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Minimizers are k-mer sampling schemes designed to generate sketches for large sequences that preserve sufficiently long matches between sequences. Despite their widespread application, learning an effective minimizer scheme with optimal sketch size is still an open question. Most work in this direction focuses on designing schemes that work well on expectation over random sequences, which have limited applicability to many practical tools. On the other hand, several methods have been proposed to construct minimizer schemes for a specific target sequence. These methods, however, require greedy approximations to solve an intractable discrete optimization problem on the permutation space of k-mer orderings. To address this challenge, we propose: (a) a reformulation of the combinatorial solution space using a deep neural network re-parameterization; and (b) a fully differentiable approximation of the discrete objective. We demonstrate that our framework, DEEPMINIMIZER, discovers minimizer schemes that significantly outperform state-of-the-art constructions on genomic sequences. 

Algorithms often have tunable parameters that impact performance metrics such as runtime and solution quality. For many algorithms used in practice, no parameter settings admit meaningful worst-case bounds, so the parameters are made available for the user to tune. Alternatively, parameters may be tuned implicitly within the proof of a worst-case guarantee. Worst-case instances, however, may be rare or nonexistent in practice. A growing body of research has demonstrated that data-driven algorithm design can lead to significant improvements in performance. This approach uses a training set of problem instances sampled from an unknown, application-specific distribution and returns a parameter setting with strong average performance on the training set.