Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 42
Filter
1.
Hum Genome Var ; 9(1): 44, 2022 Dec 12.
Article in English | MEDLINE | ID: mdl-36509753

ABSTRACT

TogoVar ( https://togovar.org ) is a database that integrates allele frequencies derived from Japanese populations and provides annotations for variant interpretation. First, a scheme to reanalyze individual-level genome sequence data deposited in the Japanese Genotype-phenotype Archive (JGA), a controlled-access database, was established to make allele frequencies publicly available. As more Japanese individual-level genome sequence data are deposited in JGA, the sample size employed in TogoVar is expected to increase, contributing to genetic study as reference data for Japanese populations. Second, public datasets of Japanese and non-Japanese populations were integrated into TogoVar to easily compare allele frequencies in Japanese and other populations. Each variant detected in Japanese populations was assigned a TogoVar ID as a permanent identifier. Third, these variants were annotated with molecular consequence, pathogenicity, and literature information for interpreting and prioritizing variants. Here, we introduce the newly developed TogoVar database that compares allele frequencies among Japanese and non-Japanese populations and describes the integrated annotations.

2.
Bioinformatics ; 38(17): 4194-4199, 2022 09 02.
Article in English | MEDLINE | ID: mdl-35801937

ABSTRACT

MOTIVATION: Understanding life cannot be accomplished without making full use of biological data, which are scattered across databases of diverse categories in life sciences. To connect such data seamlessly, identifier (ID) conversion plays a key role. However, existing ID conversion services have disadvantages, such as covering only a limited range of biological categories of databases, not keeping up with the updates of the original databases and outputs being hard to interpret in the context of biological relations, especially when converting IDs in multiple steps. RESULTS: TogoID is an ID conversion service implementing unique features with an intuitive web interface and an application programming interface (API) for programmatic access. TogoID currently supports 65 datasets covering various biological categories. TogoID users can perform exploratory multistep conversions to find a path among IDs. To guide the interpretation of biological meanings in the conversions, we crafted an ontology that defines the semantics of the dataset relations. AVAILABILITY AND IMPLEMENTATION: The TogoID service is freely available on the TogoID website (https://togoid.dbcls.jp/) and the API is also provided to allow programmatic access. To encourage developers to add new dataset pairs, the system stores the configurations of pairs at the GitHub repository (https://github.com/togoid/togoid-config) and accepts the request of additional pairs. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Subject(s)
Data Management , Software , Databases, Factual
3.
Cell Genom ; 1(2): None, 2021 Nov 10.
Article in English | MEDLINE | ID: mdl-34820659

ABSTRACT

Human biomedical datasets that are critical for research and clinical studies to benefit human health also often contain sensitive or potentially identifying information of individual participants. Thus, care must be taken when they are processed and made available to comply with ethical and regulatory frameworks and informed consent data conditions. To enable and streamline data access for these biomedical datasets, the Global Alliance for Genomics and Health (GA4GH) Data Use and Researcher Identities (DURI) work stream developed and approved the Data Use Ontology (DUO) standard. DUO is a hierarchical vocabulary of human and machine-readable data use terms that consistently and unambiguously represents a dataset's allowable data uses. DUO has been implemented by major international stakeholders such as the Broad and Sanger Institutes and is currently used in annotation of over 200,000 datasets worldwide. Using DUO in data management and access facilitates researchers' discovery and access of relevant datasets. DUO annotations increase the FAIRness of datasets and support data linkages using common data use profiles when integrating the data for secondary analyses. DUO is implemented in the Web Ontology Language (OWL) and, to increase community awareness and engagement, hosted in an open, centralized GitHub repository. DUO, together with the GA4GH Passport standard, offers a new, efficient, and streamlined data authorization and access framework that has enabled increased sharing of biomedical datasets worldwide.

