Osteoporosis is a medical condition of global concern, with increasing incidence in both sexes. Bone mineral density (BMD), a highly heritable trait, has been proven a useful diagnostic factor in predicting fracture. Because medical information is lacking about male osteoporotic genetics, we conducted a genome-wide association study of BMD in Korean men. With 1,176 participants, we analyzed 4,414,664 single nucleotide polymorphisms (SNPs) after genomic imputation, and identified five SNPs and three loci correlated with bone density and strength. Multivariate linear regression models were applied to adjust for age and body mass index interference. Rs17124500 (p = 6.42 × 10⁻⁷), rs34594869 (p = 6.53 × 10⁻⁷) and rs17124504 (p = 6.53 × 10⁻⁷) in 14q31.3 and rs140155614 (p = 8.64 × 10⁻⁷) in 15q25.1 were significantly associated with lumbar spine BMD (LS-BMD), while rs111822233 (p = 6.35 × 10⁻⁷) was linked with the femur total BMD (FT-BMD). Additionally, we analyzed the relationship between BMD and five genes previously identified in Korean men. Rs61382873 (p = 0.0009) in LRP5, rs9567003 (p = 0.0033) in TNFSF11 and rs9935828 (p = 0.0248) in FOXL1 were observed for LS-BMD. Furthermore, rs33997547 (p = 0.0057) in ZBTB and rs1664496 (p = 0.0012) in MEF2C were found to influence FT-BMD and rs61769193 (p = 0.0114) in ZBTB to influence femur neck BMD. We identified five SNPs and three genomic regions, associated with BMD. The significance of our results lies in the discovery of new loci, while also affirming a previously significant locus, as potential osteoporotic factors in the Korean male population.
Asian Continental Ancestry Group ; Body Mass Index ; Bone Density* ; Femur ; Femur Neck ; Genetics ; Genome-Wide Association Study* ; Humans ; Incidence ; Linear Models ; Male ; Osteoporosis ; Polymorphism, Single Nucleotide ; Spine

Toxoplasma gondii is an intracellular Apicomplexan parasite and a causative agent of toxoplasmosis in human. It causes encephalitis, uveitis, chorioretinitis, and congenital infection. T. gondii invades the host cell by forming a moving junction (MJ) complex. This complex formation is initiated by intermolecular interactions between the two secretory parasitic proteins—namely, apical membrane antigen 1 (AMA1) and rhoptry neck protein 2 (RON2) and is critically essential for the host invasion process. By this study, we propose two potential leads, NSC95522 and NSC179676 that can efficiently target the AMA1 hydrophobic cleft, which is a hotspot for targeting MJ complex formation. The proposed leads are the result of an exhaustive conformational search-based virtual screen with multilevel precision scoring of the docking affinities. These two compounds surpassed all the precision levels of docking and also the stringent post docking and cumulative molecular dynamics evaluations. Moreover, the backbone flexibility of hotspot residues in the hydrophobic cleft, which has been previously reported to be essential for accommodative binding of RON2 to AMA1, was also highly perturbed by these compounds. Furthermore, binding free energy calculations of these two compounds also revealed a significant affinity to AMA1. Machine learning approaches also predicted these two compounds to possess more relevant activities. Hence, these two leads, NSC95522 and NSC179676, may prove to be potential inhibitors targeting AMA1-RON2 complex formation towards combating toxoplasmosis.
Chorioretinitis ; Drug Design ; Encephalitis ; Humans ; Hydrophobic and Hydrophilic Interactions ; Machine Learning ; Membranes* ; Molecular Docking Simulation ; Molecular Dynamics Simulation ; Neck ; Parasites ; Pliability ; Toxoplasma* ; Toxoplasmosis ; Uveitis

Diverse somatic mutations have been reported to serve as cancer drivers. Recently, it has also been reported that epigenetic regulation is closely related to cancer development. However, the effect of epigenetic changes on cancer is still elusive. In this study, we analyzed DNA methylation data on colon cancer taken from The Caner Genome Atlas. We found that several promoters were significantly hypermethylated in colon cancer patients. Through clustering analysis of differentially methylated DNA regions, we were able to define subgroups of patients and observed clinical features associated with each subgroup. In addition, we analyzed the functional ontology of aberrantly methylated genes and identified the G-protein-coupled receptor signaling pathway as one of the major pathways affected epigenetically. In conclusion, our analysis shows the possibility of characterizing the clinical features of colon cancer subgroups based on DNA methylation patterns and provides lists of important genes and pathways possibly involved in colon cancer development.
Classification* ; Colon* ; Colonic Neoplasms* ; CpG Islands ; DNA ; DNA Methylation ; Epigenomics ; Genome ; Humans ; Methylation*

Since next-generation sequencing (NGS) technique was adopted into clinical practices, revolutionary advances in diagnosing rare genetic diseases have been achieved through translating genomic medicine into precision or personalized management. Indeed, several successful cases of molecular diagnosis and treatment with personalized or targeted therapies of rare genetic diseases have been reported. Still, there are several obstacles to be overcome for wider application of NGS-based precision medicine, including high sequencing cost, incomplete variant sensitivity and accuracy, practical complexities, and a shortage of available treatment options.
Diagnosis ; Humans ; Precision Medicine* ; Rare Diseases ; Translating

No abstract available.

