Dataset Information

Using Composite Phenotypes to Reveal Hidden Physiological Heterogeneity in High-Altitude Acclimatization in a Chinese Han Longitudinal Cohort.

ABSTRACT: 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 (SpO₂) 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.

SUBMITTER: Li Y

PROVIDER: S-EPMC9584130 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Using Composite Phenotypes to Reveal Hidden Physiological Heterogeneity in High-Altitude Acclimatization in a Chinese Han Longitudinal Cohort.

Li Yi Y Ma Yanyun Y Wang Kun K Zhang Menghan M Wang Yi Y Liu Xiaoyu X Hao Meng M Yin Xianhong X Liang Meng M Zhang Hui H Wang Xiaofeng X Chen Xingdong X Zhang Yao Y Duan Wenyuan W Kang Longli L Qiao Bin B Wang Jiucun J Jin Li L

Phenomics (Cham, Switzerland) 20210222 1

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 ...[more]

PMID: 36939745

Similar Datasets

Project description:Background: Altitude acclimatization is a physiological process that restores oxygen delivery to the tissues and promotes oxygen use under high altitude hypoxia. High altitude sickness occurs in individuals without acclimatization. Unraveling the molecular underpinnings of altitude acclimatization could help understand the beneficial body responses to high altitude hypoxia as well as the altered biological events in un-acclimatized individuals. This study assessed physiological adjustments and circulating microRNA (cmiRNA) profiles in individuals exposed to high altitude, aiming to explore altitude acclimatization in humans. Methods: Ninety volunteers were enrolled in this study. Among them, 22 individuals provided samples for microRNA arrays; 68 additional individuals constituted the validation set. Un-acclimatized individuals were identified by the Lake Louise Scoring System. Thirty-three phenotypes were recorded pre- and post-exposure to high altitude, including stress hormones, lipid profiles, hematological indices, myocardial enzyme spectrum, and liver and kidney function related enzymes. CmiRNA expression profiles were assessed using miRCURYTM LNA Array (v.18.0) screening, with data validated by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Then, associations of plasma microRNA expression with physiological adjustments were evaluated. The biological relevance of the main differentially expressed cmiRNAs was explored by bioinformatics prediction. Results: Nineteen of the 33 phenotypes were significantly altered during early altitude acclimatization, including hematological indices, lipid profiles, and stress hormones; meanwhile, 86 cmiRNAs (79 up-regulated and 7 down-regulated) showed differential expression with statistical significance. Among them, 32 and 25 microRNAs were strongly correlated with low-density lipoprotein-cholesterol and total cholesterol elevations, respectively. In addition, 22 microRNAs were closely correlated with cortisol increase. In un-acclimatized individuals, 55 cmiRNAs were up-regulated and 36 down-regulated, compared with acclimatized individuals. The HIF signaling pathway was suppressed in un-acclimatized individuals. Conclusion: Physiological adjustments, including the hematological system, stress hormones, and lipid molecules contributed to early altitude acclimatization, and showed strong correlations with cmiRNA reprogramming. Moreover, acclimatized and un-acclimatized individuals showed different cmiRNA profile. Suppression of the HIF-1 signaling pathway by microRNA regulation may play a key role in the pathogenesis of un-acclimatization with high altitude hypoxia.

Project description:High altitude acclimatization and disease have been the centerpiece of investigations concerning human health at high altitude. Almost all investigations have focused on either understanding and ameliorating high altitude disease or finding better methods of acclimatization/training at high altitude. The aspect of altitude de-induction/de-acclimatization has remained clouded despite the fact that it was documented since the first decade of twentieth century. A few recent studies, particularly in China, have stated unanimously that high altitude de-acclimatization involved multiple observable clinical symptoms ranging from headache to abdominal distention. These symptoms have been collectively referred to as "high altitude de-acclimatization syndrome" (HADAS). However, computational omics and network biology centric investigations concerning HADAS are nascent. In this study, we focus on the quantitative proteo-informatics, especially network biology, of human plasma proteome in individuals who successfully descended from high altitude areas after a stay of 120 days. In brief, the protein list was uploaded into STRING and IPA to compute z-score based cut-offs which were used to analyze the directionality and significance of various identified protein networks as well as the proteins within them. Relevant upstream regulators extracted using computational strategies were also validated. Time-points till the 180th day of de-induction have been investigated to comparatively assess the changes in the plasma proteome and protein pathways of such individuals since the 7th day of arrival at altitude. Our investigation revealed extensive effects of de-induction on lipid metabolism, inflammation and innate immune system as well as coagulation system. This novel study provides a conceptual framework for formulating therapeutic strategies to ease the symptoms of HADAS during de-acclimatization. Such strategies should focus on normalization of lipid metabolism, inflammatory signaling and coagulation systems.

Dataset Information

Using Composite Phenotypes to Reveal Hidden Physiological Heterogeneity in High-Altitude Acclimatization in a Chinese Han Longitudinal Cohort.

Publications

Using Composite Phenotypes to Reveal Hidden Physiological Heterogeneity in High-Altitude Acclimatization in a Chinese Han Longitudinal Cohort.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets