Identification of the associations between genes and quantitative traits using entropy-based kernel density estimation

Yee, Jaeyong,Park, Taesung,Park, Mira Korea Genome Organization 2022 Genomics & informatics Vol.20 No.2

Genetic associations have been quantified using a number of statistical measures. Entropy-based mutual information may be one of the more direct ways of estimating the association, in the sense that it does not depend on the parametrization. For this purpose, both the entropy and conditional entropy of the phenotype distribution should be obtained. Quantitative traits, however, do not usually allow an exact evaluation of entropy. The estimation of entropy needs a probability density function, which can be approximated by kernel density estimation. We have investigated the proper sequence of procedures for combining the kernel density estimation and entropy estimation with a probability density function in order to calculate mutual information. Genotypes and their interactions were constructed to set the conditions for conditional entropy. Extensive simulation data created using three types of generating functions were analyzed using two different kernels as well as two types of multifactor dimensionality reduction and another probability density approximation method called m-spacing. The statistical power in terms of correct detection rates was compared. Using kernels was found to be most useful when the trait distributions were more complex than simple normal or gamma distributions. A full-scale genomic dataset was explored to identify associations using the 2-h oral glucose tolerance test results and γ-glutamyl transpeptidase levels as phenotypes. Clearly distinguishable single-nucleotide polymorphisms (SNPs) and interacting SNP pairs associated with these phenotypes were found and listed with empirical p-values.

Construction of Synaptic Neural Network for Genetic Interaction Analysis

Jaeyong Yee,Mira Park 한국자료분석학회 2021 Journal of the Korean Data Analysis Society Vol.23 No.4

Contribution by a single gene to the association with trait may be either independent or through interactions with other genes. Examining all available genes for the main effect should be carried out without the time constraint. However the number of possible interacting combinations would soon become formidably large with the growing number of genes. Therefore it is often coerced to identify a group of candidate genes for the interaction and investigate only within it. Such an identification process should be able to select the group of genes having possibilities to interact with each other. Main effect of each gene should not necessarily be the criterion for the selection. We devised a neural network process that was quite sensitive to the interaction of a particular gene to the remaining ones. Contribution of each gene to the association by the genes as a whole was estimated. Selection was made based on the statistical significance for the existence of such contribution. It was demonstrated that this process might perform reliable candidate gene selection for the interaction even when the selected genes did not show significant main effect, through single scan of each individual gene.

Genetic Association Analysis of Fasting and 1- and 2-Hour Glucose Tolerance Test Data Using a Generalized Index of Dissimilarity Measure for the Korean Population

Yee, Jaeyong,Kim, Yongkang,Park, Taesung,Park, Mira Korea Genome Organization 2016 Genomics & informatics Vol.14 No.4

Glucose tolerance tests have been devised to determine the speed of blood glucose clearance. Diabetes is often tested with the standard oral glucose tolerance test (OGTT), along with fasting glucose level. However, no single test may be sufficient for the diagnosis, and the World Health Organization (WHO)/International Diabetes Federation (IDF) has suggested composite criteria. Accordingly, a single multi-class trait was constructed with three of the fasting phenotypes and 1- and 2-hour OGTT phenotypes from the Korean Association Resource (KARE) project, and the genetic association was investigated. All of the 18 possible combinations made out of the 3 sets of classification for the individual phenotypes were taken into our analysis. These were possible due to a method that was recently developed by us for estimating genomic associations using a generalized index of dissimilarity. Eight single-nucleotide polymorphisms (SNPs) that were found to have the strongest main effect are reported with the corresponding genes. Four of them conform to previous reports, located in the CDKAL1 gene, while the other 4 SNPs are new findings. Two-order interacting SNP pairs of are also presented. One pair (rs2328549 and rs6486740) has a prominent association, where the two single-nucleotide polymorphism locations are CDKAL1 and GLT1D1. The latter has not been found to have a strong main effect. New findings may result from the proper construction and analysis of a composite trait.

Study of reaction dynamics through the correlation function of fragments from heavy-ion collisions

Jaeyong Yee,Gary Westfall 한국물리학회 2004 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.44 No.2

Intermediate mass fragments (IMFs: 3 Z 18) in coincidence with ssion-like fragments were measured in the reaction 40Ar+232Th at Ebeam = 15 - 115 A MeV. Three distinct sources of IMF emission were identied by using the azimuthal angular correlation function among two ssion-like fragments and an IMF. Variations of the respective contributions of the three emission modes to the IMF multiplicity with the beam energy were estimated. Pre-ssion emission gains dominance in this energy range while the evaporation from the ssion-like fragments decreases to the point that its importance becomes comparable to that of simultaneous ternary breakup.

Detecting Genetic Interactions for Quantitative Traits Using <i>m</i> -Spacing Entropy Measure

Yee, Jaeyong,Kwon, Min-Seok,Jin, Seohoon,Park, Taesung,Park, Mira Hindawi Publishing Corporation 2015 BioMed research international Vol.2015 No.-

<P>A number of statistical methods for detecting gene-gene interactions have been developed in genetic association studies with binary traits. However, many phenotype measures are intrinsically quantitative and categorizing continuous traits may not always be straightforward and meaningful. Association of gene-gene interactions with an observed distribution of such phenotypes needs to be investigated directly without categorization. Information gain based on entropy measure has previously been successful in identifying genetic associations with binary traits. We extend the usefulness of this information gain by proposing a nonparametric evaluation method of conditional entropy of a quantitative phenotype associated with a given genotype. Hence, the information gain can be obtained for any phenotype distribution. Because any functional form, such as Gaussian, is not assumed for the entire distribution of a trait or a given genotype, this method is expected to be robust enough to be applied to any phenotypic association data. Here, we show its use to successfully identify the main effect, as well as the genetic interactions, associated with a quantitative trait.</P>

