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Differential expression in RNA-seq: A matter of depth

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Differential expression in RNA-seq: A matter of depth

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dc.contributor.author Tarazona Campos, Sonia es_ES
dc.contributor.author García-Alcalde, Fernando es_ES
dc.contributor.author Dopazo, Joaquín es_ES
dc.contributor.author Ferrer Riquelme, Alberto José es_ES
dc.contributor.author Conesa, Ana es_ES
dc.date.accessioned 2013-04-22T13:49:11Z
dc.date.issued 2011-09-08
dc.identifier.issn 1088-9051
dc.identifier.uri http://hdl.handle.net/10251/28113
dc.description.abstract Next-generation sequencing (NGS) technologies are revolutionizing genome research, and in particular, their application to transcriptomics (RNA-seq) is increasingly being used for gene expression profiling as a replacement for microarrays. However, the properties of RNA-seq data have not been yet fully established, and additional research is needed for understanding how these data respond to differential expression analysis. In this work, we set out to gain insights into the characteristics of RNA-seq data analysis by studying an important parameter of this technology: the sequencing depth. We have analyzed how sequencing depth affects the detection of transcripts and their identification as differentially expressed, looking at aspects such as transcript biotype, length, expression level, and fold-change. We have evaluated different algorithms available for the analysis of RNA-seq and proposed a novel approach-NOISeq-that differs from existing methods in that it is data-adaptive and nonparametric. Our results reveal that most existing methodologies suffer from a strong dependency on sequencing depth for their differential expression calls and that this results in a considerable number of false positives that increases as the number of reads grows. In contrast, our proposed method models the noise distribution from the actual data, can therefore better adapt to the size of the data set, and is more effective in controlling the rate of false discoveries. This work discusses the true potential of RNA-seq for studying regulation at low expression ranges, the noise within RNA-seq data, and the issue of replication. © 2011 by Cold Spring Harbor Laboratory Press. es_ES
dc.description.sponsorship This research was supported by grants BIO2008-05266-E and BIO2008-04638-E from the Spanish Ministry of Science and Innovation (MICINN), in the framework of ERA-Net Pathogenomics, and grants BIO2009-10799 from the MICINN; BIO2008-04212 from the MICINN, and PROMETEO/2010/001 from the GVA-FEDER. We also acknowledge the support of the National Institute of Bioinformatics (www.inab.org) and the CIBER de Enfermedades Raras, both initiatives of the ISCIII, MICINN. This work is also partly supported by a grant (RD06/0020/1019) from Red Tematica de Investigacion Cooperativa en Cancer (RTICC), ISCIII, MICINN. en_EN
dc.language Inglés es_ES
dc.publisher Cold Spring Harbor Laboratory Press es_ES
dc.relation Spanish Ministry of Science es_ES
dc.relation GVA-FEDER PROMETEO es_ES
dc.relation.ispartof Genome Research es_ES
dc.rights Reserva de todos los derechos es_ES
dc.subject Algorithm es_ES
dc.subject Article es_ES
dc.subject Biotype es_ES
dc.subject Data analysis software es_ES
dc.subject Gene expression es_ES
dc.subject Gene identification es_ES
dc.subject Genetic transcription es_ES
dc.subject Human es_ES
dc.subject Methodology es_ES
dc.subject Priority journal es_ES
dc.subject RNA sequence es_ES
dc.subject Signal noise ratio es_ES
dc.subject Transcriptomics es_ES
dc.subject Algorithms es_ES
dc.subject Expressed Sequence Tags es_ES
dc.subject Gene Expression Profiling es_ES
dc.subject Gene Expression Regulation es_ES
dc.subject Humans es_ES
dc.subject Models, Genetic es_ES
dc.subject Oligonucleotide Array Sequence Analysis es_ES
dc.subject.classification ESTADISTICA E INVESTIGACION OPERATIVA es_ES
dc.title Differential expression in RNA-seq: A matter of depth es_ES
dc.type Artículo es_ES
dc.embargo.lift 10000-01-01
dc.embargo.terms forever es_ES
dc.identifier.doi 10.1101/gr.124321.111
dc.rights.accessRights Abierto es_ES
dc.contributor.affiliation Universitat Politècnica de València. Departamento de Estadística e Investigación Operativa Aplicadas y Calidad - Departament d'Estadística i Investigació Operativa Aplicades i Qualitat es_ES
dc.description.bibliographicCitation Tarazona Campos, S.; García-Alcalde, F.; Dopazo, J.; Ferrer Riquelme, AJ.; Conesa, A. (2011). Differential expression in RNA-seq: A matter of depth. Genome Research. 21(12):2213-2223. doi:10.1101/gr.124321.111 es_ES
dc.description.accrualMethod Senia es_ES
dc.relation.publisherversion http://genome.cshlp.org/content/21/12/2213.full.pdf+html es_ES
dc.description.upvformatpinicio 2213 es_ES
dc.description.upvformatpfin 2223 es_ES
dc.type.version info:eu-repo/semantics/publishedVersion es_ES
dc.description.volume 21 es_ES
dc.description.issue 12 es_ES
dc.relation.senia 206208


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