TY - JOUR

T1 - CReSIL

T2 - accurate identification of extrachromosomal circular DNA from long-read sequences

AU - Wanchai, Visanu

AU - Jenjaroenpun, Piroon

AU - Leangapichart, Thongpan

AU - Arrey, Gerard

AU - Burnham, Charles M.

AU - Tümmler, Maria C.

AU - Delgado-Calle, Jesus

AU - Regenberg, Birgitte

AU - Nookaew, Intawat

PY - 2022

Y1 - 2022

N2 - Extrachromosomal circular DNA (eccDNA) of chromosomal origin is found in many eukaryotic species and cell types, including cancer, where eccDNAs with oncogenes drive tumorigenesis. Most studies of eccDNA employ short-read sequencing for their identification. However, short-read sequencing cannot resolve the complexity of genomic repeats, which can lead to missing eccDNA products. Long-read sequencing technologies provide an alternative to constructing complete eccDNA maps. We present a software suite, Construction-based Rolling-circle-amplification for eccDNA Sequence Identification and Location (CReSIL), to identify and characterize eccDNA from long-read sequences. CReSIL's performance in identifying eccDNA, with a minimum F1 score of 0.98, is superior to the other bioinformatic tools based on simulated data. CReSIL provides many useful features for genomic annotation, which can be used to infer eccDNA function and Circos visualization for eccDNA architecture investigation. We demonstrated CReSIL's capability in several long-read sequencing datasets, including datasets enriched for eccDNA and whole genome datasets from cells containing large eccDNA products. In conclusion, the CReSIL suite software is a versatile tool for investigating complex and simple eccDNA in eukaryotic cells.

AB - Extrachromosomal circular DNA (eccDNA) of chromosomal origin is found in many eukaryotic species and cell types, including cancer, where eccDNAs with oncogenes drive tumorigenesis. Most studies of eccDNA employ short-read sequencing for their identification. However, short-read sequencing cannot resolve the complexity of genomic repeats, which can lead to missing eccDNA products. Long-read sequencing technologies provide an alternative to constructing complete eccDNA maps. We present a software suite, Construction-based Rolling-circle-amplification for eccDNA Sequence Identification and Location (CReSIL), to identify and characterize eccDNA from long-read sequences. CReSIL's performance in identifying eccDNA, with a minimum F1 score of 0.98, is superior to the other bioinformatic tools based on simulated data. CReSIL provides many useful features for genomic annotation, which can be used to infer eccDNA function and Circos visualization for eccDNA architecture investigation. We demonstrated CReSIL's capability in several long-read sequencing datasets, including datasets enriched for eccDNA and whole genome datasets from cells containing large eccDNA products. In conclusion, the CReSIL suite software is a versatile tool for investigating complex and simple eccDNA in eukaryotic cells.

KW - CRESIL

KW - eccDNA

KW - long-read sequence

KW - bioinformatic tool

KW - AMPLIFICATION

KW - MICRODNAS

KW - ELEMENT

U2 - 10.1093/bib/bbac422

DO - 10.1093/bib/bbac422

M3 - Journal article

C2 - 36198068

VL - 23

JO - Briefings in Bioinformatics

JF - Briefings in Bioinformatics

SN - 1467-5463

IS - 6

M1 - bbac422

ER -