The process of protein engineering is currently evolving towards a heuristic understanding of the sequence-function relationship. Improved DNA sequencing capacity, efficient protein function characterization and improved quality of data points in conjunction with well-established statistical tools from other industries are changing the protein engineering field. Algorithms capturing the heuristic sequence-function relationships will have a drastic impact on the field of protein engineering. In this review, several alternative approaches to quantitatively assess sequence space are discussed and the relatively few examples of wet-lab validation of statistical sequence-function characterization/correlation are described.
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