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20
Dynamic regulatory network controlling TH17 cell differentiation. Nature. 496:461–468. [PubMed: 23467089
"... Despite their importance, the molecular circuits that control the differentiation of naïve T cells remain largely unknown. Recent studies that reconstructed regulatory networks in mammalian cells have focused on short-term responses and relied on perturbation-based approaches that cannot be readily ..."
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Cited by 17 (0 self)
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Despite their importance, the molecular circuits that control the differentiation of naïve T cells remain largely unknown. Recent studies that reconstructed regulatory networks in mammalian cells have focused on short-term responses and relied on perturbation-based approaches that cannot be readily applied to primary T cells. Here, we combine transcriptional profiling at high temporal resolution, novel computational algorithms, and innovative nanowire-based tools for performing perturbations in primary T cells to systematically derive and experimentally validate a model of the dynamic regulatory network that controls Th17 differentiation. The network consists of two self-reinforcing, but mutually antagonistic, modules, with 12 novel regulators, whose coupled action may be essential for maintaining the balance between Th17 and other CD4+ T cell subsets. Overall, our study identifies and validates 39 regulatory factors, embeds them within a comprehensive temporal network and reveals its organizational principles, and highlights novel
lnterviewed by author
, 1997
"... Creation and modification of buildings within the Close Action Environment (CAEn) wargame can be a complex and time consuming task. The CAEn Building Editor Tool, or Builder, simplifies this process by providing an efficient graphical interface to edit CAEn buildings. The use of Builder can greatly ..."
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Cited by 3 (1 self)
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Creation and modification of buildings within the Close Action Environment (CAEn) wargame can be a complex and time consuming task. The CAEn Building Editor Tool, or Builder, simplifies this process by providing an efficient graphical interface to edit CAEn buildings. The use of Builder can greatly speed up the production of urban environments within CAEn.
Optimization of transcription factor binding map accuracy utilizing knockout-mouse models
, 2014
"... Genome-wide assessment of protein–DNA interac-tion by chromatin immunoprecipitation followed by massive parallel sequencing (ChIP-seq) is a key tech-nology for studying transcription factor (TF) local-ization and regulation of gene expression. Signal-to-noise-ratio and signal specificity in ChIP-seq ..."
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Genome-wide assessment of protein–DNA interac-tion by chromatin immunoprecipitation followed by massive parallel sequencing (ChIP-seq) is a key tech-nology for studying transcription factor (TF) local-ization and regulation of gene expression. Signal-to-noise-ratio and signal specificity in ChIP-seq stud-ies depend on many variables, including antibody affinity and specificity. Thus far, efforts to improve antibody reagents for ChIP-seq experiments have fo-cused mainly on generating higher quality antibod-ies. Here we introduce KOIN (knockout implemented normalization) as a novel strategy to increase sig-nal specificity and reduce noise by using TF knock-out mice as a critical control for ChIP-seq data ex-periments. Additionally, KOIN can identify ‘hyper ChIPable regions ’ as another source of false-positive signals. As the use of the KOIN algorithm reduces false-positive results and thereby prevents misinter-pretation of ChIP-seq data, it should be considered as the gold standard for future ChIP-seq analyses, particularly when developing ChIP-assays with novel antibody reagents.
Mechanisms of Epigenetic Regulation Characterized Using Novel Single
, 2013
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Opponent
"... The originality of this thesis has been checked in accordance with the University of Turku quality assurance system using the Turnitin OriginalityCheck service. ISBN 978-951-29-5740-8 (PRINT) ISBN 978-951-29-5741-5 (PDF) ISSN 0355-9483 ..."
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The originality of this thesis has been checked in accordance with the University of Turku quality assurance system using the Turnitin OriginalityCheck service. ISBN 978-951-29-5740-8 (PRINT) ISBN 978-951-29-5741-5 (PDF) ISSN 0355-9483
Immunoprecipitation Approach Reveals Principles of Dynamic Gene Regulation in Mammals
"... Understanding the principles governing mammalian gene regulation has been hampered by the difficulty in measuring in vivo binding dynamics of large numbers of transcription factors (TF) to DNA. Here, we develop a high-throughput Chromatin Immuno-Precipitation (HT-ChIP) method to systematically map p ..."
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Understanding the principles governing mammalian gene regulation has been hampered by the difficulty in measuring in vivo binding dynamics of large numbers of transcription factors (TF) to DNA. Here, we develop a high-throughput Chromatin Immuno-Precipitation (HT-ChIP) method to systematically map protein-DNA interactions. HT-ChIP was applied to define the dynamics of DNA binding by 25 TFs and 4 chromatin marks at 4 time-points following pathogen stimulus of dendritic cells. Analyzing over 180,000 TF-DNA interactions we find that TFs vary substantially in their temporal binding landscapes. This data suggests a model for transcription regulation whereby TF networks are hierarchically organized into cell differentiation factors, factors that
Summary
, 2007
"... The production engineer’s decision regarding buffer size in a flexible production system is one of the most important factors in maximizing production efficiency. In this paper, we propose a model Flexible Production System with Sub-lines (FPSS). By using the model, we can find the buffer size of FP ..."
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The production engineer’s decision regarding buffer size in a flexible production system is one of the most important factors in maximizing production efficiency. In this paper, we propose a model Flexible Production System with Sub-lines (FPSS). By using the model, we can find the buffer size of FPSS by using GA. Also, we propose a new GA expression, referred to as a Matrix Encoding Method (MEM). This paper deals with an FPSS which consists of 5 main component lines, i.e. a main production line, parallel lines, rework path, feed-forward line and feeder line. Numerical examples show that after a number of operations based on the GA with MEM expression, the nearest optimal buffer size of FPSS could be found. The results of this study can be used to improve the production plant, and production engineers can use these results in their decisions on buffer size when they develop FPSS. Key words: Flexible production system, Buffer size, Genetic algorithm.
unknown title
, 2014
"... wide genomic enrichment domains robust against local variations ..."
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unknown title
, 2014
"... Inference of interactions between chromatin modifiers and histone modifications: from ChIP-Seq data to chromatin-signaling ..."
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Inference of interactions between chromatin modifiers and histone modifications: from ChIP-Seq data to chromatin-signaling
