An integrated genome-wide model for hookah constituents-gene-pathway-disease relationships

Hookah smoking is becoming increasingly popular worldwide and recent epidemiological studies indicate that it is significantly associated with respiratory diseases, and could contain constituents more harmful than cigarette smoking. However, the gene expression alterations and mechanisms of disease development induced by the hookah constituents are still unclear. Here, we are the first to propose a new experimental design and use RNA sequencing to profile bronchial epithelial cells from different hookah smoking exposure conditions (GSE162386). For our hookah-smoking dataset, we developed an integrated genome-wide model, hierarchical-systems biology model (HiSBiM), to systematically investigate the effects of smoking hookah and to compare the biological pathways with public cigarette smoking datasets. Our results show that the infectious disease-related pathways were enriched in hookah smoking than in cigarette smoking, which could be due to polluted hookah devices or pathogen contaminated water filters. Furthermore, we investigate the subsystem and pathway differences in hookah smoking between charcoal and electronic heating ways. We observed that cardiovascular and atherosclerosis-related pathways were activated after exposure to charcoal combustion, which may relate to combustion components carbon monoxide and polyaromatic hydrocarbons. Overall, our results show that hookah smoking could involve a higher risk in several diseases than cigarette smoking and link the relations between hookah constituents to diseases. We believe that our HiSBiM is a useful integrated method for providing multiple-level valued insights for genome-wide analysis on various omics data sets.