Carol Chen
University of British Columbia
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Featured researches published by Carol Chen.
Nucleic Acids Research | 2010
Samuel Kerrien; Bruno Aranda; L Breuza; Alan Bridge; Fiona Broackes-Carter; Carol Chen; Margaret Duesbury; Marine Dumousseau; Marc Feuermann; Ursula Hinz; Christine Jandrasits; Rafael C. Jimenez; Jyoti Khadake; Usha Mahadevan; Patrick Masson; Ivo Pedruzzi; Eric Pfeiffenberger; Pablo Porras; Arathi Raghunath; Bernd Roechert; Sandra Orchard; Henning Hermjakob
IntAct is an open-source, open data molecular interaction database populated by data either curated from the literature or from direct data depositions. Two levels of curation are now available within the database, with both IMEx-level annotation and less detailed MIMIx-compatible entries currently supported. As from September 2011, IntAct contains approximately 275 000 curated binary interaction evidences from over 5000 publications. The IntAct website has been improved to enhance the search process and in particular the graphical display of the results. New data download formats are also available, which will facilitate the inclusion of IntActs data in the Semantic Web. IntAct is an active contributor to the IMEx consortium (http://www.imexconsortium.org). IntAct source code and data are freely available at http://www.ebi.ac.uk/intact.
Nucleic Acids Research | 2014
Sandra Orchard; Mais G. Ammari; Bruno Aranda; L Breuza; Leonardo Briganti; Fiona Broackes-Carter; Nancy H. Campbell; Gayatri Chavali; Carol Chen; Noemi del-Toro; Margaret Duesbury; Marine Dumousseau; Eugenia Galeota; Ursula Hinz; Marta Iannuccelli; Sruthi Jagannathan; Rafael C. Jimenez; Jyoti Khadake; Astrid Lagreid; Luana Licata; Ruth C. Lovering; Birgit Meldal; Anna N. Melidoni; Mila Milagros; Daniele Peluso; Livia Perfetto; Pablo Porras; Arathi Raghunath; Sylvie Ricard-Blum; Bernd Roechert
IntAct (freely available at http://www.ebi.ac.uk/intact) is an open-source, open data molecular interaction database populated by data either curated from the literature or from direct data depositions. IntAct has developed a sophisticated web-based curation tool, capable of supporting both IMEx- and MIMIx-level curation. This tool is now utilized by multiple additional curation teams, all of whom annotate data directly into the IntAct database. Members of the IntAct team supply appropriate levels of training, perform quality control on entries and take responsibility for long-term data maintenance. Recently, the MINT and IntAct databases decided to merge their separate efforts to make optimal use of limited developer resources and maximize the curation output. All data manually curated by the MINT curators have been moved into the IntAct database at EMBL-EBI and are merged with the existing IntAct dataset. Both IntAct and MINT are active contributors to the IMEx consortium (http://www.imexconsortium.org).
Nucleic Acids Research | 2013
Karin Breuer; Amir K. Foroushani; Matthew R. Laird; Carol Chen; Anastasia Sribnaia; Raymond Lo; Geoffrey L. Winsor; Robert E. W. Hancock; Fiona S. L. Brinkman; David J. Lynn
InnateDB (http://www.innatedb.com) is an integrated analysis platform that has been specifically designed to facilitate systems-level analyses of mammalian innate immunity networks, pathways and genes. In this article, we provide details of recent updates and improvements to the database. InnateDB now contains >196 000 human, mouse and bovine experimentally validated molecular interactions and 3000 pathway annotations of relevance to all mammalian cellular systems (i.e. not just immune relevant pathways and interactions). In addition, the InnateDB team has, to date, manually curated in excess of 18 000 molecular interactions of relevance to innate immunity, providing unprecedented insight into innate immunity networks, pathways and their component molecules. More recently, InnateDB has also initiated the curation of allergy- and asthma-related interactions. Furthermore, we report a range of improvements to our integrated bioinformatics solutions including web service access to InnateDB interaction data using Proteomics Standards Initiative Common Query Interface, enhanced Gene Ontology analysis for innate immunity, and the availability of new network visualizations tools. Finally, the recent integration of bovine data makes InnateDB the first integrated network analysis platform for this agriculturally important model organism.
