About my research
We never know what the next emerging virus will be. The virus world is vast, dynamic, and deeply mysterious, an immense biological frontier that remains largely unexplored. I’m fascinated by this hidden universe and the extraordinary diversity that likely lies beyond current knowledge. By unveiling the hidden virosphere and tracing zoonotic risks across ecosystems, my research seeks to illuminate how viral diversity drives the emergence, evolution, and impact of infectious diseases—with the ultimate goal of advancing human and planetary health.
Approaching fundamental questions in virology through the lens of computational biology offers a new perspective and the potential to address long-standing questions in the field. By integrating interdisciplinary approaches encompassing machine learning, viral genomics and structural biology, I build new tools to systematically decode the hidden diversity and function of unknown viruses, aiming to illuminate biological process of human-associated viruses and offer new insights into combatting those human pathogens.
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🌎 Expanding the global hidden virosphere
"Uncovering the vast, uncharted diversity of RNA viruses across global ecosystems"
[Picture]
© By Zan Xu, Wan Wang, Jianye Li (2024)
🌌 Remote viral "dark matter" discovery
Current metagenomic tools can fail to identify highly divergent viral unknowns. This has spurred us to develop an novel model (i.e LucaProt) to unveil remote viral "dark matter" from diverse global ecosystems. LucaProt uncovered over 160,000 RNA viral species and 180 viral supergroups, including viruses with unusually large and complex genomes. Compared to previous tools, our methods revealed a broader and deeper layer of the hidden virosphere, reveiling immense viral dark matter while also highlighting how AI-driven approaches can reshape our understanding of viral diversity at scale.
Relevant publications:
Hou X†, He Y†, Fang P, Mei SQ, Xu Z, ..., Holmes EC, Li ZR, Shi M. Using artificial intelligence to document the hidden RNA virosphere. Cell. 2024.
Hou X†, He Y†, Fang P, Mei SQ, Xu Z, ..., Holmes EC, Li ZR, Shi M. Using artificial intelligence to document the hidden RNA virosphere. Cell. 2024.
> Featured on Cell's cover, Nature news, BBC interview, Cell Patterns preview, Sydney University news, Sun Yat-Sen University news, China Network Television news, Xinhua News Agency news, ScienceNet news, News-Medical news
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🦠 Tracing hidden zoonotic viruses and human disease
"Understanding how animal viruses cross species barriers and their origin"
🐾 Zoonotic virus discovery
Zoonotic viruses pose a persistent threat to global health due to their ability to jump across species barriers. My research focuses on uncovering the hidden diversity of zoonotic viruses and understanding their potential for zoonotic spillover. By integrating metagenomics, host association inference, and evolutionary analysis, I and my collaborators identified over 100 viruses circulating in wildlife, livestock, and other reservoirs that may have relevance to human disease. These effors not only expand our knowledge of the viral world but also contributes to early detection and risk assessment of future outbreaks.
[Picture]
© By Elena Mozhvilo (2025)
Relevant publications:
Pan YF†, Zhao H†, Gou QY†, Shi PB, Tian JH, …, Hou X, …, Li J, Wu WC, Shi M. Metagenomic analysis of individual mosquito viromes reveals the geographical patterns and drivers of viral diversity. Nat Ecol Evol. 2024.
He WT†, Hou X†, Zhao J†, Sun J, He H, …, Holmes EC, Shi M, Su S. Virome characterization of game animals in China reveals a spectrum of emerging pathogens. Cell. 2022.
> News in Nat Rev Microbio, Sydney University news, City University of Hong Kong news, News-Medical news
Shi WF†, Shi M†, Que TC†, Cui XM†, Ye RZ†, ..., Hou X, …, Jiang JF, Hu YL, Cao WC. Trafficked Malayan pangolins contain viral pathogens of humans. Nat Microbiol. 2022.