4.
Int J Mol Sci ; 21(20)2020 Oct 12.
Article in English | MEDLINE | ID: mdl-33053895

ABSTRACT

Efforts to determine the mosquito genes that affect dengue virus replication have identified a number of candidates that positively or negatively modify amplification in the invertebrate host. We used deep sequencing to compare the differential transcript abundances in Aedes aegypti 14 days post dengue infection to those of uninfected A. aegypti. The gene lethal(2)-essential-for-life [l(2)efl], which encodes a member of the heat shock 20 protein (HSP20) family, was upregulated following dengue virus type 2 (DENV-2) infection in vivo. The transcripts of this gene did not exhibit differential accumulation in mosquitoes exposed to insecticides or pollutants. The induction and overexpression of l(2)efl gene products using poly(I:C) resulted in decreased DENV-2 replication in the cell line. In contrast, the RNAi-mediated suppression of l(2)efl gene products resulted in enhanced DENV-2 replication, but this enhancement occurred only if multiple l(2)efl genes were suppressed. l(2)efl homologs induce the phosphorylation of eukaryotic initiation factor 2α (eIF2α) in the fruit fly Drosophila melanogaster, and we confirmed this finding in the cell line. However, the mechanism by which l(2)efl phosphorylates eIF2α remains unclear. We conclude that l(2)efl encodes a potential anti-dengue protein in the vector mosquito.


Subject(s)
Aedes/genetics , Aedes/virology , Dengue Virus/physiology , Dengue/virology , HSP20 Heat-Shock Proteins/genetics , Insect Proteins/genetics , Mosquito Vectors/genetics , Mosquito Vectors/virology , Animals , Computational Biology/methods , Gene Expression Profiling , Host-Pathogen Interactions , Transcriptome , Virus Replication
5.
F1000Res ; 9: 136, 2020.
Article in English | MEDLINE | ID: mdl-32308977

ABSTRACT

We report on the activities of the 2015 edition of the BioHackathon, an annual event that brings together researchers and developers from around the world to develop tools and technologies that promote the reusability of biological data. We discuss issues surrounding the representation, publication, integration, mining and reuse of biological data and metadata across a wide range of biomedical data types of relevance for the life sciences, including chemistry, genotypes and phenotypes, orthology and phylogeny, proteomics, genomics, glycomics, and metabolomics. We describe our progress to address ongoing challenges to the reusability and reproducibility of research results, and identify outstanding issues that continue to impede the progress of bioinformatics research. We share our perspective on the state of the art, continued challenges, and goals for future research and development for the life sciences Semantic Web.


Subject(s)
Biological Science Disciplines , Computational Biology , Semantic Web , Data Mining , Metadata , Reproducibility of Results
6.
Database (Oxford) ; 20192019 01 01.
Article in English | MEDLINE | ID: mdl-30624651

ABSTRACT

TogoGenome is a genome database that is purely based on the Semantic Web technology, which enables the integration of heterogeneous data and flexible semantic searches. All the information is stored as Resource Description Framework (RDF) data, and the reporting web pages are generated on the fly using SPARQL Protocol and RDF Query Language (SPARQL) queries. TogoGenome provides a semantic-faceted search system by gene functional annotation, taxonomy, phenotypes and environment based on the relevant ontologies. TogoGenome also serves as an interface to conduct semantic comparative genomics by which a user can observe pan-organism or organism-specific genes based on the functional aspect of gene annotations and the combinations of organisms from different taxa. The TogoGenome database exhibits a modularized structure, and each module in the report pages is separately served as TogoStanza, which is a generic framework for rendering an information block as IFRAME/Web Components, which can, unlike several other monolithic databases, also be reused to construct other databases. TogoGenome and TogoStanza have been under development since 2012 and are freely available along with their source codes on the GitHub repositories at https://github.com/togogenome/ and https://github.com/togostanza/, respectively, under the MIT license.


Subject(s)
Databases, Genetic , Genomics/methods , Semantic Web , Software , Humans
7.
Database (Oxford) ; 20182018 01 01.
Article in English | MEDLINE | ID: mdl-30576482

ABSTRACT

In the life sciences, researchers increasingly want to access multiple databases in an integrated way. However, different databases currently use different formats and vocabularies, hindering the proper integration of heterogeneous life science data. Adopting the Resource Description Framework (RDF) has the potential to address such issues by improving database interoperability, leading to advances in automatic data processing. Based on this idea, we have advised many Japanese database development groups to expose their databases in RDF. To further promote such activities, we have developed an RDF-based life science dataset repository called the National Bioscience Database Center (NBDC) RDF portal. All the datasets in this repository have been reviewed by the NBDC to ensure interoperability and queryability. As of July 2018, the service includes 21 RDF datasets, comprising over 45.5 billion triples. It provides SPARQL endpoints for all datasets, useful metadata and the ability to download RDF files. The NBDC RDF portal can be accessed at https://integbio.jp/rdf/.


