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Importance: With timely collection of SARS-CoV-2 viral genome sequences, it is important to apply efficient data analytics to detect emerging variants at the earliest time., Objective: To evaluate the application of a statistical learning strategy (SLS) to improve early detection of novel SARS-CoV-2 variants using viral sequence data from global surveillance., Design, Setting, and Participants: This case series applied an SLS to viral genomic sequence data collected from 63 686 individuals in Africa and 531 827 individuals in the United States with SARS-CoV-2. Data were collected from January 1, 2020, to December 28, 2021., Main Outcomes and Measures: The outcome was an indicator of Omicron variant derived from viral sequences. Centering on a temporally collected outcome, the SLS used the generalized additive model to estimate locally averaged Omicron caseload percentages (OCPs) over time to characterize Omicron expansion and to estimate when OCP exceeded 10%, 25%, 50%, and 75% of the caseload. Additionally, an unsupervised learning technique was applied to visualize Omicron expansions, and temporal and spatial distributions of Omicron cases were investigated., Results: In total, there were 2698 cases of Omicron in Africa and 12 141 in the United States. The SLS found that Omicron was detectable in South Africa as early as December 31, 2020. With 10% OCP as a threshold, it may have been possible to declare Omicron a variant of concern as early as November 4, 2021, in South Africa. In the United States, the application of SLS suggested that the first case was detectable on November 21, 2021., Conclusions and Relevance: The application of SLS demonstrates how the Omicron variant may have emerged and expanded in Africa and the United States. Earlier detection could help the global effort in disease prevention and control. To optimize early detection, efficient data analytics, such as SLS, could assist in the rapid identification of new variants as soon as they emerge, with or without lineages designated, using viral sequence data from global surveillance.