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Multilevel splitting for rare events estimation in permutation tests

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Permutation tests are widely employed in statistical analysis, especially when the assumptions of parametric tests are violated, or the data distribution is unknown. However, classical permutation tests encounter challenges when attempting to estimate the probabilities of rare events with high relative accuracy, leading to difficulties in applying corrections for multiple hypothesis testing. In this study, we propose an original method for estimating arbitrarily small P-values in permutation tests, which is based on multilevel splitting for Monte Carlo method. The proposed method involves splitting the original permutation space into non-overlapping levels based on the statistic values. This approach allows the problem of estimating the original probability of a rare event to be reduced to estimating ordinary conditional probabilities for each level. Utilizing such an approach enables efficient estimation of the desired P-values while maintaining a balance between computation time and the level of relative error. The efficacy of the method is demonstrated in its application to the task of estimating arbitrary P-values in the two-sample Kolmogorov-Smirnov test. Comparing the method results with true P-values has shown practical convergence of the method. Moreover, examples of the superiority of the proposed method over alternative asymptotic approaches have been provided. Thus, the proposed method shows significant potential for application across a broad spectrum of scientific fields, such as systems biology, immunology, and others. Furthermore, the method can be adapted for use in various statistical analysis scenarios that require handling probabilities of rare events in permutation tests. 

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