Tian J†, Hou X†, Ge M, Xu H, Yu B, ..., Holmes EC, Lei C, Shi M.The diversity and evolutionary relationships of ticks and tick-borne bacteria collected in China. Parasites & vectors. 2022.
Xu Z†, Fan N†, Hou X†, Wang J, Fu S, Song J, Shi M, Liang G. Isolation and identification of a novel Phlebovirus, Hedi virus, from sandflies collected in China. Viruses. 2021.
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He WT†, Hou X†, Zhao J†, Sun J, He H, …, Holmes EC, Shi M, Su S. Virome characterization of game animals in China reveals a spectrum of emerging pathogens. Cell. 2022.
> News in Nat Rev Microbio, Sydney University news, City University of Hong Kong news, News-Medical news
Shi WF†, Shi M†, Que TC†, Cui XM†, Ye RZ†, ..., Hou X, …, Jiang JF, Hu YL, Cao WC. Trafficked Malayan pangolins contain viral pathogens of humans. Nat Microbiol. 2022.
Tian J†, Hou X†, Ge M, Xu H, Yu B, ..., Holmes EC, Lei C, Shi M.The diversity and evolutionary relationships of ticks and tick-borne bacteria collected in China. Parasites & vectors. 2022.
Xu Z†, Fan N†, Hou X†, Wang J, Fu S, Song J, Shi M, Liang G. Isolation and identification of a novel Phlebovirus, Hedi virus, from sandflies collected in China. Viruses. 2021.
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⚒︎⚖︎ Mapping the whole infectome
"Uncovering co-existing pathogens in wildlife and domestic species"
[Picture]
© By Manuel Sardo (2025)
⚔︎ Zoonotic risks beyond viruses
Animals host a wide spectrum of infectious agents that can impact both animal and human health. I am interested in characterizing the entire infectome to simultaneously detect viruses, bacteria, and other microbial pathogens in individual hosts. I aim to uncover hidden pathogens, trace cross-species transmission events, and better understand host-pathogen ecology. This approach offers a more complete view of pathogen diversity and provides crucial insights into zoonotic risk and the complex microbial dynamics that shape emerging infectious diseases.
Relevant publications:
Hou X†✉, Wang J†, Wang DX†, Chen Y†, Li XX†, …, Holmes EC, Deng ZQ, Shi M. Comprehensive infectome analysis reveals diverse infectious agents with zoonotic potential in wildlife. bioRxiv. 2025.
Xin GY†, Wang DX†, Zhang X†, Cen QQ, Peng MW, …, Hou X, …, Holmes EC, Deng ZQ, Shi M. Infectome analysis of small mammals in Southern China reveals ecological associations and emerging threats from diverse pathogens. bioRxiv. 2025.
Huang X†, Wu W†, Tian X, Hou X, Cui X, …, Cai X, An T, Shi M. A total infectome approach to understand the etiology of infectious disease in pigs. Microbiome. 2022.
Hou X†✉, Wang J†, Wang DX†, Chen Y†, Li XX†, …, Holmes EC, Deng ZQ, Shi M. Comprehensive infectome analysis reveals diverse infectious agents with zoonotic potential in wildlife. bioRxiv. 2025.
Xin GY†, Wang DX†, Zhang X†, Cen QQ, Peng MW, …, Hou X, …, Holmes EC, Deng ZQ, Shi M. Infectome analysis of small mammals in Southern China reveals ecological associations and emerging threats from diverse pathogens. bioRxiv. 2025.
Huang X†, Wu W†, Tian X, Hou X, Cui X, …, Cai X, An T, Shi M. A total infectome approach to understand the etiology of infectious disease in pigs. Microbiome. 2022.
Wang J†, Gou QY†, Luo GY†, Hou X, Liang G, Shi M. Total RNA sequencing of Phlebotomus chinensis sandflies in China revealed viral, bacterial, and eukaryotic microbes potentially pathogenic to humans. Emerg Microbes Infect. 2022.