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Cover While next-generation sequencing technologies have greatly increased sequencing capacity, genotyping libraries composed of a large number of specimens is still challenging. Combinatorial pooling designs offer a method to harness next generation sequencers for that task. This solution has deep mathematical connections to concepts in information theory and combinatorics and is reminiscent of the solving of Sudoku puzzles. DNA Sudoku exploits a combinatorial design to genotype thousands of specimens in a single sequencing run. (Cover design by Beni Zaks and Yaniv Erlich. Photo: Ronit Zaks-Erlich. [For details, see Erlich et al., pp. 1243–1253, and related papers by Prabhu and Pe’er, pp. 1254–1261, and Xin et al., pp. 1262–1269.])