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N) bê@s S bê | -1.0a? bê | -0.3  V  ?¥o  V[ ASmith-Waterman ?E?¥s ? ??¥Kús′ V ?? N   ?V UB? μKúM ??¥?  ? ¥??7? ?  ??s¥M ????1 ? ?bV?B ?E¥' & V[ A ? ^B? ?M ??17? ^?8M ??1¥ZEb 4.12 ? ??? ?E [ á ìo ¥ ?E ??? ??? ?E¥Sb? ???¥' ± ^ ^|ˉù5s 3?D-M ?¥0ù5YV p3ò?0ù5 ?¤???ù5¥3 %Z?b? ?  ? ? ? ?μs???v¥ H? 12Taa? ^B?7 ^ V ?μ+?b ?¨? ??? ZE p3?Bù531?¨í ò backtracking / ?i? bê@s?? ?1?r? ús1¥?] ^?b? ???¥?? ^1|ò?KD0 ^? ?¤  ?K?? μK a2T¥ ^?7¤?12Tb 4.13? ?? 1¥ ? o ? ì B?? D?? ? o? ?μ? 1¥V? V[ AT ?? 1¥ ?Zb? ^1 y ? LC ? o¥ ? ìid^ Yb ?" ? o? ¥? ?v | ì ?m ì4ú ? ìr q¥ ZEbí ? ^ Needleman-Wunsch¥ ?E? ^ Smith-Waterman ?E? ? ?v¥?  ? a ? HW  V¤ sb?v? ¥ ? o ? ì ? ì?dè{ Hμ H .àíE L Cb Smith-Waterman ?EXüBt¨9 ?"d  LC è ? μv? i? ?? ?¥ ? ?¥ MPSrch??b? ^?t"d/NM??Li O ?"9 ??q¥á ??Z?÷?7$'bA ?? ?íP ^ ? o ? ì??31 I n¥B?ù5bü^  ?  ?E ?4?¥ ? o ? ì??¥? ?D}°? é# ? o ?  á MM1b FastA ? BLAST ?? ^ " -K訥? ?M ??¥ ? o ? ì?? ? ì??°s ? ? ? ¥¥ l?  ? i| ? ìü %ii¤??é¥M ?? ? ¥b ? ì¥a ]? V[  ?Y¥9 ?"d ?7?AG ?9 ??q"d73 %? ?ù5b 4.13.1 FastA FastA ?E ^? Lipman? Pearson? 1985 M?V¥ Lipman ? Pearson 1985bFastA ¥' ± ^ ^ MYD}°? M ? ¥¥? ¥?  ? ?1 k-tupleb?aé?  ? o ? ì H ? ¥éB? ^ 1-2 ??é DNA ?  ? o ? ì HYè?¨ v?¥ ′K1 6?abYV1? ?? ?¥ ? # Mê? V[?B?? ??? ?¥?LZ_ ¥Bt ? ¥ ? b FastA???¨vé heuristic approach  ?E|ê? ]B?L Mo¤í¥ ? ?¤  ?b9ü ^ aYV? ? ¥¥?|?t ? ¥? ?  ?¤  ?[L¤??é¥M ?? ? b?üi?" FastA {2T? ?C? ? ¥ ?b??/ ?|1o ¥ BLAST ???¥? ? ? ?b ?T ? ¥ u×?FastA ? ¨? ??? ?E?t ? ¥ u×W? ? bêb ? FastA ? ìá 3¥?? {2T ?m 6.8 ? Ub {2T¥?B? ?? ??? '|[#????V¥?b¤/ ?  ?4?¥?  ?' è?¥ | /F ?α " s8 ? o ???'|N)1 SWISS-PROT o? 35?b ?a ^ ?¨? ??? HW' è 1 12.42 eb ???tB??¥ ^ ? o ? ì2Tb n5  ? ì¤?¥ "S? e? a ü  ? " V?¨??lb1? 8 é?? úo  10 ? "S?  L=? H V[ ÷¥ ?  è ? - 50 ?b ? ¥ "S? ¥? ??  ? ? o ?¥ ê ?? ú ¥ SW V U SWISS-PROT "S? ¥S M ?a? |??  ??s?b ?|?S ü ? ¥?s¥? ?b?¤" ^???9 ?¤?¥ S??a?a¥s ?′bKaB  ^ ù? ′' E ′ Wn 6.7.3 ? ¨ ? ?12T¥??b¤í? 0 ¥ E ′V ü ? ¥ ? ¥?v V ? ^? ?y í/?¥b?? è0? - 10?? ¥ E′???9ü ^ a ? ì¥??dèúb  ? ì2Tóà1?a {2T?W% }°? D "S? W¥W%¥1 2T  ? "9 V[?¨?ê4b1h  { é?μ H?BQ? Ho {à1? ??sW%12Tb12Tó}°? ? "S? -W ? ¥?¥ ?  f ?? ? ? ¥¨ μ|o: pV UM ?? ? ¥¨ |o. pV Ub?