iPSC-derived microglia integrated lentiMPRA of Alzheimer’s and microglial candidate variants
Regulatory landscape of Alzheimer’s disease variants in human microgliaA pooled second-generation lentiviral MPRA tested both alleles of candidate regulatory variants nominated from Alzheimer’s disease GWAS fine-mapping, microglial eQTLs, and caQTLs in mature hiPSC-derived microglia-like cells (iMGLs). Reporter DNA and RNA barcodes were collected after 72 hours and analyzed for allelic activity.
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
The library used approximately 230-bp HiFi oligonucleotides carrying candidate sequences, both alleles, and random 15-bp barcodes, cloned upstream of a minimal promoter and eGFP reporter in a lentiviral vector. Mature iMGLs were transduced on day 5 of maturation at approximately MOI 50, using about 5 × 10^6 cells per replicate; the study used iMGLs differentiated from two control iPSC lines and biological replicates over those donors. MPRAflow v2.0 associated barcodes with constructs and MPRAnalyze v1.24.0 modeled DNA/RNA counts; log2 fold change is the alternate- versus reference-allele activity effect.
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 · 21 definitions
- variant_id
- Unique dbSNP rs identifier for the tested variant.
- chromosome
- Chromosome label for the tested variant.
- position_hg38
- 1-based genomic base-pair coordinate treated as GRCh38/hg38.
- reported_effect_allele
- Effect allele reported in the authors’ allelic-activity result.
- reported_non_effect_allele
- Non-effect comparator allele reported in the authors’ allelic-activity result.
- reference_allele_match
- Authors’ REF_match flag for whether the reported allele orientation matches the sequence-design reference.
- log2_alt_vs_ref_activity
- MPRAnalyze log2 fold change for alternate versus reference allele reporter activity; positive values indicate higher alternate-allele activity.
- fdr
- Benjamini–Hochberg-adjusted allelic-effect significance value from MPRAnalyze.
- emVar
- TRUE when the allelic-effect FDR is < 0.05, marking an expression-modulating variant.
- allelic_effect_direction
- Direction of the alternate-allele activity effect based on the log2 fold change.
- prioritization_source
- Variant-prioritization source label from the authors’ MPRA library-design table; NA means no matching library annotation was available.
- gwas_finemapping
- Indicator that the library-design table flags Bellenguez GWAS fine-mapping.
- caQTL_finemapping
- Indicator that the library-design table flags microglial caQTL fine-mapping.
- lead_eQTL
- Indicator that the library-design table flags a microglial lead eQTL.
- LD_eQTL_ABC
- Indicator that the library-design table flags an eQTL-LD variant overlapping an ABC enhancer.
- LD_eQTL_sig_peak
- Indicator that the library-design table flags an eQTL-LD variant overlapping a significant microglial ATAC peak.
- schwartzentruber_finemapping
- Indicator that the library-design table flags Schwartzentruber GWAS fine-mapping.
- bellenguez_gwas
- Indicator that the library-design table flags a Bellenguez GWAS lead variant.
- jansen_gwas
- Indicator that the library-design table flags a Jansen GWAS lead variant.
- kunkle_gwas
- Indicator that the library-design table flags a Kunkle GWAS lead variant.
- qc_status
- Final processing status; pass means the row passed the author-provided active-CRS filter and required-field checks.
Quality control
The authors retained candidate regulatory sequences with at least 10 unique barcodes, removed incomplete reference–alternate pairs, and excluded constructs with log2 RNA/DNA ≤ 0. MPRAnalyze modeled normalized DNA and RNA counts with scrambled-sequence controls, and Benjamini–Hochberg correction defined emVars at FDR < 0.05. The generated table additionally retained only rows marked CRS=active in the authors’ AllelicActivity export and required non-missing variant, allele, log2 fold-change, and FDR fields; this removed all CRS=remove rows and two active-export records with missing log2 fold-change.
Curation notes
The processed table contains 9,156 variant rows from the iMGL AllelicActivity export and 2,003 emVars, matching the manuscript’s reported iMGL emVar count. The raw export has 2,009 CRS=remove rows and two additional records with missing log2 fold-change; all were excluded. Source annotations are joined by variant_id from iMGL_MPRA_consensus_table.tsv while all activity statistics come from iMGL_MPRA_AllelicActivity.tsv.gz. The activity export does not explicitly state an assembly; GRCh38 is used because the manuscript’s functional annotations use TxDb.Hsapiens.UCSC.hg38, while some upstream fine-mapping filenames reference hg19.