The article discusses the rapid transition of clinical metagenomic next-generation sequencing (mNGS) from research to clinical laboratories, highlighting its potential to revolutionize the diagnosis and treatment of infectious diseases. mNGS is a comprehensive approach that sequences all microbial and host genetic material (DNA and RNA) from patient samples, enabling the detection of a wide range of pathogens, including bacteria, viruses, fungi, and parasites. This method has been applied to various areas such as antimicrobial resistance, the microbiome, human host gene expression, and oncology. Key applications of mNGS include: 1. **Infectious Disease Diagnostics**: mNGS can identify pathogens directly from clinical samples, predict antimicrobial resistance, and detect virulence determinants, improving diagnostic accuracy. 2. **Microbiome Analyses**: mNGS helps understand the role of the microbiome in disease states, aiding in the development of probiotic therapies. 3. **Human Host Response Analysis**: mNGS of RNA libraries provides insights into host responses to infections, which can be used for disease classification and prediction. 4. **Oncology**: mNGS can identify tumor-associated viruses and their genomic integration sites, aiding in personalized treatment strategies. Despite its potential, the clinical implementation of mNGS faces challenges such as low sensitivity due to high human host background, complex sample handling, and the need for highly trained personnel. The article also discusses methods to improve sensitivity, including host depletion and enrichment techniques, and emphasizes the importance of quality management and validation in clinical settings. Overall, mNGS is poised to transform diagnostic microbiology and advance precision medicine.The article discusses the rapid transition of clinical metagenomic next-generation sequencing (mNGS) from research to clinical laboratories, highlighting its potential to revolutionize the diagnosis and treatment of infectious diseases. mNGS is a comprehensive approach that sequences all microbial and host genetic material (DNA and RNA) from patient samples, enabling the detection of a wide range of pathogens, including bacteria, viruses, fungi, and parasites. This method has been applied to various areas such as antimicrobial resistance, the microbiome, human host gene expression, and oncology. Key applications of mNGS include: 1. **Infectious Disease Diagnostics**: mNGS can identify pathogens directly from clinical samples, predict antimicrobial resistance, and detect virulence determinants, improving diagnostic accuracy. 2. **Microbiome Analyses**: mNGS helps understand the role of the microbiome in disease states, aiding in the development of probiotic therapies. 3. **Human Host Response Analysis**: mNGS of RNA libraries provides insights into host responses to infections, which can be used for disease classification and prediction. 4. **Oncology**: mNGS can identify tumor-associated viruses and their genomic integration sites, aiding in personalized treatment strategies. Despite its potential, the clinical implementation of mNGS faces challenges such as low sensitivity due to high human host background, complex sample handling, and the need for highly trained personnel. The article also discusses methods to improve sensitivity, including host depletion and enrichment techniques, and emphasizes the importance of quality management and validation in clinical settings. Overall, mNGS is poised to transform diagnostic microbiology and advance precision medicine.