¥M ???l | %D ?¨¥M ?? s ? ?9 V[?¨?ê4b' è? P¨ BLOSUM9D ? {2T¥à1?? s b12T Z¥ ?3V U}°? ¥?ê?/Z¥ ?3V U "S? ¥?ê ?N) (?9? ?¥ bêb 4.13.2 BLAST BLAST ^' ?1 ? ìy  Basic Local Alignment Search Tool ¥ ê? Altschul?? 1990 M4b?B ?E?9 ?"d ¥úr? ?+Y ^?*ü LC  UNIX"d/¥i?? P ?1 ? o ? ì¥ @? èq1? ? ¥ ? o ? ì{ ? ê ?¥Mb BLAST ?E' &?e? ?¥'1? ^?  ?  segment pair ¥à Qb ?ì?  ?  ^· ?ó?? ?¥B0?  ? ì¥éM? O V[??í bê¥? ? ? ¥bBLAST ?E n5s}°? ? "S? W ?μ ? ¥??VB??′¥?  ?  ?a μB?é¥ ? ? ó?¥M ???′ü %¤?B?é¥M ?? ? ? ús′ ?  high-scoring pairs, HSPs b?ü ^í bê¥ BLAST1 ?E¥$9 ^ BLAST {2T¥+?bm 6.9? ?A U¥ BLAST {2T? μ 4?ús′ ? b D FastA ? ?BLAST ¥ {2T ?? ???'|[#óD)b¤/ ?  }°?  ?' è? ˉ ^ | /F ?α " s8 [# ? o ?? ú ^) ?V¥d o ? SWISS-PROT?  ? ob ?¤"ü ^ ? ì2TbD FastAB"5  "S?   ? " V?¨?l? ú ˉo  10?b "S? ? ? ? o ê ?? ú¥ spV U SWISS-PROT "S? I|a S M ???  ??s? ¤/ ? ^ "S? ?ús′ ? ¥Kú¤sús′ ?  ¥ ? "?? ? N ??bKaB  ^à q′? p ′ Wn 6.7.3 ?  V¨ ? ?1¥? ?B?¤í? 0¥ p′V ü ? ¥ ? ¥?v V ? ^? ?y í/?¥b?? è0? - 10?? ¥ p′?M??9ü ^ a ? ì¥???úb  ? ì2Tà1aü ^Gv¨?1 p ? ¥}°? ? "S? Wí bêús′ ?  ¥12T? FastAB"¨? V[ê4 ¥? ?? ?à1?¥?  ? ?? 1W%2Tb? ?B?ús′ ? ?  ? ì¥  S???ê??  ?¥ 'ê?b}°? ? "S? -W¥M] ? ¥¨M?¥? ?} ?V UbN?' è ? P¨  SEG ??¨? à7?ˉ¥ u×' *t μ?ú ?¥+???F ?¥ u× ? GAPGAPGAPGAP ?"¥×ˉ? b ? ìYè ^?e?a *" μ+ y2 ¥?  ??F[ à7??áL¥ús′ ? ¥¥Cb$ à7¥ u× ? ì2T?¨3? XV Ub  ? bê¥ BLAST ?  ? ?K¥ BLAST??o ?¨?í bê¥1büV ü12TYè?C Btí bê?? ??¥ u× ?m 6.9 ? - 10 ? "S? ¥ús′ ? ???B?b? 4X`?tús′ ?  V[YVBtM ???? Oμ bê¥ ? ?¤  ?F? Bt ÷é¥?÷  L= 3tDil¥1b ?  ? ± ^BLAST ?EüV?é ? bê? ? Altshul ?1997 b1 ê  ? o S ? ì¥ HW?¥ ?EosB?Kz¥ús′ ? i[N1$¨? ??? ZE|?B ? _  ü %K?á 3¥12T V ?μ bê? ?b?? ? ? °s ?μú s′ ? ¥???¥ ?E1e ?E y 3b BLAST ?E¥éB? ?  V[ I n ? ? 1?? 1¥μr2?/Bc|W%) ? 8 ?Eb 4.14 'cl2 ? ? ?1oMé? ? o°??? M ?? ? ì ^ ? o?¨¥ ??1Z ?b}°? ? "S? ¥M ??? ^ MY??? ?X?yEB-Wé? 1"¥B?è¨ZEb ? ? BFüV?ì?l¥3 % ?ó?ù5¥9 ?V??1 ?E??5 ^ ? E¥ 8 LCbB? ?E V[μ??]¥ LCZE 2T ? ? ??? ?M] ? L=  ? V ?μ ?μYb ? ? ?? 1K'¥ZE ^YV? ? bê|M]? / id9 ? ¥?¥? ?7¤?M ??s ?b ? ? ?é??aM ?????¥? -W¥1???¨s ? ?bs ? ??? ?M]?-W¥M ??s ?′7 O ??]?-W¥M ??s ?′b1D V ?h  bê? ?ir?KD12T31? ? bê¥@sb ? ? o I n?? ? ? ¥¥ ??1  ? v?s ?í í¥′1 0 yN MY ? ??μb? é?  ??ù¥?9D q V[¤? ?