Evidence map›Paper›PMID 33238122›Full record

ArticleCell reports2020

Comprehensive Mapping of Key Regulatory Networks that Drive Oncogene Expression.

Lin Lin, Benjamin Holmes, Max W Shen, Darnell Kammeron, Niels Geijsen, David K Gifford, Richard I Sherwood

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.0field-weighted citation impact, top 25% 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

11 citing papers in PubMed, 17 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Clinical Implications of APOBEC3-Mediated Mutagenesis in Breast Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023
    Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. The von Hippel-Lindau Cullin-RING E3 ubiquitin ligase regulates APOBEC3 cytidine deaminases.Translational research : the journal of laboratory and clinical medicine · 2021
    Article
  11. Review
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

7 authors at 4 institutions in 2 countries.

Lin LinDivision of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences, Utrecht 3584 CT, the Netherlands.
Benjamin HolmesComputer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Max W ShenComputer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Computational and Systems Biology Program, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Darnell KammeronHubrecht Institute, Royal Netherlands Academy of Arts and Sciences, Utrecht 3584 CT, the Netherlands.
Niels GeijsenHubrecht Institute, Royal Netherlands Academy of Arts and Sciences, Utrecht 3584 CT, the Netherlands; Department of Anatomy and Embryology, Leiden University Medical Center, Leiden 2300 RC, the Netherlands. Electronic address: n.geijsen@lumc.nl.
David K GiffordComputer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address: gifford@mit.edu.
Richard I SherwoodDivision of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences, Utrecht 3584 CT, the Netherlands. Electronic address: rsherwood@rics.bwh.harvard.edu.
Brigham and Women's Hospital · USMassachusetts Institute of Technology · USRoyal Netherlands Academy of Arts and Sciences · NLBroad Institute · US

Funding

Graduate Training in Computational and Systems BiologyT32GM087237 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BURGE, CHRISTOPHER B · 2009 to 2023
$4.6M
High-Throughput Native Context Mapping and Modeling of Regulatory DNAR01HG008754 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI GIFFORD, DAVID K · 2016 to 2019
$2.7M
High-throughput methods for elucidating the control of chromatin accessibilityR01HG008363 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI GIFFORD, DAVID K · 2015 to 2017
$2.3M
Distal enhancers controlling motor neuron gene expression programR01NS109217 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI WICHTERLE, HYNEK · 2019 to 2022
$2.1M
Predictive transcription factor modeling to program endodermal cell fatesK01DK101684 · NIDDK · BRIGHAM AND WOMEN'S HOSPITAL · PI SHERWOOD, RICHARD I · 2014 to 2018
$670k
Urgent Supplement: Correcting genetic disorders using predictable CRISPR/Cas9-induced exon skippingR21HG010391 · NHGRI · BRIGHAM AND WOMEN'S HOSPITAL · PI CASSA, CHRISTOPHER, SHERWOOD, RICHARD I · 2019 to 2020
$632k
Systematic unlocking of airway stem cell differentiation programR21OD025309 · OD · BRIGHAM AND WOMEN'S HOSPITAL · PI SHERWOOD, RICHARD I · 2019 to 2020
$462k
NHGRI NIH HHS R01 HG008363NHGRI NIH HHS R01 HG008754NHGRI NIH HHS R21 HG010391NIDDK NIH HHS K01 DK101684NIGMS NIH HHS T32 GM087237NIH HHS R21 OD025309NINDS NIH HHS R01 NS109217
6 · The paper itself

Abstract

Gene expression is controlled by the collective binding of transcription factors to cis-regulatory regions. Deciphering gene-centered regulatory networks is vital to understanding and controlling gene misexpression in human disease; however, systematic approaches to uncovering regulatory networks have been lacking. Here we present high-throughput interrogation of gene-centered activation networks (HIGAN), a pipeline that employs a suite of multifaceted genomic approaches to connect upstream signaling inputs, trans-acting TFs, and cis-regulatory elements. We apply HIGAN to understand the aberrant activation of the cytidine deaminase APOBEC3B, an intrinsic source of cancer hypermutation. We reveal that nuclear factor κB (NF-κB) and AP-1 pathways are the most salient trans-acting inputs, with minor roles for other inflammatory pathways. We identify a cis-regulatory architecture dominated by a major intronic enhancer that requires coordinated NF-κB and AP-1 activity with secondary inputs from distal regulatory regions. Our data demonstrate how integration of cis and trans genomic screening platforms provides a paradigm for building gene-centered regulatory networks.

Indexed as

Gene ExpressionGene Regulatory NetworksHumansOncogenesSignal TransductionAP-1 signalingCRISPR-Cas9 screeningcytidine deaminasein-cis and in-trans regulationNF-κB signaling

Identifiers

PMID33238122
PMCPMC7724632
OpenAlexW3106984292

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.