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High Quality Content by WIKIPEDIA articles! A similarity matrix is a matrix of scores which express the similarity between two data points. Similarity matrices are strongly related to their counterparts, distance matrices and substitution matrices. Similarity matrices are used in sequence alignment. Higher scores are given to more-similar characters, and lower or negative scores for dissimilar characters. Nucleotide similarity matrices are used to align nucleic acid sequences. Because there are only four nucleotides commonly found in DNA (Adenine (A), Cytosine (C), Guanine (G) and Thymine (T)), nucleotide similarity matrices are much simpler than protein similarity matrices.