Biology subjects

Bhak, J.

Publications and source records attributed to Bhak, J..

At least 19 recordsLinked to original sources

bioRxiv2026

GeroEngine: Generative single-cell aging trajectories reveal a bidirectionally traversable identity core and direction-specific inflammatory remodeling

Single-cell RNA sequencing (scRNA-seq) maps aging tissues at high resolution but is destructive, preventing longitudinal tracking; dropout and zero-inflation artifacts, amplified by shift-invariant linear simulations, confound age-associated variability. We developed Gero-Engine, a technical-artifact-aware framework combining VAE-based trajectory simulation, LOPO cross-validation, linear baselines, reverse traversal, and reverse-directed network inference. In microglia and HSCs, the VAE reduced technical-artifact carryover while preserving trajectory heterogeneity and improving alignment to artifact-reduced reference manifolds. Consensus GeroTargets and GeroRegulators defined tissue-specific GeroNetworks organized into three pillars: lineage/replication identity collapse, a sex-dimorphic endocrine/stress core, and inflammatory remodeling. Forward and reverse simulations aligned to the common young[->]old aging axis revealed a sign-coherent, direction-specific program: identity/replication targets were bidirectionally recovered, whereas MHC/NF-{kappa}B inflammatory programs were preferentially forward-recovered. These results support identity collapse as a deep traversable core of aging and nominate upstream homeostatic restoration over downstream inflammatory suppression.

bioinformatics↗

bioRxiv2026

Telomere-to-telomere, accurate, and gapless genome assembly (TTAGGA) of the Korean Jindo dog with a single-contig Y chromosome

Complete canine reference genomes are essential for studies of structural variation, sex-chromosome evolution, and breed-specific architecture, yet existing references remain incomplete on the Y chromosome and retain internal gaps across multiple chromosomes. Here, we introduce TTAGGA (Telomere-to-Telomere, Accurate, Gapless Genome Assembly), a stricter completeness standard requiring chromosomes assembled end-to-end with zero internal gaps and Merqury consensus QV [≥] 50, and present Jindo1-G-TTAGGA, the first canine assembly to meet this standard, achieved under a stringent QV [≥] 60 threshold. From 813 Gb ([~]340x coverage) of multi-platform data (PacBio HiFi [~]150x, ONT ultra-long [~]103x, parental Illumina [~]40x per parent) generated from a male Korean Jindo dog, trio binning with hifiasm produced two haplotype-resolved assemblies of 2,441.6 Mb (Hap1, maternal, chrX-carrying) and 2,340.5 Mb (Hap2, paternal, chrY-carrying). Both haplotypes are gap-free at every internal position, with canonical telomeric repeats verified at both ends of all 39 chromosomes (tidk), Merqury consensus QV of 78.0 (Hap1) and 76.8 (Hap2), trio switch-error rates below 0.13%, BUSCO completeness of 99.3% (Hap1) and 96.4% (Hap2; the lower value reflects absent X-linked orthologues in the Y-bearing haplotype), and Genome Continuity Index values of 98.2 (Hap1) and 94.7 (Hap2). Hap2 carries a single 21,255,890 bp gap-free Y chromosome with TTAGGG telomeric repeats at the q-arm terminus and an acrocentric satellite-rich p-arm, representing a 5.4-fold increase over the 3.94 Mb chrY of ROS_Cfam_1.0 and adding approximately 14 Mb of newly resolved Y-linked sequence; this corresponds to roughly 79% of the cytogenetically estimated 27 Mb full-length canine chrY. Jindo1-G-TTAGGA provides a chromosome-scale, haplotype-resolved, gap-free canine reference for studies of canine structural variation, sex-chromosome evolution, and canid phylogenomics.

genomics↗

bioRxiv2025

Telomere-to-Telomere Accurate and Gapless Korean Standard Reference Genome

We present KOREF1-G-TTAGGA, the first Telomere-to-Telomere Accurate and Gapless Genome Assembly, standing as the Korean standard reference genome. The paternal and maternal haplotypes spanned 2.91 and 3.03 Gb. Genome-wide, at least 99.15% of assembled sequences were reliably haplotype-resolved, and over 95% remained accurate even in the most error-prone loci, including centromeric satellite arrays and segmental duplications. Rare-k-mer copy-number concordance within satellite arrays held up 98.9% and 98.8% per haplotype. Bionano optical maps fully spanned all canonical rDNA arrays on the five acrocentric chromosomes. The assembly quality index (AQI) of 99.77 and 99.69 exceeded the reference-quality threshold of 90, and more than 99.99% of gene and cCRE sequence was free of structural error. Both haplotypes further showed high base-level accuracy, with consensus quality value (QV) of 81.19 and 79.03, corresponding to one error per 131 and 80 Mb. KOREF1-G-TTAGGA is among the highest-quality East Asian telomere-to-telomere assemblies. It moreover anchors a decade-spanning multi-ome reference dataset for defining individual molecular states. Together, these resources define the personal referenceome as a foundation for individual biology and precision medicine, with the assemblies, annotations, and all multi-omic data openly available at https://koreanreference.org.

