutations in the locus, those were selected by Random Forest analysis. Univariate and multivariate analysis revealed that these gene mutations were the predictor for the incidence of BSI. Interestingly, mutant CNA protein showed lower attachment ability to collagen, suggesting that the mutant protein might contribute to the dissemination of bacteria. Conclusions: These findings suggest that the bacterial genotype affects the clinical characteristics of MRSA infection. (c) 2019 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases

Monocyte chemoattractant protein-1/CCL2 produced by stromal cells promotes lung metastasis of 4T1 murine breast cancer cells

MCP-1/CCL2 plays an important role in the initiation and progression of cancer. Since tumor cells produce MCP-1, they are considered to be the main source of this chemokine. Here, we examined whether MCP-1 produced by non-tumor cells affects the growth and lung metastasis of 4T1 breast cancer cells by transplanting them into the mammary pad of WT or MCP-1−/− mice. Primary tumors at the injected site grew similarly in both mice; however, lung metastases were markedly reduced in MCP-1−/− mice, with significantly longer mouse survival. High levels of MCP-1 mRNA were detected in tumors growing in WT, but not MCP-1−/− mice. Serum MCP-1 levels were increased in tumor-bearing WT, but not MCP-1−/− mice. Transplantation of MCP-1−/− bone marrow cells into WT mice did not alter the incidence of lung metastasis, whereas transplantation of WT bone marrow cells into MCP-1−/− mice increased lung metastasis. The primary tumors of MCP-1−/− mice consistently developed necrosis earlier than those of WT mice and showed decreased infiltration by macrophages and reduced angiogenesis. Interestingly, 4T1 cells that metastasized to the lung constitutively expressed elevated levels of MCP-1, and intravenous injection of 4T1 cells producing a high level of MCP-1 resulted in increased tumor foci in the lung of WT and MCP-1−/− mice. Thus, stromal cell-derived MCP-1 in the primary tumors promotes lung metastasis of 4T1 cells, but tumor cell-derived MCP-1 can also contribute once tumor cells enter the circulation. A greater understanding of the source and role of this chemokine may lead to novel strategies for cancer treatment