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O =G-Improved hit criteria for DNA local alignment- SJOBIM 2004 Montral - June 28th Laurent No, Gregory Kucherov LORIA, Nancy France T"2@*       Plan Introduction Local alignment Heuristic methods Hit criteria Seed Models and extension proposed Single/Multiple hit strategies and extension proposed Experiments Conclusion Extensionst " Z  " Z  Local alignment methods r Why being interested in local alignment methods Improvement needed #sequences , #users , ( budget ) Dynamic programming (Smith-Waterman) Give an exact solution Quadratic cost (Best optimization in [Crochemore et al 02]) Heuristic Algorithms Fasta, Blast, PatternHunter, Blastz, Yass,& nZ0ZZ+Z%Z'Z=ZZZ,Z0                     % =,   "           Seed filtering  qStart with small conserved and easily detected fragments (seeds). Then extend seeds to build possible alignments$r:3q  Two questions usually asked rseed model: What can serve as a seed? hit criterion: What is the criterion that witnesses a potential alignment? Zr  )   s  What can serve as a seed"  AExact similarity : Seed Pattern : Contiguous Seed Example :    A #1Spaced Seed Model [Ma et al. 02: PATTERNHUNTER]*21 Seed Pattern : ###--#-##  # : obligatory match position  - : joker position ( don t care position) Weight : 6 [number of #] Span : 9 [number of all symbols] Example : ~  #     & Spaced Seeds  Some probabilistic observations: For spaced seeds, hits at subsequent positions are more independent events For contiguous vs spaced seeds of the same weight, the expected number of hits is (basically) the same but the probabilities of having at least one hit are very differentz"L!K&   6#  Some probabilistic observations:"!  ! U9 Spaced seeds   Spaced seed model is generally more sensitive than the contiguous seed model Extend spaced seed model by taking into account DNA substitutions specificityv    .Mutational events   RBiological properties Transitions are usually over-represented. Regularity phenomenon in coding sequences. Use those properties to extend the spaced seed modelV/,6$s  6 8$#BLASTZ model [Schwartz et al. 03]*$ # PA spaced seed that allows one possible transition substitution over its  # positions. Problem : running time seed of large weight to obtain reasonable speed.t5'1 /)YASS model: Transition Constrained Seeds**) Seed Pattern: ##@#-#@-###  # : obligatory match position  - : joker position ( don t care position)  @ : transition constrained position transition constrained position: position that corresponds to either a match or a transition.  , $=  0Transition Constrained Seeds 2Seed Pattern: ##@#-#@-###  # : obligatory match position  - : joker position ( don t care position)  @ : transitions constrained position Weight : 8 [number of # + half number of @] @ carries 1 bit of information whereas # carries 2 bits. @ adapted to GC-rich/poor genomes ,       4!.Spaced seeds and Transition-Constrained Seeds//. "Seed pattern ( why ##@#-#@-### and not #@-#-#-#@# ?) Not chosen randomly ! Need to: define an alignment model. search for the best (at least a good) seed pattern according to this model. ( Sensitivity : probability to detect any alignment given by the model ) Chosen model can drastically change the seed shape& Example Bernoulli model ##@-#@#--#-#-### Markov model ##@##-##@## 6Z*Z ZhZJZ6ZQZZ ff ff "    ( :6                $$ 5"Probabilistic Alignment Models:   Bernoulli [Keich et al 02] Markov [Buhler et al 03] Automata (M3/M8) and HMMs [Brejova et al 03] Homogeneous alignments [Kucherov et al 04]@|   =    &    ) Seed Design  o Alignment Model : Bernoulli P(match) = 0.7, P(transition)=0.15, P(transversion)=0.15 alignment length = 64pS    .E   ( Seed Design  q Alignment Model : Markov 5th Order, obtained on N.Menengitidis, S.Cerevisiae, Drosophila, and Human sequences.NX OH1     $ - Experiments  !S.Cerevisiae/Neisseiria sequences   D+To summarize ... We have presented several seed models (contiguous,  classic spaced seeds, BLASTZ) We introduced transition-constrained seeds and showed how they improve the sensitivity From detected seeds to detected alignments T,- 2 Hit criterion"   }What is the criterion that witnesses a potential alignment ? Restriction : only the information about seeds is available 6~'  5} ?