Subject(s)
Biological Science Disciplines , Database Management Systems , Databases, Factual , Semantics , Internet , User-Computer Interface
9.
J Plant Res ; 131(4): 709-717, 2018 Jul.
Article in English | MEDLINE | ID: mdl-29460198

ABSTRACT

Recent studies have shown that environmental DNA is found almost everywhere. Flower petal surfaces are an attractive tissue to use for investigation of the dispersal of environmental DNA in nature as they are isolated from the external environment until the bud opens and only then can the petal surface accumulate environmental DNA. Here, we performed a crowdsourced experiment, the "Ohanami Project", to obtain environmental DNA samples from petal surfaces of Cerasus × yedoensis 'Somei-yoshino' across the Japanese archipelago during spring 2015. C. × yedoensis is the most popular garden cherry species in Japan and clones of this cultivar bloom simultaneously every spring. Data collection spanned almost every prefecture and totaled 577 DNA samples from 149 collaborators. Preliminary amplicon-sequencing analysis showed the rapid attachment of environmental DNA onto the petal surfaces. Notably, we found DNA of other common plant species in samples obtained from a wide distribution; this DNA likely originated from the pollen of the Japanese cedar. Our analysis supports our belief that petal surfaces after blossoming are a promising target to reveal the dynamics of environmental DNA in nature. The success of our experiment also shows that crowdsourced environmental DNA analyses have considerable value in ecological studies.


Subject(s)
DNA, Plant/genetics , DNA/genetics , Environment , Flowers/genetics , Prunus/genetics , Chloroplasts/genetics , Cyanobacteria/genetics , Flowers/microbiology , Japan , Proteobacteria/genetics , Prunus/microbiology , Sequence Alignment , Sequence Analysis, DNA
10.
J Biomed Semantics ; 6: 3, 2015.
Article in English | MEDLINE | ID: mdl-25973165

ABSTRACT

BACKGROUND: Linked Data has gained some attention recently in the life sciences as an effective way to provide and share data. As a part of the Semantic Web, data are linked so that a person or machine can explore the web of data. Resource Description Framework (RDF) is the standard means of implementing Linked Data. In the process of generating RDF data, not only are data simply linked to one another, the links themselves are characterized by ontologies, thereby allowing the types of links to be distinguished. Although there is a high labor cost to define an ontology for data providers, the merit lies in the higher level of interoperability with data analysis and visualization software. This increase in interoperability facilitates the multi-faceted retrieval of data, and the appropriate data can be quickly extracted and visualized. Such retrieval is usually performed using the SPARQL (SPARQL Protocol and RDF Query Language) query language, which is used to query RDF data stores. For the database provider, such interoperability will surely lead to an increase in the number of users. RESULTS: This manuscript describes the experiences and discussions shared among participants of the week-long BioHackathon 2011 who went through the development of RDF representations of their own data and developed specific RDF and SPARQL use cases. Advice regarding considerations to take when developing RDF representations of their data are provided for bioinformaticians considering making data available and interoperable. CONCLUSIONS: Participants of the BioHackathon 2011 were able to produce RDF representations of their data and gain a better understanding of the requirements for producing such data in a period of just five days. We summarize the work accomplished with the hope that it will be useful for researchers involved in developing laboratory databases or data analysis, and those who are considering such technologies as RDF and Linked Data.

