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Title:
Pooling across cells to normalize single-cell RNA sequencing data with many zero counts | Genome Biology
Description:
Normalization of single-cell RNA sequencing data is necessary to eliminate cell-specific biases prior to downstream analyses. However, this is not straightforward for noisy single-cell data where many counts are zero. We present a novel approach where expression values are summed across pools of cells, and the summed values are used for normalization. Pool-based size factors are then deconvolved to yield cell-based factors. Our deconvolution approach outperforms existing methods for accurate normalization of cell-specific biases in simulated data. Similar behavior is observed in real data, where deconvolution improves the relevance of results of downstream analyses.
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Keywords {π}
cells, size, genes, data, normalization, library, cell, deconvolution, set, counts, methods, expression, values, factors, factor, zeroes, article, method, gene, additional, estimates, number, pubmed, file, singlecell, existing, deseq, pool, google, scholar, approach, tmm, theta, analysis, stochastic, linear, system, mathcal, sets, differences, large, small, similar, real, rnaseq, unique, cas, sequencing, prior, results,
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org/packages/release/bioc/html/topgo org/web/packages/limsolve/citation quantitative single-cell rna-seq single-cell rna-seq experiments org/web/packages/limsolve/index single-cell transcriptomics reveals high-throughput scrna-seq data complex rna-seq experiments multifactor rna-seq experiments single-cell rna-seq single cell rna-sequencing article download pdf single-cell sequencing experiments bulk rna-seq data normalizing rna-seq data simulating scrna-seq data noisy single-cell data cluster-specific reference pseudo-cell single-cell transcriptomics applied supplementary figures s1βs7 scrna-seq data based rank correlation-based distances cancer research uk z_{ij} = y_{ij}t_{ real scrna-seq data real scrna-seq dataβ normalizing single-cell data simulated scrna-seq data related subjects single-cell transcriptomics single baseline pseudo-cell bulk rna sequencing cluster-specific size factor rna-seq data scrna-seq experiments cluster-specific size factors full size image represent low-quality libraries privacy choices/manage cookies yield cell-based factors kolodziejczyk aa pool-based size factor scrna-seq literature [12β17] pool-based size factors scrna-seq data wellcome genome campus gene-specific nb dispersion averaged reference pseudo-cell gene-specific constant sampled creative commons license
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headline:Pooling across cells to normalize single-cell RNA sequencing data with many zero counts
description:Normalization of single-cell RNA sequencing data is necessary to eliminate cell-specific biases prior to downstream analyses. However, this is not straightforward for noisy single-cell data where many counts are zero. We present a novel approach where expression values are summed across pools of cells, and the summed values are used for normalization. Pool-based size factors are then deconvolved to yield cell-based factors. Our deconvolution approach outperforms existing methods for accurate normalization of cell-specific biases in simulated data. Similar behavior is observed in real data, where deconvolution improves the relevance of results of downstream analyses.
datePublished:2016-04-27T00:00:00Z
dateModified:2016-04-27T00:00:00Z
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Single-cell RNA-seq
Normalization
Differential expression
Animal Genetics and Genomics
Human Genetics
Plant Genetics and Genomics
Microbial Genetics and Genomics
Bioinformatics
Evolutionary Biology
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headline:Pooling across cells to normalize single-cell RNA sequencing data with many zero counts
description:Normalization of single-cell RNA sequencing data is necessary to eliminate cell-specific biases prior to downstream analyses. However, this is not straightforward for noisy single-cell data where many counts are zero. We present a novel approach where expression values are summed across pools of cells, and the summed values are used for normalization. Pool-based size factors are then deconvolved to yield cell-based factors. Our deconvolution approach outperforms existing methods for accurate normalization of cell-specific biases in simulated data. Similar behavior is observed in real data, where deconvolution improves the relevance of results of downstream analyses.
datePublished:2016-04-27T00:00:00Z
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Single-cell RNA-seq
Normalization
Differential expression
Animal Genetics and Genomics
Human Genetics
Plant Genetics and Genomics
Microbial Genetics and Genomics
Bioinformatics
Evolutionary Biology
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