genomics↗

bioRxiv2025

10,239 whole genomes with multiomic and clinical health information as the Korean population multiomic reference dataset

We present Korea10K, the largest genomic dataset of the Korean population, comprising 10,239 high-coverage whole genomes (mean depth 30x) with matched multiomic profiles and phenotype data. Korea10K achieves complete and near-complete discovery of very rare and ultra-rare alleles, respectively, at 9,000 Korean genomes. This dataset provides the high-quality population-specific imputation panel, enabling accurate inference of low-frequency variants. Admixture analyses confirm the genetic homogeneity of the Korean population, despite its diverse Y-chromosomal, mitochondrial, and HLA repertoires. This pattern reflects a long and continuous lineage history characterized by persistent internal admixture and genomic homogenization over thousands of years on the Korean peninsula. We also identified 16.8 million genomic variants that directly modify CG sites by creating or abolishing CG dinucleotides, providing the population-scale evidence of coordinated genomic-epigenomic regulatory mechanism in Koreans.

genomics↗

bioRxiv2025

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. Six key genes--SRXN1, FURIN, IL18RAP, FOXO3, GCNT4, and FKBP5--were either up-regulated or down-regulated near hypomethylated CpG sites. These genes are associated with viral infiltration, immune activation, lung damage, and oxidative stress-related multi-organ failure, which are the hallmarks of severe COVID-19. Interestingly, during the recovery phase, methylation and gene expression levels returned to baseline, underscoring the rapid and reversible nature of these molecular changes. These findings provide insight into the dynamics of epigenetic and transcriptomic shifts according to the infectious stage, supporting potential prognostic and therapeutic approaches for severe COVID-19.

bioinformatics↗

bioRxiv2024

Reversible Transcriptomic Age Shifts from Physiological Stress in Whole Blood

We developed a genome-wide transcriptomic clock for predicting chronological age using whole blood samples from 463 healthy individuals. Our findings reveal profound age acceleration, up to 24.47 years, under perturbed homeostasis in COVID-19 patients, which reverted to baseline upon recovery. This study demonstrates that the whole blood transcriptome can track reversible changes in biological age induced by stressors in real physiological time, suggesting a potential role for anti-aging interventions in disease management.

bioinformatics↗

bioRxiv2024

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

BackgroundThe Dokdo sea lion (Zalophus japonicus), commonly referred to as Gangchi in Korea and known as the Japanese sea lion, was endemic to the Northwest Pacific coast before becoming extinct in the 1950s. Little is known about its origins, speciation compared to other Otariidae species or how the rapid decline affected the species genetic diversity. ResultsTo raise the Dokdo sea lion from this relative obscurity, we sequenced DNA from 16 Z. japonicus bone fragments, obtained from Dokdo and Ulleungdo islands in Korea. Our analysis establishes Z. japonicus as the earliest diverged species within its genus, significantly redefining its evolutionary relationship with the California (Z. californianus) and Galapagos (Z. wollebaeki) sea lions. This genome-scale analysis clarifies the phylogeny of Z. japonicus, shedding light on its speciation and the evolutionary pathways that shaped its genetic diversity before its extinction. In addition, we discovered, population decline of the Z. japonicus started already 1,000 years ago, however, Z. japonicus genome maintained a relatively high heterozygosity despite, nearing extinction. ConclusionsOur genome-scale analysis eliminated ambiguity in Z. japonicus phylogeny, and shed light on the evolutionary pathways underlying its speciation. This study highlights the importance of the genome-scale analysis for extinct species to understand their complex evolutionary histories and conservation status.