11.
J Bioinform Comput Biol ; 12(6): 1442001, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25385078

ABSTRACT

Genomics is faced with the issue of many partially annotated putative enzyme-encoding genes for which activities have not yet been verified, while metabolomics is faced with the issue of many putative enzyme reactions for which full equations have not been verified. Knowledge of enzymes has been collected by IUBMB, and has been made public as the Enzyme List. To date, however, the terminology of the Enzyme List has not been assessed comprehensively by bioinformatics studies. Instead, most of the bioinformatics studies simply use the identifiers of the enzymes, i.e. the Enzyme Commission (EC) numbers. We investigated the actual usage of terminology throughout the Enzyme List, and demonstrated that the partial characteristics of reactions cannot be retrieved by simply using EC numbers. Thus, we developed a novel ontology, named PIERO, for annotating biochemical transformations as follows. First, the terminology describing enzymatic reactions was retrieved from the Enzyme List, and was grouped into those related to overall reactions and biochemical transformations. Consequently, these terms were mapped onto the actual transformations taken from enzymatic reaction equations. This ontology was linked to Gene Ontology (GO) and EC numbers, allowing the extraction of common partial reaction characteristics from given sets of orthologous genes and the elucidation of possible enzymes from the given transformations. Further future development of the PIERO ontology should enhance the Enzyme List to promote the integration of genomics and metabolomics.


Subject(s)
Biological Ontologies , Databases, Protein , Enzymes/chemistry , Enzymes/classification , Information Storage and Retrieval/methods , Terminology as Topic , Enzymes/genetics , Natural Language Processing
12.
Genome Res ; 24(9): 1433-44, 2014 Sep.
Article in English | MEDLINE | ID: mdl-25091627

ABSTRACT

To understand the molecular mechanisms of parasitism in vivo, it is essential to elucidate how the transcriptomes of the human hosts and the infecting parasites affect one another. Here we report the RNA-seq analysis of 116 Indonesian patients infected with the malaria parasite Plasmodium falciparum (Pf). We extracted RNAs from their peripheral blood as a mixture of host and parasite transcripts and mapped the RNA-seq tags to the human and Pf reference genomes to separate the respective tags. We were thus able to simultaneously analyze expression patterns in both humans and parasites. We identified human and parasite genes and pathways that correlated with various clinical data, which may serve as primary targets for drug developments. Of particular importance, we revealed characteristic expression changes in the human innate immune response pathway genes including TLR2 and TICAM2 that correlated with the severity of the malaria infection. We also found a group of transcription regulatory factors, JUND, for example, and signaling molecules, TNFAIP3, for example, that were strongly correlated in the expression patterns of humans and parasites. We also identified several genetic variations in important anti-malaria drug resistance-related genes. Furthermore, we identified the genetic variations which are potentially associated with severe malaria symptoms both in humans and parasites. The newly generated data should collectively lay a unique foundation for understanding variable behaviors of the field malaria parasites, which are far more complex than those observed under laboratory conditions.


Subject(s)
Genome, Human , Genome, Protozoan , Malaria/genetics , Plasmodium falciparum/genetics , Transcriptome , Adaptor Proteins, Signal Transducing/genetics , Adaptor Proteins, Signal Transducing/metabolism , Adolescent , Adult , Antimalarials/therapeutic use , Case-Control Studies , Child , Child, Preschool , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Drug Resistance/genetics , Expressed Sequence Tags , Female , Host-Parasite Interactions/genetics , Humans , Immunity, Innate/genetics , Infant , Intracellular Signaling Peptides and Proteins/genetics , Intracellular Signaling Peptides and Proteins/metabolism , Malaria/diagnosis , Malaria/drug therapy , Male , Nuclear Proteins/genetics , Nuclear Proteins/metabolism , Plasmodium falciparum/pathogenicity , Polymorphism, Single Nucleotide , Proto-Oncogene Proteins c-jun/genetics , Proto-Oncogene Proteins c-jun/metabolism , Toll-Like Receptor 2/genetics , Toll-Like Receptor 2/metabolism , Tumor Necrosis Factor alpha-Induced Protein 3 , Virulence/genetics
13.
J Biomed Semantics ; 5(1): 5, 2014 Feb 05.
Article in English | MEDLINE | ID: mdl-24495517

ABSTRACT

The application of semantic technologies to the integration of biological data and the interoperability of bioinformatics analysis and visualization tools has been the common theme of a series of annual BioHackathons hosted in Japan for the past five years. Here we provide a review of the activities and outcomes from the BioHackathons held in 2011 in Kyoto and 2012 in Toyama. In order to efficiently implement semantic technologies in the life sciences, participants formed various sub-groups and worked on the following topics: Resource Description Framework (RDF) models for specific domains, text mining of the literature, ontology development, essential metadata for biological databases, platforms to enable efficient Semantic Web technology development and interoperability, and the development of applications for Semantic Web data. In this review, we briefly introduce the themes covered by these sub-groups. The observations made, conclusions drawn, and software development projects that emerged from these activities are discussed.

