Transcriptomic identification of high-altitude illness candidate genes and physiological mechanisms: a multidimensional bioinformatics study with 106 drug-food homologous substance target prediction.
- 1Department of Traditional Chinese Medicine, The General Hospital of Western Theater Command, Chengdu, Sichuan, China.
- 2Department of Geriatrics, The General Hospital of Western Theater Command, Chengdu, Sichuan, China.
- 3Department of Ophthalmology, The General Hospital of Western Theater Command, Chengdu, Sichuan, China.
Abstract
Introduction
High-altitude (HA) illness threatens health after acute high-altitude exposure, but its molecular mechanisms and effective interventions remain unclear. Drug-food homologous (DFH) substances have potential for HA illness intervention, yet their active components and targets are unknown.Methods
Datasets related to HA illness, as well as 106 DFH substances and their corresponding chemical components, were obtained in this study. Differentially expressed genes were identified, and active components were screened according to the criteria of drug-likeness ≥0.18 and oral bioavailability ≥30%. The GraphBAN tool was used to predict high-confidence compound-protein interaction pairs, so as to obtain the corresponding candidate active components and candidate genes. Meanwhile, the ADMETlab3 platform was employed to evaluate the druggability and toxicity of these active components, thereby determining the core active components and core genes. Candidate genes were screened were screened out by machine learning, and relevant interaction networks were constructed. Finally, further studies such as pathway enrichment, immune infiltration, molecular docking, and molecular dynamics simulation were carried out.Results
Of the 95 candidate active components subjected to toxicological screening, only 8 passed the safety evaluation, and 6 of these met both physicochemical and toxicological criteria; five candidate genes (DNAJC19, MRFAP1L1, TBPL1, RPS21, and NABP1) and two key active components (polyacetylene PQ-2, PQ-2) were identified, and these candidate genes corresponded to the DFH substance "Panacis Quinquefolii Radix". The abovementioned candidate genes were enriched in pathways such as ribosome and oxidative phosphorylation, and they were correlated with most differential immune cells. Except for RPS21 and MRFAP1L1, the binding abilities of the other candidate genes with the key active components were good (binding energies <-5.0 kcal/mol). Molecular dynamics simulation confirmed that the interaction of their binding was stable.Discussion
Panacis Quinquefolii Radix might intervene in HA illness via active components (PQ-2) that target five candidate genes, regulating immunity and metabolism. This provided a preliminary computational basis for DFH-based HA illness prevention/treatment.
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BibTeX
@article{liu2026transcriptomic,
title = {{Transcriptomic identification of high-altitude illness candidate genes and physiological mechanisms: a multidimensional bioinformatics study with 106 drug-food homologous substance target prediction.}},
author = {Defang Liu and Jiao Yan and Ting Luo and Yu Guo and Yubo Li and Pan Long and Ling Yang},
journal = {Frontiers in physiology},
year = {2026},
month = oct,
doi = {10.3389/fphys.2026.1752620},
url = {https://europepmc.org/article/MED/42952516},
note = {CC BY},
}
RIS
TY - JOUR
TI - Transcriptomic identification of high-altitude illness candidate genes and physiological mechanisms: a multidimensional bioinformatics study with 106 drug-food homologous substance target prediction.
AU - Defang Liu
AU - Jiao Yan
AU - Ting Luo
AU - Yu Guo
AU - Yubo Li
AU - Pan Long
AU - Ling Yang
PY - 2026
DA - 2026/10/14
JO - Frontiers in physiology
DO - 10.3389/fphys.2026.1752620
UR - https://europepmc.org/article/MED/42952516
AB - Introduction High-altitude (HA) illness threatens health after acute high-altitude exposure, but its molecular mechanisms and effective interventions remain unclear. Drug-food homologous (DFH) substances have potential for HA illness intervention, yet their active components and targets are unknown.Methods Datasets related to HA illness, as well as 106 DFH substances and their corresponding chemical components, were obtained in this study. Differentially expressed genes were identified, and active components were screened according to the criteria of drug-likeness ≥0.18 and oral bioavailability ≥30%. The GraphBAN tool was used to predict high-confidence compound-protein interaction pairs, so as to obtain the corresponding candidate active components and candidate genes. Meanwhile, the ADMETlab3 platform was employed to evaluate the druggability and toxicity of these active components, thereby determining the core active components and core genes. Candidate genes were screened were screened out by machine learning, and relevant interaction networks were constructed. Finally, further studies such as pathway enrichment, immune infiltration, molecular docking, and molecular dynamics simulation were carried out.Results Of the 95 candidate active components subjected to toxicological screening, only 8 passed the safety evaluation, and 6 of these met both physicochemical and toxicological criteria; five candidate genes (DNAJC19, MRFAP1L1, TBPL1, RPS21, and NABP1) and two key active components (polyacetylene PQ-2, PQ-2) were identified, and these candidate genes corresponded to the DFH substance "Panacis Quinquefolii Radix". The abovementioned candidate genes were enriched in pathways such as ribosome and oxidative phosphorylation, and they were correlated with most differential immune cells. Except for RPS21 and MRFAP1L1, the binding abilities of the other candidate genes with the key active components were good (binding energies <-5.0 kcal/mol). Molecular dynamics simulation confirmed that the interaction of their binding was stable.Discussion Panacis Quinquefolii Radix might intervene in HA illness via active components (PQ-2) that target five candidate genes, regulating immunity and metabolism. This provided a preliminary computational basis for DFH-based HA illness prevention/treatment.
SN - 1664-042X
ER -