-The MPRAs super track contains tracks with results from -Massively Parallel Reporter Assays (MPRA), high-throughput experimental methods -that test thousands of genetic variants for their effects on gene regulation. +Massively Parallel Reporter Assays (MPRAs) are high-throughput experimental methods +that test thousands of DNA sequences or genetic variants for their effects on gene +regulation. They work by linking candidate regulatory sequences to reporter genes +and measuring transcriptional output using sequencing.
- --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. +This track collection brings together results from two MPRA databases, one for the complete sequence fragments, +one for the variants in selected fragments:
--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. -
- --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 | -
-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.
-
-The raw data can be explored interactively with the
-Table Browser or the
-Data Integrator.
-The data can also be accessed from the command line using
-bigBedToBed.
+See the individual subtrack documentation pages linked above for detailed information
+on how to download and intersect the annotations.
-Thanks to Tao Wang and colleagues at the University of Florida for creating and -maintaining the MPRAVarDB database. +Thanks to Tao Wang and colleagues at the University of Florida for +MPRAVarDB, +and to Varda Singhal and the +Ahituv Lab +at the University of California San Francisco for +MPRA Base.
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
+ + ++Zhao J, Baltoumas FA, Konnaris MA, Mouratidis I, Liu Z, Sims J, Agarwal V, Pavlopoulos GA, +Georgakopoulos-Soares I, Ahituv N. + +MPRAbase: A Massively Parallel Reporter Assay Database. +bioRxiv. 2023 Nov 22;. +PMID: 38045264; PMC: PMC10690217 +
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