("Several methods have been proposed" FASTA: Several small seeds on proximal diagonals BLAST: (single hit) One  large seed. Gapped-BLAST: (double hit) Two seeds on the same diagonal To define a good criterion we have first to define a class of similarities we want to detect : mutation modelZZZZZZZqZ  ` A)Mutation effect on Seeds &  Mutation effect Substitutions :  suppressing seeds Indels :  diagonal shifts Remaining seeds Estimation of inter-seed distances via a Waiting Time distribution Estimation of diagonals shifts via a Random Walk model vZBZZZ#Z Z ZZZ          .6   E,YASS hit criterion According to these parameters, YASS propose: An intermediate criterion between BLAST single/Gapped Blast double hit criterion. Overlap controlled multi-hits z-#2 -%, G. Sensitivity $  <Comparison of BLASTn/Gapped-BLAST/YASS hit criteria score 254   x       I/Sensitivity (cont) $   <Comparison of BLASTn/Gapped-BLAST/YASS hit criteria score 354    x       J0&YASS criterion mixed with spaced seeds&  3  Experiments  DLocal alignment sensitivity YASS software / BLASTn (2.2.6 package) :''.,   M2Ads  L1Ads {YASS web page http://www.loria.fr/projects/YASS YASS can be queried online http://yass.loria.fr YASS is Open Source # " H   5    S8 Conclusions   Two improvements: Transition-constrained spaced seeds Hit criterion combining statistical models and advantage of single/multi hit strategies. A tool that implements both of themR~$~$ Q6 Extensions  To be done Multi-seed approach [Li03, Bulher04, Noe04] Seed design on the fly (non necessary static seeds). and others & f r  / | O4 Questions   P5  !  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B B   .aggcctcgggctcgcgctcgcgcgctagacaccgggttacagcgt "/-"-  rz  P    0F,$D 0N  P    P ZB  s *D3f8c P ` ZB  s *D3f8c `B  0D3f8c`  ^T  P  #  P N  P     P rb   BZ  `B   0D P `B   0D  r  B BZGHI e  <$  dDetected alignment x  c $ԟ  @`   x  c $ @  Tz - P     ,$D 0|N  @P    @P ZB  s *D 0 ZB  s *D  ZB  s *D @P FN -    -    < -   `Detected seeds T B c $ T B c $ T B c $ H  0޽h ?O   ̙33___PPT10+D~' = @B D9' = @BA?%,( < +O%,( < +D4' =%(D' =%(D' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*%(D4' =%(D' =%(D' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*%(+m  #Yp0 (  pF   ~  Gp  ~ T Hp c $p 0  Ip < 0 *  VDot plot   Jp <p6 ~   ~.ctcgactcgggctcacgctcgcaccgggttacagcggtcgattgct//.  KpB B   .aggcctcgggctcgcgctcgcgcgctagacaccgggttacagcgt "/-"-  r p S   @`    p S î @`   x8 0 r Fp 0IV@ 0  Ep0 T  P  9p# 0  ZB :p s *D8c P ` ZB ;p s *D8c `B p# 0  rb ?p BZ  `B @p 0D P `B Ap 0D  x BpB HZGH~I  Cp B$ɮ r dDetected alignment Tz - P  Lp   ,$ 0|N  @P  Mp  @P ZB Np s *D 0 ZB Op s *D  ZB Pp s *D @P FN -   Qp -   Rp <ή -   `Detected seeds T SpB c $ T TpB c $ T UpB c $ & Vp 0Ӯ  ,$D 0 ! 1. Seed model<$&  l  pb Yp pb,$D 0rb WpB BZG0*H,I&8c Xb Xp 0Tٮ p  $! 2. Hit criterion<$& H p 0޽h ?_ ?pCpBp RpPpSp RpNpTp RpOpUpRpCpWp ̙33___PPT10+D' = @B DF' = @BA?%,( < +O%,( < +DA' =%(D' =%(D' =A@BBBB0B%(D' =1:Bvisible*o3>+B#style.visibility<*Vp%(D4' =%(D' =%(D' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*Yp%(+8+0+Vp +  6. h (  h h c $  @`     h  0,&  @`   h < F  ATCAGT |||||| ATCAGT ######80Z ( h s *P  < ATCAGTGCAATGCTCAAGA |||||.||.||||:||||| ATCAGCGCGATGCGCAAGAZ=0Z< b h s * ,$D 0 B###### ATCAGTGCAATGCTCAAGA |||||.||.||||:||||| ATCAGCGCGATGCGCAAGAZC0ZB  h s * ,$D 0 6B###### ATCAGTGCAATGCTCAAGA |||||.||.||||:||||| ATCAGCGCGATGCGCAAGAC0Z B  h s *d ,$D 0 &B###### ATCAGTGCAATGCTCAAGA |||||.||.||||:||||| ATCAGCGCGATGCGCAAGAC0Z B y  h s * ,$D 0 I ###### ATCAGTGCAATGCTCAAGA |||||.||.||||:||||| ATCAGCGCGATGCGCAAGAjJ0ZI   h s *8 ,$D 0 oI ###### ATCAGTGCAATGCTCAAGA |||||.||.||||:||||| ATCAGCGCGATGCGCAAGAJ0Z   I   h s *, ,$D 0 ?I ###### ATCAGTGCAATGCTCAAGA |||||.||.||||:||||| ATCAGCGCGATGCGCAAGAJ0Z   I H h 0޽h ? ̙33PH___PPT10(+D' = @B Dw' = @BA?