ORCID Profile
0000-0003-2991-2217
Current Organisation
University of Ljubljana
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Publisher: Frontiers Media SA
Date: 2013
Publisher: Cold Spring Harbor Laboratory
Date: 13-09-2004
DOI: 10.1101/GR.2478604
Abstract: Del(13) Svea 36H (Del36H) is a deletion of ∼20% of mouse chromosome 13 showing conserved synteny with human chromosome 6p22.1-6p22.3/6p25. The human region is lost in some deletion syndromes and is the site of several disease loci. Heterozygous Del36H mice show numerous phenotypes and may model aspects of human genetic disease. We describe 12.7 Mb of finished, annotated sequence from Del36H. Del36H has a higher gene density than the draft mouse genome, reflecting high local densities of three gene families (vomeronasal receptors, serpins, and prolactins) which are greatly expanded relative to human. Transposable elements are concentrated near these gene families. We therefore suggest that their neighborhoods are gene factories, regions of frequent recombination in which gene duplication is more frequent. The gene families show different proportions of pseudogenes, likely reflecting different strengths of purifying selection and/or gene conversion. They are also associated with relatively low simple sequence concentrations, which vary across the region with a periodicity of ∼5 Mb. Del36H contains numerous evolutionarily conserved regions (ECRs). Many lie in noncoding regions, are detectable in species as distant as Ciona intestinalis , and therefore are candidate regulatory sequences. This analysis will facilitate functional genomic analysis of Del36H and provides insights into mouse genome evolution.
Publisher: Oxford University Press (OUP)
Date: 20-11-2008
DOI: 10.1093/BIOINFORMATICS/BTN607
Abstract: Motivation: Conventional phylogenetic analysis for characterizing the relatedness between taxa typically assumes that a single relationship exists between species at every site along the genome. This assumption fails to take into account recombination which is a fundamental process for generating ersity and can lead to spurious results. Recombination induces a localized phylogenetic structure which may vary along the genome. Here, we generalize a hidden Markov model (HMM) to infer changes in phylogeny along multiple sequence alignments while accounting for rate heterogeneity the hidden states refer to the unobserved phylogenic topology underlying the relatedness at a genomic location. The dimensionality of the number of hidden states (topologies) and their structure are random (not known a priori) and are s led using Markov chain Monte Carlo algorithms. The HMM structure allows us to analytically integrate out over all possible changepoints in topologies as well as all the unknown branch lengths. Results: We demonstrate our approach on simulated data and also to the genome of a suspected HIV recombinant strain as well as to an investigation of recombination in the sequences of 15 laboratory mouse strains sequenced by Perlegen Sciences. Our findings indicate that our method allows us to distinguish between rate heterogeneity and variation in phylogeny caused by recombination without being restricted to 4-taxa data. Availability: The method has been implemented in JAVA and is available, along with data studied here, from www.stats.ox.ac.uk/~webb. Contact: cholmes@stats.ox.ac.uk Supplementary information: Supplementary data are available at Bioinformatics online.
Publisher: F1000 Research Ltd
Date: 21-06-2017
DOI: 10.12688/F1000RESEARCH.11837.1
Abstract: ELIXIR-UK is the UK node of ELIXIR, the European infrastructure for life science data. Since its foundation in 2014, ELIXIR-UK has played a leading role in training both within the UK and in the ELIXIR Training Platform, which coordinates and delivers training across all ELIXIR members. ELIXIR-UK contributes to the Training Platform’s coordination and supports the development of training to address key skill gaps amongst UK scientists. As part of this work it acts as a conduit for nationally-important bioinformatics training resources to promote their activities to the ELIXIR community. ELIXIR-UK also leads ELIXIR’s flagship Training Portal, TeSS, which collects information about a erse range of training and makes it easily accessible to the community. ELIXIR-UK also works with others to provide key digital skills training, partnering with the Software Sustainability Institute to provide Software Carpentry training to the ELIXIR community and to establish the Data Carpentry initiative, and taking a lead role amongst national stakeholders to deliver the StaTS project – a coordinated effort to drive engagement with training in statistics.
Publisher: Hindawi Limited
Date: 2004
DOI: 10.1002/CFG.430
Abstract: Ontologies are becoming increasingly important for the efficient storage, retrieval and mining of biological data. The description of phenotypes using ontologies is a particularly complex problem. We outline a schema that can be used to describe phenotypes by combining orthologous axiomatic ontologies. We also describe tools for storing, browsing and searching such complex ontologies. Central to this approach is that assays (protocols for measuring phenotypic characters) describe what has been measured as well as how this was done, allowing assays to link in idual organisms to ontologies describing phenotypes. We have evaluated this approach by automatically annotating data on 600 000 mutant mice phenotypes using the SHIRPA protocol. We believe this approach will enable the flexible, extensible and detailed description of phenotypes from any organism.
Publisher: Hindawi Limited
Date: 20-01-2009
DOI: 10.1002/HUMU.20972
Publisher: Elsevier
Date: 1993
Publisher: John Wiley & Sons, Inc.
Date: 15-10-2004
Publisher: Hindawi Limited
Date: 06-04-2012
DOI: 10.1002/HUMU.22079
Abstract: There is an increasing accumulation of data on disease-related mutations and associated phenotypes in a wide variety of databases worldwide. Exploiting these data in the context of whole genome sequencing is inhibited because the phenotype information in these databases is often difficult to search meaningfully or relate between data sets, and automated computational integration is not possible. Key to this integration is the development of ontology-based methods for describing diseases in terms of their component phenotypes. This would allow analysis of variation in disease manifestation, relationships between diseases and phenotypes in model organisms, and linking diseases to gene mutations, pathways, and phenotypes. Building a systematic link to phenotypes manifested in model organisms will be of particular importance with the advent of new, large-scale phenotyping projects such as the International Mouse Phenotyping Consortium. In addition to improved semantic description, funding and organizational innovations are required to support this integration. In particular, a series of national or international hubs to hold genotype and phenotype data are needed which could feed data to a central database. In addition, better coordination of clinical and bioinformatics experts and, crucially, development of a transnational funding and international coordination infrastructure will be required.
