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Series GSE186001 Query DataSets for GSE186001
Status Public on Oct 16, 2021
Title Functional screen of Inflammatory bowel disease genes reveals key epithelial functions: Agilent Targeted Dataset
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Background: Genetic studies have been tremendously successful in identifying genomic regions associated with a wide variety of phenotypes, although the success of these studies in identifying causal genes, their variants, and their functional impacts have been more limited.  
Methods: We identified 145 genes from IBD-associated genomic loci having endogenous expression within the intestinal epithelial cell compartment.  We evaluated the impact of lentiviral transfer of the open reading frame (ORF) of these IBD genes into the HT-29 intestinal epithelial cell line via transcriptomic analyses.  Comparing the genes whose expression was modulated by each ORF, as well as the functions enriched within these gene lists, identified ORFs with shared impacts and their putative disease-relevant biological functions.
Results: Analysis of the transcriptomic data for cell lines expressing the ORFs for known causal genes such as HNF4a, IFIH1 and SMAD3 identified functions consistent with what is known for these genes.  These analyses also identified two major clusters of genes with shared impact on the transcriptome:  Cluster 1 contained the known IBD causal genes IFIH1, SBNO2, NFKB1 and NOD2, as well as genes from other IBD loci (ZFP36L1, IRF1, GIGYF1, OTUD3, AIRE and PITX1), whereas Cluster 2 contained the known causal gene KSR1 and implicated DUSP16 from another IBD locus. Our analyses of these clusters highlighted how multiple IBD gene candidates impact on epithelial structure and function, including the protection of the mucosa from intestinal microbiota. 
Conclusions: This functional screen, based on expressing IBD genes within an appropriate cellular context, in this instance intestinal epithelial cells, resulted in changes to the cell’s transcriptome that are relevant to their endogenous biological function(s). This not only helped in identifying likely causal genes within genetic loci but also provided insight into their biological functions.  Furthermore, this work has highlighted the central role of intestinal epithelial cells in IBD pathophysiology. 
 
Overall design This dataset includes 426 samples for 145 ORFs, mostly in independently transducted triplicates. Empty vector used as controls are also included.

iGenoMed Consortium
 
Contributor(s) Ntunzwenimana JC, Boucher G, Paquette J, Gosselin H, Alikashani A, Morin N, Beauchamp C, Thauvette L, Rivard M, Dupuis F, Deschenes S, Foisy S, Latour F, Lavallée G, Daly MJ, Xavier RJ, Charron G, Goyette P, Rioux JD
Citation(s) 34758847
Submission date Oct 15, 2021
Last update date Dec 02, 2021
Contact name John D Rioux
Organization name Montreal Heart Institute
Department Research Center
Lab Genetics and genomic medecine of Inflammation
Street address 5000 Bélanger St.
City Montréal
State/province QC
ZIP/Postal code H1T 1C8
Country Canada
 
Platforms (1)
GPL30867 Agilent-059505 MHI_Inflammation_Exon_II_v2 045268
Samples (426)
GSM5628277 HT29_ORF_Empty_5
GSM5628278 HT29_ORF_ARFRP1_14
GSM5628279 HT29_ORF_ARHGEF2_17
Relations
BioProject PRJNA771679

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE186001_RAW.tar 1.3 Gb (http)(custom) TAR (of TXT)
Raw data provided as supplementary file
Processed data included within Sample table

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