GC/MS 분석과 베이지안 분류 모형을 이용한 새 윤활유와 사용 엔진 오일의 동일성 추적과 분류

김남이(Nam Yee Kim),남금문(Geum Mun Nam),김유나(Yuna Kim),이동계(Dong-Kye Lee),박세연(Seh Youn Park),이경재(Kyoungjae Lee),이재용(Jaeyong Lee) 한국분석과학회 2014 분석과학 Vol.27 No.1

Adsorption of 1,3-Benzodithiolylium Tetrafluoroborate (1,3-BDYT) on Carbon Nanotubes

Sohee Park,Ki-jeong Kong,Hye-Mi So,이정오,장현주,Jaeyong Yee 한국물리학회 2010 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.57 No.1

We present systematic first-principles studies of the adsorption of 1,3-benzodithiolylium tetrafluoroborate (1,3-BDYT) on various single-walled carbon nanotubes (CNTs). 1,3-BDYT was reported as one of the electrophilic molecules that suppress the metallic properties of CNTs when it is adsorbed on the surfaces of CNTs. It was found that 1,3-BDYT tends to be more strongly bound to metallic CNTs of smaller diameters than to semiconducting CNTs. It interacts with CNTs via covalent sp3 bonding. From the band structure calculations, we found that 1,3-BDYT could open the band gap of the metallic CNTs by generating molecular states near the Fermi level via sp3hybridization.

Phorbol 12-Myristate 13-Acetate Enhances Long-Term Potentiation in the Hippocampus through Activation of Protein Kinase $C{\delta}$ and ${\varepsilon}$

Kim, Eung Chang,Lee, Myeong Jong,Shin, Sang Yep,Seol, Geun Hee,Han, Seung Ho,Yee, Jaeyong,Kim, Chan,Min, Sun Seek The Korean Society of Pharmacology 2013 The Korean Journal of Physiology & Pharmacology Vol.17 No.1

Many intracellular proteins and signaling cascades contribute to the sensitivity of N-methyl-D-aspartate receptors (NMDARs). One such putative contributor is the serine/threonine kinase, protein kinase C (PKC). Activation of PKC by phorbol 12-myristate 13-acetate (PMA) causes activation of extracellular signal-regulated kinase (ERK) and promotes the formation of new spines in cultured hippocampal neurons. The purpose of this study was to examine which PKC isoforms are responsible for the PMA-induced augmentation of long-term potentiation (LTP) in the CA1 stratum radiatum of the hippocampus in vitro and verify that this facilitation requires NMDAR activation. We found that PMA enhanced the induction of LTP by a single episode of theta-burst stimulation in a concentration-dependent manner without affecting to magnitude of baseline field excitatory postsynaptic potentials. Facilitation of LTP by PMA (200 nM) was blocked by the nonspecific PKC inhibitor, Ro 31-8220 ($10{\mu}M$); the selective $PKC{\delta}$ inhibitor, rottlerin ($1{\mu}M$); and the $PKC{\varepsilon}$ inhibitor, TAT-${\varepsilon}V1$-2 peptide (500 nM). Moreover, the NMDAR blocker DL-APV ($50{\mu}M$) prevented enhancement of LTP by PMA. Our results suggest that PMA contributes to synaptic plasticity in the nervous system via activation of $PKC{\delta}$ and/or $PKC{\varepsilon}$, and confirm that NMDAR activity is required for this effect.

Phorbol 12-Myristate 13-Acetate Enhances Long-Term Potentiation in the Hippocampus through Activation of Protein Kinase CՄ and Յ

Eung Chang Kim,Myeong Jong Lee,Sang Yep Shin,Geun Hee Seol,Seung Ho Han,Jaeyong Yee,Chan Kim,Sun Seek Min 대한생리학회-대한약리학회 2013 The Korean Journal of Physiology & Pharmacology Vol.17 No.1

Many intracellular proteins and signaling cascades contribute to the sensitivity of N-methyl-D- aspartate receptors (NMDARs). One such putative contributor is the serine/threonine kinase, protein kinase C (PKC). Activation of PKC by phorbol 12-myristate 13-acetate (PMA) causes activation of extracellular signal-regulated kinase (ERK) and promotes the formation of new spines in cultured hippocampal neurons. The purpose of this study was to examine which PKC isoforms are responsible for the PMA-induced augmentation of long-term potentiation (LTP) in the CA1 stratum radiatum of the hippocampus in vitro and verify that this facilitation requires NMDAR activation. We found that PMA enhanced the induction of LTP by a single episode of theta-burst stimulation in a concentration- dependent manner without affecting to magnitude of baseline field excitatory postsynaptic potentials. Facilitation of LTP by PMA (200 nM) was blocked by the nonspecific PKC inhibitor, Ro 31-8220 (10ՌM); the selective PKCՄ inhibitor, rottlerin (1ՌM); and the PKCՅ inhibitor, TAT-ՅV1-2 peptide (500 nM). Moreover, the NMDAR blocker DL-APV (50ՌM) prevented enhancement of LTP by PMA. Our results suggest that PMA contributes to synaptic plasticity in the nervous system via activation of PKCՄ and/or PKCՅ, and confirm that NMDAR activity is required for this effect.