• Genomics & Informatics
• /
• v.19 no.1
• /
• pp.2.1-2.10
• /
• 2021

BRAF inhibitors (e.g., vemurafenib) are widely used to treat metastatic melanoma with the BRAF V600E mutation. The initial response is often dramatic, but treatment resistance leads to disease progression in the majority of cases. Although secondary mutations in the mitogen-activated protein kinase signaling pathway are known to be responsible for this phenomenon, the molecular mechanisms governing acquired resistance are not known in more than half of patients. Here we report a genome- and transcriptome-wide study investigating the molecular mechanisms of acquired resistance to BRAF inhibitors. A microfluidic chip with a concentration gradient of vemurafenib was utilized to rapidly obtain therapy-resistant clones from two melanoma cell lines with the BRAF V600E mutation (A375 and SK-MEL-28). Exome and transcriptome data were produced from 13 resistant clones and analyzed to identify secondary mutations and gene expression changes. Various mechanisms, including phenotype switching and metabolic reprogramming, have been determined to contribute to resistance development differently for each clone. The roles of microphthalmia-associated transcription factor, the master transcription factor in melanocyte differentiation/dedifferentiation, were highlighted in terms of phenotype switching. Our study provides an omics-based comprehensive overview of the molecular mechanisms governing acquired resistance to BRAF inhibitor therapy.

• Asian-Australasian Journal of Animal Sciences
• /
• v.31 no.6
• /
• pp.812-819
• /
• 2018

Objective: An experiment was conducted to identify and characterize the circular RNA expression and metabolic characteristics in the liver of Jinhua pigs and Landrace pigs. Methods: Three Jinhua pigs and three Landrace pigs respectively at 70-day were slaughtered to collect the liver tissue samples. Immediately after slaughter, blood samples were taken to detect serum biochemical indicators. Total RNA extracted from liver tissue samples were used to prepare the library and then sequence on HiSeq 2500. Bioinformatic methods were employed to analyze sequence data to identify the circRNAs and predict the potential roles of differentially expressed circRNAs between the two breeds. Results: Significant differences in physiological and biochemical traits were observed between growing Jinhua and Landrace pigs. We identified 84,864 circRNA candidates in two breeds and 366 circRNAs were detected as significantly differentially expressed. Their host genes are involved in lipid biosynthetic and metabolic processes according to the gene ontology analysis and associated with metabolic pathways. Conclusion: Our research represents the first description of circRNA profiles in the porcine liver from two divergent phenotype pigs. The predicted miRNA-circRNA interaction provides important basis for miRNA-circRNA relationships in the porcine liver. These data expand the repertories of porcine circRNA and are conducive to understanding the possible molecular mechanisms involved in miRNA and circRNA. Our study provides basic data for further research of the biological functions of circRNAs in the porcine liver.

• Genomics & Informatics
• /
• v.17 no.4
• /
• pp.45.1-45.3
• /
• 2019

To identify pathways associated with survival phenotypes using gene expression data, we recently proposed the hierarchical structural component model for pathway analysis of gene expression data (HisCoM-PAGE) method. The HisCoM-PAGE software can consider hierarchical structural relationships between genes and pathways and analyze multiple pathways simultaneously. It can be applied to various types of gene expression data, such as microarray data or RNA sequencing data. We expect that the HisCoM-PAGE software will make our method more easily accessible to researchers who want to perform pathway analysis for survival times.

• Journal of the Korean Data Analysis Society
• /
• v.20 no.6
• /
• pp.2711-2719
• /
• 2018

When an observable is described by a single value, the statistic significance may be estimated by construction of null distribution using permutation and counting the portion of it that exceeds the observed value by chance. Genome-wide association study usually focuses on the association measure between a single or interacting genotypes with a single phenotype. However investigation of common genotypes associated simultaneously on multiple phenotypes may involve the observables that should be described with multiple numbers. Statistical significance for such an observable would involve null distribution in multiple dimensions. In this study, extension of the p-value estimation process using null distribution in one dimension has been sought that may be applicable to two dimensional case. Comparison of the position of points within the set of points they form has been proposed to use a positioning parameter inspired by the extension of the Kolmogorov-Smirnov statistic to two dimensions.

