Jungsoo Gim

• Professor
• Chosun University

Among the more than 90 identified genetic risk loci for late-onset Alzheimer′s disease (AD) and related dementias, the apolipoprotein E gene (APOE) ϵ2/ϵ3/ϵ4 polymorphism remains the longstanding benchmark for genetic disease risk with a consistently large effect across studies. Despite this massive signal, the exact mechanisms for how ϵ4 increases...

Genome-wide association studies (GWAS) have linked genetic loci to complex traits, but their interpretation is limited by linkage disequilibrium (LD) and difficulties in identifying causal genes. Transcriptome-wide association studies (TWAS) address these challenges by leveraging predicted gene expression to map genomic risk regions. However, TWAS...

Background With a rapidly aging population, South Korea anticipates a surge in Alzheimer disease (AD). However, the genetic basis of AD in Koreans is not well understood. Method We sequenced the genomes of 3,540 Koreans (1,583 AD cases and 1,957 controls) older than age 60 and performed a genome‐wide association study (GWAS) of AD using logistic r...

INTRODUCTION The genetic basis of Alzheimer's disease (AD) in Koreans is poorly understood. METHODS We performed an AD genome‐wide association study using whole‐genome sequence data from 3540 Koreans (1583 AD cases, 1957 controls) and single‐nucleotide polymorphism array data from 2978 Japanese (1336 AD cases, 1642 controls). Significant findings...

High-throughput sequencing assays face persistent challenges when analyzing low-quality RNAs, often assessed by the RNA integrity number (RIN). Current preprocessing methods and pipelines designed for mRNA-seq presume high-quality RNAs, overlooking the nuanced complexities arising from degraded transcripts in low-quality samples. This study questio...

Bladder cancer prognosis remains a pressing clinical challenge, necessitating the identification of novel biomarkers for precise survival prediction and improved quality of life outcomes. This study proposes a comprehensive strategy to uncover key prognostic biomarkers in bladder cancer using DNA methylation analysis and extreme survival pattern ob...

Recently, there has been considerable progress in developing new technologies and equipment for the medical field, including minimally invasive surgeries. Evaluating the effectiveness of these treatments requires study designs like randomized controlled trials. However, due to the nature of certain treatments, randomization is not always feasible,...

Neoantigens are tumor-derived peptides and are biomarkers that can predict prognosis related to immune checkpoint inhibition by estimating their binding to major histocompatibility complex (MHC) proteins. Although deep neural networks have been primarily used for these prediction models, it is difficult to interpret the models reported thus far as...

We built a genetic risk score (GRS) from the most complete landscape of the Alzheimer disease (AD) genetics. We extended its analysis in 16 European countries and observed a consistent association of this GRS with AD risk, age at onset and cerebrospinal fluid (CSF) AD biomarker levels regardless of the Apolipoprotein E (APOE) genotype. This GRS was...

Motivation: Allowance for increasingly large samples is a key to identify the association of genetic variants with Alzheimer's disease (AD) in genome-wide association studies (GWAS). Accordingly, we aimed to develop a method that incorporates patients with mild cognitive impairment (MCI) and unknown cognitive status in GWAS using a machine learnin...

Background: Dropping cost and increasing clinical application of whole genome sequencing (WGS) lead a necessity of efficient (accurate and rapid) variant calling procedures from a personal WGS data (n = 1). A number of variant calling pipelines have been introduced utilizing the human genome reference GRCh38 as a reference and a benchmark dataset...

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson's disease (PD) and Alzheimer's disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects...

Neoantigens are biomarkers that can predict the prognosis associated with immune checkpoint inhibition by estimating the binding potential of candidate peptides to somatic mutation and major histocompatibility complex (MHC) proteins. Although deep neural networks have been primarily used for these prediction models, it is difficult to consider the...

Genome-wide association studies (GWAS) of Alzheimer’s disease are predominantly carried out in European ancestry individuals despite the known variation in genetic architecture and disease prevalence across global populations. We leveraged published GWAS summary statistics from European, East Asian, and African American populations, and an addition...

Most genome benchmark studies utilize hg38 as a reference genome (based on Caucasian and African samples) and ‘NA12878’ (a Caucasian sequencing read) for comparison. Here, we aimed to elucidate whether 1) ethnic match or mismatch between the reference genome and sequencing reads produces a distinct result; 2) there is an optimal workflow for single...

This study examined the single-nucleotide polymorphism heritability and genetic correlations of cognitive abilities and brain structural measures (regional subcortical volume and cortical thickness) in middle-aged and elderly East Asians (Korean) from the Gwangju Alzheimer's and Related Dementias cohort study. Significant heritability was found in...

