Experiment / E7TTVOE7VIntegrated lentiMPRA

N2 neural progenitor cell lentiMPRA of ASD promoter de novo variants

Characterization of De Novo Promoter Variants in Autism Spectrum Disorder with Massively Parallel Reporter Assays

A lentiviral MPRA tested 200-bp GRCh38 reference and alternate promoter sequences for de novo variants identified in autism spectrum disorder cases and unaffected sibling controls. Three independent human N2 neural progenitor cell cultures were infected and harvested four days later for paired DNA/RNA barcode sequencing; the processed table contains the 3,090 variant pairs represented in the published variant-level results.

Download processed table (CSV)Raw source data API documentation

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.

Organism: Human
Taxonomy ID: NCBITaxon:9606
Biosample: CL:0011020
Reference genome: GRCh38
Design focus: Variant-focused
Region of interest: Not reported / not applicable

Perturbation & assay details

Basal / Untreated

The library used 200-bp reference and alternate sequences centered on each promoter DNV, plus positive and scrambled negative controls, cloned upstream of a minimal promoter in the pLS-SceI lentiMPRA vector. A 15-nt random barcode was placed in the 5′ UTR of EGFP; approximately 1 million N2 cells were infected at MOI 50, three independent cultures were harvested four days post-infection, and barcode DNA/cDNA was quantified with custom-primer sequencing and MPRAnalyze.

Processed data

50 rows per page. Click a cell to inspect its full value.

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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 · 53 definitions

variant_pair: Paired reference and alternate construct identifiers from Supplementary Table S3.
ref_construct_id: Identifier of the reference-allele construct in the deposited FASTA.
alt_construct_id: Identifier of the alternate-allele construct in the deposited FASTA.
chromosome: Chromosome for the variant, as reported in the source annotation.
position_hg38: 1-based GRCh38 variant position.
ref_allele: Reference allele reported for the variant.
alt_allele: Alternate/de novo allele reported for the variant.
ref_sequence: 200-bp reference construct sequence from GEO; the variant base is at position 101.
alt_sequence: 200-bp alternate construct sequence from GEO; the variant base is at position 101.
mpra_p_value: MPRAnalyze p-value for differential reference-versus-alternate reporter expression.
mpra_fdr: FDR-adjusted MPRAnalyze p-value for the reference-versus-alternate comparison.
mpra_logFC_ref_over_alt: Published Supplementary Table S3 logFC; the paper describes the primary effect as ln(reference alpha / alternate alpha) when defining activators and inhibitors.
effect_class: Derived paper-style class: Activator for HcDNV with positive logFC, Inhibitor for HcDNV with negative logFC, otherwise Background.
hcdnv: Published high-confidence DNV indicator; 1 denotes FDR <= 0.2 and absolute differential expression >= 0.1.
family_id: Family identifier from the source DNV annotation.
sample_id: Sample/proband identifier from the source DNV annotation.
phenotype: ASD case or unaffected sibling control designation.
prior_findings_in_family: Source indicator for prior findings in the family.
recurrence: Source recurrence indicator for the DNV.
active_tss: Source indicator for overlap with an active transcription start site annotation.
conserved_loci: Source indicator for the conserved-locus annotation.
lasso: Source indicator for prioritization by the LASSO model.
dawn: Source indicator for prioritization by the DAWN model.
c7: Source indicator for membership in DAWN cluster C7.
c12: Source indicator for membership in DAWN cluster C12.
c18: Source indicator for membership in DAWN cluster C18.
c20: Source indicator for membership in DAWN cluster C20.
c26: Source indicator for membership in DAWN cluster C26.
c28: Source indicator for membership in DAWN cluster C28.
c42: Source indicator for membership in DAWN cluster C42.
c49: Source indicator for membership in DAWN cluster C49.
c63: Source indicator for membership in DAWN cluster C63.
chd8_target: Source indicator for overlap with a CHD8 target annotation.
phastcons: PhastCons conservation score from the source annotation.
phylop: PhyloP conservation score from the source annotation.
chme1: Source chromatin-state annotation indicator ChmE1.
chme2: Source chromatin-state annotation indicator ChmE2.
encode_tfbs: Source indicator for overlap with ENCODE transcription-factor binding sites.
rep_dnase: Source indicator for overlap with Roadmap/REP DNase sites.
encode_dnase: Source indicator for overlap with ENCODE DNase sites.
midfetal_h3k27ac: Source indicator for overlap with mid-fetal H3K27ac annotation.
gene: Nearest or associated gene symbol from the source annotation.
ensembl_gene_id: Ensembl gene identifier from the source annotation.
ensembl_transcript_id: Ensembl transcript identifier from the source annotation.
transcript_type: Ensembl transcript biotype from the source annotation.
protein: Protein identifier from the source annotation, when available.
asd_tada_fdr01: Source indicator for ASD TADA significance at FDR 0.01.
asd_tada_fdr03: Source indicator for ASD TADA significance at FDR 0.03.
pli_over90: Source indicator that the associated gene has pLI > 0.90.
dev_delay: Source indicator for developmental-delay gene annotation.
motif_match: Comma-separated FIMO motifs detected with both reference and alternate alleles in Supplementary Table S4.
motif_alt_only: Comma-separated FIMO motifs detected only with the alternate allele, interpreted as gained motifs.
motif_ref_only: Comma-separated FIMO motifs detected only with the reference allele, interpreted as disrupted motifs.

Quality control

The published pipeline retained sequence–barcode assignments supported by at least 3 unique UMIs with at least 80% of UMIs mapping to one sequence, discarded ambiguous assignments, required perfect barcode matches for MPRA counting, and retained barcodes present in at least two corresponding DNA/RNA libraries from the same replicate. MPRAnalyze applied library-size normalization, estimated alpha transcription rates, and tested sequence activity against scrambled negative controls. The generated table is restricted to the 3,090 variant pairs in Supplementary Table S3 that passed the paper's paired representation/output filter; all joined sequences are 200 bp and have the expected single central allele change. One additional pair present in the GEO count matrices but absent from the published S3 results was excluded.

Curation notes

Raw GEO files are preserved as deposited. The decompressed payload of GSE216129_RefAlt_Complete_rnacounts.tsv.gz is byte-for-byte identical to the decompressed DNA count matrix and retains DNA-labeled headers, so no RNA/DNA activity values were recomputed from those files; the processed table uses the published S3 MPRAnalyze p-value, FDR, and logFC results and joins the deposited construct sequences. Supplementary Table S4 motif results were joined for its 64 variant records. All S3 pairs matched FASTA records and validated at the 101st base. The FASTA interval headers do not state an assembly, while the authoritative variant coordinate field is Position_hg38.

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