tetano
Editor, Senior Moderator
Nat Commun
. 2026 Mar 30.
doi: 10.1038/s41467-026-71196-3. Online ahead of print.
AI-guided multi-omics analysis identifies NPC1-modulated susceptibility to SARS-CoV-2 infection under PM[SUB]2.5[/SUB] exposure
Guoqing Feng[SUP] 1 [/SUP], Zheng Dong[SUP] 2 [/SUP], Limei Ke[SUP] 3 [/SUP], Weilai Zhou[SUP] 4 [/SUP], Yu Tian[SUP] 5 [/SUP], Xingtian Li[SUP] 6 [/SUP], Wenxin Xiang[SUP] 1 [/SUP], Yanjun Li[SUP] 7 [/SUP], Qi Huang[SUP] 7 [/SUP], Linfeng Liu[SUP] 1 [/SUP], Bo Yin[SUP] 1 [/SUP], Shouyi Yan[SUP] 1 [/SUP], Jianxiu Liu[SUP] 6 [/SUP], Xindong Ma[SUP] 6 [/SUP], Huaiyong Chen[SUP] 8 9 [/SUP], Miao He[SUP] 4 [/SUP], Ke Hao[SUP] 10 [/SUP], Sijin Liu[SUP] 11 12 [/SUP], Qian Di[SUP] 13 14 [/SUP]
Affiliations
Exposure to airborne fine particulate matter (PM[SUB]2.5[/SUB]) has been linked to increased risk of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, yet the underlying mechanisms remain unclear. Here, by leveraging a fine-tuned foundation model of single-cell transcriptomics, we uncover shared transcriptional signatures between PM[SUB]2.5[/SUB] exposure and SARS-CoV-2 infection. We further validate this association using population-level epidemiological analyses and perform genome-wide association studies (GWAS) to identify genetic variants that modulate infection risk under PM[SUB]2.5[/SUB] exposure. In addition, we identify NPC1 as a key modulator involved in SARS-CoV-2 infection efficiency under virus-laden PM[SUB]2.5[/SUB] exposure through integrative functional genomic analyses and in vitro experiments. Our findings suggest that PM[SUB]2.5[/SUB] facilitates viral entry through an NPC1-modulated endo-lysosomal pathway, providing a mechanistic explanation for observed pollution-related susceptibility. By integrating artificial intelligence (AI)-guided transcriptomics, epidemiology, GWAS, functional genomics, and in vitro verification, our study elucidates how environmental and genetic factors jointly influence SARS-CoV-2 susceptibility. This work highlights how AI-assisted multi-omics integration systematically decodes the health impacts of environmental exposures from molecular to population levels and informs air quality policy and infectious disease preparedness.
. 2026 Mar 30.
doi: 10.1038/s41467-026-71196-3. Online ahead of print.
AI-guided multi-omics analysis identifies NPC1-modulated susceptibility to SARS-CoV-2 infection under PM[SUB]2.5[/SUB] exposure
Guoqing Feng[SUP] 1 [/SUP], Zheng Dong[SUP] 2 [/SUP], Limei Ke[SUP] 3 [/SUP], Weilai Zhou[SUP] 4 [/SUP], Yu Tian[SUP] 5 [/SUP], Xingtian Li[SUP] 6 [/SUP], Wenxin Xiang[SUP] 1 [/SUP], Yanjun Li[SUP] 7 [/SUP], Qi Huang[SUP] 7 [/SUP], Linfeng Liu[SUP] 1 [/SUP], Bo Yin[SUP] 1 [/SUP], Shouyi Yan[SUP] 1 [/SUP], Jianxiu Liu[SUP] 6 [/SUP], Xindong Ma[SUP] 6 [/SUP], Huaiyong Chen[SUP] 8 9 [/SUP], Miao He[SUP] 4 [/SUP], Ke Hao[SUP] 10 [/SUP], Sijin Liu[SUP] 11 12 [/SUP], Qian Di[SUP] 13 14 [/SUP]
Affiliations
- PMID: 41912520
- DOI: 10.1038/s41467-026-71196-3
Exposure to airborne fine particulate matter (PM[SUB]2.5[/SUB]) has been linked to increased risk of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, yet the underlying mechanisms remain unclear. Here, by leveraging a fine-tuned foundation model of single-cell transcriptomics, we uncover shared transcriptional signatures between PM[SUB]2.5[/SUB] exposure and SARS-CoV-2 infection. We further validate this association using population-level epidemiological analyses and perform genome-wide association studies (GWAS) to identify genetic variants that modulate infection risk under PM[SUB]2.5[/SUB] exposure. In addition, we identify NPC1 as a key modulator involved in SARS-CoV-2 infection efficiency under virus-laden PM[SUB]2.5[/SUB] exposure through integrative functional genomic analyses and in vitro experiments. Our findings suggest that PM[SUB]2.5[/SUB] facilitates viral entry through an NPC1-modulated endo-lysosomal pathway, providing a mechanistic explanation for observed pollution-related susceptibility. By integrating artificial intelligence (AI)-guided transcriptomics, epidemiology, GWAS, functional genomics, and in vitro verification, our study elucidates how environmental and genetic factors jointly influence SARS-CoV-2 susceptibility. This work highlights how AI-assisted multi-omics integration systematically decodes the health impacts of environmental exposures from molecular to population levels and informs air quality policy and infectious disease preparedness.