Comment[ArrayExpressAccession]	E-GEOD-67401
MAGE-TAB Version	1.1		
Public Release Date	2015-07-01
Investigation Title	Renal systems biology of patients with systemic inflammatory response syndrome		
Comment[Submitted Name]	Renal systems biology of patients with systemic inflammatory response syndrome
Experiment Description	A systems biology approach was used to comprehensively examine the impact of renal disease and hemodialysis (HD) on host response during critical illness. We examined the metabolome, proteome, and transcriptome of 150 patients with critical illness, stratified by renal function. Plasma metabolite values showed greater changes as renal function declined, with the greatest derangements in patients receiving chronic HD. Specifically, 6 uremic retention molecules, 17 other protein catabolites, 7 modified nucleosides, and 7 pentose phosphate sugars increased as renal function declined, consistent with decreased excretion or increased catabolism of amino acids and ribonucleotides. Similarly, the proteome showed increased levels of low-molecular weight proteins and acute phase reactants. The transcriptome revealed a broad-based decrease in mRNA levels among HD patients. Systems integration revealed an unrecognized association between plasma RNASE1 and several RNA catabolites and modified nucleosides. Further, allantoin, N1-methyl-4-pyridone-3-carboxamide, and n-acetylaspartate showed inverse correlations with the majority of significantly down-regulated genes. In conclusion, renal function broadly affected the plasma metabolome, proteome, and peripheral blood transcriptome during critical illness. These changes were not effectively mitigated by hemodialysis. These studies suggest several novel mechanisms whereby renal dysfunction contributes to critical illness. We sequenced peripheral blood RNA of 133 representative subjects with systemic inflammatory response syndrome that had Acute Kidney Injury (AKI) or Hemodialysis (HD). No injury (AKI0; n= 58); AKI Stage 1 (AKI1; n= 36); AKI stage 2 and 3 (AKI23; n= 17); HD (N=22).		
Term Source Name	ArrayExpress	EFO
Term Source File	http://www.ebi.ac.uk/arrayexpress/	http://www.ebi.ac.uk/efo/efo.owl	
Person Last Name	Langley	Langley	Miller
Person First Name	Raymond	Raymond	Neil
Person Mid Initials	J	J	A
Person Email	rlangley@lrri.org		
Person Affiliation	LRRI		
Person Phone	505-348-9614		
Person Address	immunology, LRRI, 2425 Ridgecrest Dr, Albuquerque, New Mexico, USA		
Person Roles	submitter		
Protocol Name	P-GSE67401-1		
Protocol Description	Whole blood was collected in PAXgene RNA tubes (Qiagen, CA) to stabilize intracellular RNA and subsequently stored at -80°C until use. RNA was prepared using a PaxGene Blood RNA kit (Qiagen) according to the manufacturer’s instructions. mRNA sequencing libraries were prepared from total RNA using the Illumina mRNA-Seq Sample Prep Kit (Illumina, catalog # RS‐100‐0801), according to manufacturers’ recommend protocols		
Protocol Type	nucleic acid library construction protocol		
Experimental Factor Name	patient id	sirs outcomes	
Experimental Factor Type	patient id	sirs outcomes	
Comment[SecondaryAccession]	GSE67401		
Comment[GEOReleaseDate]	2015-07-01		
Comment[ArrayExpressSubmissionDate]	2015-03-30		
Comment[GEOLastUpdateDate]	2015-07-01		
Comment[AEExperimentType]	RNA-seq of coding RNA		
Comment[AdditionalFile:Data1]	GSE67401_CAPSOD_AKI_mrna_seq_raw_unique_rpm_nonspars.txt		
Comment[SecondaryAccession]	SRP056840		
SDRF File	E-GEOD-67401.sdrf.txt