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1.  Changes in Mitochondrial Carriers Exhibit Stress-Specific Signatures in INS-1Eβ-Cells Exposed to Glucose Versus Fatty Acids 
PLoS ONE  2013;8(12):e82364.
Chronic exposure of β-cells to metabolic stresses impairs their function and potentially induces apoptosis. Mitochondria play a central role in coupling glucose metabolism to insulin secretion. However, little is known on mitochondrial responses to specific stresses; i.e. low versus high glucose, saturated versus unsaturated fatty acids, or oxidative stress. INS-1E cells were exposed for 3 days to 5.6 mM glucose, 25 mM glucose, 0.4 mM palmitate, and 0.4 mM oleate. Culture at standard 11.1 mM glucose served as no-stress control and transient oxidative stress (200 µM H2O2 for 10 min at day 0) served as positive stressful condition. Mito-array analyzed transcripts of 60 mitochondrion-associated genes with special focus on members of the Slc25 family. Transcripts of interest were evaluated at the protein level by immunoblotting. Bioinformatics analyzed the expression profiles to delineate comprehensive networks. Chronic exposure to the different metabolic stresses impaired glucose-stimulated insulin secretion; revealing glucotoxicity and lipo-dysfunction. Both saturated and unsaturated fatty acids increased expression of the carnitine/acylcarnitine carrier CAC, whereas the citrate carrier CIC and energy sensor SIRT1 were specifically upregulated by palmitate and oleate, respectively. High glucose upregulated CIC, the dicarboxylate carrier DIC and glutamate carrier GC1. Conversely, it reduced expression of energy sensors (AMPK, SIRT1, SIRT4), metabolic genes, transcription factor PDX1, and anti-apoptotic Bcl2. This was associated with caspase-3 cleavage and cell death. Expression levels of GC1 and SIRT4 exhibited positive and negative glucose dose-response, respectively. Expression profiles of energy sensors and mitochondrial carriers were selectively modified by the different conditions, exhibiting stress-specific signatures.
doi:10.1371/journal.pone.0082364
PMCID: PMC3861392  PMID: 24349266
3.  Recent advances in biocuration: Meeting Report from the fifth International Biocuration Conference 
The 5th International Biocuration Conference brought together over 300 scientists to exchange on their work, as well as discuss issues relevant to the International Society for Biocuration’s (ISB) mission. Recurring themes this year included the creation and promotion of gold standards, the need for more ontologies, and more formal interactions with journals. The conference is an essential part of the ISB's goal to support exchanges among members of the biocuration community. Next year's conference will be held in Cambridge, UK, from 7 to 10 April 2013. In the meanwhile, the ISB website provides information about the society's activities (http://biocurator.org), as well as related events of interest.
doi:10.1093/database/bas036
PMCID: PMC3483532  PMID: 23110974
4.  Toward interoperable bioscience data 
Nature genetics  2012;44(2):121-126.
To make full use of research data, the bioscience community needs to adopt technologies and reward mechanisms that support interoperability and promote the growth of an open ‘data commoning’ culture. Here we describe the prerequisites for data commoning and present an established and growing ecosystem of solutions using the shared ‘Investigation-Study-Assay’ framework to support that vision.
doi:10.1038/ng.1054
PMCID: PMC3428019  PMID: 22281772
5.  Biocurators and Biocuration: surveying the 21st century challenges 
Curated databases are an integral part of the tool set that researchers use on a daily basis for their work. For most users, however, how databases are maintained, and by whom, is rather obscure. The International Society for Biocuration (ISB) represents biocurators, software engineers, developers and researchers with an interest in biocuration. Its goals include fostering communication between biocurators, promoting and describing their work, and highlighting the added value of biocuration to the world. The ISB recently conducted a survey of biocurators to better understand their educational and scientific backgrounds, their motivations for choosing a curatorial job and their career goals. The results are reported here. From the responses received, it is evident that biocuration is performed by highly trained scientists and perceived to be a stimulating career, offering both intellectual challenges and the satisfaction of performing work essential to the modern scientific community. It is also apparent that the ISB has at least a dual role to play to facilitate biocurators’ work: (i) to promote biocuration as a career within the greater scientific community; (ii) to aid the development of resources for biomedical research through promotion of nomenclature and data-sharing standards that will allow interconnection of biological databases and better exploit the pivotal contributions that biocurators are making.
