Integrative RNA-seq and microarray data analysis reveals GC content and gene length biases in the psoriasis transcriptome.
Gene expression profiling of psoriasis has driven research advances and may soon provide the basis for clinical applications. For expression profiling studies, RNA-seq is now a competitive technology, but RNA-seq results may differ from those obtained by microarray. We therefore compared findings obtained by RNA-seq with those from eight microarray studies of psoriasis. RNA-seq and microarray datasets identified similar numbers of differentially expressed genes (DEGs), with certain genes uniquely identified by each technology. Correspondence between platforms and the balance of increased to decreased DEGs was influenced by mRNA abundance, GC content, and gene length. Weakly expressed genes, genes with low GC content, and long genes were all biased toward decreased expression in psoriasis lesions. The strength of these trends differed among array datasets, most likely due to variations in RNA quality. Gene length bias was by far the strongest trend and was evident in all datasets regardless of the expression profiling technology. The effect was due to differences between lesional and uninvolved skin with respect to the genome-wide correlation between gene length and gene expression, which was consistently more negative in psoriasis lesions. These findings demonstrate the complementary nature of RNA-seq and microarray technology and show that integrative analysis of both data types can provide a richer view of the transcriptome than strict reliance on a single method alone. Our results also highlight factors affecting correspondence between technologies, and we have established that gene length is a major determinant of differential expression in psoriasis lesions.
Department of Dermatology, University of Michigan School of Medicine, Ann Arbor, Michigan wswindel@umich.edu.
William R
WR
Swindell
Department of Dermatology, University of Michigan School of Medicine, Ann Arbor, Michigan.
Xianying
X
Xing
Department of Dermatology, University of Michigan School of Medicine, Ann Arbor, Michigan.
John J
JJ
Voorhees
Department of Dermatology, University of Michigan School of Medicine, Ann Arbor, Michigan.
James T
JT
Elder
Department of Dermatology, University of Michigan School of Medicine, Ann Arbor, Michigan.
Andrew
A
Johnston
Department of Dermatology, University of Michigan School of Medicine, Ann Arbor, Michigan.
Johann E
JE
Gudjonsson
D001482:Base Composition; D001483:Base Sequence; D001706:Biopsy; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D046228:Microarray Analysis; D020411:Oligonucleotide Array Sequence Analysis; D011565:Psoriasis / Q000235:genetics* / Q000378:metabolism*; D011786:Quality Control; D012333:RNA, Messenger / Q000378:metabolism; D017423:Sequence Analysis, RNA; D012867:Skin / Q000378:metabolism; D059467:Transcriptome
D012333:RNA, Messenger
RNase 7; RNase L; degradation; gene expression; ribonuclease