%,( < +O%,( < +DA' =%(D' =%(D' =A@BBBB0B%(D' =1:Bvisible*o3>+B#style.visibility<*h%(DA' =%(D' =%(D' =A@BBBB0B%(D' =1:Bvisible*o3>+B#style.visibility<*h%(DA' =%(D' =%(D' =A@BBBB0B%(D' =1:Bvisible*o3>+B#style.visibility<*h%(DA' =%(D' =%(D' =A@BBBB0B%(D' =1:Bvisible*o3>+B#style.visibility<* h%(DA' =%(D' =%(D' =A@BBBB0B%(D' =1:Bvisible*o3>+B#style.visibility<* h%(DA' =%(D' =%(D' =A@BBBB0B%(D' =1:Bvisible*o3>+B#style.visibility<* h%(+P+0+h ++0+h ++0+h ++0+ h ++0+ h ++0+ h +  ld  (  D  s *DU ,$ 0 < ATCAGTGCAATGCTCAAGA |||||.||.||||:||||| ATCAGCGCGATGCGCAAGAJ=0Z = x  c $W  @`   x  c $[ @`  ^r  6V`Ua  s *\ ,$D 0 I ###--#-## ATCAGTGCAATGCTCAAGA |||||.||.||||:||||| ATCAGCGCGATGCGCAAGAZJ0Z  J   s *b ,$D 0 EI ###--#-## ATCAGTGCAATGCTCAAGA |||||.||.||||:||||| ATCAGCGCGATGCGCAAGAJ0Z  J   s *4n ,$D 0 MI ###--#-## ATCAGTGCAATGCTCAAGA |||||.||.||||:||||| ATCAGCGCGATGCGCAAGAJ0Z   I Y  c $y ,$D 0 G ###--#-## ATCAGTGCAATGCTCAAGA |||||.||.||||:||||| ATCAGCGCGATGCGCAAGAZH0Z  H ]  s *t ,$D 0 G ###--#-## ATCAGTGCAATGCTCAAGA |||||.||.||||:||||| ATCAGCGCGATGCGCAAGAPH0Zffffff ff G %  s * ,$D 0 G ###--#-## ATCAGTGCAATGCTCAAGA |||||.||.||||:||||| ATCAGCGCGATGCGCAAGA H0Z ffff ff  H H  0޽h ? ̙33PH___PPT10(+c1D' = @B Dw' = @BA?%,( < +O%,( < +DA' =%(D' =%(D' =A@BBBB0B%(D' =1:Bvisible*o3>+B#style.visibility<*%(DA' =%(D' =%(D' =A@BBBB0B%(D' =1:Bvisible*o3>+B#style.visibility<*%(DA' =%(D' =%(D' =A@BBBB0B%(D' =1:Bvisible*o3>+B#style.visibility<*%(DA' =%(D' =%(D' =A@BBBB0B%(D' =1:Bvisible*o3>+B#style.visibility<* %(DA' =%(D' =%(D' =A@BBBB0B%(D' =1:Bvisible*o3>+B#style.visibility<* %(DA' =%(D' =%(D' =A@BBBB0B%(D' =1:Bvisible*o3>+B#style.visibility<* %(+P+0+ ++0+ ++0+ ++0+  ++0+  ++0+  +^   x (  r  S t  @`   r  S õ  @``  8 I  I >  <,ŵI  $||||||||||||||||| ###### ######b%0Z     \  <̵ \  *||||||||||||||||| ###--#-## ###--#-##+0Z   * z I   I ,$D 0   <@յI  $||||||||||||||||| ###### ######%0Z 3f3f       <H \  f*||||||||||||||||| ###--#-## ###--#-##+0Z 3f3f3f3f3f* H  0޽h ? ̙33~___PPT10^+WDB' = @B D' = @BA?%,( < +O%,( < +D4' =%(D' =%(D' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*%(+#  91{ (  x  c $P 0p   8 P0 &mM`  0P0T p GV # p /A   <p 7V ;ATCAGTGCAATGCTCAAGA ||||||||||||||||||| ATCAGTGCAATGCTCAAGAb<0Z <   6 G e ###--#-##, 8Z   qT G V #   /5   07 V ;ATCAGTGCAATGCTCAAGA ||||||||||||||||||| ATCAGTGCAATGCTCAAGAb<0Z <   6 G  b######,8Z  z P0 ' mM,$D 0Z ( s *P0T p G )# p }` * 6p 7 ATCAGTGCAATGCTCAAGA ||||||||||||||||||| ATCAGTGCAATGCTCAAGA ###--#-## ###--#-## ###--#-## ###--#-## ###--#-## ###--#-## ###--#-## ###--#-## ###--#-## ###--#-## ###--#-##0Z&/9   + 6P G e ###--#-##, 8Z   (T G  ,#   { - s *X 7  ATCAGTGCAATGCTCAAGA ||||||||||||||||||| ATCAGTGCAATGCTCAAGA ###### ###### ###### ###### ###### ###### ###### ###### ###### ###### ###### ###### ###### ######b0Z   . 6$G  b######,8Z  z P0 7 mM,$D 0Z 8 s *P0|T p GV 9# p /= : 6,p 7V ;ATCAGTGCAATGCTCAAGA ||||||||||||||||||| ATCAGTGCAATGCTCAAGAd<0Z <  ; 6\3 G e ###--#-##, 8Z   YT G V <#   / = s *77 V ;ATCAGTGCAATGCTCAAGA ||||||||||||||||||| ATCAGTGCAATGCTCAAGAP<0Z <  > 6<G  b######,8Z  z P0 ? mM,$D 0Z @ s *P0T p GV A# p / B 6HAp 7V +;ATCAGTGCAATGCTCAAGA |||||.||||||||||||| ATCAGCGCAATGCTCAAGA<0Zfff  <  C 6HJ G e ###--#-##, 8Z   T G V D#   /y E s *N7 V ;ATCAGTGCAATGCTCAAGA |||||.||||||||||||| ATCAGCGCAATGCTCAAGA<0Zfff <  F 6`XG  b######,8Z  # z P0 G mM,$D 0Z H s *P0T p G I# p } J 6ap 7 &ATCAGTGCAATGCTCAAGA |||||.||||||||||||| ATCAGCGCAATGCTCAAGA ###--#-## ###--#-## ###--#-## ###--#-## ###--#-## ###--#-## ###--#-## ###--#-## ###--#-## ###--#-## ###--#-##0Zfff f ff f ff)9   K 6p] G e ###--#-##, 8Z   \T G  L#   {  M s *8~7  ATCAGTGCAATGCTCAAGA |||||.||||||||||||| ATCAGCGCAATGCTCAAGA ###### ###### ###### ###### ###### ###### ###### ###### ###### ###### ###### ###### ###### ######0Zfffffff f f   N 6ȎG  b######,8Z   z P0 O mM,$D 0Z P s *P0T p G Q# p } R 6p 7 nATCAGTGCAATGCTCAAGA |||||.||||||||||||| ATCAGCGCAATGCTCAAGA ###--#-## ###--#-## ###--#-## ###--#-## ###--#-## ###--#-## ###--#-## ###--#-## ###--#-## ###--#-## ###--#-##^0Zfff fff fff  9   S 6z G e ###--#-##, 8Z   T G  T#   { U s *7  `ATCAGTGCAATGCTCAAGA |||||.