Publisher: Oxford University Press (OUP)
Date: 1982
Abstract: We describe new results obtained using the bifunctional chemical reagent phenyldiglyoxal (PDG) to study the intramolecular crosslinking of ribosomal 5S RNA from E. coli. In a previous publication (Wagner & Garrett [1]) we reported the identification of a crosslink in the stem region of 5S RNA (G2-G112) using the same reagent but were unable to obtain further information because of the presence of monofunctional adducts which confused the analyses. To overcome this problem, we have removed the monoaddition products by coupling them via their free reagent ends to a solid support bearing reactive groups. Using this system we have been able to identify a new crosslink G41-G72 in native 5S RNA which has considerable structural implications. We propose a structural model in which the proximity of both nucleotides is maintained by secondary interactions.
Publisher: Springer Science and Business Media LLC
Date: 2013
Publisher: Annual Reviews
Date: 12-2009
DOI: 10.1146/ANNUREV-GENET-102108-134143
Abstract: The mouse is central to the goal of establishing a comprehensive functional annotation of the mammalian genome that will help elucidate various human disease genes and pathways. The mouse offers a unique combination of attributes, including an extensive genetic toolkit that underpins the creation and analysis of models of human disease. An international effort to generate mutations for every gene in the mouse genome is a first and essential step in this endeavor. However, the greater challenge will be the determination of the phenotype of every mutant. Large-scale phenotyping for genome-wide functional annotation presents numerous scientific, infrastructural, logistical, and informatics challenges. These include the use of standardized approaches to phenotyping procedures for the population of unified databases with comparable data sets. The ultimate goal is a comprehensive database of molecular interventions that allows us to create a framework for biological systems analysis in the mouse on which human biology and disease networks can be revealed.
Publisher: F1000 Research Ltd
Date: 13-10-2020
DOI: 10.12688/F1000RESEARCH.24887.1
Abstract: Copy number variations (CNVs) are major causative contributors both in the genesis of genetic diseases and human neoplasias. While “High-Throughput” sequencing technologies are increasingly becoming the primary choice for genomic screening analysis, their ability to efficiently detect CNVs is still heterogeneous and remains to be developed. The aim of this white paper is to provide a guiding framework for the future contributions of ELIXIR’s recently established h uman CNV Community, with implications beyond human disease diagnostics and population genomics. This white paper is the direct result of a strategy meeting that took place in September 2018 in Hinxton (UK) and involved representatives of 11 ELIXIR Nodes. The meeting led to the definition of priority objectives and tasks, to address a wide range of CNV-related challenges ranging from detection and interpretation to sharing and training. Here, we provide suggestions on how to align these tasks within the ELIXIR Platforms strategy, and on how to frame the activities of this new ELIXIR Community in the international context.
Publisher: EMBO
Date: 09-02-2021
Publisher: Wiley
Date: 19-09-2013
Publisher: Oxford University Press (OUP)
Date: 23-10-2009
DOI: 10.1093/NAR/GKP867
Publisher: Oxford University Press (OUP)
Date: 22-01-2007
DOI: 10.1093/BFGP/ELM033
Abstract: An essential aspect to understanding the functional significance of in idual genes in the mouse genome is an understanding of the phenotypic consequences of gene mutations. A wide variety of online sites exist that provide different types of phenotypic information on the laboratory mouse. In this review, we describe the major resources that are currently available and discuss some of the bioinformatics requirements that will be necessary to make more seamless searching, comparison and analysis of these various data types possible.
Publisher: PeerJ
Date: 27-07-2017
DOI: 10.7287/PEERJ.PREPRINTS.3112V1
Abstract: We present PIsCO, a server-side JavaScript framework for the collection, registration and sharing of metrics that can be used to evaluate the impact of bioinformatics-related resources such as software, repositories, training or databases. The metrics framework can be used to capture standard definitions of metrics, facilitate the collection of data, monitor resources and share data to be reused by other teams, laboratories or academic institutions. In addition, PIsCO is able to collect those metrics and present them in a visual way to allow their easy interpretation.
Publisher: Springer Science and Business Media LLC
Date: 03-08-2007
DOI: 10.1007/S00335-007-9042-4
Abstract: The effective extraction of information from multidimensional data sets derived from phenotyping experiments is a growing challenge in biology. Data visualization tools are important resources that can aid in exploratory data analysis of complex data sets. Phenotyping experiments of model organisms produce data sets in which a large number of phenotypic measures are collected for each in idual in a group. A critical initial step in the analysis of such multidimensional data sets is the exploratory analysis of data distribution and correlation. To facilitate the rapid visualization and exploratory analysis of multidimensional complex trait data, we have developed a user-friendly, web-based software tool called Phenostat. Phenostat is composed of a dynamic graphical environment that allows the user to inspect the distribution of multiple variables in a data set simultaneously. In iduals can be selected by directly clicking on the graphs and thus displaying their identity, highlighting corresponding values in all graphs, allowing their inclusion or exclusion from the analysis. Statistical analysis is provided by R package functions. Phenostat is particularly suited for rapid distribution and correlation analysis of subsets of data. An analysis of behavioral and physiologic data stemming from a large mouse phenotyping experiment using Phenostat reveals previously unsuspected correlations. Phenostat is freely available to academic institutions and nonprofit organizations and can be used from our website at: (www.bioinfo.embl.it henostat/).