genomics↗

bioRxiv2024

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

BackgroundThe 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. MethodsA comparative differential methylation analysis was performed on whole blood samples from 94 anxiety disorder patients and 296 control samples using targeted bisulfite sequencing. Subsequent validation of identified biomarkers employed an artificial intelligence- based risk prediction models: a linear calculation-based methylation risk score model and two tree-based machine learning models: Random Forest and XGBoost. Results17 novel epigenetic methylation biomarkers were identified to be associated with anxiety disorders. These biomarkers were predominantly localized near CpG islands, and they were associated with two distinct biological processes: 1) cell apoptosis and mitochondrial dysfunction and 2) the regulation of neurosignaling. We further developed a robust diagnostic risk prediction system to classify anxiety disorders from healthy controls using the 17 biomarkers. Machine learning validation confirmed the robustness of our biomarker set, with XGBoost as the best-performing algorithm, an area under the curve of 0.876. ConclusionOur findings support the potential of blood liquid biopsy in enhancing the clinical utility of anxiety disorder diagnostics. This unique set of epigenetic biomarkers holds the potential for early diagnosis, prediction of treatment efficacy, continuous monitoring, health screening, and the delivery of personalized therapeutic interventions for individuals affected by anxiety disorders.

bioinformatics↗

bioRxiv2024

A high-quality de novo genome assembly of Asian Crested Ibis (Nipponia Nippon) using long-read and Hi-C data

We present TtaoRef1, the highest-quality de novo genome assembly of Asian Crested Ibis (Nipponia Nippon) to date consisting of 134 scaffolds with a length of 1.25 Gb and N50 of 101,183,595 bp. This assembly was generated through the utilization of long-read sequencing and Hi-C data. The assessment of assembly quality, conducted via Benchmarking Universal Single-Copy Orthologs (BUSCO), revealed the presence of 96.8% of completely predicted single-copy genes. TtaoRef1 had 18 times longer N50 value than the previous assembly (ASM70822v1), Furthermore, we conducted the annotation of 24,681 protein-coding genes within the newly assembled genome sequences.

bioinformatics↗

bioRxiv2023

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, Canis coreanus. To investigate the Korean wolf genetic affiliations and their taxonomic implications, we sequenced and analysed the genomes of a historical Korean wolf dated to the beginning of the 20th century, and a captive wolf originally located at 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. We identified regional patterns of wolf population structure and admixture in East Asia with potential conservation consequences in the Korean Peninsula and on a regional scale. We find the Korean wolf has similar diversity and inbreeding to other East Asian wolves. Finally, we show that, in contrast to the historical sample, the captive wolf is more genetically similar to wolves from the Tibetan Plateau, hence, Korean wolf conservation programs might not benefit from the inclusion of this specimen.

evolutionary biology↗

bioRxiv2022

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

We present 4,157 whole-genome sequences (Korea4K) coupled with 107 health check-up parameters as the largest whole genomic resource of Koreans. Korea4K provides 45,537,252 variants and encompasses most of the common and rare variants in Koreans. We identified 1,356 new geno-phenotype associations which were not found by the previous Korea1K dataset. Phenomics analyses revealed 24 genetic correlations, 1,131 pleiotropic variants, and 127 causal relationships from Mendelian randomization. Moreover, the Korea4K imputation reference panel showed a superior imputation performance to Korea1K. Collectively, Korea4K provides the most extensive genomic and phenomic data resources for discovering clinically relevant novel genome-phenome associations in Koreans.

genomics↗

bioRxiv2021

Diverse northern Asian and Jomon-related genetic structure discovered among socially complex Three Kingdoms period Gaya region Koreans

The genetic history of prehistoric and protohistoric Korean populations is not well understood due to the lack of ancient Korean genomes. Here, we report the first paleogenomic data from Korea; eight shotgun-sequenced genomes (0.7x[~]6.1x coverage) from two archeological sites in Gimhae: Yuha-ri shell mound and Daesung-dong tumuli, the most important funerary complex of the Gaya confederacy. All eight individuals are from the Korean Three Kingdoms period (4th-7th century CE), during which there is archaeological evidence of extensive trade connections with both northern (modern-day China) and eastern (modern-day Japan) kingdoms. All genomes are best modeled as an admixture between a northern-Chinese Iron Age genetic source and a Japanese-Jomon-related ancestry. The proportion of Jomon-related ancestry suggests the presence of two genetic groups within the population. The observed substructure indicates diversity among the Gaya population that is not related to either social status or sex. Teaser1,700-year-old genomes reveal the genetic diversity of ancient Koreans in the Gimhae region.

evolutionary biology↗

bioRxiv2021

PGP1 personal genome assembly - a hybrid assembly dataset using ONT's PromethION and PacBio's HiFi sequencing

