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Series GSE167517 Query DataSets for GSE167517
Status Public on Jun 30, 2021
Title Transcriptional-Regulatory Convergence Across Functional MDD Risk Variants Identified by Massively Parallel Reporter Assays [Expt1]
Organisms Escherichia coli; Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Using Massively Parallel Reporter Assays (MPRAs), we functionally screened over 1,000 SNPs, prioritized from 39 neuropsychiatric trait/disease GWAS loci based on overlap with predicted regulatory features—including expression quantitative trait loci (eQTL) and histone marks—from human brains and cell cultures. Using mouse neuroblastoma Neuro2a (N2a) cells, we identify over 100 SNPs with allelic effects on expression. Functional SNPs were enriched for binding sequences of retinoic acid-receptive transcription factors (TFs); with additional allelic differences unmasked in cells treated with all-trans retinoic acid (ATRA). Motifs overrepresented at functional SNPs corresponded to a set of TFs highly specific to serotonergic neurons and collectively downregulated in schizophrenia. Our application of MPRAs to screen MDD-associated SNPs suggested a shared transcriptional regulatory program across loci, a subset of which are unmasked by retinoids. Additional code and results corresponding to this GEO submission can be found at https://bitbucket.org/jdlabteam/n2a_atra_mdd_mpra_paper/src
 
Overall design n=6 replicates of plasmid-transfected N2A cells, plated at 2 different densities at the time of transfection (linear regression showed that this had no effect on expression of any barcode set).
Grants:
1. 5F30MH116654 - Bernard Mulvey - Identification and characterization of common, noncoding regulatory variants associated with Major Depressive Disorder - NIMH

2. 1R01MH116999 - Joseph Dougherty - Highly parallel analysis of 5' and 3' UTR variants in Autism Spectrum Disorders - NIMH

3. 571009 - Joseph Dougherty - Simons Foundation
 
Contributor(s) Mulvey B, Dougherty JD
Citation(s) 34294677
Submission date Feb 25, 2021
Last update date Aug 11, 2021
Contact name Joseph Dougherty
E-mail(s) mulveyb@wustl.edu, jdougherty@wustl.edu, berniejmulvey@gmail.com
Organization name Washington University in St. Louis
Department Genetics
Lab Dougherty
Street address 660 S Euclid Ave, Campus Box 8232
City St. Louis
State/province MO
ZIP/Postal code 63110
Country USA
 
Platforms (2)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
GPL18133 Illumina HiSeq 2500 (Escherichia coli)
Samples (7)
GSM5106536 High_Density_1
GSM5106537 High_Density_2
GSM5106538 High_Density_3
This SubSeries is part of SuperSeries:
GSE167519 Transcriptional-Regulatory Convergence Across Functional MDD Risk Variants Identified by Massively Parallel Reporter Assays
Relations
BioProject PRJNA704846
SRA SRP308182

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
GSE167517_Reference-Barcode_Sequences__their_paired_internal_identifiers__and_the_corresponding_sequence_placed_upstream_of_min_promoter.txt.gz 1.3 Mb (ftp)(http) TXT
GSE167517_Unfiltered_Barcode_Counts-N2A_Experiment_1.txt.gz 395.9 Kb (ftp)(http) TXT
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Raw data are available in SRA
Processed data are available on Series record

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