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Next-generation sequencing (NGS) has revolutionized the scale and depth of biomedical sciences. Because of its unique ability for the detection of sub-clonal variants within genetically diverse populations, NGS has been successfully applied to analyze and quantify the exceptionally-high diversity within viral quasispecies, and many low-frequency drug- or vaccine-resistant mutations of therapeutic importance have been discovered. Although many works have intensively discussed the latest NGS approaches and applications in general, none of them has focused on