Evidence map›Paper›PMID 38283851›Full record

ArticleComputational and structural biotechnology journal2024

Combining Off-flow, a Nextflow-coded program, and whole genome sequencing reveals unintended genetic variation in CRISPR/Cas-edited iPSCs.

Carole Shum, Sang Yeon Han, Bhooma Thiruvahindrapuram, Zhuozhi Wang, Jill de Rijke, Benjamin Zhang, Maria Sundberg, Cidi Chen, Elizabeth D Buttermore, Nina Makhortova and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Computational and structural biotechnology journal, 2024. 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

13 authors.

Carole ShumThe Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
Sang Yeon HanThe Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
Bhooma ThiruvahindrapuramThe Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
Zhuozhi WangThe Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
Jill de RijkeThe Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
Benjamin ZhangThe Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
Maria SundbergDepartment of Neurology, FM Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Cidi ChenHuman Neuron Core, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Elizabeth D ButtermoreHuman Neuron Core, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Nina MakhortovaHuman Neuron Core, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Jennifer HoweThe Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
Mustafa SahinDepartment of Neurology, FM Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Stephen W SchererThe Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.

Funding

Genetic Analysis and Manipulation Core (GAEC)P50HD105351 · NICHD · BOSTON CHILDREN'S HOSPITAL · PI Hisashi Umemori · 2021 to 2026
$9.4M
NICHD NIH HHS P50 HD105351
6 · The paper itself

Abstract

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas nucleases and human induced pluripotent stem cell (iPSC) technology can reveal deep insight into the genetic and molecular bases of human biology and disease. Undesired editing outcomes, both on-target (at the edited locus) and off-target (at other genomic loci) hinder the application of CRISPR-Cas nucleases. We developed Off-flow, a Nextflow-coded bioinformatic workflow that takes a specific guide sequence and Cas protein input to call four separate off-target prediction programs (CHOPCHOP, Cas-Offinder, CRISPRitz, CRISPR-Offinder) to output a comprehensive list of predicted off-target sites. We applied it to whole genome sequencing (WGS) data to investigate the occurrence of unintended effects in human iPSCs that underwent repair or insertion of disease-related variants by homology-directed repair. Off-flow identified a 3-base-pair-substitution and a mono-allelic genomic deletion at the target loci,

Indexed as

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)Genome editingInduced pluripotent stem cells (iPSCs)Off-target detectionWhole genome sequencing (WGS)

Identifiers

PMID38283851
PMCPMC10819409

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Registered trials

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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.