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| 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
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| 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.
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| 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.
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| 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 |
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| Submission date |
Sep 13, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Casey Dorr |
| E-mail(s) |
cdorr@mmrf.org
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| Organization name |
Minneapolis Medical Research Foundation
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| Street address |
701 Park Avenue
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| City |
Minneapolis |
| State/province |
MN |
| ZIP/Postal code |
55415 |
| Country |
USA |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (96)
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| Relations |
| BioProject |
PRJNA342822 |
| SRA |
SRP089814 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE86884_RAW.tar |
404.0 Mb |
(http)(custom) |
TAR (of XLSX) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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