Detection of Differentially Expressed Gene Sets in a Partially Paired Microarray Data Set

Lim, Johan,Kim, Jayoun,Kim, Sang-cheol,Yu, Donghyeon,Kim, Kyunga,Kim, Byung Soo Walter de Gruyter GmbH 2012 Statistical applications in genetics and molecular Vol.11 No.3

<P>Partially paired data sets often occur in microarray experiments (Kim et al., 2005; Liu, Liang and Jang, 2006). Discussions of testing with partially paired data are found in the literature (Lin and Stivers 1974; Ekbohm, 1976; Bhoj, 1978). Bhoj (1978) initially proposed a test statistic that uses a convex combination of paired and unpaired t statistics. Kim et al. (2005) later proposed the t3 statistic, which is a linear combination of paired and unpaired t statistics, and then used it to detect differentially expressed (DE) genes in colorectal cancer (CRC) cDNA microarray data. In this paper, we extend Kim et al.'s t3 statistic to the Hotelling's T2 type statistic Tp for detecting DE gene sets of size p. We employ Efron's empirical null principle to incorporate inter-gene correlation in the estimation of the false discovery rate. Then, the proposed Tp statistic is applied to Kim et al's CRC data to detect the DE gene sets of sizes p=2 and p=3. Our results show that for small p, particularly for p=2 and marginally for p=3, the proposed Tp statistic compliments the univariate procedure by detecting additional DE genes that were undetected in the univariate test procedure. We also conduct a simulation study to demonstrate that Efron's empirical null principle is robust to the departure from the normal assumption.</P>

Joint Identification of Genetic Variants for Physical Activity in Korean Population

Kim, Jayoun,Kim, Jaehee,Min, Haesook,Oh, Sohee,Kim, Yeonjung,Lee, Andy H.,Park, Taesung MDPI 2014 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.15 No.7

<P>There has been limited research on genome-wide association with physical activity (PA). This study ascertained genetic associations between PA and 344,893 single nucleotide polymorphism (SNP) markers in 8842 Korean samples. PA data were obtained from a validated questionnaire that included information on PA intensity and duration. Metabolic equivalent of tasks were calculated to estimate the total daily PA level for each individual. In addition to single- and multiple-SNP association tests, a pathway enrichment analysis was performed to identify the biological significance of SNP markers. Although no significant SNP was found at genome-wide significance level via single-SNP association tests, 59 genetic variants mapped to 76 genes were identified via a multiple SNP approach using a bootstrap selection stability measure. Pathway analysis for these 59 variants showed that maturity onset diabetes of the young (MODY) was enriched. Joint identification of SNPs could enable the identification of multiple SNPs with good predictive power for PA and a pathway enriched for PA.</P>

Poster Session : Model Organisms and Disease ; Roles of NADPH-oxidases (NOXs) in cisplatin-induced ototoxicity

( Hyung Jin Kim ),( Hong Seob So ),( Channy Park ),( Jeong Han Lee ),( Yun Ha Kim ),( Jin Kyung Kim ),( Myung JaYoun ),( Se Jin Kim ),( Jin Bin Lee ),( Eun Sook Kim ),( Rae Kil Park ) 한국생화학분자생물학회 (구 한국생화학회) 2007 생화학분자생물학회 춘계학술발표논문집 Vol.2007 No.-

Predictive performance of the new race-free Chronic Kidney Disease Epidemiology Collaboration equations for kidney outcome in Korean patients with chronic kidney disease

( Hyoungnae Kim ),( Young Youl Hyun ),( Hae-ryong Yun ),( Young Su Joo ),( Yaeni Kim ),( Ji Yong Jung ),( Jong Cheol Jeong ),( Jayoun Kim ),( Jung Tak Park ),( Tae-hyun Yoo ),( Shin-wook Kang ),( Kook 대한신장학회 2023 Kidney Research and Clinical Practice Vol.42 No.4

