The Statistics of Sequence Similarity Scores

To assess whether a given alignment constitutes evidence for homology, it helps to know how strong an alignment can be expected from chance alone. In this context, "chance" can mean the comparison of (i) real but non-homologous sequences; (ii) real sequences that are shuffled to preserve compositional properties [1-3]; or (iii) sequences that are generated randomly based upon a DNA or protein sequence model. Analytic statistical results invariably use the last of these definitions of chance, while empirical results based on simulation and curvefitting may use any of the definitions.