||||||||||||| ATCAGCGCAATGCTCAAGA ###### ###### ###### ###### ###### ###### ###### ###### ###### ###### ###### ###### ###### ######80Zfffffffff   V 60G  b######,8Z  z P0 W mM,$D 0Z X s *P0T p GV Y# p / Z 6Ҷp 7V +;ATCAGTGCAATGCTCAAGA |||||.||||||||||||| ATCAGCGCAATGCTCAAGA<0Zfff  <  [ 68۶ G e ###--#-##, 8Z   T G V \#   /y ] s *߶7 V ;ATCAGTGCAATGCTCAAGA |||||.||||||||||||| ATCAGCGCAATGCTCAAGA<0Zfff <  ^ 6PG  b######,8Z  qz P0 o mM,$D 0Z p s *P0FT p GV q# p / r 6p 7V ;ATCAGTGCAATGCTCAAGA |||||.|||||||:||||| ATCAGCGCAATGCGCAAGA.<0Zff ffff <  s 6,޶ G e ###--#-##, 8Z   7T G V t#   / u s *7 V ;ATCAGTGCAATGCTCAAGA |||||.|||||||:||||| ATCAGCGCAATGCGCAAGA.<0Zff ffff <  v 6G  b######,8Z   z P0 w mM,$D 0Z x s *P0T p G y# p } z 6p 7 ZATCAGTGCAATGCTCAAGA |||||.|||||||:||||| ATCAGCGCAATGCGCAAGA ###--#-## ###--#-## ###--#-## ###--#-## ###--#-## ###--#-## ###--#-## ###--#-## ###--#-## ###--#-## ###--#-##J0Zff fffff ff f fff ff fff   { 6\ G e ###--#-##, 8Z   T G  |#   {h } s *A7  ATCAGTGCAATGCTCAAGA |||||.|||||||:||||| ATCAGCGCAATGCGCAAGA ###### ###### ###### ###### ###### ###### ###### ###### ###### ###### ###### ###### ###### ######0Zff ffffffff f f.f fffff   ~ 6T>G  b######,8Z  az P0  mM,$D 0Z  s *P0T p G # p }F  6gp 7 ATCAGTGCAATGCTCAAGA |||||.|||||||:||||| ATCAGCGCAATGCGCAAGA ###--#-## ###--#-## ###--#-## ###--#-## ###--#-## ###--#-## ###--#-## ###--#-## ###--#-## ###--#-## ###--#-##0Zff fffffff fffff ff ff    6b G e ###--#-##, 8Z   T G  #   {  s * 7  JATCAGTGCAATGCTCAAGA |||||.|||||||:||||| ATCAGCGCAATGCGCAAGA ###### ###### ###### ###### ###### ###### ###### ###### ###### ###### ###### ###### ###### ######"0Zff ffffffffff#f f f f f f    6G  b######,8Z  az P0  mM,$D 0Z  s *P0HT p GV # p /   6 ȸp 7V ;ATCAGTGCAATGCTCAAGA |||||.|||||||:||||| ATCAGCGCAATGCGCAAGA0<0Zff ffff <   6P G e ###--#-##, 8Z   %T G V #   /  s *ٸ7 V ;ATCAGTGCAATGCTCAAGA |||||.|||||||:||||| ATCAGCGCAATGCGCAAGA<0Zff ffff <   6pG  b######,8Z  Az P0  mM,$D 0Z  s *P0T p GV # p /y  6Pp 7V ;ATCAGTGCAATGCTCAAGA |||||.||.||||:||||| ATCAGCGCGATGCGCAAGA<0Zfff ffffff <   6 G e ###--#-##, 8Z   T G V #   /Y  s *@7 V ;ATCAGTGCAATGCTCAAGA |||||.||.||||:||||| ATCAGCGCGATGCGCAAGA<0Zfff ffffff <   6G  b######,8Z  z P0  mM,$D 0Z  s *P0T p G # p }  6p 7 "ATCAGTGCAATGCTCAAGA |||||.||.||||:||||| ATCAGCGCGATGCGCAAGA ###--#-## ###--#-## ###--#-## ###--#-## ###--#-## ###--#-## ###--#-## ###--#-## ###--#-## ###--#-## ###--#-##0Zfff ffffffffffffff fffffff ffffff    6 G e ###--#-##, 8Z   T G  #   \  s *X7  NATCAGTGCAATGCTCAAGA |||||.||.||||:||||| ATCAGCGCGATGCGCAAGA ###### ###### ###### ###### ###### ###### ###### ###### ###### ###### ###### ###### ###### ######&0Zfff fffffffffffffff f f ff fffff    6YG  b######,8Z  sz P0  mM,$D 0Z  s *P0)T p G # p }  6hp 7 |ATCAGTGCAATGCTCAAGA |||||.||.||||:||||| ATCAGCGCGATGCGCAAGA ###--#-## ###--#-## ###--#-## ###--#-## ###--#-## ###--#-## ###--#-## ###--#-## ###--#-## ###--#-## ###--#-##l0Zfff fffffffffffffffffffffffff ff    6 G e ###--#-##, 8Z   VT G  #   \  s *87  ATCAGTGCAATGCTCAAGA |||||.||.||||:||||| ATCAGCGCGATGCGCAAGA ###### ###### ###### ###### ###### ###### ###### ###### ###### ###### ###### ###### ###### ######0Zfff fffffffffffffffffff f f f f f    6x G  b######,8Z  =z P0  mM,$D 0Z  s *P0T p G # p }  6p 7 FATCAGTGCAATGCTCAAGA |||||.||.||||:||||| ATCAGCGCGATGCGCAAGA ###--#-## ###--#-## ###--#-## ###--#-## ###--#-## ###--#-## ###--#-## ###--#-## ###--#-## ###--#-## ###--#-##60Zfff ffffffffff fffffffffffff        6, G e ###--#-##, 8Z   VT G  #   \  s *M7  ATCAGTGCAATGCTCAAGA |||||.||.||||:||||| ATCAGCGCGATGCGCAAGA ###### ###### ###### ###### ###### ###### ###### ###### ###### ###### ###### ###### ###### ######0Zfff fffffffffffffffffff f f f f f    6 OG  b######,8Z    0$ XFor contiguous vs spaced seeds of the same weight, the expected number of hits is (basically) the same but the probabilities of having at least one hit are very different\(.   H  0޽h ? ̙33  ___PPT10j +BA^DN ' = @B D ' = @BA?%,( < +O%,( < +D4' =%(D' =%(D' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*'%(D4' =%(D' =%(D' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*7%(D4' =%(D' =%(D' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*?