Database URL: http://biocurator.org
doi:10.1093/database/bar059
PMCID: PMC3308150  PMID: 22434828
6.  Biocuration Virtual Issue 2012 
doi:10.1093/database/bas011
PMCID: PMC3308167  PMID: 22434845
7.  neXtProt: a knowledge platform for human proteins 
Nucleic Acids Research  2011;40(D1):D76-D83.
neXtProt (http://www.nextprot.org/) is a new human protein-centric knowledge platform. Developed at the Swiss Institute of Bioinformatics (SIB), it aims to help researchers answer questions relevant to human proteins. To achieve this goal, neXtProt is built on a corpus containing both curated knowledge originating from the UniProtKB/Swiss-Prot knowledgebase and carefully selected and filtered high-throughput data pertinent to human proteins. This article presents an overview of the database and the data integration process. We also lay out the key future directions of neXtProt that we consider the necessary steps to make neXtProt the one-stop-shop for all research projects focusing on human proteins.
doi:10.1093/nar/gkr1179
PMCID: PMC3245017  PMID: 22139911
8.  BioCreative III interactive task: an overview 
BMC Bioinformatics  2011;12(Suppl 8):S4.
Background
The BioCreative challenge evaluation is a community-wide effort for evaluating text mining and information extraction systems applied to the biological domain. The biocurator community, as an active user of biomedical literature, provides a diverse and engaged end user group for text mining tools. Earlier BioCreative challenges involved many text mining teams in developing basic capabilities relevant to biological curation, but they did not address the issues of system usage, insertion into the workflow and adoption by curators. Thus in BioCreative III (BC-III), the InterActive Task (IAT) was introduced to address the utility and usability of text mining tools for real-life biocuration tasks. To support the aims of the IAT in BC-III, involvement of both developers and end users was solicited, and the development of a user interface to address the tasks interactively was requested.
Results
A User Advisory Group (UAG) actively participated in the IAT design and assessment. The task focused on gene normalization (identifying gene mentions in the article and linking these genes to standard database identifiers), gene ranking based on the overall importance of each gene mentioned in the article, and gene-oriented document retrieval (identifying full text papers relevant to a selected gene). Six systems participated and all processed and displayed the same set of articles. The articles were selected based on content known to be problematic for curation, such as ambiguity of gene names, coverage of multiple genes and species, or introduction of a new gene name. Members of the UAG curated three articles for training and assessment purposes, and each member was assigned a system to review. A questionnaire related to the interface usability and task performance (as measured by precision and recall) was answered after systems were used to curate articles. Although the limited number of articles analyzed and users involved in the IAT experiment precluded rigorous quantitative analysis of the results, a qualitative analysis provided valuable insight into some of the problems encountered by users when using the systems. The overall assessment indicates that the system usability features appealed to most users, but the system performance was suboptimal (mainly due to low accuracy in gene normalization). Some of the issues included failure of species identification and gene name ambiguity in the gene normalization task leading to an extensive list of gene identifiers to review, which, in some cases, did not contain the relevant genes. The document retrieval suffered from the same shortfalls. The UAG favored achieving high performance (measured by precision and recall), but strongly recommended the addition of features that facilitate the identification of correct gene and its identifier, such as contextual information to assist in disambiguation.
Discussion
The IAT was an informative exercise that advanced the dialog between curators and developers and increased the appreciation of challenges faced by each group. A major conclusion was that the intended users should be actively involved in every phase of software development, and this will be strongly encouraged in future tasks. The IAT Task provides the first steps toward the definition of metrics and functional requirements that are necessary for designing a formal evaluation of interactive curation systems in the BioCreative IV challenge.
doi:10.1186/1471-2105-12-S8-S4
PMCID: PMC3269939  PMID: 22151968
9.  Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium 
Briefings in Bioinformatics  2011;12(5):449-462.
