Evidence map›Paper›PMID 33711017›Full record

ArticlePLoS computational biology2021

Detection of gene cis-regulatory element perturbations in single-cell transcriptomes.

Grace Hui Ting Yeo, Oscar Juez, Qing Chen, Budhaditya Banerjee, Lendy Chu, Max W Shen, May Sabry, Ive Logister, Richard I Sherwood, David K Gifford

Open access · goldAbstract read
In one paragraph

Article in PLoS computational biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact, top 98% 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

0 citing papers in PubMed, 0 citations in OpenAlex.

No citing paper in PubMed yet.

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

10 authors at 3 institutions in 2 countries.

Grace Hui Ting YeoComputer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.ORCID 0000-0002-8920-8208
Oscar JuezDivision of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
Qing ChenDivision of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
Budhaditya BanerjeeDivision of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
Lendy ChuDivision of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
Max W ShenComputer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.ORCID 0000-0002-4226-1861
May SabryHubrecht Institute, Utrecht, the Netherlands.ORCID 0000-0003-2466-4066
Ive LogisterHubrecht Institute, Utrecht, the Netherlands.
Richard I SherwoodDivision of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.ORCID 0000-0001-7427-7713
David K GiffordComputer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.ORCID 0000-0003-1709-4034
Brigham and Women's Hospital · USMassachusetts Institute of Technology · USHubrecht Institute for Developmental Biology and Stem Cell Research · NL

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
Predictive transcription factor modeling to program endodermal cell fatesK01DK101684 · NIDDK · BRIGHAM AND WOMEN'S HOSPITAL · PI SHERWOOD, RICHARD I · 2014 to 2018
$670k
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 HG008754NIDDK NIH HHS K01 DK101684NIGMS NIH HHS T32 GM087237NIH HHS R21 OD025309
6 · The paper itself

Abstract

We introduce poly-adenine CRISPR gRNA-based single-cell RNA-sequencing (pAC-Seq), a method that enables the direct observation of guide RNAs (gRNAs) in scRNA-seq. We use pAC-Seq to assess the phenotypic consequences of CRISPR/Cas9 based alterations of gene cis-regulatory regions. We show that pAC-Seq is able to detect cis-regulatory-induced alteration of target gene expression even when biallelic loss of target gene expression occurs in only ~5% of cells. This low rate of biallelic loss significantly increases the number of cells required to detect the consequences of changes to the regulatory genome, but can be ameliorated by transcript-targeted sequencing. Based on our experimental results we model the power to detect regulatory genome induced transcriptomic effects based on the rate of mono/biallelic loss, baseline gene expression, and the number of cells per target gRNA.

Indexed as

AlgorithmsAnimalsClustered Regularly Interspaced Short Palindromic RepeatsComputational BiologyCRISPR-Cas SystemsDatabases, FactualHumansMiceRegulatory Elements, TranscriptionalRNA, Guide, CRISPR-Cas SystemsSequence Analysis, RNASingle-Cell AnalysisTranscriptomeRNA, Guide, CRISPR-Cas Systems

Identifiers

PMID33711017
PMCPMC8011753
OpenAlexW3135612183

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.