%(D4' =%(D' =%(D' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*G%(D4' =%(D' =%(D' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*O%(D4' =%(D' =%(D' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*W%(D4' =%(D' =%(D' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*o%(D4' =%(D' =%(D' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*w%(D4' =%(D' =%(D' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*%(D4' =%(D' =%(D' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*%(D4' =%(D' =%(D' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*%(D4' =%(D' =%(D' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*%(D4' =%(D' =%(D' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*%(D4' =%(D' =%(D' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*%(+  \$(  \r \ S d  @`   r \ S  @`  H \ 0޽h ? ̙33  "=P$(  x  c $T @`P    s *   ;ATCAGTGCAATGCTCAAGA |||||.||.||||:||||| ATCAGCGCGATGCGCAAGAJ<0Z; x  c $  @`   d 8 P `  80 @ _ @ @  )P ` @    !` ` @T ` `  #     0P` P @ IA 2    0೺p ` @ IT 2     0䰺` P  IG 2     0캺p `  IC 2  8T     # P @ fB   6D8c  fB  6D8c  lB  <D8cP  lB  <D8cPp p lB  <D8c  lB  <D8c    B 9  S transitions     B(źpO  c transversions     <Xɺ @  h. .<   <ͺ*  U:<  5 0˺I  M  2 l +  =m+ ,$D 0r2 2 BGH`I18c-w 9 r2 4 BGHQI8c+s  r 7 BGH͙I8cT1 wl    <  ,$D 0@  .   ; .  ` / 0Q1  ` - 0 . u ` 0 01  s * 0ں  ,$D 0 ;ATCAGTGCAATGCTCAAGA |||||.||.||||:||||| ATCAGCGCGATGCGCAAGAd<0Z ; H  0޽h ??`-2/407 ̙33jb___PPT10B+D&' = @B D' = @BA?%,( < +O%,( < +D' =%(D' =%(D' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*<%(D' =%(D' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*=%(+0   'V(  r  S   @`   r  S  @  m  6(Fm ,$D 0 m ATCAGGCATGCTAAGATCGGATCCTCAATGGCTCA |||.|||:|||.|||||.||:||||||:||.|||| ATCGGGCTTGCCAAGATTGGTTCCTCATTGCCTCA.nlm   6xFm ,$D 0  ###-#--##--#-#--#--## ATCAGGCATGCTAAGATCGGATCCTCAATGGCTCA |||.|||:|||.|||||.||:||||||:||.|||| ATCGGGCTTGCCAAGATTGGTTCCTCATTGCCTCA.l S  6Fm ,$D 0  ###-#--##--#-#--#--## ATCAGGCATGCTAAGATCGGATCCTCAATGGCTCA |||.|||:|||.|||||.||:||||||:||.|||| ATCGGGCTTGCCAAGATTGGTTCCTCATTGCCTCAffffffffffffffffffff   6Fm ,$D 0 y ###-#--##--#-#--#--## ATCAGGCATGCTAAGATCGGATCCTCAATGGCTCA |||.|||:|||.|||||.||:||||||:||.|||| ATCGGGCTTGCCAAGATTGGTTCCTCATTGCCTCAff#f#f   ! 6/Fm ,$D 0 g ###-#--##--#-#--#--## ATCAGGCATGCTAAGATCGGATCCTCAATGGCTCA |||.|||:|||.|||||.||:||||||:||.|||| ATCGGGCTTGCCAAGATTGGTTCCTCATTGCCTCAf#f#f   " 6 ;Fm ,$D 0  ###-#--##--#-#--#--## ATCAGGCATGCTAAGATCGGATCCTCAATGGCTCA |||.|||:|||.|||||.||:||||||:||.|||| ATCGGGCTTGCCAAGATTGGTTCCTCATTGCCTCA.l  # 6$EFm ,$D 0 / ###-#--##--#-#--#--## ATCAGGCATGCTAAGATCGGATCCTCAATGGCTCA |||.|||:|||.|||||.||:||||||:||.|||| ATCGGGCTTGCCAAGATTGGTTCCTCATTGCCTCAn ffff ffffffffffff  $ 6+B#style.visibility<*%(DA' =%(D' =%(D' =A@BBBB0B%(D' =1:Bvisible*o3>+B#style.visibility<*%(DA' =%(D' =%(D' =A@BBBB0B%(D' =1:Bvisible*o3>+B#style.visibility<* %(DA' =%(D' =%(D' =A@BBBB0B%(D' =1:Bvisible*o3>+B#style.visibility<*!%(DA' =%(D' =%(D' =A@BBBB0B%(D' =1:Bvisible*o3>+B#style.visibility<*"%(DA' =%(D' =%(D' =A@BBBB0B%(D' =1:Bvisible*o3>+B#style.visibility<*#%(DA' =%(D' =%(D' =A@BBBB0B%(D' =1:Bvisible*o3>+B#style.visibility<*$%(DA' =%(D' =%(D' =A@BBBB0B%(D' =1:Bvisible*o3>+B#style.visibility<*%%(DA' =%(D' =%(D' =A@BBBB0B%(D' =1:Bvisible*o3>+B#style.visibility<*&%(++0+ ++0+ ++0+  ++0+! ++0+" ++0+# ++0+$ ++0+% ++0+& +  QI (  r  S   @`   r  S ԥ @`  ^r  6V`D  s *( ,$D 0 < ATCAGTGCAATGCTCAAGA |||||.||.||||:||||| ATCAGCGCGATGCGCAAGAJ=0Z = e  s *8 ,$D 0 M ##@#-#@-### ATCAGTGCAATGCTCAAGA |||||.||.||||:||||| ATCAGCGCGATGCGCAAGAZN0Z N m  s * ,$D 0 M ##@#-#@-### ATCAGTGCAATGCTCAAGA |||||.||.||||:||||| ATCAGCGCGATGCGCAAGAbN0Zff ff ff ff N =  s *̼ ,$D 0 M ##@#-#@-### ATCAGTGCAATGCTCAAGA |||||.||.||||:||||| ATCAGCGCGATGCGCAAGA2N0Z ff ff ff N `  s *0ټ ,$D 0 H ##@#-#@-### ATCAGTGCAATGCTCAAGA |||||.||.||||:||||| ATCAGCGCGATGCGCAAGAZI0Z  I V  s *L ,$D 0 H ##@#-#@-### ATCAGTGCAATGCTCAAGA |||||.||.||||:||||| ATCAGCGCGATGCGCAAGAPI0Zffffff ff  I   s * ,$D 0 H ##@#-#@-### ATCAGTGCAATGCTCAAGA |||||.||.||||:||||| ATCAGCGCGATGCGCAAGAI0Z ffff ff  I H  0޽h ? ̙33PH___PPT10(+'D' = @B Dw' = @BA?