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Normalizing for individual cell population context in the analysis of high-content cellular screens

Bettina Knapp, Ilka Rebhan, Anil Kumar, Petr Matula, Narsis A Kiani, Marco Binder, Holger Erfle, Karl Rohr, Roland Eils, Ralf Bartenschlager, Lars Kaderali
2011 BMC Bioinformatics  
However, standard analysis methods for cellular screens do not currently take individual cell data into account unless this is important for the phenotype of interest, i.e. when studying cell morphology  ...  Each cell's individual population context is employed in normalization.  ...  P.M. was partially supported by the Ministry of Education of the Czech Republic (#2B06052 and MSM0021622419).  ... 
doi:10.1186/1471-2105-12-485 pmid:22185194 pmcid:PMC3259109 fatcat:onfdgkkgxjh6xay3d6cgtyahxq

Cell-Based High-Content Screening With Label-Free Digital Holographic Imaging

Fabien Kuttler, Gerardo Turcatti, Benjamin Rappaz
2015 Zenodo  
We automated a system for performing quantitative cellular assays using label-free Digital Holographic Microscopy (DHM) and validated its applicability for cell viability assays in a drug screening context  ...  Examples of label free imaging screens we validated or currently under development will be described:Profiling cancer cell-line sensitivities with small moleculesMonitoring the activity of the GABA A chloride  ...  Acknowledgments The Biomolecular Screening Facility team, EPFL  ... 
doi:10.5281/zenodo.33894 fatcat:nud3xo5xvfavjmk4uup5wyqzpa

Single-cell analysis of population context advances RNAi screening at multiple levels

Berend Snijder, Raphael Sacher, Pauli Rämö, Prisca Liberali, Karin Mench, Nina Wolfrum, Laura Burleigh, Cameron C Scott, Monique H Verheije, Jason Mercer, Stefan Moese, Thomas Heger (+16 others)
2012 Molecular Systems Biology  
Analysing cell-based screens at this depth reveals widespread RNAi-induced changes in the population context of individual cells leading to indirect RNAi effects, as well as perturbations of cell-to-cell  ...  Here we study the influence of the cell population context, which determines a single cell's microenvironment, in image-based RNAi screens.  ...  screening center of the ETH Zurich, and Frank Wippich for experimental help.  ... 
doi:10.1038/msb.2012.9 pmid:22531119 pmcid:PMC3361004 fatcat:pyck4gbquffflhzacw4bf7qvue

Cellular Phenotype Recognition for High-Content RNA Interference Genome-Wide Screening

J. Wang, X. Zhou, P. L. Bradley, S.-F. Chang, N. Perrimon, S. T.C. Wong
2007 Journal of Biomolecular Screening  
The authors present a framework, consisting of microscopic image segmentation and analysis components, for automatic recognition of cellular phenotypes in the context of the Rho family of small GTPases  ...  A fundamental step toward automated analysis of high-content screening is to construct a robust platform for automatic cellular phenotype identification.  ...  They also thank research members of the Life Science Imaging Group of the Center for Bioinformatics, Harvard Center for Neurodegeneration and Repair (HCNR) and Brigham and Women's Hospital, Harvard Medical  ... 
doi:10.1177/1087057107311223 pmid:18227224 fatcat:lfak4g6w25dslcszdm7xfncwjq

Cytomics: A multiparametric, dynamic approach to cell research

Guadalupe Herrera, Laura Diaz, Alicia Martinez-Romero, Angela Gomes, Eva Villamón, Robert C. Callaghan, José-Enrique O'Connor
2007 Toxicology in Vitro  
Within the context of the -omics, cytomics allows the investigation of multiple biochemical features of the heterogeneous cellular systems known as the cytomes.  ...  The multiparametric capacity of cytomics is very useful for the identiWcation, characterization and isolation of stem cell populations.  ...  systems, allows the application of cytomic assays to robotized procedures of both high-content and high-troughput screening of compound libraries, based on cellular Xuorescence in Plots represent a single  ... 
doi:10.1016/j.tiv.2006.07.003 pmid:16934431 fatcat:bc3ofijz2jfwbpil5jvmy2i2ci

