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Using genomic annotations increases statistical power to detect eGenes
Duong, Dat,Zou, Jennifer,Hormozdiari, Farhad,Sul, Jae Hoon,Ernst, Jason,Han, Buhm,Eskin, Eleazar Oxford University Press 2016 Bioinformatics Vol.32 No.12
<P><B>Motivation:</B> Expression quantitative trait loci (eQTLs) are genetic variants that affect gene expression. In eQTL studies, one important task is to find eGenes or genes whose expressions are associated with at least one eQTL. The standard statistical method to determine whether a gene is an eGene requires association testing at all nearby variants and the permutation test to correct for multiple testing. The standard method however does not consider genomic annotation of the variants. In practice, variants near gene transcription start sites (TSSs) or certain histone modifications are likely to regulate gene expression. In this article, we introduce a novel eGene detection method that considers this empirical evidence and thereby increases the statistical power.</P><P><B>Results:</B> We applied our method to the liver Genotype-Tissue Expression (GTEx) data using distance from TSSs, DNase hypersensitivity sites, and six histone modifications as the genomic annotations for the variants. Each of these annotations helped us detected more candidate eGenes. Distance from TSS appears to be the most important annotation; specifically, using this annotation, our method discovered 50% more candidate eGenes than the standard permutation method.</P><P><B>Contact:</B>buhm.han@amc.seoul.kr or eeskin@cs.ucla.edu</P>
Cyclosporin A and sanglifehrin A enhance chemotherapeutic effect of cisplatin in C6 glioma cells
Han, Xuezhe,Yoon, Sung H,Ding, Yan,Choi, Tae G,Choi, Won J,Kim, Yun H,Kim, Young-Joo,Huh, Young-Buhm,Ha, Joohun,Kim, Sung S Spandidos Publications 2010 ONCOLOGY REPORTS Vol.23 No.4
<P>Glioma is the most common type of brain tumors in adults, and treatment of high-grade gliomas is still palliative. Studies to date have revealed only modest effect in attenuating growth of these tumors with single agent therapy, but combination treatment appears to be more effective. Cyclophilin A (CypA), a target of immunosuppressive drugs cyclosporin A (CsA) and sanglifehrin A (SFA), is an intracellular protein that has peptidyl-prolyl cis-trans isomerase (PPIase) enzymatic activity. Previously, we showed that overexpressed CypA induced chemoresistance in cancer cells. Here we provide evidence that combination of cisplatin with either CsA or SFA synergistically enhances apoptotic cell death in C6 glioma cells, compared with single agent treatment. Enhanced apoptotic cell death is a result of an increase in ROS generation and a decrease in intracellular glutathione levels. Consistently, CypA knockdown by siRNA also enhances cisplatin-induced apoptosis. Immunohistochemical analysis showed increased expression of CypA in human glioblastoma multiforme, but not in normal human astrocytes. CypA was also shown to be up-regulated in C6 glioma cells during hypoxia. In conclusion, CsA or SFA in combination with cisplatin synergistically enhances cisplatin-induced apoptosis in C6 glioma cells via inhibition of PPIase activity of CypA, indicating that development of new drugs that selectively inhibit the CypA PPIase activity without immune suppression may facilitate alleviation of chemoresistance in treatment of high-grade glioma.</P>
하자보수 손해배상의 공동주택 정보 표기제도에 관한 연구
한태호 ( Han Tae-ho ),이두환 ( Lee Doo-hwan ),민수정 ( Min Soo-jung ),이민주 ( Lee Min-joo ),장범수 ( Chang Buhm-soo ) 한국구조물진단유지관리공학회 2021 한국구조물진단유지관리공학회 학술발표대회 논문집 Vol.25 No.2
하자판정·조정성립은 2010년부터 2020년 8월까지 총 16,670건으로 하자판정·조정 성립률은 약 60%로 검토되었다. 최근 1년 8개월 동안의 조정성립 사건을 분석한 결과 하자보수에 갈음하는 손해배상 지급은 120여건으로 92%에 이르렀으며, 지급범위는 천만원 이하부터 일억원 이상까지 매우 다양했다. 그러나 이러한 손해배상이 지급되더라도 건축물 이력 정보에 해당 내용이 미표기되어 있고 공동주택 거래 시 이를 확인할 수 없어 거래자 간 민원이 급증하고 있다. 따라서 본 연구에서는 공동주택 정보 표기제도로서 하자담보책임기간과 하자심사·분쟁조정위원회로부터 입주자와 사업주체 간 손해배상 지급 건의 조정성립 또는 보증보험사로부터 하자보수보증금 등의 수령내역을 건축물대장에 등록하고 중계대상물확인설명서에 활용하는 방안을 제안한다.
MergeReference: A Tool for Merging Reference Panels for HLA Imputation
Cook, Seungho,Han, Buhm Korea Genome Organization 2017 Genomics & informatics Vol.15 No.3
Recently developed computational methods allow the imputation of human leukocyte antigen (HLA) genes using intergenic single nucleotide polymorphism markers. To improve the imputation accuracy in HLA imputation, it is essential to increase the sample size and the diversity of alleles in the reference panel. Our software, MergeReference, helps achieve this goal by providing a streamlined pipeline for combining multiple reference panels into one.
Kim, Hakin,Kim, Kunhee,Han, Buhm Korea Genome Organization 2022 Genomics & informatics Vol.20 No.1
Mendelian randomization (MR) uses genetic variation as a natural experiment to investigate the causal effects of modifiable risk factors (exposures) on outcomes. Two-sample Mendelian randomization (2SMR) is widely used to measure causal effects between exposures and outcomes via genome-wide association studies. 2SMR can increase statistical power by utilizing summary statistics from large consortia such as the UK Biobank. However, the first-order term approximation of standard error is commonly used when applying 2SMR. This approximation can underestimate the variance of causal effects in MR, which can lead to an increased false-positive rate. An alternative is to use the second-order approximation of the standard error, which can considerably correct for the deviation of the first-order approximation. In this study, we simulated MR to show the degree to which the first-order approximation underestimates the variance. We show that depending on the specific situation, the first-order approximation can underestimate the variance almost by half when compared to the true variance, whereas the second-order approximation is robust and accurate.