2 seq-comparison.pdfVIP

Bio-sequence Comparison Ying Xu (徐鹰) Bio-molecules ? Three major types of bio-molecules in our cells – nucleotides (DNA, RNA) – proteins – (poly)sugar Bio-sequences ? The first two classes of bio-molecules have linear structures so they can be represented as bio-sequences – DNA sequences (consisting of four types of letters, A, C, G, T) – RNA sequences (consisting of four types of letters, A, C, G, U) – protein sequences (consisting of 20 types of letters) ccgtacgtacgtagagtgctagtctagtcgtagcgccgtagtcgatcgtgtgggtagtagctgatatgatgcga ggtaggggataggatagcaacagatgagcggatgctgagtgcagtggcatgcgatgtcgatgatagcggta ggtagacttcgcgcataaagctgcgcgagatgattgcaaagragttagatgagctgatgctagaggtcagtg actgatgatcgatgcatgcatggatgatgcagctgatcgatgtagatgcaataagtcgatgatcgatgatgatg DNA sequence SAANLEYLKNVLLQFIFLKPG-SERERLLPVINTMLQLSPEEKGKLAAV NEKNMEYLKNVFVQFLKPESVPAERDQLVIVLQRVLHLSPKEVEILKAA protein sequence Bio-sequence Comparison ? Bio-sequence comparison is one of the most basic problems in bioinformatics ? The basic computational problem is to determine if two sequences are “similar”, partially similar and how similar – AACGGTA versus ATCGGGT DNA Sequence Comparison through Sequence Alignment ? Defining DNA sequence (dis)similarity in terms of two parameters, gaps and mismatches ? Example 1: AACG and AACG ? Example 2: AAGG and AACG ? Example 3: AACGGTATGC and ATCGGGTTGC AACG AACG | | | | AAGG AACG | | | 1 mismatch AACG ATCG - G GT GT A - TGC TGC 2 gaps and 1 mismatch DNA Sequence Alignment ? Best alignment: the alignment of two sequences with the smallest possible number of mismatches and gaps ? Score: each aligned position: +2; each mismatch/ gap: -1 AACG AACG | | | | AAGG AACG | | | AACG ATCG - G GT GT A - TGC TGC score = 8 score = 5 score = 13 Protein Sequence Alignment ? Protein sequence alignment: it is more complex to measure protein sequence similarity than that of DNA sequences – protein sequence alignment: “degree” of similarity ? Each pair of amino acids