Circlehunter: a tool to identify extrachromosomal circular DNA from ATAC-Seq data

Abstract In cancer, extrachromosomal circular DNA (ecDNA), or megabase-pair amplified circular DNA, plays an essential role in intercellular heterogeneity and tumor cell revolution because of its non-Mendelian inheritance. We developed circlehunter ( https://github.com/suda-huanglab/circlehunter ),...

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Main Authors: Manqiu Yang, Shufan Zhang, Rong Jiang, Shaomu Chen, Moli Huang
Format: Article
Language:English
Published: Nature Publishing Group 2023-05-01
Series:Oncogenesis
Online Access:https://doi.org/10.1038/s41389-023-00476-0
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author Manqiu Yang
Shufan Zhang
Rong Jiang
Shaomu Chen
Moli Huang
author_facet Manqiu Yang
Shufan Zhang
Rong Jiang
Shaomu Chen
Moli Huang
author_sort Manqiu Yang
collection DOAJ
description Abstract In cancer, extrachromosomal circular DNA (ecDNA), or megabase-pair amplified circular DNA, plays an essential role in intercellular heterogeneity and tumor cell revolution because of its non-Mendelian inheritance. We developed circlehunter ( https://github.com/suda-huanglab/circlehunter ), a tool for identifying ecDNA from ATAC-Seq data using the enhanced chromatin accessibility of ecDNA. Using simulated data, we showed that circlehunter has an F1 score of 0.93 at 30× local depth and read lengths as short as 35 bp. Based on 1312 ecDNAs predicted from 94 publicly available datasets of ATAC-Seq assays, we found 37 oncogenes contained in these ecDNAs with amplification characteristics. In small cell lung cancer cell lines, ecDNA containing MYC leads to amplification of MYC and cis-regulates the expression of NEUROD1, resulting in an expression pattern consistent with the NEUROD1 high expression subtype and sensitive to Aurora kinase inhibitors. This showcases that circlehunter could serve as a valuable pipeline for the investigation of tumorigenesis.
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spelling doaj.art-82a703b381114e989f5b963f3a74711d2023-05-28T11:27:59ZengNature Publishing GroupOncogenesis2157-90242023-05-0112111210.1038/s41389-023-00476-0Circlehunter: a tool to identify extrachromosomal circular DNA from ATAC-Seq dataManqiu Yang0Shufan Zhang1Rong Jiang2Shaomu Chen3Moli Huang4School of Biology and Basic Medical Sciences, Soochow UniversitySchool of Biology and Basic Medical Sciences, Soochow UniversitySchool of Biology and Basic Medical Sciences, Soochow UniversityDepartment of Thoracic Surgery, The First Affiliated Hospital of Soochow UniversitySchool of Biology and Basic Medical Sciences, Soochow UniversityAbstract In cancer, extrachromosomal circular DNA (ecDNA), or megabase-pair amplified circular DNA, plays an essential role in intercellular heterogeneity and tumor cell revolution because of its non-Mendelian inheritance. We developed circlehunter ( https://github.com/suda-huanglab/circlehunter ), a tool for identifying ecDNA from ATAC-Seq data using the enhanced chromatin accessibility of ecDNA. Using simulated data, we showed that circlehunter has an F1 score of 0.93 at 30× local depth and read lengths as short as 35 bp. Based on 1312 ecDNAs predicted from 94 publicly available datasets of ATAC-Seq assays, we found 37 oncogenes contained in these ecDNAs with amplification characteristics. In small cell lung cancer cell lines, ecDNA containing MYC leads to amplification of MYC and cis-regulates the expression of NEUROD1, resulting in an expression pattern consistent with the NEUROD1 high expression subtype and sensitive to Aurora kinase inhibitors. This showcases that circlehunter could serve as a valuable pipeline for the investigation of tumorigenesis.https://doi.org/10.1038/s41389-023-00476-0
spellingShingle Manqiu Yang
Shufan Zhang
Rong Jiang
Shaomu Chen
Moli Huang
Circlehunter: a tool to identify extrachromosomal circular DNA from ATAC-Seq data
Oncogenesis
title Circlehunter: a tool to identify extrachromosomal circular DNA from ATAC-Seq data
title_full Circlehunter: a tool to identify extrachromosomal circular DNA from ATAC-Seq data
title_fullStr Circlehunter: a tool to identify extrachromosomal circular DNA from ATAC-Seq data
title_full_unstemmed Circlehunter: a tool to identify extrachromosomal circular DNA from ATAC-Seq data
title_short Circlehunter: a tool to identify extrachromosomal circular DNA from ATAC-Seq data
title_sort circlehunter a tool to identify extrachromosomal circular dna from atac seq data
url https://doi.org/10.1038/s41389-023-00476-0
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AT rongjiang circlehunteratooltoidentifyextrachromosomalcirculardnafromatacseqdata
AT shaomuchen circlehunteratooltoidentifyextrachromosomalcirculardnafromatacseqdata
AT molihuang circlehunteratooltoidentifyextrachromosomalcirculardnafromatacseqdata