Nature Methods | 2012
Sandra Orchard; Samuel Kerrien; Sara Abbani; Bruno Aranda; Jignesh Bhate; Shelby Bidwell; Alan Bridge; Leonardo Briganti; Fiona S. L. Brinkman; Gianni Cesareni; Andrew Chatr-aryamontri; Emilie Chautard; Carol Chen; Marine Dumousseau; Johannes Goll; Robert E. W. Hancock; Linda I. Hannick; Igor Jurisica; Jyoti Khadake; David J. Lynn; Usha Mahadevan; Livia Perfetto; Arathi Raghunath; Sylvie Ricard-Blum; Bernd Roechert; Lukasz Salwinski; Volker Stümpflen; Mike Tyers; Peter Uetz; Ioannis Xenarios
The International Molecular Exchange (IMEx) consortium is an international collaboration between major public interaction data providers to share literature-curation efforts and make a nonredundant set of protein interactions available in a single search interface on a common website (http://www.imexconsortium.org/). Common curation rules have been developed, and a central registry is used to manage the selection of articles to enter into the dataset. We discuss the advantages of such a service to the user, our quality-control measures and our data-distribution practices.
Nature Communications | 2015
Julie Brind’Amour; Sheng Liu; Matthew Hudson; Carol Chen; Mohammad M. Karimi; Matthew C. Lorincz
Combined chromatin immunoprecipitation and next-generation sequencing (ChIP-seq) has enabled genome-wide epigenetic profiling of numerous cell lines and tissue types. A major limitation of ChIP-seq, however, is the large number of cells required to generate high-quality data sets, precluding the study of rare cell populations. Here, we present an ultra-low-input micrococcal nuclease-based native ChIP (ULI-NChIP) and sequencing method to generate genome-wide histone mark profiles with high resolution from as few as 10(3) cells. We demonstrate that ULI-NChIP-seq generates high-quality maps of covalent histone marks from 10(3) to 10(6) embryonic stem cells. Subsequently, we show that ULI-NChIP-seq H3K27me3 profiles generated from E13.5 primordial germ cells isolated from single male and female embryos show high similarity to recent data sets generated using 50-180 × more material. Finally, we identify sexually dimorphic H3K27me3 enrichment at specific genic promoters, thereby illustrating the utility of this method for generating high-quality and -complexity libraries from rare cell populations.
PLOS ONE | 2013
Olga M. Pena; Nicole Afacan; Jelena Pistolic; Carol Chen; Laurence Madera; Reza Falsafi; Christopher D. Fjell; Robert E. W. Hancock
Macrophages play a critical role in the innate immune response. To respond in a rapid and efficient manner to challenges in the micro-environment, macrophages are able to differentiate towards classically (M1) or alternatively (M2) activated phenotypes. Synthetic, innate defense regulators (IDR) peptides, designed based on natural host defence peptides, have enhanced immunomodulatory activities and reduced toxicity leading to protection in infection and inflammation models that is dependent on innate immune cells like monocytes/macrophages. Here we tested the effect of IDR-1018 on macrophage differentiation, a process essential to macrophage function and the immune response. Using transcriptional, protein and systems biology analysis, we observed that differentiation in the presence of IDR-1018 induced a unique signature of immune responses including the production of specific pro and anti-inflammatory mediators, expression of wound healing associated genes, and increased phagocytosis of apoptotic cells. Transcription factor IRF4 appeared to play an important role in promoting this IDR-1018-induced phenotype. The data suggests that IDR-1018 drives macrophage differentiation towards an intermediate M1–M2 state, enhancing anti-inflammatory functions while maintaining certain pro-inflammatory activities important to the resolution of infection. Synthetic peptides like IDR-1018, which act by modulating the immune system, could represent a powerful new class of therapeutics capable of treating the rising number of multidrug resistant infections as well as disorders associated with dysregulated immune responses.
Nature Communications | 2016
Kyoko Hiragami-Hamada; Szabolcs Soeroes; Miroslav Nikolov; Bryan J. Wilkins; Sarah Kreuz; Carol Chen; Inti A. De La Rosa-Velázquez; Hans Michael Zenn; Nils Kost; Wiebke H. Pohl; Aleksandar Chernev; Dirk Schwarzer; Thomas Jenuwein; Matthew C. Lorincz; Bastian Zimmermann; Peter J. Walla; Heinz Neumann; Tuncay Baubec; Henning Urlaub; Wolfgang Fischle
Histone H3 trimethylation of lysine 9 (H3K9me3) and proteins of the heterochromatin protein 1 (HP1) family are hallmarks of heterochromatin, a state of compacted DNA essential for genome stability and long-term transcriptional silencing. The mechanisms by which H3K9me3 and HP1 contribute to chromatin condensation have been speculative and controversial. Here we demonstrate that human HP1β is a prototypic HP1 protein exemplifying most basal chromatin binding and effects. These are caused by dimeric and dynamic interaction with highly enriched H3K9me3 and are modulated by various electrostatic interfaces. HP1β bridges condensed chromatin, which we postulate stabilizes the compacted state. In agreement, HP1β genome-wide localization follows H3K9me3-enrichment and artificial bridging of chromatin fibres is sufficient for maintaining cellular heterochromatic conformation. Overall, our findings define a fundamental mechanism for chromatin higher order structural changes caused by HP1 proteins, which might contribute to the plastic nature of condensed chromatin.