14.
J Biomed Semantics ; 4(1): 6, 2013 Feb 11.
Article in English | MEDLINE | ID: mdl-23398680

ABSTRACT

BACKGROUND: BioHackathon 2010 was the third in a series of meetings hosted by the Database Center for Life Sciences (DBCLS) in Tokyo, Japan. The overall goal of the BioHackathon series is to improve the quality and accessibility of life science research data on the Web by bringing together representatives from public databases, analytical tool providers, and cyber-infrastructure researchers to jointly tackle important challenges in the area of in silico biological research. RESULTS: The theme of BioHackathon 2010 was the 'Semantic Web', and all attendees gathered with the shared goal of producing Semantic Web data from their respective resources, and/or consuming or interacting those data using their tools and interfaces. We discussed on topics including guidelines for designing semantic data and interoperability of resources. We consequently developed tools and clients for analysis and visualization. CONCLUSION: We provide a meeting report from BioHackathon 2010, in which we describe the discussions, decisions, and breakthroughs made as we moved towards compliance with Semantic Web technologies - from source provider, through middleware, to the end-consumer.

15.
Nucleic Acids Res ; 41(Database issue): D353-7, 2013 Jan.
Article in English | MEDLINE | ID: mdl-23193276

ABSTRACT

The identification of orthologous genes in an increasing number of fully sequenced genomes is a challenging issue in recent genome science. Here we present KEGG OC (http://www.genome.jp/tools/oc/), a novel database of ortholog clusters (OCs). The current version of KEGG OC contains 1 176 030 OCs, obtained by clustering 8 357 175 genes in 2112 complete genomes (153 eukaryotes, 1830 bacteria and 129 archaea). The OCs were constructed by applying the quasi-clique-based clustering method to all possible protein coding genes in all complete genomes, based on their amino acid sequence similarities. It is computationally efficient to calculate OCs, which enables to regularly update the contents. KEGG OC has the following two features: (i) It consists of all complete genomes of a wide variety of organisms from three domains of life, and the number of organisms is the largest among the existing databases; and (ii) It is compatible with the KEGG database by sharing the same sets of genes and identifiers, which leads to seamless integration of OCs with useful components in KEGG such as biological pathways, pathway modules, functional hierarchy, diseases and drugs. The KEGG OC resources are accessible via OC Viewer that provides an interactive visualization of OCs at different taxonomic levels.


Subject(s)
Databases, Genetic , Genes, Archaeal , Genes, Bacterial , Genes , Algorithms , Classification/methods , Cluster Analysis , Eukaryota/genetics , Genome, Archaeal , Genome, Bacterial , Genomics/methods , Internet , Sequence Homology, Amino Acid
16.
mBio ; 3(5): e00204-12, 2012.
Article in English | MEDLINE | ID: mdl-22951932

ABSTRACT

We sequenced the genome of Theileria orientalis, a tick-borne apicomplexan protozoan parasite of cattle. The focus of this study was a comparative genome analysis of T. orientalis relative to other highly pathogenic Theileria species, T. parva and T. annulata. T. parva and T. annulata induce transformation of infected cells of lymphocyte or macrophage/monocyte lineages; in contrast, T. orientalis does not induce uncontrolled proliferation of infected leukocytes and multiplies predominantly within infected erythrocytes. While synteny across homologous chromosomes of the three Theileria species was found to be well conserved overall, subtelomeric structures were found to differ substantially, as T. orientalis lacks the large tandemly arrayed subtelomere-encoded variable secreted protein-encoding gene family. Moreover, expansion of particular gene families by gene duplication was found in the genomes of the two transforming Theileria species, most notably, the TashAT/TpHN and Tar/Tpr gene families. Gene families that are present only in T. parva and T. annulata and not in T. orientalis, Babesia bovis, or Plasmodium were also identified. Identification of differences between the genome sequences of Theileria species with different abilities to transform and immortalize bovine leukocytes will provide insight into proteins and mechanisms that have evolved to induce and regulate this process. The T. orientalis genome database is available at http://totdb.czc.hokudai.ac.jp/.


