ArticleGenome research2016
Massively parallel cis-regulatory analysis in the mammalian central nervous system.
Article in Genome research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
85 citing papers in PubMed, 127 citations in OpenAlex.
- Unlocking the Regulatory Genome: Interpreting the Clinical Impact of Noncoding Variants in Genetic Cardiomyopathies.Circulation. Genomic and precision medicine · 2026Review
- Insertion-Site Proximity to AAV Inverted Terminal Repeats Increases Plasmid Recombination.International journal of molecular sciences · 2026Article
- A deep learning model captures position-specific effects of plant regulatory sequences and suggests genes under complex regulation.Plant physiology · 2026Article
- Technical and biological sources of noise confound multiplexed enhancer AAV screening.Nature communications · 2026Article
- Pool-packaged AAV libraries exhibit extensive length-dependent and homology-dependent chimerism.Nature biotechnology · 2026Article
- STARR-CRAAVT: A platform to identify cell type-specific regulatory elements for next-generation gene therapy.iScience · 2026Article
- Article
- Review
- Gene regulatory activity associated with polycystic ovary syndrome revealed DENND1A-dependent testosterone production.Nature communications · 2025Article
- Identification of a robust promoter in mouse and human hepatocytes by in vivo biopanning of a barcoded AAV library.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Functional Neurogenomics to Dissect Disease Mechanisms Across Models.Annual review of genomics and human genetics · 2025Review
- Lineage-specific regulatory evolution: insights from massively parallel reporter assays.Current opinion in genetics & development · 2025Review
- Review
- Just a SNP away: The future ofCell insight · 2025Review
- AnFrontiers in genetics · 2025Article
- Review
- Decoding biology with massively parallel reporter assays and machine learning.Genes & development · 2024Review
- Decoding polygenic diseases: advances in noncoding variant prioritization and validation.Trends in cell biology · 2024Review
- Proformer: a hybrid macaron transformer model predicts expression values from promoter sequences.BMC bioinformatics · 2024Article
- Strategies for dissecting the complexity of neurodevelopmental disorders.Trends in genetics : TIG · 2024Review
25 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Cis-regulatory elements (CREs, e.g., promoters and enhancers) regulate gene expression, and variants within CREs can modulate disease risk. Next-generation sequencing has enabled the rapid generation of genomic data that predict the locations of CREs, but a bottleneck lies in functionally interpreting these data. To address this issue, massively parallel reporter assays (MPRAs) have emerged, in which barcoded reporter libraries are introduced into cells, and the resulting barcoded transcripts are quantified by next-generation sequencing. Thus far, MPRAs have been largely restricted to assaying short CREs in a limited repertoire of cultured cell types. Here, we present two advances that extend the biological relevance and applicability of MPRAs. First, we adapt exome capture technology to instead capture candidate CREs, thereby tiling across the targeted regions and markedly increasing the length of CREs that can be readily assayed. Second, we package the library into adeno-associated virus (AAV), thereby allowing delivery to target organs in vivo. As a proof of concept, we introduce a capture library of about 46,000 constructs, corresponding to roughly 3500 DNase I hypersensitive (DHS) sites, into the mouse retina by ex vivo plasmid electroporation and into the mouse cerebral cortex by in vivo AAV injection. We demonstrate tissue-specific cis-regulatory activity of DHSs and provide examples of high-resolution truncation mutation analysis for multiplex parsing of CREs. Our approach should enable massively parallel functional analysis of a wide range of CREs in any organ or species that can be infected by AAV, such as nonhuman primates and human stem cell-derived organoids.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.