%,( < +O%,( < +DA' =%(D' =%(D' =A@BBBB0B%(D' =1:Bvisible*o3>+B#style.visibility<*%(DA' =%(D' =%(D' =A@BBBB0B%(D' =1:Bvisible*o3>+B#style.visibility<*%(DA' =%(D' =%(D' =A@BBBB0B%(D' =1:Bvisible*o3>+B#style.visibility<*%(DA' =%(D' =%(D' =A@BBBB0B%(D' =1:Bvisible*o3>+B#style.visibility<*%(DA' =%(D' =%(D' =A@BBBB0B%(D' =1:Bvisible*o3>+B#style.visibility<*%(DA' =%(D' =%(D' =A@BBBB0B%(D' =1:Bvisible*o3>+B#style.visibility<*%(+P+0+ ++0+ ++0+ ++0+ ++0+ ++0+ +J  (  r  S   @`   r  S t @`  ^r  6V`H  0޽h ? ̙33   $(  r  S $  @`   r  S P% @`  H  0޽h ? ̙33:  }0"!(    S N @`<$ 0  Q  s *hCZ0T,$D 0 ;ATCAGTGCAATGCTCAAGA |||||.||.||||:||||| ATCAGCGCGATGCGCAAGAP<0Z; +  s *8Z0T,$D 0  |||||.||.||||:||||| P0Z >  s *SZ0T,$D 0 ( |||||.||.||||:||||| 2222212212222022222P)0Z(   s *YZ0T,$D 0 w 2222212212222022222 *0Z   <d^`,$D 0 N^P( 2 ) = 0.7, P( 1 ) = 0.15, P( 0 ) = 0.15 0/ "l     ,$D 0   <k l   ` 222221221222      <lp )  VX  \l  5   5 ,$D 0rb  BZG0H]I28c 5 f  6o @ &l @` p @ P ,$D  0f2  6V@ P f2  6V0 pf2  6V ` rR B BZGjzH-IjzjJ; ) lR  <GHIjJ ' P rb  BG0*HiILjJ   0@vp  * ,$D  0 Transition has an emission probability for each symbol Ex : P( 2 ) = 0.8, P( 1 ) = 0.10, P( 0 ) = 0.10k % j Jl    @ P ,$D  0l2  <V0 p l2  <VP `l2  <V`  xR B HZGjzH-IjzjJT  rR  BGHI8cg  xb  HG0*HiILjJw` Y r  S ܈ @``   V " 0p0j,$D  0 \ HSP Alignments found by heuristic algorithms./. H  0޽h ?   ̙33##___PPT10".+NwD !' = @B D ' = @BA?%,( < +O%,( < +DA' =%(D' =%(D' =A@BBBB0B%(D' =1:Bvisible*o3>+B#style.visibility<*%(DA' =%(D' =%(D' =A@BBBB0B%(D' =1:Bvisible*o3>+B#style.visibility<*%(DA' =%(D' =%(D' =A@BBBB0B%(D' =1:Bvisible*o3>+B#style.visibility<*%(DA' =%(D' =%(D' =A@BBBB0B%(D' =1:Bvisible*o3>+B#style.visibility<*%(D ' =%(D' =%(D' =A@BBBB0B%(D' =1:Bvisible*o3>+B#style.visibility<*%(D' =A@BBBB0B%(D' =1:Bvisible*o3>+B#style.visibility<*8%(D' =A@BBBB0B%(D' =1:Bvisible*o3>+B#style.visibility<*:g%(D' =A@BBBB0B%(D' =1:Bvisible*o3>+B#style.visibility<*j%(DA' =%(D' =%(D' =A@BBBB0B%(D' =1:Bvisible*o3>+B#style.visibility<*%(D4' =%(D' =%(D' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*%(D4' =%(D' =%(D' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*%(D4' =%(D' =%(D' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*%(D4' =%(D' =%(D' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<* %(DA' =%(D' =%(D' =A@BBBB0B%(D' =1:Bvisible*o3>+B#style.visibility<*%(DA' =%(D' =%(D' =A@BBBB0B%(D' =1:Bvisible*o3>+B#style.visibility<*"%(++0+ ++0+ ++0+ ++0+ ++0+ ++0+ ++0+ ++0+" +     @ H (  x  c $  @`   x  c $$ @`     ^Atxp_fig8 0  z  SOURCE\documentclass{article}\pagestyle{empty} \begin{document} \begin{table*}[htb] \begin{center} \begin{tabular}{c||lc|lc} \small{weight} & \small{spaced seed} & \small{sensitivity} & \small{transition-constrained seed} & \small{sensitivity} \\ \hline 9 & {\small $ B_{9~} = $~{\tt \#\#\_\#\#\_\#\_\#\_\_\_\#\#\#}} & 0.7291 & {\small $ B_{9}^{tr} = $~{\tt \#\#@\_\#@\#\_\_\#\_\#\#\#}} & 0.7366 \\ 10 & {\small $ B_{10} = $~{\tt \#\#\_\#\#\_\_\_\#\#\_\#\_\#\#\#}} & 0.5957 & {\small $ B_{10}^{tr} = $~{\tt \#@\#\_\#\_@\#\_@\#\_\_@\#\#\#}} & 0.6056 \\ 11 & {\small $ B_{11} = $~{\tt \#\#\#\_\#\_\_\#\_\#\_\_\#\#\_\#\#\#}}& 0.4671 & {\small $ B_{11}^{tr} = $~{\tt \#\#@\#\_\#@\_\_\#\#\_\#\_@@\#\#}} & 0.4784 \\ \end{tabular} \end{center} \end{table*} \end{document} 6EXTERNALNAMEtxp_fig" BLENDFaux.TRANSPARENTFaux*KEEPFILESFaux,DEBUGPAUSEFaux*RESOLUTION600*TIMEOUT (none)&BOXWIDTH514(BOXHEIGHT344"BOXFONT10&BOXWRAPFauxJ2WORKAROUNDTRANSPARENCYBUGFauxB*ALLOWFONTSUBSTITUTIONFaux4BITMAPFORMAT bmp256(ORIGWIDTH382<PICTUREFILESIZE1325622H  0޽h ? ̙33   < 4 P (  r  S ƽ  @`   r  S ƽ @`     ^Atxp_fig0 ((    SOURCE|\documentclass{article}\pagestyle{empty} \begin{document} \begin{table*}[htb] \begin{center} \begin{tabular}{c||lc|lc} \small{weight} & \small{spaced seed} & \small{sensitivity} & \small{transition-constrained seed} & \small{sensitivity} \\ \hline 9 & {\small $ M_{9} = $~{\tt \#\#\_\#\#\_\#\#\_\#\#\#}} & 0.822 & {\small $ M_{9}^{tr} = $~{\tt \#\#@\#\#\_\#\#@\#\#}} & 0.845 \\ 10 & {\small $ M_{10} = $~{\tt \#\#\_\#\#\_\#\#\_\_\_\#\#\_\#\#}} & 