Description

The MPRAVarDB track shows 242,818 variants from 18 MPRA studies compiled in the MPRAVarDB database (Wang et al., 2024). Each variant was experimentally tested in an MPRA experiment to evaluate whether it affects transcriptional regulatory activity. The database covers over 30 cell lines and 30 human diseases and traits, including neurodegenerative diseases, immune disorders, melanoma, multiple myeloma, and autoimmune diseases.

Display Conventions

Items are colored by statistical significance:

Each item shows the variant name (rsID when available, otherwise chr:pos:ref>alt), the reference and alternate alleles, the associated disease or trait, cell line, log2 fold change, p-value, and FDR.

Studies

The following table lists the 18 MPRA studies included in MPRAVarDB, with the number of tested variants, diseases/traits, cell lines, and a brief description of the variant selection.

Study Variants Disease/Trait Cell Line(s) Description
Griesemer et al., 2021 72,588 NHGRI-EBI GWAS catalog GM12878, HEK293FT, HMEC, HepG2, K562, SKNSH 3'UTR SNPs and indels in LD with GWAS catalog variants, variants under positive selection, and rare outlier expression variants from GTEx
Kircher et al., 2019 44,647 Various (18 diseases including diabetes, cancer, blood disorders, limb malformations) HEK293T, HEL92.1.7, HaCaT, HeLa, HepG2, K562, LNCaP, MIN6, NIH/3T3, Neuro-2a, SK-MEL-28, SF7996 Saturation mutagenesis of 20 disease-associated regulatory elements at single base-pair resolution
Abell et al., 2022 29,582 eQTL (no specific disease) GM12878 30,893 variants in LD with independent, common, top-ranked eQTL across 744 eGenes in the CEU cohort
Tewhey et al., 2016 27,138 eQTL (no specific disease) GM12878 32,373 variants associated with eQTLs in lymphoblastoid cell lines
Schuster et al., 2023 26,546 Prostate cancer PC3 14,497 single-nucleotide mutations enriched in oncogenic pathways and 3'UTR regulatory elements
Mouri et al., 2022 14,551 Autoimmune diseases (Crohn's, IBD, psoriasis, MS, RA, T1D, ulcerative colitis) Jurkat GWAS variants from autoimmune disease loci tested for regulatory element activity in T cells
McAfee et al., 2023 10,310 Schizophrenia HEK293s, HNPS 5,173 fine-mapped schizophrenia GWAS variants
Cooper et al., 2022 5,340 Alzheimer's disease, Progressive supranuclear palsy HEK293T 5,706 noncoding SNVs from 25 AD and 9 PSP genome-wide significant loci
Long et al., 2022 3,980 Melanoma C283T, UACC903 1,992 risk-associated variants in tight LD (r2>0.8) from 54 melanoma risk loci
Myint et al., 2020 2,158 Schizophrenia, Alzheimer's disease K562, SH-SY5Y 1,049 SZ and 30 AD variants in 64 SZ loci and 9 AD loci
Choi et al., 2020 1,664 Melanoma HEK293FT, UACC903 GWAS melanoma risk variants
Ajore et al., 2022 1,582 Multiple myeloma L363, MOLP8 1,039 variants in high LD (r2>0.8) at 23 MM risk loci
Klein et al., 2019 1,119 Osteoarthritis Saos-2 1,605 SNPs in high LD (r2>0.8) at 35 lead SNPs associated with OA via GWAS
Lu et al., 2021 1,038 Systemic lupus erythematosus GM12878, Jurkat 18,312 variants in tight LD (r2>0.8) with 578 GWAS index variants at 531 loci
Mulvey & Dougherty, 2021 275 Major depressive disorder N2A Over 1,000 SNPs from 39 neuropsychiatric GWAS loci, selected by overlap with eQTL and histone marks
Ferraro et al., 2020 150 Rare variant expression (no specific disease) GM12878 Rare variants contributing to extreme expression, allelic expression, and splicing across 49 GTEx tissues
Rao et al., 2021 88 Alcohol use disorder BLA, CE, NAC, SFC SNPs in 3'UTR of 88 genes from allele-specific expression analysis (30 AUD subjects vs 30 controls)
Ulirsch et al., 2016 62 Red blood cell traits K562, K562+GATA1 2,756 variants in strong LD with 75 sentinel variants associated with RBC traits

Methods

Data was downloaded from the MPRAVarDB web server. Variants originally mapped to hg19 (213,689 of 242,818) were lifted to hg38 using liftOver. 114 variants could not be mapped and were excluded. The remaining variants were merged with the 29,129 natively hg38-mapped variants to produce a total of 239,028 hg38 records.

Data Access

The data can be explored interactively in table format with the Table Browser or the Data Integrator and exported from there to spreadsheet or tab-sep tables. From scripts, the data can be accessed through our API, track=mpraVarDb.

For automated download and analysis, the genome annotation is stored in a bigBed file that can be downloaded from our download server. The file for this track is called mpravardb.bb. Individual regions or the whole genome annotation can be obtained using our tool bigBedToBed, which can be compiled from the source code or downloaded as a precompiled binary for your system. Instructions for downloading source code and binaries can be found here. The tool can also be used to obtain features within a given range, e.g. bigBedToBed http://hgdownload.soe.ucsc.edu/gbdb/hg38/mpra/mpravardb.bb -chrom=chr21 -start=0 -end=100000000 stdout

The original annotation source data can be downloaded from the MPRAVarDB web server.

Credits

Thanks to Tao Wang and colleagues at the University of Florida for creating and maintaining the MPRAVarDB database.

References

Wang T, Matreyek KA, Yang X. MPRAVarDB: an online database and web server for exploring regulatory effects of genetic variants using MPRA data. Bioinformatics. 2024 Apr 15;40(4):btae201. PMID: 38617248; PMC: PMC11014600