lentiMPRA of brain QTL alleles in hiPSC-derived excitatory NGN2 neurons
Genetic regulation of cell type-specific chromatin accessibility shapes brain disease etiologyA lentiMPRA library tested 270-bp sequences centered on 19,893 candidate causal SNPs with separate reference and alternative alleles, alongside negative-control, positional-effect, literature-control, and shuffled-control constructs. Lentiviral constructs were assayed in WTC11 hiPSC-derived excitatory NGN2 neurons across three biological replicates; the public processed subset contains seven SNPs with significant MPRA allelic effects that also have GWAS associations.
Processed tables are specific to each experiment. Column names, units, measurements, and table structure are not standardized across the database. Check this experiment’s column definitions and quality-control notes before comparing or combining data.
Perturbation & assay details
Basal / Untreated
Synthetic 270-bp sequences were centered on candidate SNPs, with reference and alternative alleles synthesized separately. Oligos were cloned into a lentiviral MPRA reporter with a minimal promoter and 15-bp barcodes; the library was integrated into induced excitatory neurons at an estimated MOI of 90, and RNA/DNA barcode abundance ratios were analyzed with MPRAflow and MPRAnalyze. A subset of 994 SNPs was also tested at two non-central positions.
Processed data
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Filters apply to this table only. The CSV download contains the complete processed table; filtered rows are available through the API.
Column dictionary · 10 definitions
- variant_id
- dbSNP rs identifier for the tested variant
- chromosome
- Chromosome, with chr prefix, as reported in Supplementary Table S2
- position_start
- Reported start coordinate of the one-base variant interval
- position_end
- Reported end coordinate of the one-base variant interval
- gwas_trait
- Trait/disease code carried by the source table
- gwas_trait_label
- Human-readable label derived from the source trait code
- gwas_z_score
- GWAS association Z score reported in Supplementary Table S2
- mpra_allelic_effect_significant
- Boolean indicating that the source table identifies the SNP as having a significant MPRA allelic effect
- mpra_result_scope
- Description of the MPRA result subset represented by the row
- source_table
- Source supplementary table used to construct the row
Quality control
The study reports high consistency across three biological replicates. Barcode-to-sequence mapping and normalized counting were performed with MPRAflow; enhancer activity and allelic effects were tested with MPRAnalyze and corrected with the Benjamini-Hochberg procedure. The paper reports 933 of 994 positional-effect variants with sufficient sequencing coverage for QC and uses FDR < 5% for enhancer activity and FDR < 10% for allelic effects. The processed table retains only the seven rows in the public Table S2, which are already restricted to variants with significant MPRA allelic effects and significant GWAS associations.
Curation notes
This is one lentiMPRA experiment with enhancer-activity and allelic-effect analyses, not separate biological conditions. The open supplement exposes only the seven MPRA-significant variants that overlap GWAS-significant variants; the complete Synapse result files are controlled/certification-required and were not downloadable anonymously. Therefore MPRA effect sizes, FDR values, allele identities, and barcode counts are intentionally absent rather than inferred. The gwas_trait_label column is a transparent mapping of the source codes pd, SCZ3, and mdd2 to readable disease labels. The biosample CURIE uses CL:0000679 (glutamatergic neuron) as the closest standardized Cell Ontology term for induced excitatory NGN2 neurons.