Allelic enhancer activity of rheumatoid arthritis-associated variants in activated primary CD4+ T cells
Functional dissection of noncoding variants associated with rheumatoid arthritisA synthetic 230-nucleotide reference/alternate allele library covering 1,765 RA-associated variants at 611 H3K4me1-marked enhancers was cloned into a STARR-seq-derived episomal reporter plasmid and electroporated into activated primary human CD4+ T cells. RNA and plasmid DNA readouts were analyzed with QuASAR-MPRA to estimate allele-specific enhancer 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
Anti-CD3/anti-CD28 activation; IL-2 (10 ng/mL) added at 48 h
The authors describe the experiment as an MPRA and analyze it with QuASAR-MPRA, but the construct is STARR-seq-derived: each 230-nucleotide allele insert is transcribed from an episomal reporter and activity is read as RNA relative to plasmid DNA. The library contains reference and alternate alleles for each tested SNP; no per-construct barcode counts or replicate-level count matrix is provided in the supplemental result workbook.
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 · 20 definitions
- variant_id
- Enhancer SNP ID for the tested variant.
- snp_no
- Source Table S1 variant number.
- enhancer_id
- Study identifier for the enhancer containing the variant.
- enhancer_region_hg19
- Enhancer interval in hg19 coordinates.
- variant_position_hg19
- Tested enhancer SNP position in hg19 coordinates.
- lead_snp_id
- RA lead GWAS SNP associated with the enhancer variant.
- lead_snp_position_hg19
- Lead SNP position in hg19 coordinates.
- ld_r_squared
- Reported R-squared linkage-disequilibrium measure between the enhancer and lead SNPs.
- log2_activity_reference
- Reported log2 RNA/plasmid-DNA activity for the reference allele.
- log2_activity_alternate
- Reported log2 RNA/plasmid-DNA activity for the alternate allele.
- mpra_log2_effect_size_ref_minus_alt
- Table S1 Log2(effect_size), calculated as reference activity minus alternate activity.
- activity_direction
- Direction implied by the effect size: reference_higher, alternate_higher, or equal.
- padj_bh
- Benjamini-Hochberg-adjusted allelic test p-value from the MPRA analysis.
- mpra_fdr_5pct_significant
- true when padj_bh is less than 0.05.
- mpra_fdr_10pct_significant
- true when padj_bh is less than 0.10.
- reported_reference_allele
- Reference base reported in the TF-binding workbook; blank when S2 has no entry for the variant.
- predicted_tf_motif_count
- Number of predicted HOCOMOCO TF motifs reported in Table S2 for the enhancer SNP.
- predicted_tf_motifs
- Semicolon-separated HOCOMOCO motif identifiers from Table S2; blank when no prediction is reported.
- pchic_target_genes_chicago_ge5
- Semicolon-separated promoter-capture Hi-C bait gene names from Table S3 with a maximum reported CHiCAGO score of at least 5 across the listed CD4+ cell types.
- eqtl_target_genes
- Semicolon-separated target genes reported in the DICE, GTEx, Walsh et al., or BRI eQTL columns of Table S4; blank when none is reported.
Quality control
The study checked RNA and plasmid-library reads with FASTQC, removed adapter and Q < 20 sequence using Trim Galore, mapped trimmed reads to the amplicon library with Bowtie2, and quantified tested sequences with featureCounts. QuASAR-MPRA supplied allelic tests and Benjamini-Hochberg correction; the published result table uses an FDR < 5% threshold for significant allelic enhancer activity. All 1,765 S1 rows passed package-level structural QC: required identifiers and coordinates were present, numeric activity/effect/padj values were finite, LD R-squared values were within [0, 1], and BH-adjusted p-values were within [0, 1]; no rows were removed.
Curation notes
This is represented as one experiment because the paper reports one common allele library and activated primary CD4+ T-cell condition; biological replicates were processed together, but replicate-level counts are not available in S1. The processed table preserves all tested post-QC variants, including non-significant results, and joins S2-S4 annotations by enhancer SNP ID. The paper reports sequencing submission SUB14216588; raw reads are intentionally omitted because the package scope excludes raw sequence files.