Identification of reactive CpGs and RNA expression in early COVID-19 through cis-eQTM analysis reflecting disease severity and recovery.

Multi-omics analyses of severe COVID-19 cases are crucial in deciphering the complex interplay between genetic and epigenetic factors. Here, we present an analysis of Expression Quantitative Trait Methylation (eQTM) to investigate the complex interplay of methylation and gene expression pattern during the acute phase of severe COVID-19. We identified 16 differentially expressed genes and 30 nearby differentially methylated CpG sites.

Dokdo sea lion Zalophus japonicus genome reveals its evolutionary trajectory before extinction.

Background: The Dokdo sea lion (Zalophus japonicus), commonly referred to as Gangchi in Korea and the Japanese sea lion internationally, was endemic to the Northwest Pacific before its extinction in the 1950s. However, its origins, speciation, and genetic diversity remain poorly understood.

Results: To address this, we sequenced DNA from 16 Z.

Development of an MHC imputation panel highlights independent contributions of HLA amino acid residues and C4 copy number variations to SLE risk.

Objectives: Systemic lupus erythematosus (SLE) is a complex autoimmune disease strongly associated with the major histocompatibility complex (MHC) region, but precisely pinpointing the risk variants remains challenging. This study aimed to comprehensively profile SLE-driving variants using a newly developed East Asian MHC imputation reference panel, capable of simultaneously imputing diverse MHC variants, including multilevel human leukocyte antigen (HLA) variants and copy number variations (CNVs) of C4 elements, such as C4A, C4B, and human endogenous retrovirus (HERV).

Methods: Using the whole-genome-sequencing (WGS) data from ∼2000 Korean samples, we genotyped and phased MHC variants, including HLA variants and C4-related CNVs, to construct an MHC reference panel.

Dynamic and reversible transcriptomic age shifts induced by COVID-19 in Korean whole blood.

We developed the first genome-wide transcriptomic clock specific to Korean ethnicity to predict chronological age using whole blood samples from 440 healthy individuals. Our analysis revealed profound age acceleration - up to 21.31 years - during homeostatic disruption in COVID-19 patients, which reverted to baseline upon recovery.

Epigenetic Modulation of Vascular Smooth Muscle Cell Phenotype Switching in Early-Onset Acute Myocardial Infarction.

Background: The epigenetic mechanisms underlying early-onset acute myocardial infarction (AMI) remain insufficiently characterized. The present study aims to elucidate the pathophysiology of early-onset AMI by investigating its epigenetic features as molecular indicators.

Methods: A comparative differential methylation analysis was performed on whole blood samples from 298 patients with early-onset AMI with clinical follow-up and 247 controls using targeted bisulfite sequencing.

Identification of 17 novel epigenetic biomarkers associated with anxiety disorders using differential methylation analysis followed by machine learning-based validation.

Background: The changes in DNA methylation patterns may reflect both physical and mental well-being, the latter being a relatively unexplored avenue in terms of clinical utility for psychiatric disorders. In this study, our objective was to identify the methylation-based biomarkers for anxiety disorders and subsequently validate their reliability.

Methods: A comparative differential methylation analysis was performed on whole blood samples from 94 anxiety disorder patients and 296 control samples using targeted bisulfite sequencing.

Quantification method of ctDNA using cell-free DNA methylation profile for noninvasive screening and monitoring of colon cancer.

Background: Colon cancer ranks as the second most lethal form of cancer globally. In recent years, there has been active investigation into using the methylation profile of circulating tumor DNA (ctDNA), derived from blood, as a promising indicator for diagnosing and monitoring colon cancer.

Results: We propose a liquid biopsy-based epigenetic method developed by utilizing 49 patients and 260 healthy controls methylation profile data to screen and monitor colon cancer.

Comprehensive multiomics analysis reveals distinct differences between pediatric choroid plexus papilloma and carcinoma.

Choroid plexus tumors (CPTs) are intraventricular tumors derived from the choroid plexus epithelium and occur frequently in children. The aim of this study was to investigate the genomic and epigenomic characteristics of CPT and identify the differences between choroid plexus papilloma (CPP) and choroid plexus carcinoma (CPC). We conducted multiomics analyses of 20 CPT patients including CPP and CPC.

Korea4K: whole genome sequences of 4,157 Koreans with 107 phenotypes derived from extensive health check-ups.

Background: Phenome-wide association studies (PheWASs) have been conducted on Asian populations, including Koreans, but many were based on chip or exome genotyping data. Such studies have limitations regarding whole genome-wide association analysis, making it crucial to have genome-to-phenome association information with the largest possible whole genome and matched phenome data to conduct further population-genome studies and develop health care services based on population genomics.

Results: Here, we present 4,157 whole genome sequences (Korea4K) coupled with 107 health check-up parameters as the largest genomic resource of the Korean Genome Project.

Conservation implications of elucidating the Korean wolf taxonomic ambiguity through whole-genome sequencing.

The taxonomic status of the now likely extirpated Korean Peninsula wolf has been extensively debated, with some arguing it represents an independent wolf lineage, . To investigate the Korean wolf's genetic affiliations and taxonomic status, we sequenced and analysed the genomes of a Korean wolf dated to the beginning of the 20th century, and a captive wolf originally from the Pyongyang Central Zoo. Our results indicated that the Korean wolf bears similar genetic ancestry to other regional East Asian populations, therefore suggesting it is not a distinct taxonomic lineage.

Identification and validation of six acute myocardial infarction-associated variants, including a novel prognostic marker for cardiac mortality.

