Transcriptome analysis of psoriasis in a large case-control sample: RNA-seq provides insights into disease mechanisms.
Bingshan Li, Lam C Tsoi, William R Swindell, Johann E Gudjonsson, Trilokraj Tejasvi, Andrew Johnston, Jun Ding, Philip E Stuart, Xianying Xing, James J Kochkodan, John J Voorhees, Hyun M Kang, Rajan P Nair, Goncalo R Abecasis, James T Elder
Author Information
Bingshan Li: Department of Molecular Physiology and Biophysics, Center for Human Genetics Research, Vanderbilt University, Nashville, Tennessee, USA; Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA.
Lam C Tsoi: Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA.
William R Swindell: Department of Dermatology, University of Michigan, Ann Arbor, Michigan, USA.
Johann E Gudjonsson: Department of Dermatology, University of Michigan, Ann Arbor, Michigan, USA.
Trilokraj Tejasvi: Department of Dermatology, University of Michigan, Ann Arbor, Michigan, USA; Ann Arbor Veterans Affairs Hospital, University of Michigan, Ann Arbor, Michigan, USA.
Andrew Johnston: Department of Dermatology, University of Michigan, Ann Arbor, Michigan, USA.
Jun Ding: Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA; Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA.
Philip E Stuart: Department of Dermatology, University of Michigan, Ann Arbor, Michigan, USA.
Xianying Xing: Department of Dermatology, University of Michigan, Ann Arbor, Michigan, USA.
James J Kochkodan: Department of Dermatology, University of Michigan, Ann Arbor, Michigan, USA.
John J Voorhees: Department of Dermatology, University of Michigan, Ann Arbor, Michigan, USA.
Hyun M Kang: Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA.
Rajan P Nair: Department of Dermatology, University of Michigan, Ann Arbor, Michigan, USA.
Goncalo R Abecasis: Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA. Electronic address: goncalo@umich.edu.
James T Elder: Department of Dermatology, University of Michigan, Ann Arbor, Michigan, USA; Ann Arbor Veterans Affairs Hospital, University of Michigan, Ann Arbor, Michigan, USA. Electronic address: jelder@umich.edu.
To increase our understanding of psoriasis, we used high-throughput complementary DNA sequencing (RNA-seq) to assay the transcriptomes of lesional psoriatic and normal skin. We sequenced polyadenylated RNA-derived complementary DNAs from 92 psoriatic and 82 normal punch biopsies, generating an average of ∼38 million single-end 80-bp reads per sample. Comparison of 42 samples examined by both RNA-seq and microarray revealed marked differences in sensitivity, with transcripts identified only by RNA-seq having much lower expression than those also identified by microarray. RNA-seq identified many more differentially expressed transcripts enriched in immune system processes. Weighted gene coexpression network analysis (WGCNA) revealed multiple modules of coordinately expressed epidermal differentiation genes, overlapping significantly with genes regulated by the long noncoding RNA TINCR, its target gene, staufen-1 (STAU1), the p63 target gene ZNF750, and its target KLF4. Other coordinately expressed modules were enriched for lymphoid and/or myeloid signature transcripts and genes induced by IL-17 in keratinocytes. Dermally expressed genes were significantly downregulated in psoriatic biopsies, most likely because of expansion of the epidermal compartment. These results show the power of WGCNA to elucidate gene regulatory circuits in psoriasis, and emphasize the influence of tissue architecture in both differential expression and coexpression analysis.