Telomerase reverse transcriptase (TERT) is an enzymatic ribonucleoprotein that prolongs the replicative life span of cells by maintaining protective structures at the ends of eukaryotic chromosomes. Telomerase activity is highly up-regulated in 85-90% of human cancers, and is predominately regulated by hTERT expression. In contrast, most normal somatic tissues in humans express low or undetectable levels of telomerase activity. This expression profile identifies TERT as a potential anticancer target. By using an RNA mapping strategy based on a trans-splicing ribozyme library, we identified the regions of mouse TERT (mTERT) RNA that were accessible to ribozymes. We found that particularly accessible sites were present downstream of the AUG start codon. This mTERTspecific ribozyme will be useful for validation of the RNA replacement as cancer gene therapy approach in mouse model with syngeneic tumors.
Animals ; Catalytic Domain* ; Codon, Initiator ; Genes, Neoplasm ; Genetic Therapy ; Humans ; Mice* ; Ribonucleoproteins ; RNA* ; RNA, Catalytic ; Telomerase* ; Trans-Splicing

Many visualization tools have been designed to aid information processing during whole genome projects. We have developed a trace viewer program, ChroView, which can read a chromatogram file and display the chromatogram traces of the four bases. The program can be used to examine sequencing quality and base-calling errors. It can also help researchers to edit and save base-calling results while browsing the traces. Additionally, this program has a basecalling feature which can produce supplementary data for validation of the results from other base-calling programs.
Automatic Data Processing ; Genome

Computational virtual screening has become an essential platform of drug discovery for the efficient identification of active candidates. Moleculardocking, a key technology of receptor-centric virtual screening, is commonly used to predict the binding affinities of chemical compounds on target receptors. Despite the advancement and extensive application of these methods, substantial improvement is still required to increase their accuracy and time-efficiency. Here, we evaluate several advanced structure-based virtual screening approaches for elucidating the rank-order activity of chemical libraries, and the quantitative structureactivity relationship (QSAR). Our results show that the ensemble-average free energy estimation, including implicit solvation energy terms, significantly improves the hit enrichment of the virtual screening. We also demonstrate that the assignment of quantum mechanical-polarized (QM-polarized) partial charges to docked ligands contributes to the reproduction of the crystal pose of ligands in the docking and scoring procedure.
Drug Discovery* ; Ligands ; Mass Screening* ; Quantitative Structure-Activity Relationship ; Reproduction ; Small Molecule Libraries

Biological diversity, also known as biodiversity, is an important criterion for measuring the value of an ecosystem. As biodiversity is closely related to human welfare and quality of life, many efforts to restore and maintain the biodiversity of species have been made by government agencies and non-governmental organizations, thereby drawing a substantial amount of international attention. In the fields of biological research, biodiversity is widely measured using traditional statistical indices such as the Shannon-Wiener index, species richness, evenness, and relative dominance of species. However, some biologists and ecologists have difficulty using these indices because they require advanced mathematical knowledge and computational techniques. Therefore, we developed VBioindex, a user-friendly program that is capable of measuring the Shannon-Wiener index, species richness, evenness, and relative dominance. VBioindex serves as an easy to use interface and visually represents the results in the form of a simple chart and in addition, VBioindex offers functions for long-term investigations of datasets using time-series analyses.
Biodiversity* ; Computational Biology ; Dataset ; Ecology ; Ecosystem ; Government Agencies ; Humans ; Quality of Life

Because there are clear molecular differences entailing different treatment effectiveness between Korean and non-Korean cancer patients, identifying distinct molecular characteristics of Korean cancers is profoundly important. Here, we report a web-based data repository, namely Korean Cancer Genome Database (KCGD), for searching gene signatures associated with Korean cancer patients. Currently, a total of 1,403 cancer genomics data were collected, processed and stored in our repository, an ever-growing database. We incorporated most widely used statistical survival analysis methods including the Cox proportional hazard model, log-rank test and Kaplan-Meier plot to provide instant significance estimation for searched molecules. As an initial repository with the aim of Korean-specific marker detection, KCGD would be a promising web application for users without bioinformatics expertise to identify significant factors associated with cancer in Korean.
Computational Biology ; Gene Expression* ; Genome* ; Genomics ; Humans ; Prognosis ; Proportional Hazards Models ; Transcriptome* ; Treatment Outcome ; Biomarkers