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Modeling bi-modality improves characterization of cell cycle on gene expression in single cells [article]

Lucas Dennis, Andrew McDavid, Patrick Danaher, Greg Finak, Michael Krouse, Alice Wang, Philippa Webster, Joseph Beechem, Raphael Gottardo
2014 bioRxiv   pre-print
Our new computational framework improves the detection of previously characterized cell-cycle genes compared to approaches that do not account for the bi-modality of single-cell data.  ...  We assess the effect of cell cycle phase on gene expression in single cells by measuring 333 genes in 930 cells across three phases and three cell lines.  ...  In examining histograms of the transformed data, lCount, we found evidence of bi-modality (e.g. Figures 1C, 2 ).  ... 
doi:10.1101/002295 fatcat:uj2n7kd4cfctpdpiyck6zr5g2e

Modeling Bi-modality Improves Characterization of Cell Cycle on Gene Expression in Single Cells

Andrew McDavid, Lucas Dennis, Patrick Danaher, Greg Finak, Michael Krouse, Alice Wang, Philippa Webster, Joseph Beechem, Raphael Gottardo, Sheng Zhong
2014 PLoS Computational Biology  
Our new computational framework improves the detection of previously characterized cell-cycle genes compared to approaches that do not account for the bi-modality of single-cell data.  ...  We assess the effect of cell cycle phase on gene expression in single cells by measuring 333 genes in 930 cells across three phases and three cell lines.  ...  In this paper, we develop new analytical methods that account for the intrinsic, stochastic nature of single cell expression in order to characterize the effect of cell cycle on gene expression at the  ... 
doi:10.1371/journal.pcbi.1003696 pmid:25032992 pmcid:PMC4102402 fatcat:sfuhnpphw5gh5ei5b3ct6gvu7i

A statistical approach for identifying differential distributions in single-cell RNA-seq experiments

Keegan D. Korthauer, Li-Fang Chu, Michael A. Newton, Yuan Li, James Thomson, Ron Stewart, Christina Kendziorski
2016 Genome Biology  
We present a novel method to characterize differences in expression in the presence of distinct expression states within and among biological conditions.  ...  The ability to quantify cellular heterogeneity is a major advantage of single-cell technologies. However, statistical methods often treat cellular heterogeneity as a nuisance.  ...  Acknowledgments The authors thank the editorial staff and two anonymous reviewers for insightful comments and suggestions that helped improve the quality of the manuscript.  ... 
doi:10.1186/s13059-016-1077-y pmid:27782827 pmcid:PMC5080738 fatcat:jyc36ixjybgxnevujypfqpdwpm

LTMG: a novel statistical modeling of transcriptional expression states in single-cell RNA-Seq data

2019 Nucleic Acids Research  
A key challenge in modeling single-cell RNA-seq data is to capture the diversity of gene expression states regulated by different transcriptional regulatory inputs across individual cells, which is further  ...  LTMG infers the expression multi-modalities across single cells, meanwhile, the dropouts and low expressions are treated as left truncated.  ...  , and gene co-expression, heavily depend on an accurate characterization of the single cell expression distribution.  ... 
doi:10.1093/nar/gkz655 pmid:31372654 pmcid:PMC6765121 fatcat:co4gamnzafgoze6zpbejtam3ty

scDD: A statistical approach for identifying differential distributions in single-cell RNA-seq experiments [article]

Keegan D. Korthauer, Li-Fang Chu, Michael A. Newton, Yuan Li, James Thomson, Ron Stewart, Christina Kendziorski
2015 bioRxiv   pre-print
The ability to quantify cellular heterogeneity is a major advantage of single-cell technologies.  ...  We present a novel method to characterize differences in expression in the presence of distinct expression states within and among biological conditions.  ...  The authors thank the editorial staff and two anonymous reviewers for insightful comments and suggestions that helped improve the quality of the manuscript. Author details  ... 
doi:10.1101/035501 fatcat:eukux7hraze5xd75k77aj5gjyi

