International Genetics and Genomics of Diseases

Comparative Analysis of CXCR5 Circulating DNA Methylation Levels in Autoimmune Rheumatic Diseases Objective To assess CXC chemokine receptor 5 (CXCR5) circulating DNA methylation differences in autoimmune rheumatic diseases and their relation with clinical features. Methods Targeted methylation sequencing was performed using peripheral blood from 164 rheumatoid arthritis (RA), 30 systemic lupus erythematosus (SLE), 30 ankylosing spondylitis (AS), 30 psoriatic arthritis (PsA), 24 Sjögren's syndrome (SS) patients, and 30 healthy controls (HC). Results Significant differences in CXCR5 cg19599951 methylation were found between RA and HC, as well as AS and SLE. RA patients exhibited higher methylation than HC and AS (p < 0.01) but lower than SLE (p < 0.05). SLE patients showed higher methylation compared to HC, AS, and PsA (p < 0.001, 0.01, and 0.05, respectively). No significant differences were found in patients with SS compared to other autoimmune diseases and HC. Methylatio...

Application of Anti-Motion Ultra-Fast Quantitative MRI in Neurological Disorder Imaging: Insights From Huntington's Disease Background Conventional quantitative MRI (qMRI) scan is time-consuming and highly sensitive to movements, posing great challenges for quantitative images of individuals with involuntary movements, such as Huntington's disease (HD). Purpose To evaluate the potential of our developed ultra-fast qMRI technique, multiple overlapping-echo detachment (MOLED), in overcoming involuntary head motion and its capacity to quantitatively assess tissue changes in HD. Phantom/Subjects A phantom comprising 13 tubes of MnCl2 at varying concentrations, 5 healthy volunteers (male/female: 1/4), 22 HD patients (male/female: 14/8) and 27 healthy controls (male/female: 15/12). Field Strength/Sequence 3.0 T. MOLED-T2 sequence, MOLED-T2* sequence, T2-weighted spin-echo sequence, T1-weighted gradient echo sequence, and T2-dark-fluid sequence. Assessment T1-weighted images were rec...

Transcriptome analysis of early- and late-onset Alzheimer's disease in Korean cohorts INTRODUCTION The molecular mechanisms underlying early-onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease (LOAD) remain incompletely understood, particularly in Asian populations. METHODS RNA-sequencing was carried out on blood samples from 248 participants in the Seoul National University Bundang Hospital cohort to perform differential gene expression (DGE) and weighted gene co-expression network analysis. Findings were replicated in an independent Korean cohort (N = 275). RESULTS DGE analysis identified 18 and 88 dysregulated genes in EOAD and LOAD, respectively. Network analysis identified a LOAD-associated module showing a significant enrichment in pathways related to mitophagy, 5′ adenosine monophosphate-activated protein kinase signaling, and ubiquitin-mediated proteolysis. In the replication cohort, downregulation of SMOX and PLVAP in LOAD was replicated, and the LO...

DNA logic nanomachine for the accurate identification of multiple microRNAs in tumor cells The use of dynamic DNA logic circuits for disease diagnosis at the molecular level plays a considerable role in biomedical fields. Nevertheless, how to create programmable nanomachines based on molecular logical gates to accurately identify multiple biomarkers from tumor cells remains a pivotal challenge. Herein, we developed a DNA-based nanomachine for analyzing and imaging multiple microRNAs (miRNAs) in cancerous cells with a logical AND operation. The triangular prism design of DNA nanomachine improved its performance in living cell research with high stability and served as a modularized framework for toehold-mediated strand displacement reactions and catalytic hairpin assembly circuits. The results suggested that the nanomachine could efficiently enter cells with great biocompatibility and rapidly recognize the correct biomolecules with high sensitivity. The well-designed DNA-logic gate nan...

Comprehensive analysis of multi-omics single-cell data using the single-cell analyst The rapid advancement of multi-omics single-cell technologies has significantly enhanced our ability to investigate complex biological systems at unprecedented resolution. However, many existing analysis tools are complex, requiring substantial coding expertize, which can be a barrier for computationally less competent researchers. To address this challenge, we present single-cell analyst, a user-friendly, web-based platform to facilitate comprehensive multi-omics analysis. Single-cell analyst supports a wide range of data types, including six single-cell omics: single-cell RNA sequencing (scRNA-sequencing), single-cell assay for transposase accessible chromatin sequencing (scATAC-seq sequencing), single-cell immune profiling (scImmune profiling), single-cell copy number variation, cytometry by time-of-flight, and flow cytometry and spatial transcriptomics, and enables researchers to perform integrated...

