Biology subjects

Chung, O.

Publications and source records attributed to Chung, O..

9 recordsLinked to original sources

bioRxiv2025

BRCA1-A and LIG4 complexes mediate ecDNA biogenesis and cancer drug resistance

Extrachromosomal circular DNA (ecDNA) are commonly produced within the nucleus to drive genome dynamics and heterogeneity, enabling cancer cell evolution and adaptation. However, the mechanisms underlying ecDNA biogenesis remain poorly understood. Here using genome-wide CRISPR screening in human cells, we identified the BRCA1-A and the LIG4 complexes mediate ecDNA production. Following DNA fragmentation, the upstream BRCA1-A complex protects DNA ends from excessive resection, promoting end-joining for circularization. Conversely, the MRN complex, which mediates end resection and thus antagonizes the BRCA1-A complex, suppresses ecDNA formation. Downstream, LIG4 conservatively catalyzes ecDNA production in Drosophila and mammals, with patient tumor ecDNA harboring junctions marked by LIG4 activity. Notably, disrupting LIG4 or BRCA1-A in cancer cells impairs ecDNA-mediated adaptation, hindering resistance to both chemotherapy and targeted therapies. Together, our study reveals the roles of the LIG4 and BRCA1-A complexes in ecDNA biogenesis, and uncovers new therapeutic targets to block ecDNA-mediated adaptation for cancer treatment.

cancer biology↗

bioRxiv2022

Retrotransposons hijack alt-EJ DNA repair process for mobilization and eccDNA biogenesis

Parasitic retrotransposons populate in the genome to rewrite the hosts genetic code. How retrotransposons use the host factors to achieve their propagation remains largely unclear. Here we report retrotransposons hijack the alternative end-joining (alt-EJ) DNA repair process to accomplish mobilization cycle. We applied Nanopore sequencing to examine the fates of replicated retrotransposon DNA, and found that only 10% of them achieve integration, while 90% exist as extrachromosomal circular DNA (eccDNA). Using eccDNA production as a readout, further genetic screens identified factors from alt-EJ as essential for retrotransposon replication. alt-EJ drives the 2nd-strand synthesis of the retrotransposon DNA via a circularization process, thus is necessitated for eccDNA production and integrations. Our study reveals a conserved function of alt-EJ in promoting selfish element propagation, which potentially causes disease or drives evolution.

cell biology↗

bioRxiv2020

Comparative analysis of seven short-reads sequencing platforms using the Korean Reference Genome: MGI and Illumina sequencing benchmark for whole-genome sequencing

BackgroundMGISEQ-T7 is a new whole-genome sequencer developed by Complete Genomics and MGI utilizing DNA nanoball and combinatorial probe anchor synthesis technologies for generating short reads at a very large scale - up to 60 human genomes per day. However, it has not been objectively and systematically compared against Illumina short-read sequencers. FindingsBy using the same KOREF sample, the Korean Reference Genome, we have compared seven sequencing platforms including BGISEQ-500, MGISEQ-T7, HiSeq2000, HiSeq2500, HiSeq4000, HiSeqX10, and NovaSeq6000. We measured sequencing quality by comparing sequencing statistics (base quality, duplication rate, and random error rate), mapping statistics (mapping rate, depth distribution, and %GC coverage), and variant statistics (transition/transversion ratio, dbSNP annotation rate, and concordance rate with SNP genotyping chip) across the seven sequencing platforms. We found that MGI platforms showed a higher concordance rate of SNP genotyping than HiSeq2000 and HiSeq4000. The similarity matrix of variant calls confirmed that the two MGI platforms have the most similar characteristics to the HiSeq2500 platform. ConclusionsOverall, MGI and Illumina sequencing platforms showed comparable levels of sequencing quality, uniformity of coverage, %GC coverage, and variant accuracy, thus we conclude that the MGI platforms can be used for a wide range of genomics research fields at approximately half the cost of the Illumina platforms.

bioinformatics↗

bioRxiv2019

Raptor genomes reveal evolutionary signatures of predatory and nocturnal lifestyles

