Computing Scan Statistic p Values Using Importance Sampling,With Applications to Genetics and Medical Image Analysis

We present an importance sampling method for deciding, based on an observed random field, if a scan statistic provides significant evidence of increased activity in some localized region of time or space. Our method allows consideration of scan statistics based simultaneously on multiple scan geometries. Our approach yields an unbiased p value estimate whose variance is typically smaller than that of the naive hit-or-miss Monte Carlo technique when the p value is small. Furthermore, our p value estimate is often accurate for critical values that are not far enough in the tails of the null distribution to allow for accurate approximations via extreme value theory. The importance sampling approach unifies the analysis of various random field models, from (spatial) point processes to Gaussian random fields. For a scan statistic M, the method produces a p value of the form PM ≥ τ] = Bρ, where B is the Bonferroni upper bound and the correction factor ρ measures the conservativeness of this upper bound. We present the application of our importance sampling estimator to multinomial sequences (molecular genetics), spatial point processes (digital mammography), and Gaussian random fields (PET scan brain imagery).