Genome-Wide Identification and Expression Analysis of the Mediator Complex Subunit Gene The Mediator complex (MED) functions as a co-activator in plants, transmitting transcriptional signals to regulate gene expression, including responses to environmental stresses. While the MED gene family has been identified in several species, it has not yet been reported in cassava. In this study, we identified 32 members of the MeMED gene family in cassava ( Manihot esculenta Crantz ) distributed across 13 chromosomes. These genes were categorized into distinct Mediator subunits based on their similarity to Arabidopsis modules. Promoter analysis revealed the presence of various cis-regulatory elements, which likely play key roles in regulating plant growth, development, and stress responses. RNA-seq data showed tissue-specific expression patterns for the MeMED genes, with significant expression observed in leaves, roots, petioles, stems, friable embryogenic callus, and shoot apical meristems. Fur...

Drug Resistance Analysis of Pancreatic Cancer Based on Universally Differentially Expressed Genes Pancreatic ductal adenocarcinoma (PDAC) is considered one of the most aggressive malignant neoplasms, with a 12.8% five-year survival rate according to National Cancer Institute statistics. Complete surgery resection is the only possible cure for resectable PDAC, but most patients are already in an advanced stage at diagnosis. Chemotherapy with/without radiotherapy has been a mainstay strategy for treating PDAC, but it only provides a modest improvement in survival. Only 3% to 11% of patients have pathological complete responses after receiving chemotherapy with/without radiation therapy, which may be due to the high heterogeneity between patients and the ubiquitous drug resistance of PDAC. Immune checkpoint blockade (ICB) has changed the standard of care for multiple cancers and has brought hope to pancreatic cancer patients; however, almost all tentative trials have had little effect or...

The Radiation Oncology Perspective: Genomic vs Genetic Testing in Prostate Cancer A Frontline Forum hosted by CancerNetwork during the 2025 American College of Radiation Oncology Summit in March focused on gene expression testing options for patients with prostate cancer. The discussion centered on genetic vs genomic testing, current NCCN guidelines, and decisions based on which testing options to use. Following the program, CancerNetwork spoke with leading clinicians in the radiation oncology space regarding the use of these tests, androgen deprivation therapy (ADT), and the thought process for selecting patients for active surveillance. To begin, the distinction between a genomic biomarker vs germline testing was mentioned. A genomic biomarker includes a measurable DNA or RNA characteristic that can be used to indicate normal biological processes, disease, or response to treatment. Germline testing is the analysis of DNA to identify genetic variations that may be associated with heal...

Genome-Wide Association Study of Body Size Traits in Luning Chickens Using Whole-Genome Sequencing Chickens are one of the most economically important animals in the world with a population of over 34.4 billion in 2023 according to Food and Agriculture Organization (FAO) statistics. The broiler industry has evolved significantly over the past century, with a focus on rapid growth rates, efficient feed conversion, and high meat yield. Chicken is the second most numerous meat product in China, and mainly comes from white-feather and yellow-feather chickens.  With the development of breeding technology, marker-assisted selection (MAS) and genomic selection (GS) have been increasingly utilized in the broiler industry to improve breeding efficiency and enhance target traits. Single-nucleotide polymorphisms (SNPs) and causal genes across the genome can be utilized to accurately estimate each chicken’s genetic potential for specific traits. Therefore, the identification of candidate ...

Unveiling the shared genetic architecture between testosterone and polycystic ovary syndrome Testosterone (T) is a critical predictor of polycystic ovary syndrome (PCOS) but the genetic overlap between T and PCOS has not been established. Here by leveraging genetic datasets from large-scale genome-wide association studies, we assessed the genetic correlation and polygenic overlap between PCOS and three T-related traits using linkage disequilibrium score regression and the bivariate causal mixture model methods. The conjunctional false discovery rate (conjFDR) method was employed to identify shared causal variants. Functional annotation of variants was conducted using FUMA. Total T and bioavailable T exhibited positive correlations with PCOS, while sex hormone-binding globulin (SHBG) showed a negative correlation. All three traits demonstrated extensive genetic overlap with PCOS, with a minimum of 68% of T-related variants influencing PCOS. The conjFDR revealed 4 to 6 causal variants wi...

