Cas9-chromatin binding information enables more accurate CRISPR off-target prediction

Ritambhara Singh, Cem Kuscu, Aaron Quinlan, Yanjun Qi, Mazhar Adli

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

The CRISPR system has become a powerful biological tool with a wide range of applications. However, improving targeting specificity and accurately predicting potential off-targets remains a significant goal. Here, we introduce a web-based CRISPR/Cas9 Off-target Prediction and Identification Tool (CROPIT) that performs improved off-target binding and cleavage site predictions. Unlike existing prediction programs that solely use DNA sequence information; CROP-IT integrates whole genome level biological information from existing Cas9 binding and cleavage data sets. Utilizing whole-genome chromatin state information from 125 human cell types further enhances its computational prediction power. Comparative analyses on experimentally validated datasets show that CROP-IT outperforms existing computational algorithms in predicting both Cas9 binding as well as cleavage sites. With a user-friendly webinterface, CROP-IT outputs scored and ranked list of potential off-targets that enables improved guide RNA design and more accurate prediction of Cas9 binding or cleavage sites.

Original languageEnglish (US)
Article numbere118
JournalNucleic acids research
Volume43
Issue number18
DOIs
StatePublished - Jan 1 2015

Fingerprint

Clustered Regularly Interspaced Short Palindromic Repeats
Chromatin
Guide RNA
Genome
Binding Sites
Datasets

All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

Cas9-chromatin binding information enables more accurate CRISPR off-target prediction. / Singh, Ritambhara; Kuscu, Cem; Quinlan, Aaron; Qi, Yanjun; Adli, Mazhar.

In: Nucleic acids research, Vol. 43, No. 18, e118, 01.01.2015.

Research output: Contribution to journalArticle

Singh, Ritambhara ; Kuscu, Cem ; Quinlan, Aaron ; Qi, Yanjun ; Adli, Mazhar. / Cas9-chromatin binding information enables more accurate CRISPR off-target prediction. In: Nucleic acids research. 2015 ; Vol. 43, No. 18.
@article{ba292238ec0c4fd597bbb78bc58ff474,
title = "Cas9-chromatin binding information enables more accurate CRISPR off-target prediction",
abstract = "The CRISPR system has become a powerful biological tool with a wide range of applications. However, improving targeting specificity and accurately predicting potential off-targets remains a significant goal. Here, we introduce a web-based CRISPR/Cas9 Off-target Prediction and Identification Tool (CROPIT) that performs improved off-target binding and cleavage site predictions. Unlike existing prediction programs that solely use DNA sequence information; CROP-IT integrates whole genome level biological information from existing Cas9 binding and cleavage data sets. Utilizing whole-genome chromatin state information from 125 human cell types further enhances its computational prediction power. Comparative analyses on experimentally validated datasets show that CROP-IT outperforms existing computational algorithms in predicting both Cas9 binding as well as cleavage sites. With a user-friendly webinterface, CROP-IT outputs scored and ranked list of potential off-targets that enables improved guide RNA design and more accurate prediction of Cas9 binding or cleavage sites.",
author = "Ritambhara Singh and Cem Kuscu and Aaron Quinlan and Yanjun Qi and Mazhar Adli",
year = "2015",
month = "1",
day = "1",
doi = "10.1093/nar/gkv575",
language = "English (US)",
volume = "43",
journal = "Nucleic Acids Research",
issn = "0305-1048",
publisher = "Oxford University Press",
number = "18",

}

TY - JOUR

T1 - Cas9-chromatin binding information enables more accurate CRISPR off-target prediction

AU - Singh, Ritambhara

AU - Kuscu, Cem

AU - Quinlan, Aaron

AU - Qi, Yanjun

AU - Adli, Mazhar

PY - 2015/1/1

Y1 - 2015/1/1

N2 - The CRISPR system has become a powerful biological tool with a wide range of applications. However, improving targeting specificity and accurately predicting potential off-targets remains a significant goal. Here, we introduce a web-based CRISPR/Cas9 Off-target Prediction and Identification Tool (CROPIT) that performs improved off-target binding and cleavage site predictions. Unlike existing prediction programs that solely use DNA sequence information; CROP-IT integrates whole genome level biological information from existing Cas9 binding and cleavage data sets. Utilizing whole-genome chromatin state information from 125 human cell types further enhances its computational prediction power. Comparative analyses on experimentally validated datasets show that CROP-IT outperforms existing computational algorithms in predicting both Cas9 binding as well as cleavage sites. With a user-friendly webinterface, CROP-IT outputs scored and ranked list of potential off-targets that enables improved guide RNA design and more accurate prediction of Cas9 binding or cleavage sites.

AB - The CRISPR system has become a powerful biological tool with a wide range of applications. However, improving targeting specificity and accurately predicting potential off-targets remains a significant goal. Here, we introduce a web-based CRISPR/Cas9 Off-target Prediction and Identification Tool (CROPIT) that performs improved off-target binding and cleavage site predictions. Unlike existing prediction programs that solely use DNA sequence information; CROP-IT integrates whole genome level biological information from existing Cas9 binding and cleavage data sets. Utilizing whole-genome chromatin state information from 125 human cell types further enhances its computational prediction power. Comparative analyses on experimentally validated datasets show that CROP-IT outperforms existing computational algorithms in predicting both Cas9 binding as well as cleavage sites. With a user-friendly webinterface, CROP-IT outputs scored and ranked list of potential off-targets that enables improved guide RNA design and more accurate prediction of Cas9 binding or cleavage sites.

UR - http://www.scopus.com/inward/record.url?scp=84983752643&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84983752643&partnerID=8YFLogxK

U2 - 10.1093/nar/gkv575

DO - 10.1093/nar/gkv575

M3 - Article

VL - 43

JO - Nucleic Acids Research

JF - Nucleic Acids Research

SN - 0305-1048

IS - 18

M1 - e118

ER -