Experiment / E35BEHP6GEpisomal Plasmid MPRA

K-562 barcoded episomal MPRA — enhancer activity and allelic skew

Integrating natural and engineered genetic variations to decode regulatory influence on blood traits

The 19,050-oligonucleotide allele-specific barcoded library was nucleofected into human K-562 chronic myeloid leukemia cells in seven replicates. Table S4 provides 137 cross-tile meta-analysis rows for index-variant, control, and diplotype comparisons.

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 paper used a barcoded plasmid reporter based on hSTARR-seq_ORI with GFP and a poly(A)-separated barcode/candidate-sequence configuration. Each reference or alternative allele was represented in five partially overlapping 148-bp tiles, with 15 unique 11-bp barcodes per allele-tile; the 200-mers also contained 15-bp amplification arms and restriction sites. The pooled library covered 94 index variants plus positive and negative controls. K-562 cells were nucleofected with the library, harvested after 48 h, and processed in parallel for gDNA and mRNA. UMI-tagged cDNA and gDNA libraries were sequenced on a HiSeq 2500, counted after perfect barcode matching and UMI deduplication, and analyzed with MPRAmodel for per-tile activity and allelic skew followed by cross-tile meta-analysis.

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 · 35 definitions
tested_variant_id
VAR identifier from Table S4 for the tested single variant or compound/diplotype comparison.
variant_context
SNP identifier from Table S4 describing the sequence context and, for diplotypes, the component variants.
comparison
Allelic comparison tested by the source model, such as ref_vs_alt or a ref/ref versus alt/ref diplotype comparison.
rsid
Resolved dbSNP rs identifier(s) from Table S2; NA for controls or unresolved identifiers.
chromosome
Chromosome parsed from a single-variant identifier; NA for compound identifiers.
position_grch37
1-based GRCh37 position parsed from a single-variant identifier; NA for compound identifiers.
reference_allele
Reference allele parsed from a single-variant identifier; NA for compound identifiers.
alternate_allele
Alternate allele parsed from a single-variant identifier; NA for compound identifiers.
variant_components
Semicolon-separated component VAR identifiers represented by the tested sequence.
maf_ukbb
UK Biobank minor-allele frequency from Table S2 when an exact single-variant annotation was available.
variant_tier
Variant prioritization class from Table S2.
paper_group
Paper grouping label from Table S2, such as index-variant grouping or control grouping.
vep_consequence
Collapsed VEP consequence label from Table S2.
cell_type
Assayed cell type reported by Table S4; this table contains K562 rows.
library_project
Source Table S4 project label distinguishing the primary library and experimental/negative controls.
tiles_assayed
Number of distinct tile windows in Table S3 contributing to the corresponding Table S4 meta-analysis row.
allele_a_activity_log2fc_meta
Cross-tile meta-analyzed activity estimate in the source log2FC_A_meta field.
activity_log2fc_meta
Cross-tile meta-analyzed enhancer activity log2 fold-change; positive values indicate enhancer activity and negative values repressor activity according to the paper.
activity_log2fc_se_meta
Standard error of activity_log2fc_meta from the source meta-analysis.
allelic_skew_log2_meta
Cross-tile meta-analyzed allelic-skew log2 effect; positive values favor the alternate allele and negative values favor the reference allele according to the paper.
allelic_skew_log2_se_meta
Standard error of allelic_skew_log2_meta from the source meta-analysis.
activity_nlogp_meta
Source log2FC_meta_nlogp negative-log p statistic for activity.
allelic_skew_nlogp_meta
Source log2Skew_meta_nlogp negative-log p statistic for allelic skew.
activity_padj_nlogp_meta
Source lof2FC_meta_padj adjusted-activity significance statistic; Inf is preserved exactly when supplied by the source.
allelic_skew_padj_nlogp_meta
Source lof2Skew_meta_padj adjusted allelic-skew significance statistic.
active_enhancer_meta
Boolean source active_meta call from the activity thresholding procedure.
allelic_skew_significant_meta
Boolean source emVar_meta call indicating significant allelic skew.
activity_call
Source categorical activity call, ACTIVE or INACTIVE.
mpra_class
Source MPRA_CLASS designation, MPRA_positive or MPRA_negative.
candidate_effector_gene
Candidate effector gene annotation joined from Table S6 when available.
mechanistic_class
Mechanistic classification joined from Table S6 when available.
lineage
Blood-cell lineage annotation joined from Table S6 when available.
phenotypes
Semicolon-separated blood phenotypes joined from Table S6 when available.
published_mpra_positive_cells
Cell types called MPRA-positive in the paper-level Table S6 annotation.
source_table
Provenance for the processed row and its derived annotations.

Quality control

The authors checked barcode-to-sequence association and design dropout in an intermediate PolyA-minus library, targeted at least 100 bacterial colonies per oligo, retained only primary alignments with perfect barcode matches, deduplicated UMIs, and summed unique UMIs across each sequence's barcodes. MPRAmodel estimated per-tile log2FC and allelic skew, then combined tiles by meta-analysis. The paper defined active enhancer activity as log2FC > 0.25 at 1% global FDR and required significant allelic skew at 10% global FDR for the MPRA-positive class. Package QC required non-empty source identifiers, valid numeric effect/SE/significance fields, and at least one matching tile in Table S3; all 137 K-562 Table S4 rows passed. The seven literal Inf values in the source adjusted-activity significance field were retained as the source's zero/underflow sentinel, and biologically valid inactive variants and controls were retained.

Curation notes

K-562 was resolved to Cellosaurus CVCL:0004. The source labels this cell type K562; the experiment is one condition of the shared seven-replicate screen, not a separate library. Coordinates in the MPRA source tables are GRCh37. The processed table retains the source's 137 meta-analysis rows, including negative controls and nonsignificant measurements; no rows were removed by package QC.

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