NDLI: RNA-seq data analysis at the gene and CDS levels provides a comprehensive view of transcriptome responses induced by 4-hydroxynonenal

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Molecular BioSystems Vol - 9 Issue - 9

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RNA-seq data analysis at the gene and CDS levels provides a comprehensive view of transcriptome responses induced by 4-hydroxynonenal

Content Provider	Royal Society of Chemistry (RSC)
Author	Ullery, Jody Liebler, Daniel C. Zhang, Bing Marnett, Lawrence J. Zhu, Jing Liu, Qi
Copyright Year	2013
Abstract	Reactive electrophiles produced during oxidative stress, such as 4-hydroxynonenal (HNE), are increasingly recognized as contributing factors in a variety of degenerative and inflammatory diseases. Here we used the RNA-seq technology to characterize transcriptome responses in RKO cells induced by HNE at subcytotoxic and cytotoxic doses. RNA-seq analysis rediscovered most of the differentially expressed genes reported by microarray studies and also identified novel gene responses. Interestingly, differential expression detection at the coding DNA sequence (CDS) level helped to further improve the consistency between the two technologies, suggesting the utility and importance of the CDS level analysis. RNA-seq data analysis combining gene and CDS levels yielded an informative and comprehensive picture of gradually evolving response networks with increasing HNE doses, from cell protection against oxidative injury at low dose, initiation of cell apoptosis and DNA damage at intermediate dose to significant deregulation of cellular functions at high dose. These evolving dose-dependent pathway changes, which cannot be observed by the gene level analysis alone, clearly reveal the HNE cytotoxic effect and are supported by IC50 experiments. Additionally, differential expression at the CDS level provides new insights into isoform regulation mechanisms. Taken together, our data demonstrate the power of RNA-seq to identify subtle transcriptome changes and to characterize effects induced by HNE through the generation of high-resolution data coupled with differential analysis at both gene and CDS levels.
Starting Page	3036
Ending Page	3046
Page Count	11
File Format	HTM / HTML PDF
ISSN	1742206X
Volume Number	9
Issue Number	12
Journal	Molecular BioSystems
DOI	10.1039/c3mb70114j
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Open
Subject Keyword	Oxidative stress 4-Hydroxynonenal Gene RNA-Seq DNA Transcriptome IC50 Cytotoxicity Inflammation RKO Pictures Microarray Apoptosis
Content Type	Text
Resource Type	Article
Subject	Molecular Biology Biotechnology

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RNA-seq data analysis at the gene and CDS levels provides a comprehensive view of transcriptome responses induced by 4-hydroxynonenal