Background: The new Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations without a race coefficient have gained recognition across the United States. We aimed to test whether these new equations performed well in Korean patients with chronic kidney disease (CKD). Methods: This study included 2,149 patients with CKD G1-G5 without kidney replacement therapy from the Korean Cohort Study for Outcome in Patients with CKD (KNOW-CKD). The estimated glomerular filtration rate (eGFR) was calculated using the new CKD-EPI equations with serum creatinine and cystatin C. The primary outcome was 5-year risk of kidney failure with replacement therapy (KFRT). Results: When we adopted the new creatinine equation [eGFR_cr (NEW)], 81 patients (23.1%) with CKD G3a based on the current creatinine equation (eGFR_cr) were reclassified as CKD G2. Accordingly, the number of patients with eGFR of <60 mL/min/1.73 m² decreased from 1,393 (64.8%) to 1,312 (61.1%). The time-dependent area under the receiver operating characteristic curve for 5-year KFRT risk was comparable between the eGFR_cr (NEW) (0.941; 95% confidence interval [CI], 0.922-0.960) and eGFRcr (0.941; 95% CI, 0.922-0.961). The eGFR_cr (NEW) showed slightly better discrimination and reclassification than the eGFR_cr. However, the new creatinine and cystatin C equation [eGFR_cr-cys (NEW)] performed similarly to the current creatinine and cystatin C equation. Furthermore, eGFR_cr-cys (NEW) did not show better performance for KFRT risk than eGFR_cr (NEW). Conclusion: Both the current and the new CKD-EPI equations showed excellent predictive performance for 5-year KFRT risk in Korean patients with CKD. These new equations need to be further tested for other clinical outcomes in Koreans.

Bayesian estimation of median household income for small areas with some longitudinal pattern

Lee, Jayoun,Kim, Dal Ho The Korean Data and Information Science Society 2015 한국데이터정보과학회지 Vol.26 No.3

One of the main objectives of the U.S. Census Bureau is the proper estimation of median household income for small areas. These estimates have an important role in the formulation of various governmental decisions and policies. Since direct survey estimates are available annually for each state or county, it is desirable to exploit the longitudinal trend in income observations in the estimation procedure. In this study, we consider Fay-Herriot type small area models which include time-specific random effect to accommodate any unspecified time varying income pattern. Analysis is carried out in a hierarchical Bayesian framework using Markov chain Monte Carlo methodology. We have evaluated our estimates by comparing those with the corresponding census estimates of 1999 using some commonly used comparison measures. It turns out that among three types of time-specific random effects the small area model with a time series random walk component provides estimates which are superior to both direct estimates and the Census Bureau estimates.

결측되었거나 구간중도절단된 중간사건을 가진 준경쟁적위험 자료에 대한 가산위험모형

김자연,김진흠,Kim, Jayoun,Kim, Jinheum 한국통계학회 2017 응용통계연구 Vol.30 No.4

본 논문에서는 사망과 같은 종말사건의 발생 유무는 알고 있지만 치매 발병과 같은 중간사건이 구간중도절단 되었거나 연구 기간 도중에 추적이 끊겨 결측된 준경쟁적위험 자료에 대해 다중상태모형을 적용하여 모수를 추정하는 방법을 제안하였다. 이를 위해 본 논문에서는 상태 간의 전이강도는 로그정규 프레일티를 랜덤효과로 가진 Lin과 Ying(1994)의 가산위험모형을 따른다고 가정하였다. 다섯 가지 상태를 가진 다중상태모형에서 가능한 여섯 가지 경로별로 조건부우도를 정의하였고, 주변우도를 구하기 위해 조정중요표본추출법을 적용하였으며 반복유사뉴튼 방법으로 최적해를 구하였다. 소표본 모의실험을 통해 모수의 95% 신뢰구간 포함률이 명목값에 얼마나 가까운지 살펴보았으며, 제안한 모형을 Persones $Ag{\acute{e}}es$ Quid (PAQUID) 자료 (Helmer 등, 2001)에 적용하고 그 결과를 해석하였다. We propose a multi-state model to analyze semi-competing risks data with interval-censored or missing intermediate events. This model is an extension of the three states of the illness-death model: healthy, disease, and dead. The 'diseased' state can be considered as the intermediate event. Two more states are added into the illness-death model to incorporate the missing events, which are caused by a loss of follow-up before the end of a study. One of them is a state of the lost-to-follow-up (LTF), and the other is an unobservable state that represents an intermediate event experienced after the occurrence of LTF. Given covariates, we employ the Lin and Ying additive hazards model with log-normal frailty and construct a conditional likelihood to estimate transition intensities between states in the multi-state model. A marginalization of the full likelihood is completed using adaptive importance sampling, and the optimal solution of the regression parameters is achieved through an iterative quasi-Newton algorithm. Simulation studies are performed to investigate the finite-sample performance of the proposed estimation method in terms of empirical coverage probability of true regression parameters. Our proposed method is also illustrated with a dataset adapted from Helmer et al. (2001).