The goal of the Gene Ontology (GO) project is to provide a uniform way to describe the functions of gene products from organisms across all kingdoms of life and thereby enable analysis of genomic data. Protein annotations are either based on experiments or predicted from protein sequences. Since most sequences have not been experimentally characterized, most available annotations need to be based on predictions. To make as accurate inferences as possible, the GO Consortium's Reference Genome Project is using an explicit evolutionary framework to infer annotations of proteins from a broad set of genomes from experimental annotations in a semi-automated manner. Most components in the pipeline, such as selection of sequences, building multiple sequence alignments and phylogenetic trees, retrieving experimental annotations and depositing inferred annotations, are fully automated. However, the most crucial step in our pipeline relies on software-assisted curation by an expert biologist. This curation tool, Phylogenetic Annotation and INference Tool (PAINT) helps curators to infer annotations among members of a protein family. PAINT allows curators to make precise assertions as to when functions were gained and lost during evolution and record the evidence (e.g. experimentally supported GO annotations and phylogenetic information including orthology) for those assertions. In this article, we describe how we use PAINT to infer protein function in a phylogenetic context with emphasis on its strengths, limitations and guidelines. We also discuss specific examples showing how PAINT annotations compare with those generated by other highly used homology-based methods.
doi:10.1093/bib/bbr042
PMCID: PMC3178059  PMID: 21873635
gene ontology; genome annotation; reference genome; gene function prediction; phylogenetics
10.  Comparative genomics of the social amoebae Dictyostelium discoideum and Dictyostelium purpureum 
Genome Biology  2011;12(2):R20.
Background
The social amoebae (Dictyostelia) are a diverse group of Amoebozoa that achieve multicellularity by aggregation and undergo morphogenesis into fruiting bodies with terminally differentiated spores and stalk cells. There are four groups of dictyostelids, with the most derived being a group that contains the model species Dictyostelium discoideum.
Results
We have produced a draft genome sequence of another group dictyostelid, Dictyostelium purpureum, and compare it to the D. discoideum genome. The assembly (8.41 × coverage) comprises 799 scaffolds totaling 33.0 Mb, comparable to the D. discoideum genome size. Sequence comparisons suggest that these two dictyostelids shared a common ancestor approximately 400 million years ago. In spite of this divergence, most orthologs reside in small clusters of conserved synteny. Comparative analyses revealed a core set of orthologous genes that illuminate dictyostelid physiology, as well as differences in gene family content. Interesting patterns of gene conservation and divergence are also evident, suggesting function differences; some protein families, such as the histidine kinases, have undergone little functional change, whereas others, such as the polyketide synthases, have undergone extensive diversification. The abundant amino acid homopolymers encoded in both genomes are generally not found in homologous positions within proteins, so they are unlikely to derive from ancestral DNA triplet repeats. Genes involved in the social stage evolved more rapidly than others, consistent with either relaxed selection or accelerated evolution due to social conflict.
Conclusions
The findings from this new genome sequence and comparative analysis shed light on the biology and evolution of the Dictyostelia.
doi:10.1186/gb-2011-12-2-r20
PMCID: PMC3188802  PMID: 21356102
11.  Towards BioDBcore: a community-defined information specification for biological databases 
The present article proposes the adoption of a community-defined, uniform, generic description of the core attributes of biological databases, BioDBCore. The goals of these attributes are to provide a general overview of the database landscape, to encourage consistency and interoperability between resources; and to promote the use of semantic and syntactic standards. BioDBCore will make it easier for users to evaluate the scope and relevance of available resources. This new resource will increase the collective impact of the information present in biological databases.
doi:10.1093/database/baq027
PMCID: PMC3017395  PMID: 21205783
12.  Meeting Report from the Second “Minimum Information for Biological and Biomedical Investigations” (MIBBI) workshop 
Standards in Genomic Sciences  2010;3(3):259-266.