Accurate parcellation of cortical regions is crucial for distinguishing morphometric changes in aged brains, particularly in degenerative brain diseases. Normal aging and neurodegeneration precipitate brain structural changes, leading to distinct tissue contrast and shape in people aged >60 years. Manual parcellation by trained radiologists can yie...

Genome-wide association studies (GWAS) of Alzheimer's disease are predominantly carried out in European ancestry individuals despite the known variation in genetic architecture and disease prevalence across global populations. We leveraged published and de novo GWAS from European, East Asian, African American, and Caribbean Hispanic populations to...

Accurate parcellation of cortical regions is crucial for distinguishing morphometric changes in aged brains, particularly in degenerative brain diseases. Normal aging and neurodegeneration precipitate brain structural changes, leading to distinct tissue contrast and shape in people aged > 60 years. Manual parcellation by trained radiologists can yi...

Using genome-wide association data, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s (PD) or Alzheimer’s (AD) disease versus controls across ancestry groups. A shared genetic association was observed across diseases at rs601945 (PD: odds ratio (OR)=0.84; 95% confidence interval, [0.80; 0.88]; p=2.2...

Using genome-wide association data, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson's (PD) or Alzheimer's (AD) disease versus controls across ancestry groups. A shared genetic association was observed across diseases at rs601945 (PD: odds ratio (OR)=0.84; 95% confidence interval, [0.80; 0.88]; p=2.2...

Established genetic risk factors for Alzheimer’s disease (AD) account for only a portion of AD heritability. The aim of this study was to identify novel associations between genetic variants and AD-specific brain atrophy. We conducted genome-wide association studies for brain magnetic resonance imaging measures of hippocampal volume and entorhinal...

The present study reports two novel genome-wide significant loci for late-onset Alzheimer’s disease (LOAD) identified from APOE ε4 non-carrier subjects of East Asian origin. A genome-wide association study of Alzheimer’s disease was performed in 2,291 Korean seniors in the discovery phase, from the Gwangju Alzheimer’ and Related Dementias (GARD) co...

Gastric cancer is a malignant tumor with a high incidence and mortality rate worldwide. Nevertheless, anticancer drugs that can be used for gastric cancer treatment are limited. Therefore, it is important to develop targeted anticancer drugs for the treatment of gastric cancer. Dehydroabietic acid (DAA) is a diterpene found in tree pine. Previous s...

The high genetic heritability of Alzheimer's disease has contributed to the multi-directional and large-scale genomic studies to discover genetic factors, and so far many massive studies have been reported. However, the majority of genetic factors have been identified through European races, and relatively few studies using East Asians to discover...

Heterogeneity of lung function levels and risk for developing chronic obstructive pulmonary disease (COPD) among people exposed to the same environmental risk factors, such as cigarette smoking, suggest an important role of genetic factors in COPD susceptibility. To investigate the possible role of different genetic factors in COPD susceptibility a...

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Variants in the APOE gene region may explain ethnic differences in the association of Alzheimer’s disease (AD) with ε4. Ethnic differences in allele frequencies for three APOE region SNPs (single nucleotide polymorphisms) were identified and tested for association in 19,398 East Asians (EastA), including Koreans and Japanese, 15,836 European ancest...

Background: Transcriptomic profiles can improve our understanding of the phenotypic molecular basis of biological research, and many statistical methods have been proposed to identify differentially expressed genes (DEGs) under two or more conditions with RNA-seq data. However, statistical analyses with RNA-seq data are often limited by small samp...

Background: To evaluate the impact of neutrophil-to-lymphocyte ratios (NLR) as a prognostic factor in predicting treatment outcomes after radiotherapy (RT) for solid tumors. Methods: PubMed and Embase databases were used to search for articles published by February 2019 based on the Preferred Reporting Items for Systematic Reviews and Meta-Analy...

Glutamate-mediated cytotoxicity has been implicated in the pathogenesis of neurological diseases, including Parkinson’s disease, Alzheimer’s disease, and stroke. In this study, we investigated the protective effects of alpha-lipoic acid (ALA), a naturally occurring thiol antioxidant, on glutamate-induced cytotoxicity in cultured C6 astroglial cells...

Abstract The purpose of this study was to identify genotypes associated with dose-adjusted tacrolimus trough concentrations (C0/D) in kidney transplant recipients using whole-exome sequencing (WES). This study included 147 patients administered tacrolimus, including seventy-five patients in the discovery set and seventy-two patients in the replicat...

Background Discovering reliable protein biomarkers is one of the most important issues in biomedical research. The ELISA is a traditional technique for accurate quantitation of well-known proteins. Recently, the multiple reaction-monitoring (MRM) mass spectrometry has been proposed for quantifying newly discovered protein and has become a popular a...