BackgroundBirds of prey (raptors) are dominant apex predators in terrestrial communities, with hawks (Accipitriformes) and falcons (Falconiformes) hunting by day, and owls (Strigiformes) hunting by night.\n\nResultsHere, we report new genomes and transcriptomes for 20 species of birds, including 16 species of birds of prey, and high-quality reference genomes for the Eurasian eagle-owl (Bubo bubo), oriental scops-owl (Otus sunia), eastern buzzard (Buteo japonicus), and common kestrel (Falco tinnunculus). Our extensive genomic analysis and comparisons with non-raptor genomes identified common molecular signatures that underpin anatomical structure and sensory, muscle, circulatory, and respiratory systems related to a predatory lifestyle. Compared with diurnal birds, owls exhibit striking adaptations to the nocturnal environment, including functional trade-offs in the sensory systems (e.g., loss of color vision genes and selection for enhancement of nocturnal vision and other sensory systems) that are probably convergent with other nocturnal avian orders. Additionally, we found that a suite of genes associated with vision and circadian rhythm were differentially expressed between nocturnal and diurnal raptors, indicating adaptive expression change during the transition to nocturnality.\n\nConclusionsOverall, raptor genomes showed genomic signatures associated with the origin and maintenance of several specialized physiological and morphological features essential to be apex predators.

genomics↗

bioRxiv2018

Genomic perspectives on adaptation and conservation in the endangered long-tailed goral (Naemorhedus caudatus).

Native to the mountains of East Asia, the long-tailed goral (Naemorhedus caudatus) is a vulnerable wild ungulate in the tribe Caprini. To understand key conservation issues related to fragmentation and subsequent endangerment of this montane species, we sequenced and analyzed the genome of a long-tailed goral to explore historical demography, contemporary levels of genetic diversity, and potential immune response. When compared to ten additional mammalian reference genomes, we identified 357 positively selected genes (PSGs) in the long-tailed goral and 364 PSGs in the Caprini lineage. Gene Ontology analyses showed statistical enrichment in biological processes related to immune function and in genes and pathways related to blood coagulation. We also identified low levels of heterozygosity (0.00114) in the long-tailed goral along with decreases in population size relative to other species of Caprini. Finally, we provide evidence for positive selection on the muscle development gene myostatin (MSTN) in the Caprini lineage, which may have increased the muscle development and climbing ability in the caprine common ancestor. Low effective population size and decreased heterozygosity of the long-tailed goral raise conservation concern about the effects of habitat fragmentation, over harvest, and inbreeding on this vulnerable species.

bioinformatics↗

bioRxiv2018

The jellyfish genome sheds light on the early evolution of active predation

BackgroundUnique among cnidarians, jellyfish have remarkable morphological and biochemical innovations that allow them to actively hunt in the water column. One of the first animals to become free-swimming, jellyfish employ pulsed jet propulsion and venomous tentacles to capture prey.\n\nResultsTo understand these key innovations, we sequenced the genome of the giant Nomuras jellyfish (Nemopilema nomurai), the transcriptomes of its bell and tentacles, and transcriptomes across tissues and developmental stages of the Sanderia malayensis jellyfish. Analyses of Nemopilema and other cnidarian genomes revealed adaptations associated with swimming, marked by codon bias in muscle contraction and expansion of neurotransmitter genes, along with expanded Myosin type II family and venom domains; possibly contributing to jellyfish mobility and active predation. We also identified gene family expansions of Wnt and posterior Hox genes, and discovered the important role of retinoic acid signaling in this ancient lineage of metazoans, which together may be related to the unique jellyfish body plan (medusa formation).\n\nConclusionsTaken together, the jellyfish genome and transcriptomes genetically confirm their unique morphological and physiological traits that have combined to make these animals one of the worlds earliest and most successful multi-cellular predators.

genomics↗

bioRxiv2017

A whole genome analysis of the red-crowned crane provides insight into avian longevity

