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  • 1
    Language: English
    In: PloS one, 2018, Vol.13(11), pp.e0208349
    Description: [This corrects the article DOI: 10.1371/journal.pone.0205499.].
    Keywords: Sciences (General);
    E-ISSN: 1932-6203
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  • 2
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States of America, 19 February 2013, Vol.110(8), pp.2946-51
    Description: Much of the knowledge about cell differentiation and function in the immune system has come from studies in mice, but the relevance to human immunology, diseases, and therapy has been challenged, perhaps more from anecdotal than comprehensive evidence. To this end, we compare two large compendia of transcriptional profiles of human and mouse immune cell types. Global transcription profiles are conserved between corresponding cell lineages. The expression patterns of most orthologous genes are conserved, particularly for lineage-specific genes. However, several hundred genes show clearly divergent expression across the examined cell lineages, and among them, 169 genes did so even with highly stringent criteria. Finally, regulatory mechanisms--reflected by regulators' differential expression or enriched cis-elements--are conserved between the species but to a lower degree, suggesting that distinct regulation may underlie some of the conserved transcriptional responses.
    Keywords: Gene Expression Profiling ; Transcription, Genetic ; Immune System -- Metabolism
    ISSN: 00278424
    E-ISSN: 1091-6490
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  • 3
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States of America, 27 January 2015, Vol.112(4), pp.E346
    Description: Author contributions: T.S., J.A.L., and C.B. wrote the paper.
    Keywords: Databases, Genetic ; Disease Models, Animal ; Gene Expression Profiling ; Gene Expression Regulation ; Inflammation
    ISSN: 00278424
    E-ISSN: 1091-6490
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  • 4
    In: PLoS ONE, 2018, Vol.13(10)
    Description: Single-cell RNA sequencing (scRNA-seq) is an emerging technology for profiling the gene expression of thousands of cells at the single cell resolution. Currently, the labeling of cells in an scRNA-seq dataset is performed by manually characterizing clusters of cells or by fluorescence-activated cell sorting (FACS). Both methods have inherent drawbacks: The first depends on the clustering algorithm used and the knowledge and arbitrary decisions of the annotator, and the second involves an experimental step in addition to the sequencing and cannot be incorporated into the higher throughput scRNA-seq methods. We therefore suggest a different approach for cell labeling, namely, classifying cells from scRNA-seq datasets by using a model transferred from different (previously labeled) datasets. This approach can complement existing methods, and–in some cases–even replace them. Such a transfer-learning framework requires selecting informative features and training a classifier. The specific implementation for the framework that we propose, designated ''CaSTLe–classification of single cells by transfer learning,'' is based on a robust feature engineering workflow and an XGBoost classification model built on these features. Evaluation of CaSTLe against two benchmark feature-selection and classification methods showed that it outperformed the benchmark methods in most cases and yielded satisfactory classification accuracy in a consistent manner. CaSTLe has the additional advantage of being parallelizable and well suited to large datasets. We showed that it was possible to classify cell types using transfer learning, even when the databases contained a very small number of genes, and our study thus indicates the potential applicability of this approach for analysis of scRNA-seq datasets.
    Keywords: Research Article ; Biology And Life Sciences ; Medicine And Health Sciences ; Biology And Life Sciences ; Biology And Life Sciences ; Biology And Life Sciences ; Medicine And Health Sciences ; Biology And Life Sciences ; Medicine And Health Sciences ; Computer And Information Sciences ; Engineering And Technology ; Biology And Life Sciences ; Research And Analysis Methods ; Biology And Life Sciences ; Computer And Information Sciences
    E-ISSN: 1932-6203
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  • 5
    Language: English
    In: Trends in Immunology, December 2013, Vol.34(12), pp.602-609
    Description: Immunological studies of single proteins in a single cell type have been complemented in recent years by larger studies, enabled by emerging high-throughput technologies. This trend has recently been exemplified by the discovery of gene networks controlling regulatory and effector αβ T cell subset development and human hematopoiesis. The Immunological Genome Project (ImmGen) aims to decipher the gene networks underpinning mouse hematopoiesis. The first phase, completed in 2012, profiled the transcriptome of 249 immune cell types. We discuss the utilities of the datasets in high-resolution mapping of the hematopoietic system. The immune transcriptome compendium has revealed unsuspected cell lineage relations and the network reconstruction has identified novel regulatory factors of hematopoiesis.
