Biology subjects

Choe, E. K.

Publications and source records attributed to Choe, E. K..

3 recordsLinked to original sources

bioRxiv2020

NETMAGE: a humaN-disEase phenoType MAp GEnerator for the Visualization of PheWAS

SummaryGiven genetic associations from a PheWAS, a disease-disease network can be constructed where nodes represent phenotypes and edges represent shared genetic associations between phenotypes. To improve the accessibility of the visualization of shared genetic components across phenotypes, we developed the humaN-disEase phenoType MAp GEnerator (NETMAGE), a web-based tool that produces interactive phenotype network visualizations from summarized PheWAS results. Users can search the map by a variety of attributes, and they can select nodes to view information such as related phenotypes, associated SNPs, and other network statistics. As a test case, we constructed a network using UK BioBank PheWAS summary data. By examining the associations between phenotypes in our map, we can potentially identify novel instances of pleiotropy, where loci influence multiple phenotypic traits. Thus, our tool provides researchers with a means to identify prospective genetic targets for drug design, contributing to the exploration of personalized medicine. Availability and implementationOur service runs at https://hdpm.biomedinfolab.com. Source code can be downloaded at https://github.com/dokyoonkimlab/netmage. Contactdokyoon.kim@pennmedicine.upenn.edu Supplementary informationSupplementary data and user guide are available at Bioinformatics online.

genetics↗

bioRxiv2020

Multi-layered network-based pathway activity inference using directed random walks: application to predicting clinical outcomes in urologic cancer

MotivationTo better understand the molecular features of cancers, a comprehensive analysis using multi-omics data has been conducted. Additionally, a pathway activity inference method has been developed to facilitate the integrative effects of multiple genes. In this respect, we have recently proposed a novel integrative pathway activity inference approach, iDRW, and demonstrated the effectiveness of the method with respect to dichotomizing two survival groups. However, there were several limitations, such as a lack of generality. In this study, we designed a directed gene-gene graph using pathway information by assigning interactions between genes in multiple layers of networks. ResultsAs a proof-of-concept study, it was evaluated using three genomic profiles of urologic cancer patients. The proposed integrative approach achieved improved outcome prediction performances compared with a single genomic profile alone and other existing pathway activity inference methods. The integrative approach also identified common/cancer-specific candidate driver pathways as predictive prognostic features in urologic cancers. Furthermore, it provides better biological insights into the prioritized pathways and genes in an integrated view using a multi-layered gene-gene network. Our framework is not specifically designed for urologic cancers and can be generally applicable for various datasets. AvailabilityiDRW is implemented as the R software package. The source codes are available at https://github.com/sykim122/iDRW.

bioinformatics↗

bioRxiv2020

Phenome-wide association study of a comprehensive health check-up database in a Korea population: Clinical application & trans-ethnic comparison

AbstractsO_ST_ABSBackgroundC_ST_ABSThe expanding use of the phenome-wide association study (PheWAS) faces challenges in the context of using International Classification of Diseases billing codes for phenotype definition, imbalanced study population ethnicity, and constrained application of the results to clinical practice or research. MethodsWe performed a PheWAS utilizing deep phenotypes corroborated by comprehensive health check-ups in a Korean population, along with trans-ethnic comparisons through the UK Biobank and Biobank Japan Project. Network analysis, visualization of cross-phenotype mapping, and causal inference mapping with Mendelian randomization were conducted in order to make robust, clinically applicable interpretations. ResultsOf the 136 phenotypes extracted from the health check-up database, the PheWAS associated 65 phenotypes with 14,101 significant variants (P < 4.92x10-10). In the association study for body mass index, our population showed 583 exclusive loci relative to the Japanese population and 669 exclusive loci relative to the European population. In the meta-analysis with Korean and Japanese populations, 72.5% of phenotypes had uniquely significant variants. Tumor markers and hematologic phenotypes had a high degree of phenotype-phenotype pairs. By Mendelian randomization, one skeletal muscle mass phenotype was causal and two were outcomes. Among phenotype pairs from the genotype-driven cross-phenotype associations, 71.65% also demonstrated penetrance in correlation analysis using a clinical database. ConclusionsThis comprehensive analysis of PheWAS results based on a health check-up database will provide researchers and clinicians with a panoramic overview of the networks among multiple phenotypes and genetic variants, laying groundwork for the practical application of precision medicine.

genetics↗