Publisher: Oxford University Press (OUP)
Date: 16-10-2019
DOI: 10.1093/BIB/BBZ075
Abstract: The corpus of bioinformatics resources is huge and expanding rapidly, presenting life scientists with a growing challenge in selecting tools that fit the desired purpose. To address this, the European Infrastructure for Biological Information is supporting a systematic approach towards a comprehensive registry of tools and databases for all domains of bioinformatics, provided under a single portal (bio.tools). We describe here the practical means by which scientific communities, including in idual developers and projects, through major service providers and research infrastructures, can describe their own bioinformatics resources and share these via bio.tools.
Publisher: Springer Science and Business Media LLC
Date: 2010
Publisher: IEEE
Date: 09-2009
Publisher: Springer Science and Business Media LLC
Date: 2009
Publisher: Oxford University Press (OUP)
Date: 18-11-2004
DOI: 10.1093/BIOINFORMATICS/BTI147
Abstract: Motivation: A major challenge in modern biology is to link genome sequence information to organismal function. In many organisms this is being done by characterizing phenotypes resulting from mutations. Efficiently expressing phenotypic information requires combinatorial use of ontologies. However tools are not currently available to visualize combinations of ontologies. Here we describe CRAVE (Concept Relation Assay Value Explorer), a package allowing storage, active updating and visualization of multiple ontologies. Results: CRAVE is a web-accessible JAVA application that accesses an underlying MySQL database of ontologies via a JAVA persistent middleware layer (Chameleon). This maps the database tables into discrete JAVA classes and creates memory resident, interlinked objects corresponding to the ontology data. These JAVA objects are accessed via calls through the middleware's application programming interface. CRAVE allows simultaneous display and linking of multiple ontologies and searching using Boolean and advanced searches. Availability: Direct access: www.mgu.har.mrc.ac.uk/CRAVE/ Contact: g.gkoutos@har.mrc.ac.uk
Publisher: Elsevier BV
Date: 2005
DOI: 10.1016/J.GENE.2004.11.023
Abstract: Only 5-6% of mammalian genomes are genes the remainders are made up primarily of transposable elements and different types of simple sequence repeat (SSRs) (micro- and minisatellites and cryptic repeats), which tend to accumulate in organisms with larger genomes. SSRs are also found at the level of protein sequences and may or may not be encoded by SSRs at the DNA sequence level. Studies of proteins containing SSRs indicate that they tend to belong to particular functional classes, particularly transcription factors and protein kinases. Protein SSRs coded for by pure codon repeats evolve rapidly while those encoded by mixtures of codons evolve slowly. We outline a conceptualization of how protein SSRs may arise and become fixed in proteins during evolution, and suggest that emergence and change in length of protein SSRs may affect the topology of protein interaction networks.
Publisher: F1000 Research Ltd
Date: 08-11-2021
DOI: 10.12688/F1000RESEARCH.74502.1
Abstract: Toxicology has been an active research field for many decades, with academic, industrial and government involvement. Modern omics and computational approaches are changing the field, from merely disease-specific observational models into target-specific predictive models. Traditionally, toxicology has strong links with other fields such as biology, chemistry, pharmacology and medicine. With the rise of synthetic and new engineered materials, alongside ongoing prioritisation needs in chemical risk assessment for existing chemicals, early predictive evaluations are becoming of utmost importance to both scientific and regulatory purposes. ELIXIR is an intergovernmental organisation that brings together life science resources from across Europe. To coordinate the linkage of various life science efforts around modern predictive toxicology, the establishment of a new ELIXIR Community is seen as instrumental. In the past few years, joint efforts, building on incidental overlap, have been piloted in the context of ELIXIR. For ex le, the EU-ToxRisk, diXa, HeCaToS, transQST, and the nanotoxicology community have worked with the ELIXIR TeSS, Bioschemas, and Compute Platforms and activities. In 2018, a core group of interested parties wrote a proposal, outlining a sketch of what this new ELIXIR Toxicology Community would look like. A recent workshop (held September 30th to October 1st, 2020) extended this into an ELIXIR Toxicology roadmap and a shortlist of limited investment-high gain collaborations to give body to this new community. This Whitepaper outlines the results of these efforts and defines our vision of the ELIXIR Toxicology Community and how it complements other ELIXIR activities.
Publisher: Elsevier BV
Date: 2022
DOI: 10.1016/J.BBAGRM.2021.194785
Abstract: Omics has broadened our view of transcriptional and gene regulatory networks of multifactorial diseases, such as metabolism associated liver disease and its advanced stages including hepatocellular carcinoma. Identifying liver disease biomarkers and potential treatment targets makes use of experimental models, e.g. genetically engineered mice, which show molecular features of human pathologies but are experimentally tractable. We compared gene expression profiling data from human to our studies on transgenic mice with hepatocyte deletion of Cyp51 from cholesterol synthesis with the aim of identifying the human liver disease state best matched by the Cyp51 knockout model. Gene Expression Omnibus was used to identify relevant human datasets. We identified enriched and deregulated genes, pathways and transcription factors of mouse and human disease s les. Analysis showed a closer match of the Cyp51 knockout to the female patient s les. Importantly, CYP51 was depleted in both mouse and female human data. Among the enriched genes were the oxysterol-binding protein-related protein 3 (OSBPL3), which was enriched in all datasets, and the collagen gene COL1A2, which was enriched in both the mouse and one human dataset. KEGG and Reactome analyses revealed the most enriched pathway to be ECM-receptor interaction. Numerous transcription factors were differentially expressed in mice of both sexes and in the human female dataset, while depleted HNF4α and RXRα:PPARα-isoform1 were a hallmark in all cases. Our analysis exposed novel potential biomarkers, which may provide new avenues towards more personalized approaches and different targets in females and males. The analysis was only possible because of availability of open data resources and tools and broadly consistent annotation.
Publisher: Wiley
Date: 2004
DOI: 10.1002/BIES.20121
Abstract: Rattus norvegicus is an important experimental organism and interesting to evolutionary biologists. The recently published draft rat genome sequence provides us with insights into both the rat's evolution and its physiology. We learn more about genome evolution and, in particular, the adaptive significance of gene family expansions and the evolution of rodent genomes, which appears to have decelerated since the ergence of mouse and rat. An important observation is that some regions of genomes, many in noncoding regions, show very high sequence conservation, while others show unexpectedly fast evolution. Both of these may be pointers to functional significance.
Publisher: The Company of Biologists
Date: 28-04-2010
DOI: 10.1242/DMM.002790
Abstract: A major challenge of the post-genomic era is coding phenotype data from humans and model organisms such as the mouse, to permit the meaningful translation of phenotype descriptions between species. This ability is essential if we are to facilitate phenotype-driven gene function discovery and empower comparative pathobiology. Here, we review the current state of the art for phenotype and disease description in mice and humans, and discuss ways in which the semantic gap between coding systems might be bridged to facilitate the discovery and exploitation of new mouse models of human diseases.
Publisher: Frontiers Media SA
Date: 2014
Publisher: Frontiers Media SA
Date: 07-01-2015
Publisher: Oxford University Press (OUP)
Date: 18-11-2010
DOI: 10.1093/NAR/GKQ1173
Publisher: Springer Science and Business Media LLC
Date: 27-07-2015
DOI: 10.1038/NG.3360
Publisher: Springer Science and Business Media LLC
Date: 25-05-2011
Abstract: Cellular ATP levels are generated by glucose-stimulated mitochondrial metabolism and determine metabolic responses, such as glucose-stimulated insulin secretion (GSIS) from the β-cells of pancreatic islets. We describe an analysis of the evolutionary processes affecting the core enzymes involved in glucose-stimulated insulin secretion in mammals. The proteins involved in this system belong to ancient enzymatic pathways: glycolysis, the TCA cycle and oxidative phosphorylation. We identify two sets of proteins, or protein coalitions, in this group of 77 enzymes with distinct evolutionary patterns. Members of the glycolysis, TCA cycle, metabolite transport, pyruvate and NADH shuttles have low rates of protein sequence evolution, as inferred from a human-mouse comparison, and relatively high rates of evolutionary gene duplication. Respiratory chain and glutathione pathway proteins evolve faster, exhibiting lower rates of gene duplication. A small number of proteins in the system evolve significantly faster than co-pathway members and may serve as rapidly evolving adapters, linking groups of co-evolving genes. Our results provide insights into the evolution of the involved proteins. We find evidence for two coalitions of proteins and the role of co-adaptation in protein evolution is identified and could be used in future research within a functional context.
Publisher: Elsevier BV
Date: 11-2005
DOI: 10.1016/J.TIG.2005.08.008
Abstract: Gene duplication has long been considered an important force in genome evolution. In this article, I consider families of tandemly duplicated genes that show 'microfunctionalization' - genes encoding similar proteins with subtly different functions, such as olfactory receptors. I discuss the genomic processes giving rise to such microfunctionalized gene families and suggest that, like sites of chromosomal rearrangement and breakage, they are associated with relatively high concentrations of repetitive elements. I suggest that microfunctionalized gene families arise within gene factories: genomic regions rich in repetitive elements that undergo increased levels of unequal crossing-over.
Publisher: F1000 Research Ltd
Date: 22-04-2020
DOI: 10.12688/F1000RESEARCH.20559.1
Abstract: Structural bioinformatics provides the scientific methods and tools to analyse, archive, validate, and present the biomolecular structure data generated by the structural biology community. It also provides an important link with the genomics community, as structural bioinformaticians also use the extensive sequence data to predict protein structures and their functional sites. A very broad and active community of structural bioinformaticians exists across Europe, and 3D-Bioinfo will establish formal platforms to address their needs and better integrate their activities and initiatives. Our mission will be to strengthen the ties with the structural biology research communities in Europe covering life sciences, as well as chemistry and physics and to bridge the gap between these researchers in order to fully realize the potential of structural bioinformatics. Our Community will also undertake dedicated educational, training and outreach efforts to facilitate this, bringing new insights and thus facilitating the development of much needed innovative applications e.g. for human health, drug and protein design. Our combined efforts will be of critical importance to keep the European research efforts competitive in this respect. Here we highlight the major European contributions to the field of structural bioinformatics, the most pressing challenges remaining and how Europe-wide interactions, enabled by ELIXIR and its platforms, will help in addressing these challenges and in coordinating structural bioinformatics resources across Europe. In particular, we present recent activities and future plans to consolidate an ELIXIR 3D-Bioinfo Community in structural bioinformatics and propose means to develop better links across the community. These include building new consortia, organising workshops to establish data standards and seeking community agreement on benchmark data sets and strategies. We also highlight existing and planned collaborations with other ELIXIR Communities and other European infrastructures, such as the structural biology community supported by Instruct-ERIC, with whom we have synergies and overlapping common interests.
Publisher: Springer Science and Business Media LLC
Date: 11-2013
DOI: 10.1007/S00335-013-9481-Z
Abstract: We have applied the Neuro Behavior Ontology (NBO), an ontology for the annotation of behavioral gene functions and behavioral phenotypes, to the annotation of more than 1,000 genes in the mouse that are known to play a role in behavior. These annotations can be explored by researchers interested in genes involved in particular behaviors and used computationally to provide insights into the behavioral phenotypes resulting from differences in gene expression. We developed the OntoFUNC tool and have applied it to enrichment analyses over the NBO to provide high-level behavioral interpretations of gene expression datasets. The resulting increase in the number of gene annotations facilitates the identification of behavioral or neurologic processes by assisting the formulation of hypotheses about the relationships between gene, processes, and phenotypic manifestations resulting from behavioral observations.
