Altitude acclimatization is a human physiological process of adjusting to the decreased oxygen availability.Since several physiological processes are involved and their correlations are complicated,the analyses of sin...Altitude acclimatization is a human physiological process of adjusting to the decreased oxygen availability.Since several physiological processes are involved and their correlations are complicated,the analyses of single traits are insufficient in revealing the complex mechanism of high-altitude acclimatization.In this study,we examined these physiological responses as the composite phenotypes that are represented by a linear combination of physiological traits.We developed a strategy that combines both spectral clustering and partial least squares path modeling(PLSPM)to define composite phenotypes based on a cohort study of 883 Chinese Han males.In addition,we captured 14 composite phenotypes from 28 physiological traits of high-altitude acclimatization.Using these composite phenotypes,we applied k-means clustering to reveal hidden population physiological heterogeneity in high-altitude acclimatization.Furthermore,we employed multivariate linear regression to systematically model(Models 1 and 2)oxygen saturation(SpO_(2))changes in high-altitude acclimatization and evaluated model fitness performance.Composite phenotypes based on Model 2 fit better than single trait-based Model 1 in all measurement indices.This new strategy of using composite phenotypes may be potentially employed as a general strategy for complex traits research such as genetic loci discovery and analyses of phenomics.展开更多
基金supported by Shanghai Municipal Science and Technology Major Project(2017SHZDZX01)National Science Foundation of China(31330038)+5 种基金CAMS Innovation Fund for Medical Sciences(2019-I2M-5-066)Science and Technology Committee of Shanghai Municipality(16JC1400500)Ministry of Science and Technology(2015FY1117000)the 111 Project(B13016)Major Project of Special Development Funds of Zhangjiang National Independent Innovation Demonstration Zone(ZJ2019-ZD-004)supported by the Postdoctoral Science Foundation of China(2018M640333).
文摘Altitude acclimatization is a human physiological process of adjusting to the decreased oxygen availability.Since several physiological processes are involved and their correlations are complicated,the analyses of single traits are insufficient in revealing the complex mechanism of high-altitude acclimatization.In this study,we examined these physiological responses as the composite phenotypes that are represented by a linear combination of physiological traits.We developed a strategy that combines both spectral clustering and partial least squares path modeling(PLSPM)to define composite phenotypes based on a cohort study of 883 Chinese Han males.In addition,we captured 14 composite phenotypes from 28 physiological traits of high-altitude acclimatization.Using these composite phenotypes,we applied k-means clustering to reveal hidden population physiological heterogeneity in high-altitude acclimatization.Furthermore,we employed multivariate linear regression to systematically model(Models 1 and 2)oxygen saturation(SpO_(2))changes in high-altitude acclimatization and evaluated model fitness performance.Composite phenotypes based on Model 2 fit better than single trait-based Model 1 in all measurement indices.This new strategy of using composite phenotypes may be potentially employed as a general strategy for complex traits research such as genetic loci discovery and analyses of phenomics.
