Evidence map›Paper›PMID 40968372›Full record

ArticleGenome biology2025

A compendium of synthetic lethal gene pairs defined by extensive combinatorial pan-cancer CRISPR screening.

Victoria Harle, Victoria Offord, Birkan Gökbağ, Lazaros Fotopoulos, Thomas Williams, Diana Alexander, Ishan Mehta, Nicola A Thompson, Rebeca Olvera-León, Stefan Peidli and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Genome biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. Article
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

18 authors.

Victoria HarleWellcome Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK.
Victoria OffordWellcome Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK.
Birkan GökbağDepartment of Biomedical Informatics, The Ohio State University, College of Medicine, Columbus, OH, 43210, USA.
Lazaros FotopoulosCentre for Gene Therapy and Regenerative Medicine, King's College London, 28Th Floor, Tower Wing, Guy's Hospital, Great Maze Pond, London, UK.
Thomas WilliamsCentre for Gene Therapy and Regenerative Medicine, King's College London, 28Th Floor, Tower Wing, Guy's Hospital, Great Maze Pond, London, UK.
Diana AlexanderWellcome Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK.
Ishan MehtaWellcome Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK.
Nicola A ThompsonWellcome Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK.
Rebeca Olvera-LeónWellcome Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK.
Stefan PeidliEuropean Molecular Biology Laboratory (EMBL), Meyerhofstr. 1 69117, Heidelberg, Germany.
Vivek IyerWellcome Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK.
Emanuel GonçalvesWellcome Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK.
Narod KebabciConway Institute and School of Computer Science, University College Dublin, Dublin, Ireland.
Barbara De KegelConway Institute and School of Computer Science, University College Dublin, Dublin, Ireland.
Joris van de HaarThe Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, Netherlands.
Lang LiDepartment of Biomedical Informatics, The Ohio State University, College of Medicine, Columbus, OH, 43210, USA.
Colm J RyanConway Institute and School of Computer Science, University College Dublin, Dublin, Ireland.
David J AdamsWellcome Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK. da1@sanger.ac.uk.

Funding

Health Research Charities Ireland 20/FFP-P/8641 and 18/CRT/6214Wellcome Trust
6 · The paper itself

Abstract

backgroundSynthetic lethal interactions are attractive therapeutic candidates as they enable selective targeting of cancer cells in which somatic alterations have disrupted one member of a synthetic lethal gene pair while leaving normal tissues untouched, thus minimising off-target toxicity. Despite this potential, the number of well-established and validated synthetic lethal gene pairs is modest.

resultsWe generate a dual-guide CRISPR/Cas9 Library and analyse 472 predicted synthetic lethal pairs in 27 cancer cell Lines from melanoma, pancreatic and lung cancer Lineages. We report a robust collection of 117 genetic interactions within and across cancer types and explore their candidacy as therapeutic targets. We show that SLC25A28 is an attractive target since its synthetic lethal paralog partner SLC25A37 is homozygously deleted pan-cancer. We generate knockout mice for Slc25a28 revealing that, except for cataracts in some mice, these animals are normal; suggesting inhibition of SLC25A28 is unlikely to be associated with profound toxicity.

conclusionsWe provide and validate an extensive collection of synthetic lethal interactions across cancer types.

Indexed as

CRISPR-Cas SystemsGenes, LethalNeoplasmsSynthetic Lethal MutationsAnimalsCell Line, TumorHumansMiceMice, KnockoutCRISPREpistasisHigh-throughput screeningSynthetic lethality

Identifiers

PMID40968372
PMCPMC12445041

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.