ArticleNature communications2025
Massively parallel reporter assays and mouse transgenic assays provide correlated and complementary information about neuronal enhancer activity.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed.
- Non-Coding Negative Regulatory Features in Livestock Genomes: Functional Annotation and Causal Validation.Animals : an open access journal from MDPI · 2026Review
- Uniform processing and analysis of IGVF massively parallel reporter assay data with MPRAsnakeflow.Genome research · 2026Article
- Massively parallel characterization and predictive modelling of neuronal regulatory variation.bioRxiv : the preprint server for biology · 2026Article
- Autoimmune non-coding variants perturb transcription factor-cofactor complex assembly linked to enhancer activity.bioRxiv : the preprint server for biology · 2026Article
- Enhancer Dynamics for Gene Regulation in the Cardiovascular System.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- Large-scale discovery of neural enhancers for cis-regulation therapies.bioRxiv : the preprint server for biology · 2025Article
- Iterative improvement of deep learning models using synthetic regulatory genomics.Genome research · 2025Article
- Uniform processing and analysis of IGVF massively parallel reporter assay data with MPRAsnakeflow.bioRxiv : the preprint server for biology · 2025Article
- Lineage-specific regulatory evolution: insights from massively parallel reporter assays.Current opinion in genetics & development · 2025Review
- Advancing precision diagnosis in autism: Insights from large-scale genomic studies.Molecules and cells · 2025Review
- Spatial-scERA: a method for reconstructing spatial single-cell enhancer activity in multicellular organisms.Nucleic acids research · 2025Article
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- Using individual barcodes to increase quantification power of massively parallel reporter assays.BMC bioinformatics · 2025Article
- Just a SNP away: The future ofCell insight · 2025Review
- Rapid and quantitative functional interrogation of human enhancer variant activity in live mice.Nature communications · 2025Article
- AnFrontiers in genetics · 2025Article
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19 authors.
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Abstract
High-throughput massively parallel reporter assays (MPRAs) and phenotype-rich in vivo transgenic mouse assays are two potentially complementary ways to study the impact of noncoding variants associated with psychiatric diseases. Here, we investigate the utility of combining these assays. Specifically, we carry out an MPRA in induced human neurons on over 50,000 sequences derived from fetal neuronal ATAC-seq datasets and enhancers validated in mouse assays. We also test the impact of over 20,000 variants, including synthetic mutations and 167 common variants associated with psychiatric disorders. We find a strong and specific correlation between MPRA and mouse neuronal enhancer activity. Four out of five tested variants with significant MPRA effects affected neuronal enhancer activity in mouse embryos. Mouse assays also reveal pleiotropic variant effects that could not be observed in MPRA. Our work provides a catalog of functional neuronal enhancers and variant effects and highlights the effectiveness of combining MPRAs and mouse transgenic assays.
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