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Series GSE86884 Query DataSets for GSE86884
Status Public on Sep 13, 2016
Title Differentially Expressed Gene Transcripts Using RNA Sequencing from the Blood of Immunosuppressed Kidney Allograft Recipients
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary We performed RNA sequencing (RNAseq) on peripheral blood mononuclear cells (PBMCs) to identify differentially expressed gene transcripts (DEGs) after kidney transplantation and after the start of immunosuppressive drugs. RNAseq is superior to microarray to determine DEGs because it’s not limited to available probes, has increased sensitivity, and detects alternative and previously unknown transcripts. DEGs were determined in adult kidney recipients, without clinical acute rejection (AR), treated with antibody induction, calcineurin inhibitor, mycophenolate, with and without steroids. Blood was obtained pre-transplant (baseline), week 1, months 3 and 6 post-transplant. PBMCs were isolated, RNA extracted and gene expression measured using RNAseq. Principal components (PCs) were computed using a surrogate variable approach. DEGs post-transplant were identified by controlling false discovery rate (FDR) at < 0.01 with at least a 2 fold change in expression from pre-transplant. The top 5 DEGs with higher levels of transcripts in blood at week 1 were TOMM40L, TMEM205, OLFM4, MMP8, and OSBPL9 compared to baseline. The top 5 DEGs with lower levels at week 1 post-transplant were IL7R, KLRC3, CD3E, CD3D, and KLRC2(Striking Image) compared to baseline. The top pathways from genes with lower levels at 1 week post-transplant compared to baseline, were T cell receptor signaling and iCOS-iCOSL signaling while the top pathways from genes with higher levels than baseline were axonal guidance signaling and LXR/RXR activation. Gene expression signatures at month 3 were similar to week 1. DEGs at 6 months post-transplant create a different gene signature than week 1 or month 3 post-transplant. RNAseq analysis identified more DEGs with lower than higher levels in blood compared to baseline at week 1 and month 3. The number of DEGs decreased with time post-transplant. Further investigations to determine the specific lymphocyte(s) responsible for differential gene expression may be important in selecting and personalizing immune suppressant drugs and may lead to targeted therapies.
Overall design RNAseq data are from blood specimens from kidney transplant patients as a time course before and after kidney transplant from living donors. There are 96 samples analyzed in total from 34 patients; however, only 32 patients with baseline data and pre-transplant RNA. None of the patients in the study developed acute rejection within the 6 month study period. Time points include: pre-transplant, 1 week following transplant, 3 and 6 months following transplant.
Contributor(s) Dorr C, Wu B, Guan W, Muthusamy A, Sanghavi K, Schladt DP, Maltzman JS, Scherer SE, Brott MJ, Matas AJ, Jacobson PA, Oetting WS, Israni AK
Citation(s) 25946140
Submission date Sep 13, 2016
Last update date May 15, 2019
Contact name Casey Dorr
Organization name Minneapolis Medical Research Foundation
Street address 701 Park Avenue
City Minneapolis
State/province MN
ZIP/Postal code 55415
Country USA
Platforms (1)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
Samples (96)
GSM2309837 03-1-0006-0
GSM2309838 03-1-0006-3
GSM2309839 03-1-0006-6 
BioProject PRJNA342822
SRA SRP089814

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Supplementary file Size Download File type/resource
GSE86884_RAW.tar 404.0 Mb (http)(custom) TAR (of XLSX)
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Raw data are available in SRA
Processed data provided as supplementary file

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