序列比对2教学课件.ppt

Sequence Alignment 全局比对和局部比对 全局比对 Global alignment 准全局比对 Semiglobal alignment 算法改动：不对两端空位进行罚分 局部比对 Local alignment 算法改动：小于0的位置填上0 e.g. AAACACGTGTCT ----ACGT---- e.g. AACCTATAGCT -GCGTATA--- Database Search 数据库搜索 Most common use of pairwise sequence alignments is to search databases for related sequences. For instance: find probable function of newly isolated protein by identifying similar proteins with known function. Most often, local alignment ( “Smith-Waterman”) is used for database searching: you are interested in finding out if ANY domain in your protein looks like something that is known. Often, full Smith-Waterman is too time-consuming for searching large databases, so heuristic methods are used (FASTA, BLAST). * Heuristic Search Algorithms FASTA (Pearson 1995) Uses heuristics to avoid calculating the full dynamic programming matrix Speed up searches by an order of magnitude compared to full Smith- Waterman The statistical side of FASTA is still stronger than BLAST BLAST (Altschul 1990, 1997) Uses rapid word lookup methods to completely skip most of the database entries Extremely fast One order of magnitude faster than FASTA Two orders of magnitude faster than Smith-Waterman Almost as sensitive as FASTA BLAST Algorithm 输入序列：AILVPTV 拆分： AILV ILVP LVPT VPTV …… 在数据库中搜索单词匹配 从单词两端延伸该匹配，直至局部比对得分低于给定的阈值 FASTA Algorithm 将查询序列拆分为单词，记录各单词在序列中出现的位置 为目标序列（数据库）建立表格 比较偏移表，得到合理比对 FAMLGFIKYLPGCM |||||||| TGFIKYLPGACT 对于序列FAMLGFIKYLPGCM 单词 A C D E F G H I K L M N P Q R S T V W Y 位置1 2 13 1 5 7 8 4 3 11 9 位置2 6 12 10 14 对于序列TGFIKYLPGACT 1 2 3 4 5 6 7 8 9 10 11 12 T G F I K Y L P G A C T 3 -2 3 3 3 -3 3 -4 -8 2 10 3 3 3 * 数据库搜索结果的统计显著性分析 S 比对得分 P 随机从数据库中选取一条序列，它的比对得分 大于等于S的可能性 E 随机抽取E条序列，这些序列的比对得分大于 等于S （10-3） NCBI BLAST /Blast.cgi Choose the right blast tool * http://www.ebi.ac.uk/Tools/sss/fasta/ FASTA 蛋白质序列模体（模式, motif） 序列比对后，序列之间共有的一些短的序列模式。 结构模体：构成特定的三维空间结构 序列模体：保守的序列区段 序列模体可以是连续的，也可以是分散的 Application of sequence align