組員 : B 沈冠宇 B 林哲宇 B 翁以諾 B 歐柏宏
Outline 生物信息，序列比對，來找出不同序列之間的相似之處，並鑒定這些 相似之處可能在功能、結構、進化關係等上的相關性的方法。 DNA 序列比對 是本系 白敦文 ( 葉問 ) 教授 的專長之一此學年白老師的 專題奕是此 話說白老師實驗室買了所謂的 次世代定序儀 全台僅有 20 台左右 人類身上 僅有 A 、 C 、 T 、 G 四種 但白老師表示存成純文字檔將有 3GigaBytes 即使有次世代定序儀 亦要消耗大量時間比對 ( 生物方面 資工系不予深究 ) ( 白老師表示 : 我現在生物還是很爛 …)
Scoring Role Match Mismatch
Scoring Role(Cont’d) a i =b j Score=2 a i or b j align with a blank Score=-1 a i ≠b j Score=-1
Scoring Role(Cont’d)
Find an alignment which has the Highest score 基本上有點類似 Dynamic Programming 中的 LCS 1)A(i,j) = the score of optimal alignment 2)A(0,0)=0 3)A(i,0)= -i 4)A(0,j)= -j 5) If ( a i =b j )then A(i, j)= A(i-1, j-1) +2 Else A(i, j)=Max{ (A(i-1,j) –1, A(i,j-1) –1, A(i-1,j-1) –1 ) }
Find an alignment which has the Highest score(Cont’d)
Score = = -1
Find an alignment which has the Highest score(Cont’d) Score= = -1
Find an alignment which has the Highest score(Cont’d) Score= = -1
February 26, 2002Sequence Alignment -- Gary Jackoway12 Algorithm Description DP algorithms have a strong relationship to recursion: define a base case and prove that you can extend. If you already have the optimal solution to: X…Y A…B then you know the next pair of characters will either be: X…YZ orX…Y- orX…YZ A…BCA…BC A…B- (where “-” indicates a gap). So you can extend the match by determining which of these has the highest score.
February 26, 2002Sequence Alignment -- Gary Jackoway13 Global versus Local Alignment Want to find local matching areas, even when far removed from each other in the sequence: ACTTAGCAGACTAACGTAAC CCATGACTAACGGGACCTAC Smith-Waterman: Use Needleman-Wunsch but add: IF value<0, replace with 0 (and set backtrack to none). When matrix is complete, backtrack from all local maxima, creating local matching alignments.
February 26, 2002Sequence Alignment -- Gary Jackoway14 PAM: Percent Accepted Mutation Substitution Matrix (Dayhoff) Substitution matrices based on sound evolutionary principles. Find PAM1 by comparing groups of proteins known to be evolutionarily closely related. Find PAM-n my multiplying PAM1 by itself n times. PAM60: ~60% similar, PAM250: ~20% similar. The more distant the expected relationship, the higher PAM-n should be used.
February 26, 2002Sequence Alignment -- Gary Jackoway15 BLOSUM: BLOcks SUbstition Matrix Start with highly-conserved patterns (blocks) in a large set of closely related proteins. Use the likelihood of substitutions found in those sequences to create a substitution probability matrix. BLOSUM-n means that the sequences used were n% identical. BLOSUM62 is “standard”.