My research focuses on developing biophysical and analytical tools for data-driven systems biology. We integrate advances in chemistry, engineering, and data science to characterize native biological systems at unprecedented resolution and details and to quantitatively profile the fundamental mechanisms that govern the system’s ensemble behavior. We have pioneered 'Single Virus Genomics' by developing microfluidic platforms that enable direct profiling of individual virus genomes, bypassing the need for virus culture. This technology allows large-scale, unbiased profiling of single virus genomes, enabling a quantitative assessment of viral evolution and infection dynamics. In parallel, we are actively developing and applying spatial omics tools to leverage spatial information to identify the key molecular and cellular features that drive system-level phenotypes. Molecular and cellular interactions are mediated by physical contact. Thus, the spatial organization of molecules and cells is strongly linked to their functional organization. In my talk, I will present our technical innovations in achieving single virus sequencing and demonstrate the application of this novel technology in the quantitative assessment of influenza reassortment. Reassortment is a crucial mechanism for zoonosis, facilitating the transmission of viruses from animals to humans. Thus, analysis of reassortment statistics between natural influenza strains provides valuable insights into influenza evolution and emerging human strains. In addition, I will present insights gained from a spatial transcriptomics map of the honey bee brain, demonstrating how spatial information reveals new biological insights into the collective performance of molecules and cells in system-level functions.