Evaluation of Penalized and Nonpenalized Methods for Disease Prediction with Large-Scale Genetic Data

Owing to recent improvement of genotyping technology, large-scale genetic data can be utilized to identify disease susceptibility loci and this successful finding has substantially improved our understanding of complex diseases. However, in spite of these successes, most of the genetic effects for many complex diseases were found to be very small, which have been a big hurdle to build disease prediction model. Recently, many statistical methods based on penalized regressions have been proposed to tackle the so-called "large P and small N" problem. Penalized regressions including least absolute selection and shrinkage operator (LASSO) and ridge regression limit the space of parameters, and this constraint enables the estimation of effects for very large number of SNPs. Various extensions have been suggested, and, in this report, we compare their accuracy by applying them to several complex diseases. Our results show that penalized regressions are usually robust and provide better accuracy than the existing methods for at least diseases under consideration

Analysis of spike protein variants evolved in a novel in vivo long-term replication model for SARS-CoV-2

IntroductionThe spectrum of SARS-CoV-2 mutations have increased over time, resulting in the emergence of several variants of concern. Persistent infection is assumed to be involved in the evolution of the variants. Calu-3 human lung cancer cells persistently grow without apoptosis and release low virus titers after infection.MethodsWe established a novel in vivo long-term replication model using xenografts of Calu-3 human lung cancer cells in immunodeficient mice. Virus replication in the tumor was monitored for 30 days and occurrence of mutations in the viral genome was determined by whole-genome deep sequencing. Viral isolates with mutations were selected after plaque forming assays and their properties were determined in cells and in K18-hACE2 mice.ResultsAfter infection with parental SARS-CoV-2, viruses were found in the tumor tissues for up to 30 days and acquired various mutations, predominantly in the spike (S) protein, some of which increased while others fluctuated for 30 days. Three viral isolates with different combination of mutations produced higher virus titers than the parental virus in Calu-3 cells without cytopathic effects. In K18-hACE2 mice, the variants were less lethal than the parental virus. Infection with each variant induced production of cross-reactive antibodies to the receptor binding domain of parental SARS-CoV-2 S protein and provided protective immunity against subsequent challenge with parental virus.DiscussionThese results suggest that most of the SARS-CoV-2 variants acquired mutations promoting host adaptation in the Calu-3 xenograft mice. This model can be used in the future to further study SARS-CoV-2 variants upon long-term replication in vivo

Ground-based Observations of the Polar Region Space Environment

Jang Bogo Station (JBS), the second Korean Antarctic research station, was established in Terra Nova Bay, Antarctica (74.62°S 164.22°E) in February 2014 in order to expand the Korea Polar Research Institute (KOPRI) research capabilities. One of the main research areas at JBS is space environmental research. The goal of the research is to better understand the general characteristics of the polar region ionosphere and thermosphere and their responses to solar wind and the magnetosphere. Ground-based observations at JBS for upper atmospheric wind and temperature measurements using the Fabry-Perot Interferometer (FPI) began in March 2014. Ionospheric radar (VIPIR) measurements have been collected since 2015 to monitor the state of the polar ionosphere for electron density height profiles, horizontal density gradients, and ion drifts. To investigate the magnetosphere and geomagnetic field variations, a search-coil magnetometer and vector magnetometer were installed in 2017 and 2018, respectively. Since JBS is positioned in an ideal location for auroral observations, we installed an auroral all-sky imager with a color sensor in January 2018 to study substorms as well as auroras. In addition to these observations, we are also operating a proton auroral imager, airglow imager, global positioning system total electron content (GPS TEC)/scintillation monitor, and neutron monitor in collaboration with other institutes. In this article, we briefly introduce the observational activities performed at JBS and the preliminary results of these observations

Breaking the Negative Feedback Loop of Disaster, Conflict, and Fragility: Analyzing Development Aid by Japan and South Korea

Disaster risk reduction (DRR) has become an important element of donor policy, because numerous governments have expressed their commitment to helping countries vulnerable to natural hazards by mainstreaming DRR into their development programs. Meanwhile, countries that are considered fragile, as well as conflict-affected states, have faced a high risk of disasters brought on by natural hazards. However, there has been little research that addresses the complex relationship between disasters, conflict, and fragility in the context of development cooperation. Against this backdrop, this study analyzed the determinants of DRR aid allocation from Japan and South Korea—two East Asian countries that have shown a strong commitment to disaster resilience and peacebuilding—to investigate whether they are responsive to countries experiencing the combined risks of disasters and conflicts and/or fragility. Despite the vulnerable countries being in the most need, the study found that both Japan and Korea’s aid allocation has not been influenced much by the concurrence of disasters and conflict. Rather, it has been more driven by the level of a country’s climate vulnerability than the level of a country’s fragility. This suggests that developing countries facing multiple risks and challenges are at a major disadvantage in terms of the responsiveness of donors toward their needs and vulnerability

Breaking the Negative Feedback Loop of Disaster, Conflict, and Fragility: Analyzing Development Aid by Japan and South Korea

Disaster risk reduction (DRR) has become an important element of donor policy, because numerous governments have expressed their commitment to helping countries vulnerable to natural hazards by mainstreaming DRR into their development programs. Meanwhile, countries that are considered fragile, as well as conflict-affected states, have faced a high risk of disasters brought on by natural hazards. However, there has been little research that addresses the complex relationship between disasters, conflict, and fragility in the context of development cooperation. Against this backdrop, this study analyzed the determinants of DRR aid allocation from Japan and South Korea-two East Asian countries that have shown a strong commitment to disaster resilience and peacebuilding-to investigate whether they are responsive to countries experiencing the combined risks of disasters and conflicts and/or fragility. Despite the vulnerable countries being in the most need, the study found that both Japan and Korea's aid allocation has not been influenced much by the concurrence of disasters and conflict. Rather, it has been more driven by the level of a country's climate vulnerability than the level of a country's fragility. This suggests that developing countries facing multiple risks and challenges are at a major disadvantage in terms of the responsiveness of donors toward their needs and vulnerability.N