PLOS Genetics | 2015
Peter J. Thompson; Vered Dulberg; Kyung-Mee Moon; Leonard J. Foster; Carol Chen; Mohammad M. Karimi; Matthew C. Lorincz
Retrotransposition of endogenous retroviruses (ERVs) poses a substantial threat to genome stability. Transcriptional silencing of a subset of these parasitic elements in early mouse embryonic and germ cell development is dependent upon the lysine methyltransferase SETDB1, which deposits H3K9 trimethylation (H3K9me3) and the co-repressor KAP1, which binds SETDB1 when SUMOylated. Here we identified the transcription co-factor hnRNP K as a novel binding partner of the SETDB1/KAP1 complex in mouse embryonic stem cells (mESCs) and show that hnRNP K is required for ERV silencing. RNAi-mediated knockdown of hnRNP K led to depletion of H3K9me3 at ERVs, concomitant with de-repression of proviral reporter constructs and specific ERV subfamilies, as well as a cohort of germline-specific genes directly targeted by SETDB1. While hnRNP K recruitment to ERVs is dependent upon KAP1, SETDB1 binding at these elements requires hnRNP K. Furthermore, an intact SUMO conjugation pathway is necessary for SETDB1 recruitment to proviral chromatin and depletion of hnRNP K resulted in reduced SUMOylation at ERVs. Taken together, these findings reveal a novel regulatory hierarchy governing SETDB1 recruitment and in turn, transcriptional silencing in mESCs.
Genome Research | 2018
Carol Chen; Preeti Goyal; Mohammad M. Karimi; Marie H. Abildgaard; Hiroshi Kimura; Matthew C. Lorincz
Phosphorylation of histone H3 at serine 10 (H3S10ph) by Aurora kinases plays an important role in mitosis; however, H3S10ph also marks regulatory regions of inducible genes in interphase mammalian cells, implicating mitosis-independent functions. Using the fluorescent ubiquitin-mediated cell cycle indicator (FUCCI), we found that 30% of the genome in interphase mouse embryonic stem cells (ESCs) is marked with H3S10ph. H3S10ph broadly demarcates gene-rich regions in G1 and is positively correlated with domains of early DNA replication timing (RT) but negatively correlated with H3K9me2 and lamin-associated domains (LADs). Consistent with mitosis-independent kinase activity, this pattern was preserved in ESCs treated with Hesperadin, a potent inhibitor of Aurora B/C kinases. Disruption of H3S10ph by expression of nonphosphorylatable H3.3S10A results in ectopic spreading of H3K9me2 into adjacent euchromatic regions, mimicking the phenotype observed in Drosophila JIL-1 kinase mutants. Conversely, interphase H3S10ph domains expand in Ehmt1 (also known as Glp) null ESCs, revealing that H3S10ph deposition is restricted by H3K9me2. Strikingly, spreading of H3S10ph at RT transition regions (TTRs) is accompanied by aberrant transcription initiation of genes co-oriented with the replication fork in Ehmt1-/- and Ehmt2-/- ESCs, indicating that establishment of repressive chromatin on the leading strand following DNA synthesis may depend upon these lysine methyltransferases. H3S10ph is also anti-correlated with H3K9me2 in interphase murine embryonic fibroblasts (MEFs) and is restricted to intragenic regions of actively transcribing genes by EHMT2. Taken together, these observations reveal that H3S10ph may play a general role in restricting the spreading of repressive chromatin in interphase mammalian cells.
PLOS Genetics | 2016
Peter J. Thompson; Vered Dulberg; Kyung-Mee Moon; Leonard J. Foster; Carol Chen; Mohammad M. Karimi; Matthew C. Lorincz
[This corrects the article DOI: 10.1371/journal.pgen.1004933.].