Evidence map›Paper›PMID 35973998›Full record

ArticleCell death & disease2022

EPIKOL, a chromatin-focused CRISPR/Cas9-based screening platform, to identify cancer-specific epigenetic vulnerabilities.

Ozlem Yedier-Bayram, Bengul Gokbayrak, Alisan Kayabolen, Ali Cenk Aksu, Ayse Derya Cavga, Ahmet Cingöz, Ezgi Yagmur Kala, Goktug Karabiyik, Rauf Günsay, Beril Esin and 9 more

Open access · goldAbstract read
In one paragraph

Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.4field-weighted citation impact, top 19% 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

12 citing papers in PubMed, 17 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

19 authors at 3 institutions in 3 countries.

Ozlem Yedier-BayramKoç University Research Center for Translational Medicine (KUTTAM), Istanbul, Türkiye.
Bengul GokbayrakKoç University Research Center for Translational Medicine (KUTTAM), Istanbul, Türkiye.
Alisan KayabolenKoç University Research Center for Translational Medicine (KUTTAM), Istanbul, Türkiye.ORCID 0000-0001-5997-0894
Ali Cenk AksuKoç University Research Center for Translational Medicine (KUTTAM), Istanbul, Türkiye.
Ayse Derya CavgaKoç University Research Center for Translational Medicine (KUTTAM), Istanbul, Türkiye.
Ahmet CingözKoç University Research Center for Translational Medicine (KUTTAM), Istanbul, Türkiye.
Ezgi Yagmur KalaKoç University Research Center for Translational Medicine (KUTTAM), Istanbul, Türkiye.ORCID 0000-0002-0827-1767
Goktug KarabiyikKoç University Research Center for Translational Medicine (KUTTAM), Istanbul, Türkiye.
Rauf GünsayKoç University School of Medicine, Istanbul, Türkiye.
Beril EsinKoç University Research Center for Translational Medicine (KUTTAM), Istanbul, Türkiye.
Tunc MorovaKoç University School of Medicine, Istanbul, Türkiye.
Fırat UyulurKoç University Department of Computational Biology, Istanbul, Türkiye.
Hamzah SyedKoç University Research Center for Translational Medicine (KUTTAM), Istanbul, Türkiye.ORCID 0000-0001-6981-6962
Martin PhilpottBotnar Research Centre, Nuffield Department of Orthopedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.
Adam P CribbsBotnar Research Centre, Nuffield Department of Orthopedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.
Sonia H Y KungVancouver Prostate Centre, University of British Columbia, Vancouver, BC, Canada.
Nathan A LackKoç University Research Center for Translational Medicine (KUTTAM), Istanbul, Türkiye.ORCID 0000-0001-7399-5844
Tamer T OnderKoç University Research Center for Translational Medicine (KUTTAM), Istanbul, Türkiye. tonder@ku.edu.tr.ORCID 0000-0002-2372-9158
Tugba Bagci-OnderKoç University Research Center for Translational Medicine (KUTTAM), Istanbul, Türkiye. tuonder@ku.edu.tr.ORCID 0000-0003-3646-2613
Koç University · TRNuffield Orthopaedic Centre · GBUniversity of British Columbia · CA

Funding

Medical Research Council MR/V010182/1
6 · The paper itself

Abstract

Dysregulation of the epigenome due to alterations in chromatin modifier proteins commonly contribute to malignant transformation. To interrogate the roles of epigenetic modifiers in cancer cells, we generated an epigenome-wide CRISPR-Cas9 knockout library (EPIKOL) that targets a wide-range of epigenetic modifiers and their cofactors. We conducted eight screens in two different cancer types and showed that EPIKOL performs with high efficiency in terms of sgRNA distribution and depletion of essential genes. We discovered novel epigenetic modifiers that regulate triple-negative breast cancer (TNBC) and prostate cancer cell fitness. We confirmed the growth-regulatory functions of individual candidates, including SS18L2 and members of the NSL complex (KANSL2, KANSL3, KAT8) in TNBC cells. Overall, we show that EPIKOL, a focused sgRNA library targeting ~800 genes, can reveal epigenetic modifiers that are essential for cancer cell fitness under in vitro and in vivo conditions and enable the identification of novel anti-cancer targets. Due to its comprehensive epigenome-wide targets and relatively high number of sgRNAs per gene, EPIKOL will facilitate studies examining functional roles of epigenetic modifiers in a wide range of contexts, such as screens in primary cells, patient-derived xenografts as well as in vivo models.

Indexed as

CRISPR-Cas SystemsTriple Negative Breast NeoplasmsCell Line, TumorChromatinEarly Detection of CancerHumansMaleChromatin

Identifiers

PMID35973998
PMCPMC9381743
OpenAlexW4291825011

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.