This report summarizes the proceedings of the second workshop of the ‘Minimum Information for Biological and Biomedical Investigations’ (MIBBI) consortium held on Dec 1-2, 2010 in Rüdesheim, Germany through the sponsorship of the Beilstein-Institute. MIBBI is an umbrella organization uniting communities developing Minimum Information (MI) checklists to standardize the description of data sets, the workflows by which they were generated and the scientific context for the work. This workshop brought together representatives of more than twenty communities to present the status of their MI checklists and plans for future development. Shared challenges and solutions were identified and the role of MIBBI in MI checklist development was discussed. The meeting featured some thirty presentations, wide-ranging discussions and breakout groups. The top outcomes of the two-day workshop as defined by the participants were: 1) the chance to share best practices and to identify areas of synergy; 2) defining a series of tasks for updating the MIBBI Portal; 3) reemphasizing the need to maintain independent MI checklists for various communities while leveraging common terms and workflow elements contained in multiple checklists; and 4) revision of the concept of the MIBBI Foundry to focus on the creation of a core set of MIBBI modules intended for reuse by individual MI checklist projects while maintaining the integrity of each MI project. Further information about MIBBI and its range of activities can be found at http://mibbi.org/.
doi:10.4056/sigs.147362
PMCID: PMC3035314  PMID: 21304730
13.  Meeting Report: BioSharing at ISMB 2010 
Standards in Genomic Sciences  2010;3(3):254-258.
This report summarizes the proceedings of the one day BioSharing meeting held at the Intelligent Systems for Molecular Biology (ISMB) 2010 conference in Boston, MA, USA This inaugural BioSharing event was hosted by the Genomic Standards Consortium as part of its M3 & BioSharing special interest group (SIG) workshop. The BioSharing event included invited talks from a range of community leaders and a panel discussion at the end of the day. The panel session led to the formal agreement among community leaders to join together to promote cross-community knowledge exchange and collaborations. A key focus of the newly formed Biosharing community will be linking up resources to promote real-world data sharing (virtuous cycle of data) and supporting compliance with data policies through the creation of a one-stop-portal of information. Further information about the newly established BioSharing effort can be found at http://biosharing.org.
doi:10.4056/sigs/1403501
PMCID: PMC3035313  PMID: 21304729
14.  Towards BioDBcore: a community-defined information specification for biological databases 
Nucleic Acids Research  2010;39(Database issue):D7-D10.
The present article proposes the adoption of a community-defined, uniform, generic description of the core attributes of biological databases, BioDBCore. The goals of these attributes are to provide a general overview of the database landscape, to encourage consistency and interoperability between resources and to promote the use of semantic and syntactic standards. BioDBCore will make it easier for users to evaluate the scope and relevance of available resources. This new resource will increase the collective impact of the information present in biological databases.
doi:10.1093/nar/gkq1173
PMCID: PMC3013734  PMID: 21097465
15.  dictyBase update 2011: web 2.0 functionality and the initial steps towards a genome portal for the Amoebozoa 
Nucleic Acids Research  2010;39(Database issue):D620-D624.
dictyBase (http://www.dictybase.org), the model organism database for Dictyostelium, aims to provide the broad biomedical research community with well integrated, high quality data and tools for Dictyostelium discoideum and related species. dictyBase houses the complete genome sequence, ESTs, and the entire body of literature relevant to Dictyostelium. This information is curated to provide accurate gene models and functional annotations, with the goal of fully annotating the genome to provide a ‘reference genome’ in the Amoebozoa clade. We highlight several new features in the present update: (i) new annotations; (ii) improved interface with web 2.0 functionality; (iii) the initial steps towards a genome portal for the Amoebozoa; (iv) ortholog display; and (v) the complete integration of the Dicty Stock Center with dictyBase.
doi:10.1093/nar/gkq1103
PMCID: PMC3013695  PMID: 21087999
16.  PANTHER version 7: improved phylogenetic trees, orthologs and collaboration with the Gene Ontology Consortium 
Nucleic Acids Research  2009;38(Database issue):D204-D210.