ATRT-25. INTEGRATED QUANTITATIVE SWATH-MS PROTEOMICS ANALYSIS OF ATRTs UNCOVERS NEW THERAPEUTIC OPPORTUNITIES

Martina Anna Finetti, James Hacking, Emma Lishman-Walker, Silvia A Synowsky, Stephen Crosier, Emmma Martin, Jess Burns, Sally L Shirran, Simon Bailey, Steven C Clifford, Paul Huang, Daniel Williamson
2020 Neuro-Oncology  
We performed unlabeled discovery proteomics using MS-SWATH on MRT cells in which SMARCB1 was forcibly re-expressed (5 cell lines, +/-SMARCB1); analyzing changes in protein abundance within 3 fractions  ...  The consequences of SMARCB1 loss in Atypical Teratoid Rhabdoid Tumors (ATRTs) have been extensively characterized at the epigenetic/transcriptomic level.  ...  We also identified a subpopulation of cells with a clear overexpression of cell cycle associated genes (CDK4, CDKN3), predominantly present in ATRT-MYC samples, a finding which may harbour important consequences  ... 
doi:10.1093/neuonc/noaa222.024 fatcat:y7hqzs7uyjgihj7dx57blnidte

Learning Cell-Type-Specific Gene Regulation Mechanisms by Multi-Attention Based Deep Learning With Regulatory Latent Space

Minji Kang, Sangseon Lee, Dohoon Lee, Sun Kim
2020 Frontiers in Genetics  
Most existing methods for modeling control mechanisms of gene expression use only a single epigenetic marker and very few methods are successful in modeling complex mechanisms of gene regulations using  ...  In experiments with 18 cell line multi-omics data, our proposed model predicted the gene expression level more accurately than the state-of-the-art model.  ...  Moreover, the model characterizes cell-typespecific gene regulation mechanisms for 18 cell lines, based on the weights of the Multi-Attention network.  ... 
doi:10.3389/fgene.2020.00869 pmid:33133123 pmcid:PMC7561362 fatcat:rxbuiiqwzbb7jojlh7jughiptm

Cell differentiation unravelled by single-cell RNA sequencing

Anna Alemany
2020 EurophysicsNews  
All of us originate from a single cell, known as the zygote.  ...  It is during embryo development that, through multiple cell divisions, the zygote gives rise to each of the cell types present in the different organs of each organism.  ...  Each cell can be assigned to a cell type based on its gene expression patterns.  ... 
doi:10.1051/epn/2020505 fatcat:cfyhidqbm5d3zgod2omiaemouq

Polo-like kinase 1 inhibition causes decreased proliferation by cell cycle arrest, leading to cell death in glioblastoma

J A Pezuk, M S Brassesco, A G Morales, J C de Oliveira, R G de Paula Queiroz, H R Machado, C G Carlotti, L Neder, C A Scrideli, L G Tone
2013 Cancer Gene Therapy  
We evaluated PLK1, 2, 3 and 4 gene expression in 8 GBM cell lines and 17 tumor samples, and analyzed the effect of the PLK1 inhibition on SF188 and T98G GBM cell lines and 13 primary cultures.  ...  Our data showed PLK1 overexpression and a variable altered expression of PLK2, 3 and 4 genes in GBM tumor samples and cell lines.  ...  We also thank the Foundation for Research Support of São Paulo (FAPESP # 2009/50118-2 and 2009/11053-2) and the Coordination of Improvement of Higher Education Personnel (CAPES) for financial support.  ... 
doi:10.1038/cgt.2013.46 pmid:23887645 fatcat:xhoud5kslnaslaobpbvxiybam4

61 Functional characterization of ribosomal RNA methyltransferase NSUN5 in glioblastoma

Jiesi Zhou, Krista Vincent, Scott Findlay, Daniel Choi, Roseline Godbout, Lynne-Marie Postovit, YangXin Fu
2018 Canadian Journal of Neurological Sciences  
Western blotting showed that NSUN5 is expressed in 7 out of 9 established glioblastoma cell lines and in 8 out of 12 primary patient-derived glioblastoma cell lines.  ...  Bisulfite sequencing confirmed that NSUN5 methylates C3782 of human 28S rRNA in glioblastoma cells.  ...  After 8 cycles, the patient reported marked improvement in hearing.  ... 
doi:10.1017/cjn.2018.289 fatcat:ayznbfpxirfr3kijvzcqw2v2kq