Publisher: F1000 Research Ltd
Date: 03-07-2017
DOI: 10.12688/F1000RESEARCH.11718.1
Abstract: Quality training in computational skills for life scientists is essential to allow them to deliver robust, reproducible and cutting-edge research. A pan-European bioinformatics programme, ELIXIR, has adopted a well-established and progressive programme of computational lab and data skills training from Software and Data Carpentry , aimed at increasing the number of skilled life scientists and building a sustainable training community in this field. This article describes the Pilot action, which introduced the Carpentry training model to the ELIXIR community.
Publisher: Elsevier BV
Date: 10-2012
DOI: 10.1016/J.GENE.2012.07.039
Abstract: The locations of microsatellites in mammalian genomes are restricted by purifying selection in a number of ways. For ex le, with the exception of some trinucleotide repeats they are excluded from protein coding regions of genomes because of their tendency to cause frameshift mutations. Here we investigate whether purifying selection might affect the types and frequencies of microsatellites in microRNA (miRNA). We concentrate on miRNAs expressed in neurons and the brain (NB-miRNAs) as microsatellites in these genes might give rise to similar effects as disease-causing repeats in protein coding genes. We show that in human miRNAs in general AG and AT microsatellites are reduced in frequency compared to AC repeats and that NB-miRNA genes contain significantly fewer microsatellites than expected from frequencies of microsatellites in other miRNA genes. NB-miRNAs show lower levels of sequence ergence in comparisons of human-macaque orthologues and more often have detectable orthologues in non-human mammals than non-NB-miRNAs. This suggests that microsatellites in miRNAs may indeed be constrained by purifying selection and that the strength of this selection may differ between NB-miRNAs and non-NB-miRNAs. We identify a number of ways in which the potential disruption of pre-miRNA secondary structure might result in purifying selection. However other, non-selective forces could also play a role in generating the biases observed in miRNA microsatellites.
Publisher: Cold Spring Harbor Laboratory
Date: 23-03-2023
DOI: 10.1101/2023.03.21.512712
Abstract: The field of metabolic modelling at the genomescale continues to grow with more models being created and curated. This comes with an increasing demand for adopting common principles regarding transparency and versioning, in addition to standardisation efforts regarding file formats, annotation and testing. Here, we present a standardised template for git-based and GitHub-hosted genome-scale metabolic models (GEMs) supporting both new models and curated ones, following FAIR principles (findability, accessibility, interoperability, and reusability), and incorporating bestpractices. standard-GEM facilitates the reuse of GEMs across web services and platforms in the metabolic modelling field and enables automatic validation of GEMs. The use of this template for new models, and its adoption for existing ones, paves the way for increasing model quality, openness, and accessibility with minimal effort. standard-GEM is available from github.com/MetabolicAtlas/standard-GEM under the conditions of the CC BY 4.0 licence along with additional supporting material.
Publisher: Frontiers Media SA
Date: 24-04-2014
Publisher: American Association for the Advancement of Science (AAAS)
Date: 29-10-2010
Abstract: Globalization of biomedical research requires sustained investment for databases and biorepositories.
Publisher: Oxford University Press (OUP)
Date: 12-04-2017
DOI: 10.1093/BIOINFORMATICS/BTX213
Abstract: The vast, uncoordinated proliferation of bioinformatics resources (databases, software tools, training materials etc.) makes it difficult for users to find them. To facilitate their discovery, various services are being developed to collect such resources into registries. We have developed BioCIDER, which, rather like online shopping ‘recommendations’, provides a contextualization index to help identify biological resources relevant to the content of the sites in which it is embedded. BioCIDER (www.biocider.org) is an open-source platform. Documentation is available online (goo.gl/Klc51G), and source code is freely available via GitHub (github.com/BioCIDER). The BioJS widget that enables websites to embed contextualization is available from the BioJS registry (biojs.io/). All code is released under an MIT licence.
Publisher: John Wiley & Sons, Inc.
Date: 15-10-2004
Publisher: Frontiers Media SA
Date: 2014
Publisher: Springer Science and Business Media LLC
Date: 25-08-2007
Publisher: Elsevier BV
Date: 1999
Abstract: The assembly of atherogenic lipoproteins requires the formation in the endoplasmic reticulum of a complex between apolipoprotein (apo)B, a microsomal triglyceride transfer protein (MTP) and protein disulphide isomerase (PDI). Here we show by molecular modelling and mutagenesis that the globular amino-terminal regions of apoB and MTP are closely related in structure to the ancient egg yolk storage protein, vitellogenin (VTG). In the MTP complex, conserved structural motifs that form the reciprocal homodimerization interfaces in VTG are re-utilized by MTP to form a stable heterodimer with PDI, which anchors MTP at the site of apoB translocation, and to associate with apoB and initiate lipid transfer. The structural and functional evolution of the VTGs provides a unifying scheme for the invertebrate origins of the major vertebrate lipid transport system.
