Multiple Sequence Alignment Slides

Multiple Sequence Alignment Slides - Computational Biology...

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Unformatted text preview: Computational Biology Multiple Sequence Alignment (MSA) – p.1/49 D e fi n i t i o n o f a G l o b a l M S A Generalization of a pairwise alignment to more than 2 sequences Insert spaces into each of the ¡ strings such that resulting strings have all the same length ¢ Modified strings are arrayed in ¡ rows and ¢ columns where each character and space of each string is in a unique column. – p.2/49 E x a m p l e : S e q u e n c e s f r o m T r i o s e p h o s p h a t e I s o m e r a s e Rice: CNGTTDQVDKIVKILNEGQIASTDVVEVVV...KGVSA Mosquito: MNGDKASIADLCKVLTTGPLNADTEVVVGC...ISP Human: MNGRKQSLGELIGTLNAAKVPADTEVVCAP...ISP Monkey: MNGRKQNLGELIGTLNAAKVPADTEVVCAP...ISP as a result we get: 1 CNGTTDQVDKIVKILNEGQIASTDVVEVVV...VSA 4 MNGRKQNLGELIGTLNAAKVPAD__TEVVC...ISP 3 MNGRKQSLGELIGTLNAAKVPAD__TEVVC...ISP 2 MNGDKASIADLCKVLTTGPLNAD__TEVVV...ISP – p.3/49 M S A i n v e r s e t o P S A In database searches, pairwise alignment is used to identify previously unknown biological relationship based on sequence similarity In MSA we are doing the inverse problem, based on known biological relationships between sequences, we want to identify unknown conserved subpatterns – p.4/49 B i o l o g i c a l R e l e v a n c e o f M S A High sequence similarity implies high functional or structural similarity Sequences with functional or structural similarity can differ a lot in their sequences Pairwise alignments cannot detect the latter cases – p.5/49 B i o l o g i c a l R e l e v a n c e o f M S A I I Example: Hemoglobin 4 chains of about 140 AA each contained in organisms as diverse as mammals and insects about 100 AA-mutations in each of the chains since divergence of insects and invertebrates – p.6/49 E x a m p l e lengths=141,141 simil=385.3, PAM_dist=105, identity=40.4% ID=HBA_HUMAN AC=P01922; DE=Hemoglobin alpha chain. OS=Homo sapiens (Human), Pan troglodytes (Chimpanzee), and Pan paniscus (Pygmy chimpanzee) (Bonobo). OC=Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. KW=Heme; Oxygen transport; Transport; Erythrocyte; Disease mutation; Polymorphism; Acetylation; 3D-structure. RES=1.5 VLSPADKTNVKAAWGKVGAHAGEYGAEALERMFLSFPTTKTYFPHFDLSHGSAQVKGHGKKVADALTNAVAH |||| ||:.|..|||:|||::|: .|...|!!|:.||.:..| |.:|:|||:|.!.|||!||.|:.|::... VLSPFDKAGVIKAWGQVGANTGQGDAMGAEKLFFDFPRSAGYNPALDVSHGAAYITGHGRKVLDTATDTYKM VDDMPNALSALSDLHAHKLRVDPVNFKLLSHCLLVTLAAHLPAEFTPAVHASLDKFLASVSTVLTSKYR !|. |.:!.:||| :...|.|.|.:!|.|:. !.|.!|:. ..|:|..|...||.||||...!!| .|| IDAGPASMCSLSDGQPRGLVVGPFKYKQLTTEIAVPMATCEADELTQGVEGMLDTFLASPIEIITLSYR – p.7/49 B o t t o m l i n e Structurally and functionally conserved molecules can differ in sequence pairwise alignments will not reveal conserved patterns Other extreme: Comparison of 2 sequences with very high similarity important patterns lost in high similarity MSA: compare multiple related sequences simultaneously to reveal critical patterns – p.8/49 G r a p h i c a l e x p l a n a t i o n A B C D E F G too similar too far apart – p.9/49 U...
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This note was uploaded on 02/13/2012 for the course CS 91.510 taught by Professor Staff during the Fall '09 term at UMass Lowell.

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Multiple Sequence Alignment Slides - Computational Biology...

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