Background: Acute myocardial infarction (AMI) is one of the leading causes of death worldwide, and approximately half of AMI-related deaths occur before the affected individual reaches the hospital. The present study aimed to identify and validate genetic variants associated with AMI and their role as prognostic markers.

Materials And Methods: We conducted a replication study of 29 previously identified novel loci containing 85 genetic variants associated with early-onset AMI using a new independent set of 2,920 Koreans [88 patients with early- and 1,085 patients with late-onset AMI, who underwent percutaneous coronary intervention (PCI), and 1,747 healthy controls].

Germline DNA-Repair Genes and HOXB13 Mutations in Korean Men with Metastatic Prostate Cancer: Data from a Large Korean Cohort.

Purpose: Germline mutations in DNA damage repair (DDR) genes such as have been associated with prostate cancer (PC) risk but has not been thoroughly evaluated for metastatic prostate cancer (mPC) in Asian men. This study attempts to evaluate frequency of DDR mutations in the largest cohort of Koreans.

Materials And Methods: We recruited 340 patients with mPC unselected for family history of cancer and compared to 495 controls.

LT1, an ONT long-read-based assembly scaffolded with Hi-C data and polished with short reads.

We present LT1, the first high-quality human reference genome from the Baltic States. LT1 is a female human reference genome assembly, constructed using 57× nanopore long reads and polished using 47× short paired-end reads. We utilized 72 GB of Hi-C chromosomal mapping data for scaffolding, to maximize assembly contiguity and accuracy.

A database of 5305 healthy Korean individuals reveals genetic and clinical implications for an East Asian population.

Despite substantial advances in disease genetics, studies to date have largely focused on individuals of European descent. This limits further discoveries of novel functional genetic variants in other ethnic groups. To alleviate the paucity of East Asian population genome resources, we established the Korean Variant Archive 2 (KOVA 2), which is composed of 1896 whole-genome sequences and 3409 whole-exome sequences from healthy individuals of Korean ethnicity.

Northeastern Asian and Jomon-related genetic structure in the Three Kingdoms period of Gimhae, Korea.

The genetic history of prehistoric and protohistoric Korean populations is not well understood because only a small number of ancient genomes are available. Here, we report the first paleogenomic data from the Korean Three Kingdoms period, a crucial point in the cultural and historic formation of Korea. These data comprise eight shotgun-sequenced genomes from ancient Korea (0.

The Kiss of Death: Serratia marcescens Antibacterial Activities against Staphylococcus aureus Requires Both Prodigiosin Synthesis and Direct Contact.

Prodigiosin possesses antibacterial activities, but as a highly hydrophobic compound, it raised the question about how Serratia marcescens introduce this compound to other microbes. Here, we demonstrate that the production of prodigiosin by newly isolated S. marcescens RH10 correlates with its antibacterial activity against a multidrug-resistant strain of S.

Multiple types of genomic variation contribute to adaptive traits in the mustelid subfamily Guloninae.

Species of the mustelid subfamily Guloninae inhabit diverse habitats on multiple continents, and occupy a variety of ecological niches. They differ in feeding ecologies, reproductive strategies and morphological adaptations. To identify candidate loci associated with adaptations to their respective environments, we generated a de novo assembly of the tayra (Eira barbara), the earliest diverging species in the subfamily, and compared this with the genomes available for the wolverine (Gulo gulo) and the sable (Martes zibellina).

KOREF_S1: phased, parental trio-binned Korean reference genome using long reads and Hi-C sequencing methods.

Background: KOREF is the Korean reference genome, which was constructed with various sequencing technologies including long reads, short reads, and optical mapping methods. It is also the first East Asian multiomic reference genome accompanied by extensive clinical information, time-series and multiomic data, and parental sequencing data. However, it was still not a chromosome-scale reference.

Regional TMPRSS2 V197M Allele Frequencies Are Correlated with COVID-19 Case Fatality Rates.

Coronavirus disease, COVID-19 (coronavirus disease 2019), caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), has a higher case fatality rate in European countries than in others, especially East Asian ones. One potential explanation for this regional difference is the diversity of the viral infection efficiency. Here, we analyzed the allele frequencies of a nonsynonymous variant rs12329760 (V197M) in the gene, a key enzyme essential for viral infection and found a significant association between the COVID-19 case fatality rate and the V197M allele frequencies, using over 200,000 present-day and ancient genomic samples.

Comparative analysis of 7 short-read sequencing platforms using the Korean Reference Genome: MGI and Illumina sequencing benchmark for whole-genome sequencing.

Background: DNBSEQ-T7 is a new whole-genome sequencer developed by Complete Genomics and MGI using DNA nanoball and combinatorial probe anchor synthesis technologies to generate 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.

Findings: By using the same KOREF sample, the Korean Reference Genome, we have compared 7 sequencing platforms including BGISEQ-500, DNBSEQ-T7, HiSeq2000, HiSeq2500, HiSeq4000, HiSeqX10, and NovaSeq6000.

Welfare Genome Project: A Participatory Korean Personal Genome Project With Free Health Check-Up and Genetic Report Followed by Counseling.

The Welfare Genome Project (WGP) provided 1,000 healthy Korean volunteers with detailed genetic and health reports to test the social perception of integrating personal genetic and healthcare data at a large-scale. WGP was launched in 2016 in the Ulsan Metropolitan City as the first large-scale genome project with public participation in Korea. The project produced a set of genetic materials, genotype information, clinical data, and lifestyle survey answers from participants aged 20-96.