Publisher: F1000 Research Ltd
Date: 21-12-2016
DOI: 10.12688/F1000RESEARCH.10473.1
Abstract: ELIXIR is the European infrastructure established specifically for the sharing and sustainability of life science data. To provide up-to-date resources and services, ELIXIR needs to undergo a continuous process of refreshing the services provided by its national Nodes. Here we present the approach taken by ELIXIR-UK to address the advice by the ELIXIR Scientific Advisory Board that Nodes need to develop “ mechanisms to ensure that each Node continues to be representative of the Bioinformatics efforts within the country”. ELIXIR-UK put in place an open and transparent process to identify potential ELIXIR resources within the UK during late 2015 and early to mid-2016. Areas of strategic strength were identified and Expressions of Interest in these priority areas were requested from the UK community. A set of criteria were established, in discussion with the ELIXIR Hub, and prospective ELIXIR-UK resources were assessed by an independent committee set up by the Node for this purpose. Of 19 resources considered, 14 were judged to be immediately ready to be included in the UK ELIXIR Node’s portfolio. A further five were placed on the Node’s roadmap for future consideration for inclusion. ELIXIR-UK expects to repeat this process regularly to ensure its portfolio continues to reflect its community’s strengths.
Publisher: Springer Science and Business Media LLC
Date: 05-2009
Publisher: Wiley
Date: 05-1996
Abstract: Recent analysis of the contribution of replication slippage to genome evolution shows that it has played a significant role in all species from eubacteria to humans. The overall level of repetition in genomes is related to genome size and to the degree of repetition that can be measured within in idual ribosomal RNA genes, suggesting that the entire genome accepts simple sequences in a concerted manner when its size increases. Although coding sequences accept simple sequences much less readily than non-coding sequences, they accept some repeats, particularly (CAG)n, preferentially. This may have consequences for the evolution of the genes involved in trinucleotide expansion diseases and the transcriptional networks of which they may form a part.
Publisher: IEEE
Date: 10-2008
Publisher: Springer Berlin Heidelberg
Date: 2008
Publisher: Center for Open Science
Date: 24-02-2020
Abstract: The thesis is concerned with an experimental investigation of the mechanisms of the various chromosome banding techniques. The findings are put in the context of the mechanisms of the various banding procedures, and some suggestions are made for future lines of investigation.
Publisher: Springer Science and Business Media LLC
Date: 09-2009
DOI: 10.1038/461171A
Publisher: F1000 Research Ltd
Date: 07-11-2022
DOI: 10.12688/F1000RESEARCH.126734.1
Abstract: In this white paper, we describe the founding of a new ELIXIR Community - the Systems Biology Community - and its proposed future contributions to both ELIXIR and the broader community of systems biologists in Europe and worldwide. The Community believes that the infrastructure aspects of systems biology - databases, (modelling) tools and standards development, as well as training and access to cloud infrastructure - are not only appropriate components of the ELIXIR infrastructure, but will prove key components of ELIXIR’s future support of advanced biological applications and personalised medicine. By way of a series of meetings, the Community identified seven key areas for its future activities, reflecting both future needs and previous and current activities within ELIXIR Platforms and Communities. These are: overcoming barriers to the wider uptake of systems biology linking new and existing data to systems biology models interoperability of systems biology resources further development and embedding of systems medicine provisioning of modelling as a service building and coordinating capacity building and training resources and supporting industrial embedding of systems biology. A set of objectives for the Community has been identified under four main headline areas: Standardisation and Interoperability, Technology, Capacity Building and Training, and Industrial Embedding. These are grouped into short-term (3-year), mid-term (6-year) and long-term (10-year) objectives.
Publisher: Oxford University Press (OUP)
Date: 11-07-2008
DOI: 10.1093/BIB/BBN040
Abstract: The torrent of data emerging from the application of new technologies to functional genomics and systems biology can no longer be contained within the traditional modes of data sharing and publication with the consequence that data is being deposited in, distributed across and disseminated through an increasing number of databases. The resulting fragmentation poses serious problems for the model organism community which increasingly rely on data mining and computational approaches that require gathering of data from a range of sources. In the light of these problems, the European Commission has funded a coordination action, CASIMIR (coordination and sustainability of international mouse informatics resources), with a remit to assess the technical and social aspects of database interoperability that currently prevent the full realization of the potential of data integration in mouse functional genomics. In this article, we assess the current problems with interoperability, with particular reference to mouse functional genomics, and critically review the technologies that can be deployed to overcome them. We describe a typical use-case where an investigator wishes to gather data on variation, genomic context and metabolic pathway involvement for genes discovered in a genome-wide screen. We go on to develop an automated approach involving an in silico experimental workflow tool, Taverna, using web services, BioMart and MOLGENIS technologies for data retrieval. Finally, we focus on the current impediments to adopting such an approach in a wider context, and strategies to overcome them.
Publisher: Springer Science and Business Media LLC
Date: 2002
Abstract: The relationship between the level of repetitiveness in genomic sequences and genome size has been re-investigated making use of the rapidly growing database of complete eubacterial and archaeal genome sequences combined with the fragmentary but now large amount of data from eukaryotic genomes. Relative simplicity factors (RSFs), which measure the repetitiveness of sequences, were calculated and significantly simple motifs (SSMs), which identify the kinds of sequences that are repeated, were identified. A previously reported correlation between genome size and repetitiveness was confirmed, but it was shown that the higher RSFs seen in eukaryotic genomes also reflect a generally higher level of repetitiveness independent of genome size differences. Differences in genome size are responsible for about 10% of the variance in RSF seen between species. The spectrum of SSMs seen within a genome differed markedly within the eubacteria but less so in eukaryotes and, particularly, in archaea. Species with SSM spectra that differ from the norm tend also to have high RSFs for their genome size and to be pathogens that make use of repetitive sequences to avoid host defence responses. Some of the variance in repetitiveness seen in other species may therefore also reflect the action of selection, although other forces such as variation in the effectiveness of mechanisms for regulating slippage errors of replication, may also be important.