PURPOSE: Heat shock factor 1 (HSF1) is a key regulator of the heat shock response and plays an important role in various cancers. However, the role of HSF1 in gastric cancer is still unknown. The present study evaluated the function of HSF1 and related mechanisms in gastric cancer.

Motivation: Transcriptomic profiles can improve our understanding of the phenotypic molecular basis of biological research, and many statistical methods have been proposed to identify differentially expressed genes under two or more conditions with RNA-seq data. However, statistical analyses with RNA-seq data often suffer from small sample sizes, a...

Protein tyrosine kinase 7 (PTK7), also known as colon carcinoma kinase 4 (CCK-4), is a member of the catalytically defective receptor protein tyrosine kinase family and is upregulated in various cancers, where it is known to act as either an oncoprotein or a tumor suppressor. To understand the contrasting roles of PTK7 in tumorigenesis, we analyzed...

Background Undirected graphical models or Markov random fields have been a popular class of models for representing conditional dependence relationships between nodes. In particular, Markov networks help us to understand complex interactions between genes in biological processes of a cell. Local Poisson models seem to be promising in modeling posit...

Despite the many successes of genome-wide association studies (GWAS), the known susceptibility variants identified by GWAS have modest effect sizes, leading to notable skepticism about the effectiveness of building a risk prediction model from large-scale genetic data. However, in contrast to genetic variants, the family history of diseases has bee...

This study was aimed to identify blood-based biomarkers to predict a sustained complete response (CR) after transarterial chemoembolization (TACE) using targeted proteomics. Consecutive patients with HCC who had undergone TACE were prospectively enrolled [training (n=100) and validation set (n=80)]. Serum samples were obtained before and 6 months a...

Background Recently, a modified insulin-like growth factor-1 (IGF)–Child-Turcotte-Pugh (CTP) classification was proposed to improve the original CTP classification. This study aimed to validate the new IGF-CTP classification system as a prognostic maker for patients with hepatocellular carcinoma (HCC) in a hepatitis B virus endemic area. Methods W...

Patient distribution in the cohort for IGF-CTP class by CTP class. (DOCX)

Adjusted Cox model results for overall survival of the cohort based on insulin-like growth factor 1. (DOCX)

The new modified CTP (IGF-CTP) classification. (DOCX)

High throughput sequencing technology in transcriptomics studies contribute to the understanding of gene regulation mechanism and its cellular function, but also increases a need for accurate statistical methods to assess quantitative differences between experiments. Many methods have been developed to account for the specifics of count data: non-n...

RNA-Sequencing (RNA-Seq) provides valuable information for characterizing the molecular nature of the cells, in particular, identification of differentially expressed transcripts on a genome-wide scale. Unfortunately, cost and limited specimen availability often lead to studies with small sample sizes, and hypothesis testing on differential express...

Autism spectrum disorders (ASDs) are a group of developmental disorders that cause variable and heterogeneous phenotypes across three behavioral domains such as atypical social behavior, disrupted communications, and highly restricted and repetitive behaviors. In addition to these core symptoms, other neurological abnormalities are associated with...

FDR and TPR of LPEseq with correlated genes. The effect of correlated genes in DE analysis with LPEseq is shown in boxplot for FDR (left) and TPR (right). The different proportions of correlated genes (blue) and the difference correlation coefficient between correlated genes (pink) were denoted in each plot. The analysis was repeated 100 times. (TI...

The most significant DEGs and their chromosome position (top 8 genes are shown). (DOCX)

MAQC data analysis. Venn diagram of DEGs is shown for MAQC dataset. Five different methods, i.e., LPEseq (brown), edgeR (sky blue), DESeq (green), DESeq2 (violet) and NBPSeq (red) were used. A density plot of the mean difference between classes of uniquely found DE transcripts in each method was indicated. X- and Y-axis represent group mean differe...

An excel file containing DEG list and GSEA result of each method for Hammer’s dataset. (XLSX)

Suggestive threshold value D for non-replicated data analysis. Six different datasets were used to suggest optimal threshold value used in LPEseq method. Reproducibility score versus D values is plotted in blue line with 95% confidence interval colored in red. The D value giving the highest reproducibility score is shown in the center of each plot....

The number of DEGs with varying number of bins. The number of DEGs is plotted with different number of bins (from 50 to 150 bins). (TIF)

Reproducibility of the different methods with varying number of samples. The overlapped proportion of DEGs with varying number of technical replicates (left) and biological replicates (right) are shown. The overlap proportion indicates the number of DEGs identified both with subset of samples and with total samples divided by the number of DEGs ide...

Variance curve comparison. The plot shows the variance curve estimated with different numbers of samples. The X-axis represents log-transformed intensity and the Y-axis does the variance estimates. The solid blue line indicates the ‘true’ variance curve (estimated using the total samples) and all other dashed lines the variance curve estimates usin...

