Evidence map›Paper›PMID 30568279›Full record

ArticleNature communications2018

High-resolution genome-wide functional dissection of transcriptional regulatory regions and nucleotides in human.

Xinchen Wang, Liang He, Sarah M Goggin, Alham Saadat, Li Wang, Nasa Sinnott-Armstrong, Melina Claussnitzer, Manolis Kellis

Open access · goldAbstract readEvaluation Study
In one paragraph

Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.

0numbers the graph read from it
0cells of the map it votes in
91citing papers in PubMed
7.3field-weighted citation impact, top 2% of its field
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

91 citing papers in PubMed, 186 citations in OpenAlex.

  1. Article
  2. Enhancer hubs govern chromatin topology and Th17 cell identity.bioRxiv : the preprint server for biology · 2026
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  17. AnFrontiers in genetics · 2025
    Article
  18. Article
  19. Article
  20. An autoimmune transcriptional circuit drives FOXP3Science translational medicine · 2024
    Article

31 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 1 institution in 2 countries.

Xinchen WangDepartment of Biology, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.ORCID http://orcid.org/0000-0002-5198-6581
Liang HeBroad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Sarah M GogginBroad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Alham SaadatBroad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Li WangBroad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Nasa Sinnott-ArmstrongBroad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Melina ClaussnitzerBroad Institute of MIT and Harvard, Cambridge, MA, 02142, USA. melina@broadinstitute.org.
Manolis KellisBroad Institute of MIT and Harvard, Cambridge, MA, 02142, USA. manoli@mit.edu.ORCID http://orcid.org/0000-0001-7113-9630
Broad Institute · US

Funding

Powering whole genome sequence-based genetic discovery for common human diseases- Extended 2021-2022.U01HG009088 · NHGRI · HARVARD SCHOOL OF PUBLIC HEALTH · PI LIN, XIHONG, NEALE, BENJAMIN MICHAEL · 2016 to 2021
$5.1M
Epigenomic variation atlas across human tissues and individuals in GTExU01HG007610 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI KELLIS, MANOLIS · 2014 to 2016
$3.0M
Interpreting non-coding variants using epigenomics, regulatory models, & validation experimentsR01HG008155 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI KELLIS, MANOLIS · 2015 to 2017
$2.3M
Comparative analysis and regulatory architecture of epigenomics datasetsR01GM113708 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI KELLIS, MANOLIS · 2015 to 2017
$852k
NHGRI NIH HHS R01 HG008155NHGRI NIH HHS U01 HG007610NHGRI NIH HHS U01 HG009088NIGMS NIH HHS R01 GM113708NIH HHS R01 GM113708NIH HHS R01 HG008155NIH HHS U01 HG007610
6 · The paper itself

Abstract

Genome-wide epigenomic maps have revealed millions of putative enhancers and promoters, but experimental validation of their function and high-resolution dissection of their driver nucleotides remain limited. Here, we present HiDRA (High-resolution Dissection of Regulatory Activity), a combined experimental and computational method for high-resolution genome-wide testing and dissection of putative regulatory regions. We test ~7 million accessible DNA fragments in a single experiment, by coupling accessible chromatin extraction with self-transcribing episomal reporters (ATAC-STARR-seq). By design, fragments are highly overlapping in densely-sampled accessible regions, enabling us to pinpoint driver regulatory nucleotides by exploiting differences in activity between partially-overlapping fragments using a machine learning model (SHARPR-RE). In GM12878 lymphoblastoid cells, we find ~65,000 regions showing enhancer function, and pinpoint ~13,000 high-resolution driver elements. These are enriched for regulatory motifs, evolutionarily-conserved nucleotides, and disease-associated genetic variants from genome-wide association studies. Overall, HiDRA provides a high-throughput, high-resolution approach for dissecting regulatory regions and driver nucleotides.

Indexed as

Gene Expression RegulationGenetic TechniquesGenome, HumanRegulatory Sequences, Nucleic AcidGenome-Wide Association StudyHumansPolymorphism, Single Nucleotide

Identifiers

PMID30568279
PMCPMC6300699
OpenAlexW2903823332

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.