Evidence map›Paper›PMID 38308274›Full record

ArticleGenome biology2024

Mapping the functional impact of non-coding regulatory elements in primary T cells through single-cell CRISPR screens.

Celia Alda-Catalinas, Ximena Ibarra-Soria, Christina Flouri, Jorge Esparza Gordillo, Diana Cousminer, Anna Hutchinson, Bin Sun, William Pembroke, Sebastian Ullrich, Adam Krejci and 6 more

Open access · goldAbstract read
In one paragraph

Article in Genome biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
3.0field-weighted citation impact, top 9% 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

13 citing papers in PubMed, 13 citations in OpenAlex.

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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

16 authors at 1 institution in 1 country.

Celia Alda-Catalinas *Genomic Sciences, GSK, Stevenage, UK.
Ximena Ibarra-Soria *Genomic Sciences, GSK, Stevenage, UK.
Christina FlouriGenomic Sciences, GSK, Stevenage, UK.
Jorge Esparza GordilloGenomic Sciences, GSK, Stevenage, UK.
Diana CousminerGenomic Sciences, GSK, Collegeville, PA, USA.
Anna HutchinsonGenomic Sciences, GSK, Stevenage, UK.
Bin SunGenomic Sciences, GSK, Stevenage, UK.
William PembrokeGenomic Sciences, GSK, Stevenage, UK.
Sebastian UllrichGenomic Sciences, GSK, Stevenage, UK.
Adam KrejciMyllia Biotechnology, Vienna, Austria.
Adrian CortesGenomic Sciences, GSK, Stevenage, UK.
Alison AcevedoGenomic Sciences, GSK, Stevenage, UK.
Sunir MallaGenomic Sciences, GSK, Stevenage, UK.
Carl FishwickGenomic Sciences, GSK, Stevenage, UK.
Gerard DrewesGenomic Sciences, GSK, Stevenage, UK.
Radu RapiteanuGenomic Sciences, GSK, Stevenage, UK. radu.a.rapiteanu@gsk.com.ORCID 0000-0002-6900-3053
Age UK · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundDrug targets with genetic evidence are expected to increase clinical success by at least twofold. Yet, translating disease-associated genetic variants into functional knowledge remains a fundamental challenge of drug discovery. A key issue is that the vast majority of complex disease associations cannot be cleanly mapped to a gene. Immune disease-associated variants are enriched within regulatory elements found in T-cell-specific open chromatin regions.

resultsTo identify genes and molecular programs modulated by these regulatory elements, we develop a CRISPRi-based single-cell functional screening approach in primary human T cells. Our pipeline enables the interrogation of transcriptomic changes induced by the perturbation of regulatory elements at scale. We first optimize an efficient CRISPRi protocol in primary CD4

conclusionsWe describe "primary T cell crisprQTL" - a scalable, single-cell functional genomics approach for mapping regulatory elements to genes in primary human T cells. We show how this framework can facilitate the interrogation of immune disease GWAS hits and propose that the combination of experimental and QTL-based techniques is likely to address the variant-to-function problem.

Indexed as

Clustered Regularly Interspaced Short Palindromic RepeatsImmune System DiseasesChromatinGenome-Wide Association StudyHumansPolymorphism, Single NucleotideRegulatory Sequences, Nucleic AcidT-LymphocytesChromatinCRISPRcrisprQTLCROPseqEnhancerGWASRegulatory elementscRNA-seqT cellsVariant to function

Identifiers

PMID38308274
PMCPMC10835965
OpenAlexW4391474387

What OpenQuestion holds

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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.