Subject(s)
Genome, Protozoan , Theileria/genetics , Theileria/pathogenicity , Virulence Factors/genetics , Animals , Cattle , Cell Proliferation , Leukocytes/parasitology , Synteny
17.
J Biomed Semantics ; 2: 4, 2011 Aug 02.
Article in English | MEDLINE | ID: mdl-21806842

ABSTRACT

BACKGROUND: The interaction between biological researchers and the bioinformatics tools they use is still hampered by incomplete interoperability between such tools. To ensure interoperability initiatives are effectively deployed, end-user applications need to be aware of, and support, best practices and standards. Here, we report on an initiative in which software developers and genome biologists came together to explore and raise awareness of these issues: BioHackathon 2009. RESULTS: Developers in attendance came from diverse backgrounds, with experts in Web services, workflow tools, text mining and visualization. Genome biologists provided expertise and exemplar data from the domains of sequence and pathway analysis and glyco-informatics. One goal of the meeting was to evaluate the ability to address real world use cases in these domains using the tools that the developers represented. This resulted in i) a workflow to annotate 100,000 sequences from an invertebrate species; ii) an integrated system for analysis of the transcription factor binding sites (TFBSs) enriched based on differential gene expression data obtained from a microarray experiment; iii) a workflow to enumerate putative physical protein interactions among enzymes in a metabolic pathway using protein structure data; iv) a workflow to analyze glyco-gene-related diseases by searching for human homologs of glyco-genes in other species, such as fruit flies, and retrieving their phenotype-annotated SNPs. CONCLUSIONS: Beyond deriving prototype solutions for each use-case, a second major purpose of the BioHackathon was to highlight areas of insufficiency. We discuss the issues raised by our exploration of the problem/solution space, concluding that there are still problems with the way Web services are modeled and annotated, including: i) the absence of several useful data or analysis functions in the Web service "space"; ii) the lack of documentation of methods; iii) lack of compliance with the SOAP/WSDL specification among and between various programming-language libraries; and iv) incompatibility between various bioinformatics data formats. Although it was still difficult to solve real world problems posed to the developers by the biological researchers in attendance because of these problems, we note the promise of addressing these issues within a semantic framework.

18.
J Biomed Semantics ; 1(1): 8, 2010 Aug 21.
Article in English | MEDLINE | ID: mdl-20727200

ABSTRACT

Web services have become a key technology for bioinformatics, since life science databases are globally decentralized and the exponential increase in the amount of available data demands for efficient systems without the need to transfer entire databases for every step of an analysis. However, various incompatibilities among database resources and analysis services make it difficult to connect and integrate these into interoperable workflows. To resolve this situation, we invited domain specialists from web service providers, client software developers, Open Bio* projects, the BioMoby project and researchers of emerging areas where a standard exchange data format is not well established, for an intensive collaboration entitled the BioHackathon 2008. The meeting was hosted by the Database Center for Life Science (DBCLS) and Computational Biology Research Center (CBRC) and was held in Tokyo from February 11th to 15th, 2008. In this report we highlight the work accomplished and the common issues arisen from this event, including the standardization of data exchange formats and services in the emerging fields of glycoinformatics, biological interaction networks, text mining, and phyloinformatics. In addition, common shared object development based on BioSQL, as well as technical challenges in large data management, asynchronous services, and security are discussed. Consequently, we improved interoperability of web services in several fields, however, further cooperation among major database centers and continued collaborative efforts between service providers and software developers are still necessary for an effective advance in bioinformatics web service technologies.