PGP1 is the first participant of Personal Genome Project. We present the PGP1s chromosome-scale genome assembly. It was constructed using 255 Gb ultra-long PromethION reads and 97 Gb short paired-end reads. For reducing base calling errors, we corrected PromethION reads using 72 Gb PacBio HiFi reads. 327 Gb Hi-C chromosomal mapping data were utilized to maximize the assemblys contiguity. PGP1s contig assembly was 3.01 Gb in length comprising of 4,234 contigs with an N50 value of 33.8 Mb. After scaffolding with Hi-C data and extensive manual curation, we obtained a chromosome-scale assembly that represents 3,880 scaffolds with an N50 value of 142 Mb. From the Merqury assessment, PGP1 assembly achieved a high QV score of Q45.45. For a gene annotation, we predicted 106,789 genes with a liftover from the Gencode 38 and an assembly of transcriptome data.

genomics↗

bioRxiv2021

The Lithuanian reference genome LT1 - a human de novo genome assembly with short and long read sequence and Hi-C data

We present LT1, the first high-quality human reference genome from the Baltic States. LT1 is a female de novo human reference genome assembly constructed using 57x of ultra-long nanopore reads and 47x of short paired-end reads. We also utilized 72 Gb of Hi-C chromosomal mapping data to maximize the assemblys contiguity and accuracy. LT1s contig assembly was 2.73 Gbp in length comprising of 4,490 contigs with an N50 value of 13.4 Mbp. After scaffolding with Hi-C data and extensive manual curation, we produced a chromosome-scale assembly with an N50 value of 138 Mbp and 4,699 scaffolds. Our gene prediction quality assessment using BUSCO identify 89.3% of the single-copy orthologous genes included in the benchmarking set. Detailed characterization of LT1 suggested it has 73,744 predicted transcripts, 4.2 million autosomal SNPs, 974,000 short indels, and 12,330 large structural variants. These data are shared as a public resource without any restrictions and can be used as a benchmark for further in-depth genomic analyses of the Baltic populations.

genomics↗

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↗

bioRxiv2020

Complete genome sequence and analysis of nine Egyptian females with clinical information from different geographic regions in Egypt

Egyptians are at a crossroad between Africa and Eurasia, providing useful genomic resources for analyzing both genetic and environmental factors for future personalized medicine. Two personal Egyptian whole genomes have been published previously and here nine female whole genome sequences with clinical information have been added to expand the genomic resource of Egyptian personal genomes. Here we report the analysis of whole genomes of nine Egyptian females from different regions using Illumina short-read sequencers. At 30x sequencing coverage, we identified 12 SNPs that were shared in most of the subjects associated with obesity which are concordant with their clinical diagnosis. Also, we found mtDNA mutation A4282G is common in all the samples and this is associated with chronic progressive external ophthalmoplegia (CPEO). Haplogroup and Admixture analyses revealed that most Egyptian samples are close to the other north Mediterranean, Middle Eastern, and European, respectively, possibly reflecting the into-Africa influx of human migration. In conclusion, we present whole-genome sequences of nine Egyptian females with personal clinical information that cover the diverse regions of Egypt. Although limited in sample size, the whole genomes data provides possible geno-phenotype candidate markers that are relevant to the regions diseases.

bioinformatics↗

bioRxiv2019

Chromosome-scale assembly comparison of the Korean Reference Genome KOREF from PromethION and PacBio with Hi-C mapping information

BackgroundLong DNA reads produced by single molecule and pore-based sequencers are more suitable for assembly and structural variation discovery than short read DNA fragments. For de novo assembly, PacBio and Oxford Nanopore Technologies (ONT) are favorite options. However, PacBios SMRT sequencing is expensive for a full human genome assembly and costs over 40,000 USD for 30x coverage as of 2019. ONT PromethION sequencing, on the other hand, is one-twelfth the price of PacBio for the same coverage. This study aimed to compare the cost-effectiveness of ONT PromethION and PacBios SMRT sequencing in relation to the quality.\n\nFindingsWe performed whole genome de novo assemblies and comparison to construct an improved version of KOREF, the Korean reference genome, using sequencing data produced by PromethION and PacBio. With PromethION, an assembly using sequenced reads with 64x coverage (193 Gb, 3 flowcell sequencing) resulted in 3,725 contigs with N50s of 16.7 Mbp and a total genome length of 2.8 Gbp. It was comparable to a KOREF assembly constructed using PacBio at 62x coverage (188 Gbp, 2,695 contigs and N50s of 17.9 Mbp). When we applied Hi-C-derived long-range mapping data, an even higher quality assembly for the 64x coverage was achieved, resulting in 3,179 scaffolds with an N50 of 56.4 Mbp.\n\nConclusionThe pore-based PromethION approach provides a good quality chromosome-scale human genome assembly at a low cost with long maximum contig and scaffold lengths and is more cost-effective than PacBio at comparable quality measurements.

genomics↗

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↗