High content cellular imaging for drug development

Xiaobo Zhou, S.T.C. Wong
2006 IEEE Signal Processing Magazine  
The images in this article were supplied by our collaborators. The image processing and computational modeling work is the original contribution of the authors with the input from L. Ji and G. Xiong  ...  ACKNOWLEDGMENTS The authors acknowledge rewarding collaborations with biology colleagues Timothy Mitchison, Junying Yuan, Randall King, and Norbert Perrimon at Harvard Medical School.  ...  for simple cellular image processing, are extremely limited in their scope and capacity for high content cellular analysis.  ... 
doi:10.1109/msp.2006.1598095 fatcat:xw5cptpbdnegdden6ecy5du7ju

Rapid Assessment and Visualization of Normality in High-Content and Other Cell-Level Data and Its Impact on the Interpretation of Experimental Results

Steven A. Haney
2014 Journal of Biomolecular Screening  
Such analysis is not possible for many technologies; however, high-content screening (HCS) measures events of individual cells, which are averaged over the well.  ...  When investigators monitor effects on a population of cells following a perturbation, these events rarely occur in a classical normal (or Gaussian) distribution.  ...  Guey is thanked for several helpful discussions on statistical approaches to high-content data.  ... 
doi:10.1177/1087057114526432 pmid:24652972 fatcat:bkcfj3atkvaxjjsqio36tn3soe

Functional genomic and high-content screening for target discovery and deconvolution

Susanne Heynen-Genel, Lars Pache, Sumit K Chanda, Jonathan Rosen
2012 Expert Opinion on Drug Discovery  
The considerations for high content screening applied to functional genomics are also presented.  ...  The utility of this approach has been further enhanced through the application of image-based high content screening, an automated microscopy and quantitative image analysis platform.  ...  In addition, the ability to examine individual cells allows normalization of the desired endpoint to a secondary cellular readout for each cell and enables the extraction of activities that may be masked  ... 
doi:10.1517/17460441.2012.711311 pmid:22860749 pmcid:PMC3954969 fatcat:3gk7e5f7ynezpoj37ewh46sf2a

Increasing the Content of High-Content Screening

Shantanu Singh, Anne E. Carpenter, Auguste Genovesio
2014 Journal of Biomolecular Screening  
One type of phenotypic screening, image-based high-content screening (HCS), has been seen as particularly promising. In this article, we assess whether HCS is as high content as it can be.  ...  each cell population.  ...  Funding The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: this work was supported by the National Science Foundation (NSF  ... 
doi:10.1177/1087057114528537 pmid:24710339 pmcid:PMC4230961 fatcat:5z26i76hcjbjdp3npsifpcjynq

Nuclear morphology for the detection of alterations in bronchial cells from lung cancer: an attempt to improve sensitivity and specificity

Mélanie Fafin-Lefevre, Fabrice Morlais, Lydia Guittet, Bénédicte Clin, Guy Launoy, Françoise Galateau-Sallé, Benoît Plancoulaine, Paulette Herlin, Marc Letourneux
2011 Analytical and quantitative cytology and histology  
Analysis of modification in morphologic parameters via distribution analysis proved promising for screening bronchopulmonary cancer from sputum.  ...  and develop a bronchopulmonary cancer screening method relying on analysis of sputum sample cell nuclei.  ...  IOD was calculated pixel by pixel for the entire cell nucleus. IOD of each nucleus could be calibrated in ploidy value based on a normal cell population, the DNA content of which was defined as 2c.  ... 
pmid:21980622 fatcat:6exjydrk2jgkljuvwpo2mttep4

Identifying and Quantifying Heterogeneity in High Content Analysis: Application of Heterogeneity Indices to Drug Discovery

