TY - JOUR
T1 - Transcriptome analysis of psoriasis in a large case-control sample
T2 - RNA-seq provides insights into disease mechanisms
AU - Li, Bingshan
AU - Tsoi, Lam C.
AU - Swindell, William R.
AU - Gudjonsson, Johann E.
AU - Tejasvi, Trilokraj
AU - Johnston, Andrew
AU - Ding, Jun
AU - Stuart, Philip E.
AU - Xing, Xianying
AU - Kochkodan, James J.
AU - Voorhees, John J.
AU - Kang, Hyun M.
AU - Nair, Rajan P.
AU - Abecasis, Goncalo R.
AU - Elder, James T.
N1 - Funding Information:
We thank the many volunteers who provided skin biopsies for this study. This research was supported by NIH grants R01 AR042742, R01 AR050511, and AR054966 to JTE, K08 AR060802 to JEG, and K01 AR064765-01 to AJ. JTE and TT are supported by the Ann Arbor Veterans Affairs Hospital, AJ is supported by the Dermatology Foundation, and JEG is supported by the Frances and Kenneth Eisenberg Emerging Scholar Fund and the National Psoriasis Foundation. We also acknowledge generous support from the Dawn and Dudley Holmes Memorial Fund and the Babcock Endowment Fund to the Department of Dermatology at the University of Michigan.
PY - 2014/7
Y1 - 2014/7
N2 - 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.
AB - 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.
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U2 - 10.1038/jid.2014.28
DO - 10.1038/jid.2014.28
M3 - Article
C2 - 24441097
AN - SCOPUS:84902544820
SN - 0022-202X
VL - 134
SP - 1828
EP - 1838
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 7
ER -