Protein Analysis THrough Evolutionary Relationships (PANTHER) is a comprehensive software system for inferring the functions of genes based on their evolutionary relationships. Phylogenetic trees of gene families form the basis for PANTHER and these trees are annotated with ontology terms describing the evolution of gene function from ancestral to modern day genes. One of the main applications of PANTHER is in accurate prediction of the functions of uncharacterized genes, based on their evolutionary relationships to genes with functions known from experiment. The PANTHER website, freely available at http://www.pantherdb.org, also includes software tools for analyzing genomic data relative to known and inferred gene functions. Since 2007, there have been several new developments to PANTHER: (i) improved phylogenetic trees, explicitly representing speciation and gene duplication events, (ii) identification of gene orthologs, including least diverged orthologs (best one-to-one pairs), (iii) coverage of more genomes (48 genomes, up to 87% of genes in each genome; see http://www.pantherdb.org/panther/summaryStats.jsp), (iv) improved support for alternative database identifiers for genes, proteins and microarray probes and (v) adoption of the SBGN standard for display of biological pathways. In addition, PANTHER trees are being annotated with gene function as part of the Gene Ontology Reference Genome project, resulting in an increasing number of curated functional annotations.
doi:10.1093/nar/gkp1019
PMCID: PMC2808919  PMID: 20015972
17.  dictyBase—a Dictyostelium bioinformatics resource update 
Nucleic Acids Research  2008;37(Database issue):D515-D519.
dictyBase (http://dictybase.org) is the model organism database for Dictyostelium discoideum. It houses the complete genome sequence, ESTs and the entire body of literature relevant to Dictyostelium. This information is curated to provide accurate gene models and functional annotations, with the goal of fully annotating the genome. This dictyBase update describes the annotations and features implemented since 2006, including improved strain and phenotype representation, integration of predicted transcriptional regulatory elements, protein domain information, biochemical pathways, improved searching and a wiki tool that allows members of the research community to provide annotations.
doi:10.1093/nar/gkn844
PMCID: PMC2686522  PMID: 18974179
18.  An anatomy ontology to represent biological knowledge in Dictyostelium discoideum 
BMC Genomics  2008;9:130.
Background
Dictyostelium discoideum is a model system for studying many important physiological processes including chemotaxis, phagocytosis, and signal transduction. The recent sequencing of the genome has revealed the presence of over 12,500 protein-coding genes. The model organism database dictyBase hosts the genome sequence as well as a large amount of manually curated information.
Results
We present here an anatomy ontology for Dictyostelium based upon the life cycle of the organism.
Conclusion
Anatomy ontologies are necessary to annotate species-specific events such as phenotypes, and the Dictyostelium anatomy ontology provides an essential tool for curation of the Dictyostelium genome.
doi:10.1186/1471-2164-9-130
PMCID: PMC2323390  PMID: 18366659
19.  Generation, annotation, and analysis of an extensive Aspergillus niger EST collection 
BMC Microbiology  2006;6:7.
Background
Aspergillus niger, a saprophyte commonly found on decaying vegetation, is widely used and studied for industrial purposes. Despite its place as one of the most important organisms for commercial applications, the lack of available information about its genetic makeup limits research with this filamentous fungus.
Results
We present here the analysis of 12,820 expressed sequence tags (ESTs) generated from A. niger cultured under seven different growth conditions. These ESTs identify about 5,108 genes of which 44.5% code for proteins sharing similarity (E ≤ 1e -5) with GenBank entries of known function, 38% code for proteins that only share similarity with GenBank entries of unknown function and 17.5% encode proteins that do not have a GenBank homolog. Using the Gene Ontology hierarchy, we present a first classification of the A. niger proteins encoded by these genes and compare its protein repertoire with other well-studied fungal species. We have established a searchable web-based database that includes the EST and derived contig sequences and their annotation. Details about this project and access to the annotated A. niger database are available.