Publisher: Wiley
Date: 15-07-2004
DOI: 10.1002/0471650129
Publisher: Oxford University Press (OUP)
Date: 04-1998
Abstract: Variable regions within ribosomal RNAs frequently vary in length as a result of incorporating products of slippage. This makes constructing secondary structure models problematic because base homology is difficult or impossible to establish between species. Here, we model such a region by comparing the results of the MFOLD suboptimal folding algorithm for different species to identify conserved structures. Based on the reconstruction of base change on a phylogenetic tree of the species and comparison against null models of character change, we devise a statistical analysis to assess support of these structures from compensatory and semi-compensatory (i.e. G.C to G.U or A.U to G.U) mutations. As a model system we have used variable region V4 from cicindelid (tiger beetle) small subunit ribosomal RNAs (SSU rRNAs). This consists of a mixture of conserved and highly variable subregions and has been subject to extensive comparative analysis in the past. The model that results is similar to a previously described model of this variable region derived from a different set of species and contains a novel structure in the central, highly variable part. The method we describe may be useful in modelling other RNA regions that are subject to slippage.
Publisher: Springer Science and Business Media LLC
Date: 26-07-2011
Publisher: Oxford University Press (OUP)
Date: 30-01-2019
DOI: 10.1093/BIB/BBZ007
Abstract: There are multiple definitions for low complexity regions (LCRs) in protein sequences. In this critical review, we focus on the definition of sequence complexity of LCRs and their connection with structure. We present statistics and methodological approaches that measure low complexity (LC) and related sequence properties. Composition bias is often associated with LC and disorder, but repeats, while compositionally biased, might also induce ordered structures. We illustrate this dichotomy, plus overlaps between different properties related to LCRs, using ex les.
Publisher: Springer Science and Business Media LLC
Date: 07-2007
Publisher: John Wiley & Sons, Inc.
Date: 15-10-2004
Publisher: Springer Science and Business Media LLC
Date: 14-05-2013
Abstract: Cells in some tissues acquire a polarisation in the plane of the tissue in addition to apical-basal polarity. This polarisation is commonly known as planar cell polarity and has been found to be important in developmental processes, as planar polarity is required to define the in-plane tissue coordinate system at the cellular level. We have built an in - silico functional model of cellular polarisation that includes cellular asymmetry, cell-cell signalling and a response to a global cue. The model has been validated and parameterised against domineering non-autonomous wing hair phenotypes in Drosophila . We have carried out a systematic comparison of in - silico polarity phenotypes with patterns observed in vivo under different genetic manipulations in the wing. This has allowed us to classify the specific functional roles of proteins involved in generating cell polarity, providing new hypotheses about their specific functions, in particular for Pk and Dsh. The predictions from the model allow direct assignment of functional roles of genes from genetic mosaic analysis of Drosophila wings.
Publisher: Oxford University Press (OUP)
Date: 18-05-2020
DOI: 10.1093/NAR/GKAA339
Abstract: Low complexity regions (LCRs) in protein sequences are characterized by a less erse amino acid composition compared to typically observed sequence ersity. Recent studies have shown that LCRs may co-occur with intrinsically disordered regions, are highly conserved in many organisms, and often play important roles in protein functions and in diseases. In previous decades, several methods have been developed to identify regions with LCRs or amino acid bias, but most of them as stand-alone applications and currently there is no web-based tool which allows users to explore LCRs in protein sequences with additional functional annotations. We aim to fill this gap by providing PlaToLoCo - PLAtform of TOols for LOw COmplexity—a meta-server that integrates and collects the output of five different state-of-the-art tools for discovering LCRs and provides functional annotations such as domain detection, transmembrane segment prediction, and calculation of amino acid frequencies. In addition, the union or intersection of the results of the search on a query sequence can be obtained. By developing the PlaToLoCo meta-server, we provide the community with a fast and easily accessible tool for the analysis of LCRs with additional information included to aid the interpretation of the results. The PlaToLoCo platform is available at: platoloco.aei.polsl.pl/.
Publisher: CRC Press
Date: 19-04-2014
DOI: 10.1201/B16437-4
Publisher: Elsevier BV
Date: 03-2000
Publisher: John Wiley & Sons, Inc.
Date: 15-10-2004
Publisher: Hindawi Limited
Date: 13-06-2003
DOI: 10.1002/HUMU.10235
Abstract: The identification of deleterious mutations within candidate genes is a crucial step in the elucidation of the genetic bases of human disease. However, the significance of any base or amino acid change within a gene is unknown until detailed structural and functional analysis has been carried out. A potentially rapid way of identifying functionally important sites within a gene is to identify evolutionarily conserved regions. Mutations affecting such sites are assumed to be deleterious for the carrier. In this communication we generalize this approach and present a formal framework to assess whether a specific mutation is deleterious given sequence data from a set of homologues. We propose a score that takes into account the nature of the mutation, the conservation of the affected residue among the different species, and their phylogenetic relationships. Its performance is examined using published TP53 mutations and frequent polymorphic variants.
Publisher: Wiley
Date: 10-1998
Publisher: F1000 Research Ltd
Date: 15-11-2017
DOI: 10.12688/F1000RESEARCH.11301.2
Abstract: The Brassica Information Portal (BIP) is a centralised repository for brassica phenotypic data. The site hosts trait data associated with brassica research and breeding experiments conducted on brassica crops, that are used as oilseeds, vegetables, livestock forage and fodder and for biofuels. A key feature is the explicit management of meta-data describing the provenance and relationships between experimental plant materials, as well as trial design and trait descriptors. BIP is an open access and open source project, built on the schema of CropStoreDB, and as such can provide trait data management strategies for any crop data. A new user interface and programmatic submission/retrieval system helps to simplify data access for researchers, breeders and other end-users. BIP opens up the opportunity to apply integrative, cross-project analyses to data generated by the Brassica Research Community. Here, we present a short description of the current status of the repository.