Supplementary Note. A file describing how optimal threshold value ‘D’ was defined and evaluated for LPEseq. (DOCX)

Family-based designs have been repeatedly shown to be powerful in detecting the significant rare variants associated with human diseases. Furthermore, human diseases are often defined by the outcomes of multiple phenotypes, and thus we expect multivariate family-based analyses may be very efficient in detecting associations with rare variants. Howe...

Preoperative chemoradiotherapy (CRT) has become a widely used treatment for improving local control of disease and increasing survival rates of rectal cancer patients. We aimed to identify a set of genes that can be used to predict responses to CRT in patients with rectal cancer. Gene expression profiles of pre-therapeutic biopsy specimens obtained...

Despite many successes of genome-wide association (GWA) studies, known susceptibility variants identified by GWAS have the modest effect sizes and we met noticeable skepticism about the risk prediction model building with large-scale genetic data. However, in contrast with genetic variants, family history of diseases has been largely accepted as an...

Genome-wide association studies have identified many causal candidate loci associated with common complex phenotypes, such as type-2 diabetes and obesity. However, most of these studies have been drawn from non-randomised case/control experiments, where the units exposed to one group generally differ from those exposed to the other group. The aim o...

High accuracy and reproducibility provided by selected or multiple reaction monitoring (SRM/MRM) experiments suggest that it is likely to become the platform of choice for identifying and verifying candidate biomarkers. Although several methods have been developed to quantify and discover the significant changes in SRM/MRM expression, we show norma...

Genome-wide association studies have identified many candidate causal variants associated with common complex diseases and traits, but most of them have been drawn from nonrandomized case/control designs. In nonrandomized experiments, the results drawn from two different groups can be misleading because the units exposed to one group generally diff...

Smad3, a major intracellular mediator of transforming growth factor-β (TGF-β) signaling, functions as both a positive and negative regulator in carcinogenesis. In response to TGF-β, the TGF-β receptor phosphorylates serine residues at the Smad3 C-tail. Cancer cells often contain high levels of the mitogen-activated protein kinase (MAPK) and cyclin-...

Identification of causative genes for hereditary nonsyndromic hearing loss (NSHL) is important to decide treatment modalities and to counsel the patients. Due to the genetic heterogeneity in sensorineural genetic disorders, the high-throughput method can be adapted for the efficient diagnosis. To this end, we designed a new diagnostic pipeline to s...

Audiogram and pedigree for 20 familial NSHL for targeted resequencing. (DOCX)

Heatmap for percentage of bases ≥ depth 10, 50 or 100 within all target exons and samples. Most exons were uncaptured in common samples and samples were grouped by the common uncaptured exons. (DOCX)

Qualities of targeted resequencing in 20 familial NSHL. (DOCX)

Audiogram and pedigree for 12 familial NSHL used in PCR-Sanger sequencing. (DOCX)

Barplot for comparison between experimental and expected distribution in number of exons that were commonly uncaptured within from 0 to 20 samples. Note that the exons in n = 0 were captured in all 20 samples and at n = 0, the experimental counts are greater than the expected ones due to common uncapured exons. (DOCX)

List of 80 genes related to NSHL for targeted resequencing. (DOCX)

Background The genetic heterogeneity of sensorineural hearing loss is a major hurdle to the efficient discovery of disease-causing genes. We designed a multiphasic analysis of copy number variation (CNV), linkage, and single nucleotide variation (SNV) of whole exome sequencing (WES) data for the efficient discovery of mutations causing nonsyndromic...

TGF-β1 is a multifunctional cytokine that mediates diverse biological processes. However, the mechanisms by which the intracellular signals of TGF-β1 are terminated are not well understood. Here, we demonstrate that DRAK2 serves as a TGF-β1-inducible antagonist of TGF-β signaling. TGF-β1 stimulation rapidly induces DRAK2 expression and enhances end...

Transcriptional process is a starting point of biological function. In particular, transcriptomes that display differential expression in different conditions are likely to be key elements in understanding mechanisms causing those differences. A number of statistical approaches have been suggested for discovery of differential expression in microar...

Motivation: Viewing a cellular system as a collection of interacting parts can lead to new insights into the complex cellular behavior. In this study, we have investigated aryl hydrocarbon receptor (AhR) signal transduction pathway from such a system-level perspective. AhR detects various xenobiotics, such as drugs or endocrine disruptors (e.g. di...

Signal transduction pathways affected by TCDD 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is one specific type of polychlorinated dibenzodioxins (PCDDs). It gets bioaccumulated in animals due to its hydrophobicity, and is recently known as a potential carcinogen. Penetrating the membrane of a cell, TCDD binds aryl hydrocarbon receptor (AhR) with a s...