• Pediatric Gastroenterology, Hepatology & Nutrition
• /
• v.21 no.4
• /
• pp.306-314
• /
• 2018

Purpose: The objective of this study was to describe the clinical phenotypes of children and adolescents with cystic fibrosis (CF); and to assess the role of pancreatic insufficiency and neonatal screening in diagnosis. Methods: A cross-sectional study was conducted, which included 77 patients attending a reference center of CF between 2014 and 2016. Epidemiological data, anthropometric measurements, and the presence of pulmonary, pancreatic, gastrointestinal and hepatobiliary manifestations were evaluated based on clinical data and complementary examinations. Results: Of the 77 patients, 51.9% were male, with a median age of 147 months (7.0-297.0 months), and the majority showed adequate nutritional status. The most common phenotype was pulmonary (92.2%), followed by pancreatic (87.0%), with pancreatic insufficiency in most cases. Gastrointestinal manifestation occurred in 46.8%, with constipation being the more common factor. Hepatobiliary disease occurred in 62.3% of patients. The group with pancreatic insufficiency was diagnosed earlier (5.0 months) when compared to the group with sufficiency (84.0 months) (p=0.01). The age of diagnosis was reduced following implementation of neonatal screening protocols for CF (6.0 months before vs. 3.0 months after, p=0.02). Conclusion: The pulmonary phenotype was the most common, although extrapulmonary manifestations were frequent and clinically relevant, and should mandate early detection and treatment. Neonatal screening for CF led to earlier diagnosis in patients with pancreatic failure, and therefore, should be adopted universally.

• Journal of Nutrition and Health
• /
• v.55 no.2
• /
• pp.309-320
• /
• 2022

Purpose: This study aimed to investigate the association between steamed food intake and risk of metabolic syndrome (MetS) in Korean females. Methods: Using Ansan/Ansung data of Korean Genome and Epidemiology Study, general characteristics, nutritional intake and biochemical and anthropometric markers of a total of 4,056 females aged 40 to 69 years were analyzed. MetS was defined following National Cholesterol Education Program Adult Treatment Panel III with some minor modifications. Logistic regression models were established to present the association between steamed food intake and the risk of MetS. Levels of food and nutrient intake by the frequency of steamed food intake and MetS phenotype were analyzed using general linear models. Results: A total of 38.4% of females had MetS. Among them, 24.9% of females with MetS had steamed food more than 1-3 times per week, which reduced the risk for MetS by about 25% (95% confidence interval [CI], 0.650-0.865). However, such association was not evident when various lifestyle factors were considered in statistical models. In rural residents, the benefit of having more steamed food was observed (adjusted odds ratio: 0.747; 95% CI, 0.583-0.958). The frequency of steamed food intake was associated with various food and nutritional intakes. However, trends in those did not differ by MetS phenotype. Conclusion: Having steamed food more than 1-3 times per week may reduce the risk of MetS compared to those who had less steamed food in Korean females. This protective effect of steamed food intake may differ by lifestyle and environmental factors. Although a clear difference in food and nutritional intake was not observed in this study, steaming could be an effective cooking method for a healthy diet for disease prevention and management.

• Proceedings of the Korean Society for Bioinformatics Conference
• /
• 2001.10a
• /
• pp.1-9
• /
• 2001

scale genomic and postgenomic data means that many of the challenges in biomedical research are now challenges in computational sciences and information technology. The informatics revolutions both in clinical informatics and bioinformatics will change the current paradigm of biomedical sciences and practice of clinical medicine, including diagnostics, therapeutics, and prognostics. Postgenome informatics, powered by high throughput technologies and genomic-scale databases, is likely to transform our biomedical understanding forever much the same way that biochemistry did a generation ago. In this talk, 1 will describe how these technologies will in pact biomedical research and clinical care, emphasizing recent advances in biochip-based functional genomics. Basic data preprocessing with normalization and filtering, primary pattern analysis, and machine teaming algorithms will be presented. Issues of integrated biochip informatics technologies including multivariate data projection, gene-metabolic pathway mapping, automated biomolecular annotation, text mining of factual and literature databases, and integrated management of biomolecular databases will be discussed. Each step will be given with real examples from ongoing research activities in the context of clinical relevance. Issues of linking molecular genotype and clinical phenotype information will be discussed.