0.716 & {\small $ M_{10}^{tr} = $~{\tt \#@@\#\#\_\#\#\_\#\#@\#@}} & 0.746 \\ 11 & {\small $ M_{11} = $~{\tt \#\#\_\#\#\_\#\#\_\#\#\_\#\#\#}} & 0.603 & {\small $ M_{11}^{tr} = $~{\tt \#\#@\#\#\_\#\#\_\#\#@\#\#}} & 0.632 \\ \end{tabular} \end{center} \end{table*} \end{document} 6EXTERNALNAMEtxp_fig" BLENDFaux.TRANSPARENTFaux*KEEPFILESFaux,DEBUGPAUSEFaux*RESOLUTION600*TIMEOUT (none)&BOXWIDTH514(BOXHEIGHT344"BOXFONT10&BOXWRAPFauxJ2WORKAROUNDTRANSPARENCYBUGFauxB*ALLOWFONTSUBSTITUTIONFaux4BITMAPFORMAT bmp256(ORIGWIDTH376<PICTUREFILESIZE1305654H  0޽h ? ̙33   d \  (  x  c $ݽ  @`   x  c $l޽ @`     ^Atxp_fig^bDS . &  SOURCE\documentclass{article}\pagestyle{empty} \begin{document} \begin{table*}[htb] \begin{center} {\small \begin{tabular}{l||rr|rr} sequences & $B_{9}$ & $B_{9}^{tr}$ & $M_{9}$ & $M_{9}^{tr}$ \\ \hline IX /XVI &342 &354 &349 &357 \\ IX /IV &457 &476 &456 &491 \\ V /XVI &777 &813 &820 &832 \\ V /IV &1152 &1176 &1177 &1192 \\ XVI /IV &1314 &1361 &1309 &1348 \\ MC58 &180373 &189580 &195077 &198713 \\ MC58/Z2491 &361896 &380028 &385444 &392164 \\ Z2491 &185397 &195184 &199440 &203651 \\ \end{tabular} } \caption{\label{expseeds} Number of high-scoring similarities found with different seed patterns} \end{center} \end{table*} \end{document} 6EXTERNALNAMEtxp_fig" BLENDFaux.TRANSPARENTFaux*KEEPFILESFaux,DEBUGPAUSEFaux*RESOLUTION600*TIMEOUT (none)&BOXWIDTH720(BOXHEIGHT523"BOXFONT10&BOXWRAPFauxJ2WORKAROUNDTRANSPARENCYBUGFauxB*ALLOWFONTSUBSTITUTIONFaux4BITMAPFORMAT bmp256(ORIGWIDTH343<PICTUREFILESIZE2861078H  0޽h ? ̙33  0 $(  r  S 4  @`   r  S  @  H  0޽h ? ̙33C  "N(    S   @`    r  S  @`  F   ~  . x ~ T / c $p 0  0 < 0 *  VDot plot   1 <\6 ~   ~.ctcgactcgggctcacgctcgcaccgggttacagcggtcgattgct//.  2B B   .aggcctcgggctcgcgctcgcgcgctagacaccgggttacagcgt "/-"-  F 0 r 3  01lN 0  4 0 T  P  5# 0  ZB 6 s *D8c P ` ZB 7 s *D8c `B 8 0D8c`  ~N 0  9 0 T  P  :# 0  rb ; BZ  `B < 0D P `B = 0D  r >B BZGH~I  ? <  r eDetected alignment  Tz - P  @   ,$ 0|N  @P  A  @P ZB B s *D 0 ZB C s *D  ZB D s *D @P FN -   E -   F < -   `Detected seeds T GB c $ T HB c $ T IB c $ z  pb K j pJ,$D 0rb LB BZG0*H,I&8c Xb M 0l p  $! 2. Hit criterion<$& H  0޽h ?_;?> FDG FBH FCI F?L ̙33$  |@6P(  r  S $%  @`   r  S % @``  h8    m  N   ~     T  c $p 0   <( 0 *  VDot plot    </6 ~   ~.ctcgactcgggctcacgctcgcaccgggttacagcggtcgattgct//.  B B.   .aggcctcgggctcgcgctcgcgcgctagacaccgggttacagcgt "/-"-  T  @P   # 3ZB   s *D 0 ZB   s *D  ZB   s *D @P z  m  | m  ,$D 0T   ~  }#  m T ~ c $p 0   <9 0 *  VDot plot    <?6 ~   ~.ctcgactcgggctcacgctcgcaccgggttacagcggtcgattgct//.  B B=   .aggcctcgggctcgcgctcgcgcgctagacaccgggttacagcgt "/-"-  ZB  s *D#0ZB  s *DcpZB  s *DcPZB  s *D1CCZB  s *D1--z  N S m  ,$D 0T   ~  T#  NT U c $p 0  V <xI 0 *  VDot plot   W <M6 ~   ~.ctcgactcgggctcacgctcgcaccgggttacagcggtcgattgct//.  XB BQ   .aggcctcgggctcgcgctcgcgcgctagacaccgggttacagcgt "/-"-  ZB Y s *Ds  ZB Z s *DpS  ZB [ s *D 0 FT `P \#   ZB ] s *D>0ZB ^ s *D>00ZB _ s *D>0PZB ` s *D>`ZB a s *D>z P  b m  ,$D 0T   ~  c# P T d c $p 0  e <Y 0 *  VDot plot   f <^6 ~   ~.ctcgactcgggctcacgctcgcaccgggttacagcggtcgattgct//.  gB B|a   .aggcctcgggctcgcgctcgcgcgctagacaccgggttacagcgt "/-"-  ZB h s *D sP ZB i s *D S0 ZB j s *D0FT  k#  p0 ZB l s *D>@pZB m s *D>ppZB n s *D>pZB o s *D>@@ZB p s *D>@H  0޽h ? ̙33___PPT10+fD' = @B Du' = @BA?%,( < +O%,( < +D4' =%(D' =%(D' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*|%(D4' =%(D' =%(D' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*S%(D4' =%(D' =%(D' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*b%(+X    @ Pn (   r   S x  @`   r   S y   8 8  ? hp Z   s *B6    BX{H8 ~.ctcgactcgggctcacgctcgcaccgggttacagcggtcgattgct//.   B Ha  .aggcctcgggctcgcgctcgcgcgctagacaccgggttacagcgt "/-"-  L  P   # p$T2 ZB !  s *D3f8c P ` ZB "  s *D3f8c `B #  0D3f8c`    @P  , # j ,$D 0ZB -  s *D 0 ZB .  s *D  ZB /  s *D @P l `0p@ = `$ ,$D 0fB 6  6DoTB 8  c $D`0P TB :  c $DPp@l pp > MP ,$D 0fB 7  6Dop@@TB ;  c $DpppTB <  c $DpH   0޽h ? ̙33___PPT10+.lD' = @B Du' = @BA?