중간 사건이 결측되었거나 구간 중도절단된 준 경쟁 위험 자료에 대한 회귀모형

김진흠,김자연,Kim, Jinheum,Kim, Jayoun 한국통계학회 2016 응용통계연구 Vol.29 No.7

본 논문에서는 종말 사건에 대한 정보는 주어져 있지만 중간 사건이 구간 중도절단되었거나 연구 기간 도중에 추적이 끊겨 중간 사건의 발생 유무를 모르는 준 경쟁 위험 자료에 다중상태모형을 적용하여 모수를 추정하는 방법을 제안하였다. 이를 위해 상태 간 전이 강도는 정규 프레일티를 랜덤효과로 가진 Cox 비례위험모형을 따른다고 가정하였다. 다섯 가지 상태를 가진 다중상태모형에서 가능한 여섯 가지 경로별로 조건부 우도를 정의하였고 주변 우도를 구하기 위해 조정 가우스 구적법을 적용하였으며 뉴튼-랩슨 방법으로 최적 해를 구하였다. 모수의 95% 신뢰구간 포함률을 통해 제안한 방법의 소표본 성질을 살펴보기 위해 모의실험을 수행하였으며, Persones $Ag{\acute{e}}es$ Quid(PAQUID) 자료 (Helmer 등, 2001)에 제안한 모형을 적용하고 그 결과를 해석하였다. We propose a multi-state model for analyzing semi-competing risks data with interval-censored or missing intermediate events. This model is an extension of the 'illness-death model', which composes three states, such as 'healthy', 'diseased', and 'dead'. The state of 'diseased' can be considered as an intermediate event. Two more states are added into the illness-death model to describe missing events caused by a loss of follow-up before the end of the study. One of them is a state of 'LTF', representing a lost-to-follow-up, and the other is an unobservable state that represents the intermediate event experienced after LTF occurred. Given covariates, we employ the Cox proportional hazards model with a normal frailty and construct a full likelihood to estimate transition intensities between states in the multi-state model. Marginalization of the full likelihood is completed using the adaptive Gaussian quadrature, and the optimal solution of the regression parameters is achieved through the iterative Newton-Raphson algorithm. Simulation studies are carried out to investigate the finite-sample performance of the proposed estimation procedure in terms of the empirical coverage probability of the true regression parameter. Our proposed method is also illustrated with the dataset adapted from Helmer et al. (2001).

베이지안 모형을 활용한 국내 노인 자살률 질병지도

이자연,김달호,Lee, Jayoun,Kim, Dal Ho 한국통계학회 2015 응용통계연구 Vol.28 No.2

한국의 고령화는 매우 빠른 속도로 진행되고 있고, 노인자살은 노인의 주요 사망원인이며 노인은 다른 연력층보다 자살의 고위험군으로 알려져있다. 고령화 시대에서 노인의 자살은 사회적인 문제로 대두되고 있으며 이를 예방하기 위해 노인자살에 대한 위험요인을 파악하고, 지역적 차이를 확인하는 것이 중요하다. 특히 노인의 자살문제에서는 지역사회와의 통합결여 등이 큰 원인으로 고려되기 때문이다. 따라서, 본 논문에서는 공간적 상관관계를 고려하여 추정된 표준화사망률을 이용하여 질병지도를 작성하고자 하였다. 공간적 상관관계를 고려하기 위해서 simultaneous CAR model을 사용하였다. 2006년부터 2010년까지 통계청 사망자료를 이용하여 국내 시군구별 노인자살자수에 대해 두 모형을 적합시켜본 결과, 공간적 상관관계를 고려하지 않은 모형보다 공간적 상관관계를 고려한 모형이 더 좋은 모형임을 보였다. 또한 효율적인 베이지안 추론을 위해 격자망 방법 등을 고려하였다. Elderly suicide rates tend to be high in Korea. Suicide by the elderly is no longer a personal problem; consequently, further research on risk and regional factors is necessary. Disease mapping in epidemiology estimates spatial patterns for disease risk over a geographical region. In this study, we use a simultaneous conditional autoregressive model for spatial correlations between neighboring areas to estimate standard mortality ratios and mapping. The method is illustrated with cause of death data from 2006 and 2010 to analyze regional patterns of elderly suicide in Korea. By considering spatial correlations, the Bayesian spatial models, mean educational attainment and percentage of the elderly who live alone was the significant regional characteristic for elderly suicide. Gibbs sampling and grid method are used for computation.

The KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD): A Korean Chronic Kidney Disease Cohort

Kook-Hwan Oh,Sue K. Park,Jayoun Kim,Curie Ahn 대한예방의학회 2022 예방의학회지 Vol.55 No.4

The KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD) was launched in 2011 with the support of the Korea Disease Control and Prevention Agency. The study was designed with the aim of exploring the various clinical features and characteristics of chronic kidney disease (CKD) in Koreans, and elucidating the risk factors for CKD progression and adverse outcomes of CKD. For the cohort study, nephrologists at 9 tertiary university-affiliated hospitals participated in patient recruitment and follow-up. Biostatisticians and epidemiologists also participated in the basic design and structuring of the study. From 2011 until 2016, the KNOW-CKD Phase I recruited 2238 adult patients with CKD from stages G1 to G5, who were not receiving renal replacement therapy. The KNOW-CKD Phase II recruitment was started in 2019, with an enrollment target of 1500 subjects, focused on diabetic nephropathy and hypertensive kidney diseases in patients with reduced kidney function who are presumed to be at a higher risk of adverse outcomes. As of 2021, the KNOW-CKD investigators have published articles in the fields of socioeconomics, quality of life, nutrition, physical activity, renal progression, cardiovascular disease and outcomes, anemia, mineral bone disease, serum and urine biomarkers, and international and inter-ethnic comparisons. The KNOW-CKD researchers will elaborate a prediction model for various outcomes of CKD such as the development of end-stage kidney disease, major adverse cardiovascular events, and death.

Which donor is better when a matched donor is not available domestically? Comparison of outcomes of allogeneic stem cell transplantation with haploidentical and international donors in a homogenous ethnic population

Park, Hyunkyung,Lee, Yoo Jin,Shin, Sang-Jin,Lee, Jayoun,Park, Silvia,Kim, Inho,Moon, Joon-ho,Lee, Hyewon,Jang, Jun Ho,Yoon, Sung-Soo,Koh, Youngil Elsevier 2018 Leukemia research Vol.69 No.-

<P><B>Abstract</B></P> <P>A substantial proportion of patients requiring allogeneic stem cell transplantation (alloSCT) do not have a human leukocyte antigen-matched sibling donor and need an alternative donor. In this multicenter retrospective study, we compared the outcomes of 176 patients with myelodysplastic syndrome and acute leukemia undergoing alloSCT from haploidentical (<I>n</I> = 121) and international (<I>n</I> = 55) donors between 2002 and 2016. For recipients of haploidentical and international donors, the 2-year overall survival rates were 33.4% and 35.3%, respectively (<I>P</I> = 0.347), and relapse-free survival rates were 31.7% and 34.4% (<I>P</I> = 0.264), respectively. In addition, there were no significant differences in the cumulative incidences of acute and chronic graft versus host disease or incidences of infection within 30 days (all <I>P ></I> 0.05). Similarly, there were no significant differences in these measures for acute leukemia patients (<I>n</I> = 143; all <I>P ></I> 0.05). A multivariate analysis revealed that the donor type was not an independent prognostic or predictive factor. These data suggest that both haploidentical and international donors are feasible alternative sources for alloSCT when a matched donor is not available domestically.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Haploidentical and international donor recipients have similar survival rates. </LI> <LI> Transplant-related complications occur similarly with both donor types. </LI> <LI> Both donor types are alternatives if a matched donor is not available domestically. </LI> </UL> </P>