The expanded MPRA library tested reference and alternate alleles of candidate multiple-myeloma risk variants in KMS11 cells. Candidate regulatory sequences were represented by 230-bp oligos, cloned into a lentiviral barcode reporter, and measured in three biological replicates by matched DNA and RNA sequencing.
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Organism
Human
Taxonomy ID
NCBITaxon:9606
Biosample
CVCL:2989
Reference genome
GRCh38
Design focus
Variant-focused
Region of interest
Not reported / not applicable
Perturbation & assay details
Basal / Untreated
The expanded library covered 23 MM risk loci and included single-base variants at LD r2 >= 0.4 with the locus lead variant. Forward and reverse reference/alternate candidate regulatory sequences were centered in 200-bp regions, synthesized as 230-bp Agilent oligos between 15-bp adapters, and amplified to add a minimal promoter and 15-bp random barcode. Inserts were cloned into the SbfI/AgeI site of pLS-SceI, amplified in E. coli, packaged as lentivirus in HEK293T cells, and used to transduce KMS11 in triplicate. Plasmid DNA and reporter cDNA were sequenced on Illumina NovaSeq; MPRAflow mapped barcodes and calculated log2 DNA/RNA ratios, and MPRAnalyze modeled CRS direction, barcode, and replicate covariates for alternate-versus-reference activity.
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 · 29 definitions
variant_id
rsID of the tested variant from Supplementary Data 9.
assayed_cell_line
Cell line corresponding to the MPRA statistics in this table.
chromosome_band
Cytogenetic chromosome band reported in SD9.
position_grch38
Variant position from SD9, interpreted on GRCh38 based on the supplied coordinates.
ld_r2
Linkage disequilibrium r2 with the MM lead variant.
ld_d
Linkage disequilibrium D value with the MM lead variant.
reference_allele
Reference allele represented in the CRS library.
alternate_allele
Alternate allele represented in the CRS library.
mm_lead_variant
MM risk-locus lead variant used for LD grouping.
chromhmm_state_kms11
ChromHMM state in KMS11 at the variant.
chromhmm_state_molp8
ChromHMM state in MOLP8 at the variant.
chromhmm_state_l363
ChromHMM state in L363 at the variant.
chromhmm_state_jjn3
ChromHMM state in JJN3 at the variant.
chromhmm_state_gm12878
GM12878 ChromHMM state from Roadmap data.
chromhmm_state_bmsc
Bone-marrow mesenchymal stem-cell ChromHMM state from Roadmap data.
micro_c_loop_genes_l363
Genes contacted by the variant region in L363 Micro-C data.
micro_c_loop_genes_kms11
Genes contacted by the variant region in KMS11 Micro-C data.
micro_c_to_tss_gene
Gene TSS linked to the variant region in the SD9 annotation.
annotation_type
SD9 regulatory annotation such as potential enhancer, enhancer with looping, or TSS.
mm_risk_allele
MM GWAS risk allele reported in SD9.
mm_gwas_odds_ratio
MM GWAS meta-analysis odds ratio reported in SD9.
mm_gwas_p_value
MM GWAS meta-analysis P-value reported in SD9.
mpra_log2fc_alt_vs_ref
New-MPRA log2 fold-change for alternate versus reference activity; positive values indicate higher alternate-allele transcription.
mpra_p_value
New-MPRA allele-activity P-value for the cell line.
Derived direction of alternate-allele activity relative to reference.
source_supplementary_sheet
Source sheet in the Nature supplementary workbook.
Quality control
The authors used MPRAflow barcode-to-CRS mapping and count processing followed by MPRAnalyze alternate-versus-reference modeling with CRS direction, barcode, and replicate covariates. Their biological nomination rule was FDR < 0.05 in at least two of the three new-MPRA cell lines and absolute log2 fold-change > 0.2 in at least one cell line; this rule is retained as table flags rather than used to remove measured null variants. Package QC retained only SD9 rows with a non-missing variant ID and finite complete KMS11 log2 fold-change, P-value, and FDR values, with P-value and FDR constrained to [0,1]. This retained 781 of 2,133 SD9 annotation rows; the remaining rows had missing/NA KMS11 assay statistics.
Curation notes
This child represents the new KMS11 arm of the expanded MPRA, not the previously published L363/MOLP8 dataset also shown in SD9. The SD9 coordinate for rs34562254 (chr17:16939677) matches GRCh38; the paper separately reports hg19/GRCh37 alignment for ChIPmentation annotations. No oligo sequences or raw KMS11 reads were publicly supplied in the source workbook, so the table contains the published variant-level MPRA statistics and annotations.