    Keywords: Hematopoiesis ; Transcriptional Regulation ; Systems Immunology ; Medicine ; Biology
    ISSN: 1471-4906
    E-ISSN: 1471-4981
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  • 6
    Language: English
    In: Plasmid, March 2012, Vol.67(2), pp.167-173
    Description: ► Plasmid copy numbers have not been accurately measured in single cells. ► Most current methods confound plasmid fluctuations with other stochastic processes. ► In some cases, measurement errors mask plasmid fluctuations. ► Some problematic methods could be rectified by modifications to existing protocols. The life of plasmids is a constant battle against fluctuations: failing to correct copy number fluctuations can increase the plasmid loss rate by many orders of magnitude, as can a failure to more evenly divide the copies between daughters at cell division. Plasmids are therefore long-standing model systems for stochastic processes in cells, much thanks to the efforts of Kurt Nordström to whose memory this issue is dedicated. Here we analyze a range of experimental methods for measuring plasmid copy numbers in single cells, focusing on challenges, trade-offs, and necessary experimental controls. In particular we analyze published and unpublished strategies to infer copy numbers from expression of plasmid-encoded reporters, direct labeling of plasmids with fluorescent probes or DNA binding proteins fused to fluorescent reporters, PCR based methods applied to single cell lysates, and plasmid-specific replication arrest. We conclude that no method currently exists to measure plasmid copy numbers in single cells, and that most methods are overwhelmed by various types of experimental noise. We also discuss how accurate methods can be developed.
    Keywords: Plasmid Fluctuations ; Single Cell Measurements ; Copy Number Distributions ; Biology
    ISSN: 0147-619X
    E-ISSN: 1095-9890
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  • 7
    Language: English
    In: Science, 2009, Vol.325(5939), pp.429-432
    Description: Transcriptional regulatory circuits govern how cis and trans factors transform signals into messenger RNA (mRNA) expression levels. With advances in quantitative and high-throughput technologies that allow measurement of gene expression state in different conditions, data that can be used to build and test models of transcriptional regulation is being generated at a rapid pace. Here, we review experimental and computational methods used to derive detailed quantitative circuit models on a small scale and cruder, genome-wide models on a large scale. We discuss the potential of combining small- and large-scale approaches to understand the working and wiring of transcriptional regulatory circuits. ; Includes references ; p. 429-432.
    Keywords: Mathematical Models ; Circuits ; Construction ; Control ; Carbon Monoxide ; Small Scale ; Gene Expression ; Transforms ; Miscellaneous Sciences (So) ; Article;
    ISSN: 0036-8075
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  • 8
    Language: English
    In: Journal of the American Chemical Society, 13 July 2005, Vol.127(27), pp.9848-54
    Description: A new pi-conjugated electroactive 4,4'-bipyridinium that bears two pyridazone self-complementary units was prepared and characterized. The new system readily assembles and forms at least two stable charge-transfer crystalline structures having a thermal population of unpaired electrons. The crystals of one phase exhibit electrical bistability, displaying either high (ON) and low (OFF) conductivity, at the same applied bias, depending on the electrical history of the system. The relation between the supramolecular structure of the crystals and their electrical properties is also discussed.
    Keywords: Pyridinium Compounds -- Chemical Properties ; Pyridinium Compounds -- Electric Properties ; Electrons -- Research ; Charge Transfer -- Research;
    ISSN: 0002-7863
    E-ISSN: 15205126
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  • 9
    Language: English
    In: Science (New York, N.Y.), 24 July 2009, Vol.325(5939), pp.429-32
    Description: Transcriptional regulatory circuits govern how cis and trans factors transform signals into messenger RNA (mRNA) expression levels. With advances in quantitative and high-throughput technologies that allow measurement of gene expression state in different conditions, data that can be used to build and test models of transcriptional regulation is being generated at a rapid pace. Here, we review experimental and computational methods used to derive detailed quantitative circuit models on a small scale and cruder, genome-wide models on a large scale. We discuss the potential of combining small- and large-scale approaches to understand the working and wiring of transcriptional regulatory circuits.
    Keywords: Gene Expression Regulation ; Gene Regulatory Networks ; Models, Genetic
    ISSN: 00368075
    E-ISSN: 1095-9203
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  • 10
    Language: English
    In: Journal of the American Chemical Society, 08 February 2006, Vol.128(5), pp.1398-9
    Description: Genes of interest can be selectively metallized via the incorporation of modified triphosphates. These triphosphates bear functions that can be further derivatized with aldehyde groups via the use of click chemistry. Treatment of the aldehyde-labeled gene mixture with the Tollens reagent, followed by a development process, results in the selective metallization of the gene of interest in the presence of natural DNA strands.
    Keywords: DNA, Complementary -- Chemistry ; Silver -- Chemistry
    ISSN: 0002-7863
    E-ISSN: 15205126
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