19.
Parasitol Int ; 59(2): 206-10, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20153838

ABSTRACT

The Toxoplasma gondii genome project has revealed two putative isoforms (TgPGM-I and TgPGM-II) of alpha-phosphoglucomutase (EC 5.4.2.2). We obtained recombinant proteins of these isoforms from the Beverley strain of T. gondii and characterized their properties, particularly the kinetic properties of these isoforms. The specific activities of TgPGM-I and TgPGM-II for alpha-D-glucose 1-phosphate were 338+/-9 and 84+/-6micromol/min/mg protein, respectively, at 37 degrees C under optimal conditions. The Kcat and Km values of TgPGM-I were 398+/-11/s and 0.19+/-0.03mM and those for TgPGM-II were 93+/-7/s and 3.53+/-0.91mM, respectively, for alpha-d-glucose 1-phosphate. Magnesium ions were the most effective divalent cations for both the enzyme activities. The maximum activities of both the enzymes were obtained in the presence of more than 0.2mM alpha-D-glucose 1,6-bisphosphate. Although both enzymes were attached to the alpha-phosphohexomutase superfamily, amino acid sequence homology between TgPGM-I and TgPGM-II showed very low overall identity (25%). No alpha-phosphomannomutase (EC 5.4.2.8) activity was detected for either enzyme. The data indicated that TgPGM-I, but not TgPGM-II, may play an important role in alpha-D-glucose 6-phosphate production.


Subject(s)
Isoenzymes , Phosphoglucomutase , Toxoplasma/enzymology , Amino Acid Sequence , Animals , Glucose-6-Phosphate/metabolism , Glycolysis , Isoenzymes/chemistry , Isoenzymes/genetics , Isoenzymes/isolation & purification , Isoenzymes/metabolism , Kinetics , Molecular Sequence Data , Phosphoglucomutase/chemistry , Phosphoglucomutase/genetics , Phosphoglucomutase/isolation & purification , Phosphoglucomutase/metabolism , Phylogeny , Recombinant Proteins/chemistry , Recombinant Proteins/genetics , Recombinant Proteins/isolation & purification , Recombinant Proteins/metabolism , Sequence Alignment , Sequence Analysis, DNA , Toxoplasma/genetics
20.
Mol Biosyst ; 5(6): 588-602, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19462016

ABSTRACT

Systems biology aims to understand the nonlinear interactions of multiple biomolecular components that characterize a living organism. One important aspect of systems biology approaches is to identify the biological pathways or networks that connect the differing elements of a system, and examine how they evolve with temporal and environmental changes. The utility of this method becomes clear when applied to multifactorial diseases with complex etiologies, such as inflammatory-related diseases, herein exemplified by atherosclerosis. In this paper, the initial studies in this discipline are reviewed and examined within the context of the development of the field. In addition, several different software tools are briefly described and a novel application for the KEGG database suite called KegArray is presented. This tool is designed for mapping the results of high-throughput omics studies, including transcriptomics, proteomics and metabolomics data, onto interactive KEGG metabolic pathways. The utility of KegArray is demonstrated using a combined transcriptomics and lipidomics dataset from a published study designed to examine the potential of cholesterol in the diet to influence the inflammatory component in the development of atherosclerosis. These data were mapped onto the KEGG PATHWAY database, with a low cholesterol diet affecting 60 distinct biochemical pathways and a high cholesterol exposure affecting 76 biochemical pathways. A total of 77 pathways were differentially affected between low and high cholesterol diets. The KEGG pathways "Biosynthesis of unsaturated fatty acids" and "Sphingolipid metabolism" evidenced multiple changes in gene/lipid levels between low and high cholesterol treatment, and are discussed in detail. Taken together, this paper provides a brief introduction to systems biology and the applications of pathway mapping to the study of cardiovascular disease, as well as a summary of available tools. Current limitations and future visions of this emerging field are discussed, with the conclusion that combining knowledge from biological pathways and high-throughput omics data will move clinical medicine one step further to individualize medical diagnosis and treatment.


Subject(s)
Cardiovascular Diseases/metabolism , Metabolic Networks and Pathways , Software , Systems Biology/methods , Animals , Cardiovascular Diseases/genetics , Gene Expression Profiling , Humans , Lipid Metabolism , Models, Biological , Systems Biology/trends
SELECTION OF CITATIONS
SEARCH DETAIL
...