× ?? ? ? ?]?-W¥ ? ¥?íM ??s ?′? 9F± D?|¥] H99F  ?. 2b ??Vú <¥. 2??4 |? D¥?| ^? s?¥Bv 45b ? ? Dayhoff lM ? ? PAM ? V¤ s?lMà QbPAM250 ?é ?  ?M?? ?? -W¥M ??1 20%'? 1?¥ ′ uyN PAM250 ? ^? 1 H訥 ? 8 ?b ? ? BLOSUM ? ^? BLOCKS ? o?üV1¥?   v¥9Dà q y¥bD Dayhoff lM ? ?M1BLOSUM ? MYé?  ??ù¥M ? ?? ÷F V Ly1 -?¥9D q ^VúM ??? ?w?¤ ?¥b ? ? ? 12Ti? ?¨ ?£ ü ?? -WB?M1b? 12TYè ?μ V?d9′ ? ?? 1 H?¨¥à q′ p ù?′ Eb ? ? ??m ^ ?? 1¥K'ZEb??m¨ V j?ZEV U ?? - W¥M ??b??m¨ X àV UB?? Y àV U 6B?? M]?? ¥ ?í í¨3??V Ub ? ?? ? ?M]5??m 1BH?W¥ ?L ? ? ì?? ?M]5 V[ A?Wb ? ? ? 1??]¥ ?D ?V?]?Q?? ?c¥ 3tD+ ?b ?[? 12T?ip-sb? 1s?81? ?1  ? ' Needleman-Wunsch ?E? Smith-Waterman ?Eb ? ? Needleman-Wunsch ?E? Smith-Waterman ?E?¨? ???ZE|B? ˉù5s31?éM ?¥0ù5iVBF μús′¥1?sa?¥2Tb ?  ? ?E ( Es{ Hb ? ? FastA ? BLAST ^? ?M ??¥ ? o ? ì?? ? ì (Vùs? ? ? ¥¥ ?  ? ?iN$ ¤?K?12Tb ? ì?¨vé ?E4 ú? ?b?é¥ BLAST??? ?÷ yi ? bê? ?b 4.15 éB?· 2 ? 1 ?E DAYHOFF,M.O.,SCHWARTZ,R.M. and ORCUTT,B.C. (1978) In Atlas of Protein Sequence and Structure,Vol.5,suppl. 3, Dayhoff, M.O. (ed), NBRF, Washington, DC, p.345. Henikoff, S. and Henikoff, J.G. (1992) Amino acid substitution matrices from protein blocks. Proceedings of the National Academy of Sciences, USA, 89, 10915-10919. NEEDLEMAN, S.B. and WUNSCH, C.D. (1970) A general method applicable to the search for similarities in the amino acid sequences of two proteins. Journal of Molecular Biology, 48, 443-453. SMITH, T.F. and WATERMAN, M.S. (1981) Identification of common molecular subsequences. Journal of Molecular Biology, 147, 195-197. ? o ? ìZE ALTSCHUL, S.F., GISH, W., MILLER, W., MYERS, E.W. and LIPMAN, D.J. (1990) Basic local alignment search tool. Journal of Molecular Biology, 215, 403-410. ALTSCHUL, S.F., BOGUSKI, M.S., GISH, W. and WOOTTON, J.C. (1994) Issues in searching molecular sequence databases. Nature Genetics, 6, 119-129 ALTSHUL, S.F., MADDEN, T.L., SCHA?FFER, A.A., ZHANG, J., ZHANG, Z., MILLER, W. and LIPMAN, D.J. (1997) Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Research, 25(17), 2289-3402. LIPMAN, D.J. and PEARSON, W.R. (1985) Rapid and sensitive protein similarity searches. Sciences, 227, 1435-1441.