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In this paper, a novel efficient FPGA-based architecture for the acceleration of the hmmsearch tool for biological sequence-to-profile alignment, which is based on the Viterbi algorithm, is presented. Typical hardware implementations of this Dynamic Programming-based algorithm require an amount of block RAMs proportional to the profile length in order to hold emission and transition probability scores for alignment matrix computation. In contrast, the proposed architecture uses the abundant logic slices available on FPGA as look-up tables or configuration elements (CEs) to hold the probability scores. Moreover, double buffering is used to efficiently manage a fixed number of CEs (equal to two i.e. CE ₀ and CE ₁ ) by scheduling both alignment matrix computation and processing element (PE) configuration to run simultaneously. This way, both time and space complexities are optimized, thus supporting multiple …