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The diatom Didymosphenia geminate is a single-celled alga found in lakes, streams, and rivers. Nuisance blooms of D. geminate affect the diversity, abundance, and productivity of other aquatic organisms. Because D. geminate can be transported by humans on waders and other gear, accurate spatial prediction of habitat suitability is urgently needed for early detection and rapid response, as well as for evaluation of monitoring and control programs. We compared four modeling methods to predict D geminata’s habitat distribution; two methods use presence-absence data (logistic regression and classification and regression tree [CART]), and two involve presence data (maximum entropy model [Maxent] and genetic algorithm for rule-set production [GARP]). Using these methods, we evaluated spatially explicit, bioclimatic and environmental variables as predictors of diatom distribution. The Maxent model provided the most accurate predictions, followed by logistic regression, CART, and GARP. The most suitable habitats were predicted to occur in the western US, in relatively cool sites, and at high elevations with a high base-flow index. The results provide insights into the factors that affect the distribution of D geminate and a spatial basis for the prediction of nuisance blooms.