The red-crowned crane (Grus japonensis) is an endangered and large-bodied crane native to East Asia. It is a traditional symbol of longevity and its long lifespan has been confirmed both in captivity and in the wild. Lifespan in birds is positively correlated with body size and negatively correlated with metabolic rate; although the genetic mechanisms for the red-crowned cranes long lifespan have not previously been investigated. Using whole genome sequencing and comparative evolutionary analyses against the grey-crowned crane and other avian genomes, we identified candidate genes that are correlated with longevity. Included among these are positively selected genes with known associations with longevity in metabolism and immunity pathways (NDUFA5, NDUFA8, NUDT12 IL9R, SOD3, NUDT12, PNLIP, CTH, and RPA1). Our analyses provide genetic evidence for low metabolic rate and longevity, accompanied by possible convergent adaptation signatures among distantly related large and long-lived birds. Finally, we identified low genetic diversity in the red-crowned crane, consistent with its listing as an endangered species, and we hope this genome will provide a useful genetic resource for future conservation studies of this rare and iconic species.

bioinformatics↗

bioRxiv2017

KoVariome: Korean National Standard Reference Variome database of whole genomes with comprehensive SNV, indel, CNV, and SV analyses

High-coverage whole-genome sequencing data of a single ethnicity can provide a useful catalogue of population-specific genetic variations. Herein, we report a comprehensive analysis of the Korean population, and present the Korean National Standard Reference Variome (KoVariome). As a part of the Korean Personal Genome Project (KPGP), we constructed the KoVariome database using 5.5 terabases of whole genome sequence data from 50 healthy Korean individuals with an average coverage depth of 31x. In total, KoVariome includes 12.7M single-nucleotide variants (SNVs), 1.7M short insertions and deletions (indels), 4K structural variations (SVs), and 3.6K copy number variations (CNVs). Among them, 2.4M (19%) SNVs and 0.4M (24%) indels were identified as novel. We also discovered selective enrichment of 3.8M SNVs and 0.5M indels in Korean individuals, which were used to filter out 1,271 coding-SNVs not originally removed from the 1,000 Genomes Project data when prioritizing disease-causing variants. CNV analyses revealed gene losses related to bone mineral densities and duplicated genes involved in brain development and fat reduction. Finally, KoVariome health records were used to identify novel disease-causing variants in the Korean population, demonstrating the value of high-quality ethnic variation databases for the accurate interpretation of individual genomes and the precise characterization of genetic variations.

genomics↗

bioRxiv2017

Myotis rufoniger Genome Sequence and Analyses: M. rufoniger’s Genomic Feature and the Decreasing Effective Population Size of Myotis Bats

Myotis rufoniger is a vesper bat in the genus Myotis. Here we report the whole genome sequence and analyses of the M. rufoniger. We generated 124 Gb of short-read DNA sequences with an estimated genome size of 1.88 Gb at a sequencing depth of 66x fold. The sequences were aligned to M. brandtii bat reference genome at a mapping rate of 96.50% covering 95.71% coding sequence region at 10x coverage. The divergence time of Myotis bat family is estimated to be 11.5 million years, and the divergence time between M. rufoniger and its closest species M. davidii is estimated to be 10.4 million years. We found 1,239 function-altering M. rufoniger specific amino acid sequences from 929 genes compared to other Myotis bat and mammalian genomes. The functional enrichment test of the 929 genes detected amino acid changes in melanin associated DCT, SLC45A2, TYRP1, and OCA2 genes possibly responsible for the M. rufonigers red fur color and a general coloration in Myotis. N6AMT1 gene, associated with arsenic resistance, showed a high degree of function alteration in M. rufoniger. We further confirmed that M. rufoniger also has bat-specific sequences within FSHB, GHR, IGF1R, TP53, MDM2, SLC45A2, RGS7BP, RHO, OPN1SW, and CNGB3 genes that have already been published to be related to bats reproduction, lifespan, flight, low vision, and echolocation. Additionally, our demographic history analysis found that the effective population size of Myotis clade has been consistently decreasing since [~]30k years ago. M. rufonigers effective population size was the lowest in Myotis bats, confirming its relatively low genetic diversity.

genomics↗