• Journal of Preventive Medicine and Public Health
• /
• v.35 no.2
• /
• pp.83-91
• /
• 2002

Bioinformatics is a rapidly emerging field of biomedical research. A flood of large-scale genomic and postgenomic data means that many of the challenges in biomedical research are now challenges in computational sciences. Clinical informatics has long developed methodologies to improve biomedical research and clinical care by integrating experimental and clinical information systems. The informatics revolutions both in bioinformatics and clinical informatics will eventually change the current practice of medicine, including diagnostics, therapeutics, and prognostics. Postgenome informatics, powered by high throughput technologies and genomic-scale databases, is likely to transform our biomedical understanding forever much the same way that biochemistry did a generation ago. The paper describes how these technologies will impact biomedical research and clinical care, emphasizing recent advances in biochip-based functional genomics and proteomics. Basic data preprocessing with normalization, primary pattern analysis, and machine learning algorithms will be presented. Use of integrated biochip informatics technologies, text mining of factual and literature databases, and integrated management of biomolecular databases will be discussed. Each step will be given with real examples in the context of clinical relevance. Issues of linking molecular genotype and clinical phenotype information will be discussed.

• Journal of Korea Society of Industrial Information Systems
• /
• v.25 no.6
• /
• pp.25-32
• /
• 2020

The seed, the most basic component, is an important factor in increasing production and efficiency in agriculture. Seeds with superior genes can be expected to improve agricultural productivity, crop survival, and reproduction. Currently, however, screening of superior seeds depends mostly on manual work, which requires a lot of time and manpower. In this paper, we propose a system that can extract the characteristics of seed phenotypes by using computer image processing technology, so that even a small number of people and a short period of time are needed to extract the characteristics of seeds. The proposed system detects individual seeds from images containing large quantities of seeds, and extracts and stores various characteristics such as representative colors, area, perimeter and roundness for each individual seed. Due to the regularity of input images, the accuracy of individual seed extraction in the proposed system is 99.12% for soybean seeds and 99.76% for rice seeds. The extracted data will be used as basic data for various data analyses that reflect the opinions of experts in the future, and will be used as basic data to determine the expressive nature of each seed.

• Asian-Australasian Journal of Animal Sciences
• /
• v.21 no.7
• /
• pp.928-935
• /
• 2008

The myostatin gene of seven important meat (Beltex (Australia), Beltex$\times$Huyang (F1), Meat and Multi-Prolific Chinese Merino Fine Wool, Meat Chinese Merino Fine Wool and Dorper (South Africa)) and non-meat (Huyang and Kazak) sheep breeds was analyzed to study the genetic basis of muscular hypertrophy (double muscling) phenotype in sheep. SNPs, four in regulatory regions and several in the introns in the myostatin gene, were identified, and the former four SNPs were used for further studies. Twelve haplotypes were predicted by PHASE program, of which four main haplotypes (1, 3, 7, 9) were present in 90% of the 364 sheep in the study. Haplotypes 1-4 were mainly present in meat breeds while haplotypes 7 and 9 dominated the non-meat breeds. The association between haplotypes and average daily gain (ADG) was analyzed among 116 sheep with production data, Haplo2 (CGAA) and Haplo8 (TGAA) were identified to have significant (p<0.05) effect on ADG by the model (JMP5.1 software) taking into account the effects of breed, family background, haplotype, birth weight and sex. ADG of these haplotype groups also correlated well (r = 0.82) with hypertrophic phenotype scores. In conclusion, the mutations -956 (T$\rightarrow$C), -41 (C$\rightarrow$A) and 6223 (G$\rightarrow$A) involved in Haplo2 and 8 may be associated with the double-muscling trait by influencing myostatin function and be suitable markers in selecting meat sheep.