Genetic therapy in gliomas: Historical analysis and future perspectives

TobiasAlecio Mattei, Ricardo Ramina, FlavioKey Miura, PauloHenrique Aguiar, Leandroda Costa Valiengo
2005 Neurology India  
Although several gene therapy systems proved to be efficient in controlling or eradicating these tumors in animal models, the clinical studies performed so far were not equally successful.  ...  Along with the exposition we will also review of the history of the genetic therapy for gliomas, with special focus on the main problems found during the advancement of scientific discoveries in this area  ...  [63] Targeted adenovirus The application of adenoviral vectors in cancer gene therapy is hampered by low receptor expression on tumor cells and high receptor expression on normal epithelial cells.  ... 
doi:10.4103/0028-3886.15046 pmid:15805650 fatcat:oweild5b2zhybamrpdr37a2gvy

Rationale for MYC imaging and targeting in pancreatic cancer

Günter Schneider, Matthias Wirth, Ulrich Keller, Dieter Saur
2021 EJNMMI Research  
In sum, we propose MYC-associated biology as a basis for the development of concepts for precision oncology in PDAC.  ...  AbstractThe incidence and lethality of pancreatic ductal adenocarcinoma (PDAC) will continue to increase in the next decade.  ...  Acknowledgements We apologize for not citing any relevant reports due to the need to selectively choose examples, a lack of space, or an oversight on our part. Drawing tools from motifolio.com.  ... 
doi:10.1186/s13550-021-00843-1 pmid:34637026 pmcid:PMC8511206 fatcat:mjmsspjezzavnjxboff2kcljly

Discriminating cellular heterogeneity using microwell-based RNA cytometry

Ivan K. Dimov, Rong Lu, Eric P. Lee, Jun Seita, Debashis Sahoo, Seung-min Park, Irving L. Weissman, Luke P. Lee
2014 Nature Communications  
We also show that changes in expression of genes such as Birc6 during ageing can be attributed to the shift of relative portions of cells in the high-expressing subgroup versus low-expressing subgroup.  ...  We apply this system to characterize the RNA distributions of ageing-related genes in a highly purified mouse haematopoietic stem cell population.  ...  (c) Histograms of the single-cell well intensities of the RT-PCR reactions of mouse peripheral blood mononuclear cells (PBMCs) cells, which are known to be heterogeneous (bi-modal) for Mac-1 expression  ... 
doi:10.1038/ncomms4451 pmid:24667995 pmcid:PMC4075946 fatcat:fb3767vz7rgmfewgfcnlx3v654

Hematopoietic stem cells differentiate into restricted myeloid progenitors before cell division [article]

Tatyana Grinenko, Anne Eugster, Lars Thielecke, Beata Ramasz, Anja Krueger, Sevina Dietz, Ingmar Glauche, Alexander Gerbaulet, Malte von Bonin, Onur Basak, Hans Clevers, Triantafyllos Chavakis (+1 others)
2018 bioRxiv   pre-print
To this end, we used an HSC cell tracing approach and Ki67RFP knock-in mice to assess simultaneously divisional history, cell cycle progression, and differentiation of adult HSCs in vivo.  ...  division and even before entering the S phase of the cell cycle.  ...  Modeling bi-modality improves characterization of cell cycle on gene 373 expression in single cells.  ... 
doi:10.1101/256024 fatcat:5u44ytngivau5eh2y2sk2nvilm

HDAC Inhibitors Augmented Cell Migration and Metastasis through Induction of PKCs Leading to Identification of Low Toxicity Modalities for Combination Cancer Therapy

K.-T. Lin, Y.-W. Wang, C.-T. Chen, C.-M. Ho, W.-H. Su, Y.-S. Jou
2012 Clinical Cancer Research  
Experimental Design: Because metastasis is the major cause of cancer mortality, we measured cell migration activity and profiled metastasis-related gene expressions in HDACi-treated cancer cells.  ...  Conclusion: Treatments of different structural classes of HDACi simultaneously induced cell death and promoted cell migration and metastasis in multiple cancer cell types.  ...  The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C.  ... 
doi:10.1158/1078-0432.ccr-12-0633 pmid:22811583 fatcat:lji6z4kxvva6zaztp2tatjlpwa
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