Albert H. Gough, Ning Chen, Tong Ying Shun, Timothy R. Lezon, Robert C. Boltz, Celeste E. Reese, Jacob Wagner, Lawrence A. Vernetti, Jennifer R. Grandis, Adrian V. Lee, Andrew M. Stern, Mark E. Schurdak (+2 others)
2014 PLoS ONE  
The standard practice for cell-based, high content assays has been to assume a normal distribution and to report a well-to-well average value with a standard deviation.  ...  Although heterogeneity has become an accepted characteristic of a population of cells, in drug discovery it is not routinely evaluated or reported.  ...  Acknowledgments The authors thank the members of their laboratories for fruitful discussions. The western blot in Figure S5 was prepared with the assistance of Malabika Sen, Ph.D.  ... 
doi:10.1371/journal.pone.0102678 pmid:25036749 pmcid:PMC4103836 fatcat:xa4suzh7d5bedledwfe2tva33m

Visualizing quantitative microscopy data: History and challenges

Heba Z. Sailem, Sam Cooper, Chris Bakal
2016 Critical reviews in biochemistry and molecular biology  
However, data visualization is challenging when microscopy experiments entail imaging of millions of cells, and complex cellular phenotypes are quantified in a high-content manner.  ...  Most wellestablished visualization tools are inappropriate for displaying high-content data, which has driven the development of new visualization methodology.  ...  Acknowledgements We thank Julia Sero for images of breast cancer cell lines. We are also grateful to Alexis Barr and Vicky Bousgouni for helpful comments on the manuscript.  ... 
doi:10.3109/10409238.2016.1146222 pmid:26906253 pmcid:PMC4819578 fatcat:elkkm4uua5glnlejxly7baiq2i

Patient-derived stem cells: pathways to drug discovery for brain diseases

Alan Mackay-Sim
2013 Frontiers in Cellular Neuroscience  
The first is automated cell microscopy with concurrent advances in image acquisition and analysis, known as high content screening (HCS).  ...  HCS has developed from the requirements of the pharmaceutical industry for high throughput assays to screen thousands of chemical compounds in the search for new drugs.  ...  ACKNOWLEDGMENTS This work was funded in part by grants from the Hereditary Spastic Paraplegia Research Foundation Inc., the National Health and Medical Research Council of Australia, and the Australian  ... 
doi:10.3389/fncel.2013.00029 pmid:23543597 pmcid:PMC3608922 fatcat:dbsyw4ixlvahjmb37jyjabyh3i

Differential Mitochondrial Toxicity Screening and Multi-Parametric Data Analysis

Maria V. Tsiper, Jennifer Sturgis, Larisa V. Avramova, Shilpa Parakh, Raymond Fatig, Ana Juan-García, Nianyu Li, Bartek Rajwa, Padma Narayanan, C. W. Qualls, J. Paul Robinson, V. Jo Davisson (+1 others)
2012 PLoS ONE  
Multi-parametric high-content screening (mp-HCS) of mitochondrial toxicity holds promise as a lead in-vitro strategy for drug testing and safety evaluations.  ...  These results also demonstrate that the number of drugs in a training set, the choice of parameters used in analysis, and statistical measures are fundamental for specific hypothesis testing and assessment  ...  Schematic demonstration of high content screen and analysis. The screen algorithm is schematically represented the steps from cell culturing to data collection and comprehensive data analysis.  ... 
doi:10.1371/journal.pone.0045226 pmid:23077490 pmcid:PMC3471932 fatcat:t3mkywtjjzbobbdzjims2pwi7y

High-throughput RNA interference screens integrative analysis: Towards a comprehensive understanding of the virus-host interplay

Sandeep Amberkar
2013 World Journal of Virology  
High-throughput RNA interference screens integrative analysis: Towards a comprehensive understanding of the virus-host interplay.  ...  Population context normalization Very recently it was shown that different cells in a population display heterogeneity in their cellular behaviours [53, 54] .  ...  [38] ; High-Content Imaging Screens: they are designed to identify those genes that alter the cellular phenotype in a desired manner (i.e., decreases in the pro-duction of cellular products, nuclear  ... 
doi:10.5501/wjv.v2.i2.18 pmid:24175227 pmcid:PMC3785050 fatcat:jpltfxygnrekvhigej6phqobyu
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