Comparisons between two nucleotide sequences can be performed by customized integrated circuitry that can implement a Smith Waterman analysis in series, as opposed to the parallel implementations known in the art. Series performance enables such customized integrated circuitry to take advantage of optimizations, including enveloping thresholds that demarcate between cells of a two-dimensional matrix for which nucleotide comparisons are to be performed, and cells of the two-dimensional matrix for which no such comparison need be performed, and, instead, a value of zero can simply be entered. Additionally, such customized integrated circuitry facilitates the combination of multiple control units, each directing the comparison of a unique pair of nucleotides, with a single calculation engine that can generate values for individual cells of the two-dimensional matrices by which such pairs of nucleotides are compared.