Evaluation of Penalized and Nonpenalized Methods for Disease Prediction with Large-Scale Genetic Data

Owing to recent improvement of genotyping technology, large-scale genetic data can be utilized to identify disease susceptibility loci and this successful finding has substantially improved our understanding of complex diseases. However, in spite of these successes, most of the genetic effects for many complex diseases were found to be very small, which have been a big hurdle to build disease prediction model. Recently, many statistical methods based on penalized regressions have been proposed to tackle the so-called “large P and small N” problem. Penalized regressions including least absolute selection and shrinkage operator (LASSO) and ridge regression limit the space of parameters, and this constraint enables the estimation of effects for very large number of SNPs. Various extensions have been suggested, and, in this report, we compare their accuracy by applying them to several complex diseases. Our results show that penalized regressions are usually robust and provide better accuracy than the existing methods for at least diseases under consideration

Expression of uncharacterized male germ cell-specific genes and discovery of novel sperm-tail proteins in mice.

The identification and characterization of germ cell-specific genes are essential if we hope to comprehensively understand the mechanisms of spermatogenesis and fertilization. Here, we searched the mouse UniGene databases and identified 13 novel genes as being putatively testis-specific or -predominant. Our in silico and in vitro analyses revealed that the expressions of these genes are testis- and germ cell-specific, and that they are regulated in a stage-specific manner during spermatogenesis. We generated antibodies against the proteins encoded by seven of the genes to facilitate their characterization in male germ cells. Immunoblotting and immunofluorescence analyses revealed that one of these proteins was expressed only in testicular germ cells, three were expressed in both testicular germ cells and testicular sperm, and the remaining three were expressed in sperm of the testicular stages and in mature sperm from the epididymis. Further analysis of the latter three proteins showed that they were all associated with cytoskeletal structures in the sperm flagellum. Among them, MORN5, which is predicted to contain three MORN motifs, is conserved between mouse and human sperm. In conclusion, we herein identify 13 authentic genes with male germ cell-specific expression, and provide comprehensive information about these genes and their encoded products. Our finding will facilitate future investigations into the functional roles of these novel genes in spermatogenesis and sperm functions

Fresh Crab Plays an Important Role as a Nutrient Reservoir for the Rapid Propagation of Vibrio vulnificus

Vibrio vulnificus is a well-known opportunistic pathogen causing food-borne illnesses by ingestion of contaminated seafood. A new strain of V. vulnificus FORC_016 was isolated from a patient's blood sample in South Korea. The genome consists of two circular DNA chromosomes: chromosome I (3,234,424 bp with a G + C contents of 46.60% containing 2,889 ORFs, 106 tRNA genes, and 31 rRNA genes) and chromosome II (1,837,945 bp with a GC content of 47.00% containing 1,572 ORFs, 13 tRNA genes, and 3 rRNA genes). In addition, chromosome I has a super integron (SI) containing 209 ORFs, which is probably associated with various additional functions including antibiotic resistance and pathogenicity. Pan-genome analysis with other V. vulnificus genomes revealed that core genome regions contain most of the important virulence factors. However, accessory genome regions are located in the SI region and contain unique genes regarding cell wall biosynthesis and generation of host cell protecting capsule, suggesting possible resistance ability against environmental stresses. Comparative RNA-Seq analysis of samples between contact and no contact to the crab conditions showed that expressions of amino acid/peptide and carbohydrate transport and utilization genes were down-regulated, but expressions of cell division and growth-related genes were up-regulated, suggesting that the crab may be a nutrition reservoir for rapid propagation of V. vulnificus. Therefore, consumption of the contaminated fresh crab would provide a large number of V. vulnificus to humans, which may be more dangerous. Consequently, biocontrol of V. vulnificus may be critical to ensure the safety in seafood consumption.Y

Impaired fasting glucose and development of chronic kidney disease in non-diabetic population: a Mendelian randomization study

Introduction Diabetes mellitus is a risk factor of chronic kidney disease (CKD); however, the relationship between fasting glucose and CKD remains controversial in non-diabetic population. This study aimed to assess causal relationship between genetically predicted fasting glucose and incident CKD.Research design and methods This study included 5909 participants without diabetes and CKD from the Korean Genome Epidemiology Study. The genetic risk score (GRS9) was calculated using nine genetic variants associated with fasting glucose in previous genome-wide association studies. Incident CKD was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 and/or proteinuria (≥1+). The causal relationship between fasting glucose and CKD was evaluated using the Mendelian randomization (MR) approach.Results The GRS9 was strongly associated with fasting glucose (β, 1.01; p<0.001). During a median follow-up of 11.6 years, 490 (8.3%) CKD events occurred. However, GRS9 was not significantly different between participants with CKD events and those without. After adjusting for confounding factors, fasting glucose was not associated with incident CKD (OR 0.990; 95% CI 0.977 to 1.002; p=0.098). In the MR analysis, GRS9 was not associated with CKD development (OR per 1 SD increase, 1.179; 95% CI 0.819 to 1.696; p=0.376). Further evaluation using various other MR methods and strict CKD criteria (decrease in the eGFR of ≥30% to a value of <60 mL/min/1.73 m2) found no significant relationship between GRS9 and incident CKD.Conclusions Fasting glucose was not causally associated with CKD development in non-diabetic population