Genotype of PAX2-related disorders correlates with kidney and ocular manifestations PAX2-related disorders encompass renal coloboma syndrome (RCS) and hereditary focal segmental glomerulosclerosis (FSGS) type 7. We retrospectively analyzed 27 Korean patients with PAX2 pathogenic variants detected between 2004 and 2022 and conducted a literature review of 328 cases, including 301 previously reported. In our cohort, 19 had RCS, 4 had FSGS, and 4 had isolated congenital anomalies of the kidneys and urinary tract. Patients were classified by variant type into predicted loss of function (pLoF) and non-pLoF variant groups, and by variant location into paired domain and other sites group. pLoF variants were predominantly associated with RCS, observed in 82% of patients in both our data (18 of 22, P = 0.017) and the literature (140 of 171, P < 0.001). Kidney failure developed in 52% of Korean patients at a median age of 14.5 years, with no difference in kidney survival between variant types...

Loss of Genetic Plant Diversity Is Now Visible From Space A new study combining satellite imagery with genetic analysis reveals that climate and land use changes are driving increased vegetation growth in Europe’s mountain regions, ultimately leading to a decline in the genetic diversity of medicinal plants such as Greek mountain tea. Mountain regions are among the most biodiverse areas on Earth, hosting some of the richest and most varied ecosystems. However, these habitats are undergoing rapid and profound changes due to global environmental pressures. Over the last 50 years, increasing temperatures and shifts in land use at high elevations have promoted the expansion of vigorous, competitive vegetation such as shrubs and trees, a phenomenon known as “ mountain greening .” This encroachment is displacing the specialized, low-growing plant species that characterize open montane grasslands. One such plant affected by this trend is Sideritis, a key component of Mediterranean montane gra...

Frequency-encoded eye tracking smart contact lens for human–machine interaction Eye tracking techniques enable high-efficient, natural, and effortless human-machine interaction by detecting users’ eye movements and decoding their attention and intentions. Here, a miniature, imperceptible, and biocompatible smart contact lens is proposed for in situ eye tracking and wireless eye-machine interaction. Employing the frequency encoding strategy, the chip-free and battery-free lens successes in detecting eye movement and closure. Using a time-sequential eye tracking algorithm, the lens has a great angular accuracy of <0.5°, which is even less than the vision range of central fovea. Multiple eye-machine interaction applications, such as eye-drawing, Gluttonous Snake game, web interaction, pan-tilt-zoom camera control, and robot vehicle control, are demonstrated on the eye movement model and in vivo rabbit. Furthermore, comprehensive biocompatibility tests are implemented, demonstrating low...

Targeting initial tumour–osteoclast spatiotemporal interaction to prevent bone metastasis Bone is the most common site of metastasis, and although low proliferation and immunoediting at the early stage make existing treatment modalities less effective, the microenvironment-inducing behaviour could be a target for early intervention. Here we report on a spatiotemporal coupling interaction between tumour cells and osteoclasts, and named the tumour-associated osteoclast ‘tumasteoclast’—a subtype of osteoclasts in bone metastases induced by tumour-migrasome-mediated cytoplasmic transfer. We subsequently propose an in situ decoupling–killing strategy in which tetracycline-modified nanoliposomes encapsulating sodium bicarbonate and sodium hydrogen phosphate are designed to specifically release high concentrations of hydrogen phosphate ions triggered by tumasteoclasts, which depletes calcium ions and forms calcium-phosphorus crystals. This can inhibit the formation of migrasomes for decouplin...

Novel single-chain fragment variable antibody targeting plasma membrane epitopes on porcine Y-chromosome-bearing sperm The aim of this study was to construct and produce a single-chain fragment variable (scFv) antibody targeting the plasma membrane epitope on porcine Y-chromosome-bearing sperm (Y-sperm). The hybridoma cloned from 4D1-E8 exhibited the highest specificity, and Y-sperm was used to generate the scFv gene. The expected combination of 450 bp (VH) and 300 bp (VL) resulted in a 795 bp scFv gene. The scFv gene was inserted into the pET22b expression vector and expressed in E. coli BL21 (DE3). The resulting H4:L4 clone produced a highly specific scFv antibody to Y-sperm.  The reactivity of the H4:L4 scFv antibody to porcine Y-sperm was confirmed via ELISA and flow cytometry. The H4:L4 scFv antibody exhibited low cross-reactivity with X-sperm (4.14%). The soluble H4:L4 scFv antibody exhibited significantly less cross-reactivity with X-sperm than did the 4D1-E8 mAb (4.14% vs....