Researchers used mass spectrometry (MS) to analyze viral sequence variations in the SARS outbreak in Singapore, revealing new insights into transmission patterns. The study found that 95% of SARS-CoV sequence variations could be detected using MS, allowing for the identification of molecular relationships between viral isolates. This method helped clarify an unresolved epidemiological link involving a German patient and identified a new route of SARS-CoV introduction into Singapore. The analysis also detected heterogeneous viral sequences in lung tissues, suggesting coevolution of virus quasispecies within a host. The study demonstrated the importance of genetic analysis in understanding pathogen transmission and highlighted the sensitivity and accuracy of MS-based methods for characterizing SARS-CoV genetic variations. The findings suggest that MS-based analysis should be used routinely during outbreaks to enable effective control. The study also confirmed the Singapore origin of a German SARS-CoV isolate, indicating transmission via an aircraft event. The results emphasize the value of genetic analysis in tracking pathogen transmission and improving epidemiological investigations. The method is sensitive, accurate, and cost-effective, making it suitable for large-scale studies. The study underscores the importance of combining genetic sequencing with MS-based analysis for efficient outbreak investigations.Researchers used mass spectrometry (MS) to analyze viral sequence variations in the SARS outbreak in Singapore, revealing new insights into transmission patterns. The study found that 95% of SARS-CoV sequence variations could be detected using MS, allowing for the identification of molecular relationships between viral isolates. This method helped clarify an unresolved epidemiological link involving a German patient and identified a new route of SARS-CoV introduction into Singapore. The analysis also detected heterogeneous viral sequences in lung tissues, suggesting coevolution of virus quasispecies within a host. The study demonstrated the importance of genetic analysis in understanding pathogen transmission and highlighted the sensitivity and accuracy of MS-based methods for characterizing SARS-CoV genetic variations. The findings suggest that MS-based analysis should be used routinely during outbreaks to enable effective control. The study also confirmed the Singapore origin of a German SARS-CoV isolate, indicating transmission via an aircraft event. The results emphasize the value of genetic analysis in tracking pathogen transmission and improving epidemiological investigations. The method is sensitive, accurate, and cost-effective, making it suitable for large-scale studies. The study underscores the importance of combining genetic sequencing with MS-based analysis for efficient outbreak investigations.