Conclusion
This EST collection and its annotation provide a significant resource for fundamental and applied research with A. niger. The gene set identified in this manuscript will be highly useful in the annotation of the genome sequence of A. niger, the genes described in the manuscript, especially those encoding hydrolytic enzymes will provide a valuable source for researchers interested in enzyme properties and applications.
doi:10.1186/1471-2180-6-7
PMCID: PMC1434744  PMID: 16457709
20.  dictyBase, the model organism database for Dictyostelium discoideum 
Nucleic Acids Research  2005;34(Database issue):D423-D427.
dictyBase () is the model organism database (MOD) for the social amoeba Dictyostelium discoideum. The unique biology and phylogenetic position of Dictyostelium offer a great opportunity to gain knowledge of processes not characterized in other organisms. The recent completion of the 34 MB genome sequence, together with the sizable scientific literature using Dictyostelium as a research organism, provided the necessary tools to create a well-annotated genome. dictyBase has leveraged software developed by the Saccharomyces Genome Database and the Generic Model Organism Database project. This has reduced the time required to develop a full-featured MOD and greatly facilitated our ability to focus on annotation and providing new functionality. We hope that manual curation of the Dictyostelium genome will facilitate the annotation of other genomes.
doi:10.1093/nar/gkj090
PMCID: PMC1347453  PMID: 16381903
21.  dictyBase: a new Dictyostelium discoideum genome database 
Nucleic Acids Research  2004;32(Database issue):D332-D333.
Dictyostelium discoideum is a powerful and genetically tractable model system used for the study of numerous cellular molecular mechanisms including chemotaxis, phagocytosis and signal transduction. The past 2 years have seen a significant expansion in the scope and accessibility of online resources for Dictyostelium. Recent advances have focused on the development of a new comprehensive online resource called dictyBase (http://dictybase.org). This database not only provides access to genomic data including functional annotation of genes, gene products and chromosomal mapping, but also to extensive biological information such as mutant phenotypes and corresponding reference material. In conjunction with additional sites (http://genome.imb-jena.de/dictyostelium/, http://dictyensembl.bioch.bcm.tmc.edu and http://www.sanger.ac.uk/Projects/D_discoideum/) from the genome sequencing and assembly centers, these improvements have expanded the scope of the Dictyostelium databases making them accessible and useful to any researcher interested in comparative and functional genomics in metazoan organisms.
doi:10.1093/nar/gkh138
PMCID: PMC308872  PMID: 14681427
22.  Inducible expression of exogenous genes in Dictyostelium discoideum using the ribonucleotide reductase promoter 
Nucleic Acids Research  2001;29(2):e5.
We report here the development of a regulated gene expression system for Dictyostelium discoideum based on the DNA-damage inducibility of the rnrB gene. rnrB, which codes for the small subunit of the enzyme ribonucleotide reductase, responds to DNA-damaging agents at all stages of the D.discoideum life cycle. Doses that have little effect on development have previously been shown to increase the level of the rnrB transcript by up to 15-fold. Here we show that all elements necessary for DNA-damage induction are contained in a 450 bp promoter fragment. We used a fusion of the rnrB promoter with the gene encoding GFP to demonstrate an up to 10-fold induction at the RNA level, which appears in all aspects similar to induction of the endogenous rnrB transcript. Using a fusion with the lacZ gene we observed an up to 7-fold induction at the protein level. These results indicate that the rnrB promoter can be used to regulate the expression of specific genes in D.discoideum. This controllable gene expression system provides the following new characteristics: the induction is rapid, taking place in the order of minutes, and the promoter is responsive at all stages of the D.discoideum life cycle.
PMCID: PMC29686  PMID: 11139635

Results 1-22 (22)