Publisher: Elsevier BV
Date: 07-2010
DOI: 10.1016/J.YEXCR.2010.02.027
Abstract: The KY protein underlies a form of muscular dystrophy in the mouse but its role in muscle remains elusive. Immunodetection of endogenous KY protein in C2C12-derived myotubes and expression of a recombinant form in neonatal cardiomyocytes indicated that KY is a Z-band associated protein. Moreover, characterization of a KY interacting protein fragment led to the identification of Igfn1 (Immunoglobulin-like and fibronectin type 3 domain containing 1). Igfn1 is a transcriptionally complex locus encoding many protein variants. A yeast two-hybrid screen identified the Z-band protein filamin C (FLNC) as an interacting partner. Consistent with this, expression of an IGFN1 recombinant fragment showed that the three N-terminal globular domains, common to at least five IGFN1 variants, are sufficient to provide Z-band targeting. Taken together, the yeast two-hybrid, biochemical and immunofluorescence data support the notion that KY, IGFN1 and FLNC are part of a Z-band associated protein complex likely to provide structural support to the skeletal muscle sarcomere.
Publisher: Elsevier BV
Date: 1999
Publisher: Proceedings of the National Academy of Sciences
Date: 09-01-1996
Abstract: Five human diseases are due to an excessive number of CAG repeats in the coding regions of five different genes. We have analyzed the repeat regions in four of these genes from nonhuman primates, which are not known to suffer from the diseases. These primates have CAG repeats at the same sites as in human alleles, and there is similar polymorphism of repeat number, but this number is smaller than in the human genes. In some of the genes, the segment of poly(CAG) has expanded in nonhuman primates, but the process has advanced further in the human lineage than in other primate lineages, thereby predisposing to diseases of CAG reiteration. Adjacent to stretches of homogeneous present-day codon repeats, previously existing codons of the same kind have undergone nucleotide substitutions with high frequency. Where these lead to amino acid substitutions, the effect will be to reduce the length of the original homopolymeric stretch in the protein.
Publisher: Public Library of Science (PLoS)
Date: 19-05-2011
Publisher: Springer Science and Business Media LLC
Date: 10-04-2007
Publisher: Springer Science and Business Media LLC
Date: 08-2009
Publisher: Wiley
Date: 15-10-2004
Publisher: Oxford University Press (OUP)
Date: 12-04-2005
DOI: 10.1093/BIOINFORMATICS/BTI441
Abstract: Standardized phenotyping protocols are essential for the characterization of phenotypes so that results are comparable between different laboratories and phenotypic data can be related to ontological descriptions in an automated manner. We describe a web-based resource for the visualization, searching and downloading of standard operating procedures and other documents, the European Mouse Phenotyping Resource for Standardized Screens-EMPReSS. Direct access: www.empress.har.mrc.ac.uk e.green@har.mrc.ac.uk.
Publisher: IEEE
Date: 10-2008
Publisher: Public Library of Science (PLoS)
Date: 25-08-2006
Publisher: F1000 Research Ltd
Date: 15-10-2019
DOI: 10.12688/F1000RESEARCH.20136.1
Abstract: Intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs) are now recognised as major determinants in cellular regulation. This white paper presents a roadmap for future e-infrastructure developments in the field of IDP research within the ELIXIR framework. The goal of these developments is to drive the creation of high-quality tools and resources to support the identification, analysis and functional characterisation of IDPs. The roadmap is the result of a workshop titled “An intrinsically disordered protein user community proposal for ELIXIR” held at the University of Padua. The workshop, and further consultation with the members of the wider IDP community, identified the key priority areas for the roadmap including the development of standards for data annotation, storage and dissemination integration of IDP data into the ELIXIR Core Data Resources and the creation of benchmarking criteria for IDP-related software. Here, we discuss these areas of priority, how they can be implemented in cooperation with the ELIXIR platforms, and their connections to existing ELIXIR Communities and international consortia. The article provides a preliminary blueprint for an IDP Community in ELIXIR and is an appeal to identify and involve new stakeholders.
Publisher: Oxford University Press (OUP)
Date: 23-12-2007
DOI: 10.1093/NAR/GKM728
Publisher: IEEE
Date: 10-2008
Publisher: The American Association of Immunologists
Date: 07-2018
Abstract: Myeloid-derived suppressor cells (MDSCs) are known suppressors of antitumor immunity, affecting amino acid metabolism and T cell function in the tumor microenvironment. However, it is unknown whether MDSCs regulate B cell responses during tumor progression. Using a syngeneic mouse model of lung cancer, we show reduction in percentages and absolute numbers of B cell subsets including pro–, pre–, and mature B cells in the bone marrow (BM) of tumor-bearing mice. The kinetics of this impaired B cell response correlated with the progressive infiltration of MDSCs. We identified that IL-7 and downstream STAT5 signaling that play a critical role in B cell development and differentiation were also impaired during tumor progression. Global impairment of B cell function was indicated by reduced serum IgG levels. Importantly, we show that anti–Gr-1 Ab-mediated depletion of MDSCs not only rescued serum IgG and IL-7 levels but also reduced TGF-β1, a known regulator of stromal IL-7, suggesting MDSC-mediated regulation of B cell responses. Furthermore, blockade of IL-7 resulted in reduced phosphorylation of downstream STAT5 and B cell differentiation in tumor-bearing mice and administration of TGF-β–blocking Ab rescued these IL-7–dependent B cell responses. Adoptive transfer of BM-derived MDSCs from tumor-bearing mice into congenic recipients resulted in significant reductions of B cell subsets in the BM and in circulation. MDSCs also suppressed B cell proliferation in vitro in an arginase-dependent manner that required cell-to-cell contact. Our results indicate that tumor-infiltrating MDSCs may suppress humoral immune responses and promote tumor escape from immune surveillance.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for John Hancock.