ArticleNature biotechnology2012
Systematic dissection and optimization of inducible enhancers in human cells using a massively parallel reporter assay.
Article in Nature biotechnology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 471 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
471 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Genetic variation in cis-regulatory domains suggests cell type-specific regulatory mechanisms in immunity.Communications biology · 2023Pooled it
- Regulatory Evolution and the Genetic Basis of Human Brain Expansion.Journal of molecular evolution · 2026Review
- Robust regulatory interplay of enhancers, facilitators, and promoters in a native chromatin context.Cell · 2026Article
- Cross-Model Uncertainty-Aware Minimal Editing of Cis-Regulatory Elements for Cell-Type-Selective Design.Genes · 2026Article
- Uniform processing and analysis of IGVF massively parallel reporter assay data with MPRAsnakeflow.Genome research · 2026Article
- The shape of fitness functions and the distribution of mutational effect sizes jointly limit adaptation by regulatory mutations.Nature ecology & evolution · 2026Article
- Genomic language model for predicting enhancers and their allele-specific activity in the human genome.Bioinformatics (Oxford, England) · 2026Article
- Bridging precision agriculture and human medicine through comparative genetics.Nature reviews. Genetics · 2026Review
- Systematic comparison of estimates of transcription factor activity by ATAC-seq and multiplexed reporter assays.Molecular systems biology · 2026Article
- DeepGeSeq: deep learning library for genomic sequence modeling and analysis.Bioinformatics (Oxford, England) · 2026Article
- Motif-Cluster: Motif driven prioritization of transcription factor binding clusters.PLoS computational biology · 2026Article
- Toward generalizable and interpretable AI in regulatory genomics.Nature genetics · 2026Review
- Locus-Scale Massively Parallel Reporter Assays.bioRxiv : the preprint server for biology · 2026Article
- Lentiviral single-cell MPRA of synthetic enhancers reveals motif affinity-based encoding of cell state specificity.Genome biology · 2026Article
- Using a modular massively parallel reporter assay to discover context-dependent regulatory activity in type 2 diabetes-linked noncoding regions.HGG advances · 2026Article
- Functional motif detection via in silico ablation using AlphaGenome.Briefings in bioinformatics · 2026Article
- Regulatory mechanisms driven by functional 3'-UTR variants in alcohol use disorder and related traits.Genome biology · 2026Article
- Expression-linked promoter selection (ELiPS) engineers short, strong ubiquitous promoters for gene therapy applications.bioRxiv : the preprint server for biology · 2026Article
- Intrinsic promoter responsiveness dictates sensitivity to transcriptional activation by enhancers.bioRxiv : the preprint server for biology · 2026Article
- Informational blueprints reveal condition-dependent gene regulatory architectures.bioRxiv : the preprint server for biology · 2026Article
411 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Commented on by
Authors and funding
13 authors.
Funding
Abstract
Learning to read and write the transcriptional regulatory code is of central importance to progress in genetic analysis and engineering. Here we describe a massively parallel reporter assay (MPRA) that facilitates the systematic dissection of transcriptional regulatory elements. In MPRA, microarray-synthesized DNA regulatory elements and unique sequence tags are cloned into plasmids to generate a library of reporter constructs. These constructs are transfected into cells and tag expression is assayed by high-throughput sequencing. We apply MPRA to compare >27,000 variants of two inducible enhancers in human cells: a synthetic cAMP-regulated enhancer and the virus-inducible interferon-β enhancer. We first show that the resulting data define accurate maps of functional transcription factor binding sites in both enhancers at single-nucleotide resolution. We then use the data to train quantitative sequence-activity models (QSAMs) of the two enhancers. We show that QSAMs from two cellular states can be combined to design enhancer variants that optimize potentially conflicting objectives, such as maximizing induced activity while minimizing basal activity.
Indexed as
Identifiers
What OpenQuestion holds
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.