%,( < +O%,( < +D4' =%(D' =%(D' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*, %(D4' =%(D' =%(D' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*= %(D4' =%(D' =%(D' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*> %(+   ` 0(   r   S   @`   r   S  @`  z I     P ,$D 0   <lI  $|:|||||||:|||:||| ###### ######%0Z 3f3f       < \  f*|:||||:|||||:|.|. ###--#-## ###--#-##+0Z 3f3f3f3f3f*  l   @   @,$D 0   <  @ O7    <   O9 H   0޽h ? ̙33___PPT10+dD~' = @B D9' = @BA?%,( < +O%,( < +D4' =%(D' =%(D' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<* %(D4' =%(D' =%(D' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<* %(+  P(D(  (~ ( s *d  @`   x ( c $8  `  d ( c <Aproba_25_12r ( c >A proba_25_123r,$D 0H ( 0޽h ? f [f f3̙~___PPT10^+!A`DB' = @B D' = @BA?%,( < +O%,( < +D4' =%(D' =%(D' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*(%(+  ,D(  ,~ , s *  @`   x , c $d  `  d , c <A proba_35_12 , c >A proba_35_123,$D 0H , 0޽h ? f [f f3̙~___PPT10^+!A`DB' = @B D' = @BA?%,( < +O%,( < +D4' =%(D' =%(D' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*,%(+  40(  4r 4 S   @`   ~ 4 BA ? ?s0P H 4 0޽h ? ̙33~"  d\ (  r  S    @`   r  S  @`  "  ^Atxp_fig>  SOURCE\documentclass{article}\pagestyle{empty} \begin{document} % \begin{table*}[htb]% \begin{center}% {\scriptsize \begin{tabular}{|ll|ll|rr|rr|rr|rr|} \hline \multicolumn{2}{|c|}{sequence 1} & \multicolumn{2}{c|}{sequence 2} & \multicolumn{2}{c|}{time (sec)} & \multicolumn{2}{c|}{\# align.} & \multicolumn{2}{c|}{\# ex. align.}& \multicolumn{2}{c|}{ex. align. length}\\ \multicolumn{1}{|c}{name} & \multicolumn{1}{c|}{size} & \multicolumn{1}{c}{name} & \multicolumn{1}{c|}{size} & \multicolumn{1}{r}{{\tt Y.}} & \multicolumn{1}{r|}{{\tt B.}} & \multicolumn{1}{r}{{\tt Y.}} & \multicolumn{1}{r|}{{\tt B.}} & \multicolumn{1}{r}{{\tt Y.}} & \multicolumn{1}{r|}{{\tt B.}} & \multicolumn{1}{r}{{\tt Y.}} & \multicolumn{1}{r|}{{\tt B.}} \\ \hline {\em S. s.} & 3.6 & {\em M. t.} & 4.4 & 122 & 148 & 494 & 310 & 130 & 27 & 29145 & 7970\\ %{\em S. s.} & 3.6 & {\em C. g. ATCC 13032} & 3.3 & 161 & 163 & 578 & 369 & 168 & 63 & 37310 & 30138\\ {\em S. s.} & 3.6 & {\em Y. p.} & 4.6 & 156 & 253 & 901 & 617 & 186 & 54 & 39354 & 19994\\ {\em S. s.} & 3.6 & {\em V. p.} & 3.3 & 164 & 167 & 940 & 465 & 349 & 60 & 65788 & 28883\\ %{\em M. t.} & 4.4 & {\em C. g. ATCC 13032} & 3.3 & 211 & 542 & 1851& 1265& 397 & 160 & 102103& 80012\\ {\em M. t.} & 4.4 & {\em Y. p.} & 4.6 & 168 & 255 & 738 & 515 & 197 & 86 & 44348 & 23361\\ {\em M. t.} & 4.4 & {\em V. p.} & 3.3 & 72 & 69 & 498 & 295 & 171 & 30 & 36474 & 12021\\ %{\em C. g. ATCC 13032} & 3.3 & {\em Y. p. KIM } & 4.6 & 130 & 161 & 962 & 640 & 186 & 45 & 34538 & 11277\\ %{\em C. g. ATCC 13032} & 3.3 & {\em V. p. 2210633} & 3.3 & 95 & 93 & 1109& 687 & 197 & 72 & 42009 & 21575\\ {\em Y. p.} & 4.6 & {\em V. p.} & 3.3 & 149 & 217 & 2900& 1953& 622 & 264 & 186585& 110352\\ %{\em __name1__} & __size1__ & {\em __name2__ } & __size2__ & __time1__ & __time2__ & __rep1__ & __rep2__ & __exrep1__ & __exrep2__ & __len1__ & __len2__ \\ \hline \end{tabular}% }% \end{center}% \end{table*}% \end{document} 6EXTERNALNAMEtxp_fig" BLENDFaux.TRANSPARENTFaux*KEEPFILESFaux,DEBUGPAUSEFaux*RESOLUTION600*TIMEOUT (none)&BOXWIDTH941(BOXHEIGHT677"BOXFONT10&BOXWRAPFauxJ2WORKAROUNDTRANSPARENCYBUGFauxB*ALLOWFONTSUBSTITUTIONFaux4BITMAPFORMAT bmp256(ORIGWIDTH340<PICTUREFILESIZE1560878  68c 0 ,$D 0  68c 0 ,$D 0j  < ` ~M.t : M. tuberculosis CDC1551 S.s : Synechocystis sp. PCC 6803 V.p : Vibrio p. RIMD 2210633 I Y.p : Yersinia pestis KIM|)          H  0޽h ? ̙33___PPT10+"D~' = @B D9' = @BA?%,( < +O%,( < +D4' =%(D' =%(D' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<* %(D4' =%(D' =%(D' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<* %(+  (  <(  <T < C ,Ascr_query`  < C *Ascr_mainP F,$D 0  < B  P`    H < 0޽h ? ̙33~___PPT10^+ksDB' = @B D' = @BA?%,( < +O%,( < +D4' =%(D' =%(D' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*<%(+"  8b(  8 8 BA )scr_maina P,$D 0l 8 DA )scr_queryQ  8 Bh#  P    r 8 S <$   H 8 0޽h ? ̙33  T$(  Tr T S +  @`   r T S , @`  H T 0޽h ? ̙33  pL$(  Lr L S 02  @`   r L S 3 @`  H L 0޽h ? ̙33   DE(  D~ D s *;  @`   ~ D s *x< @`  F H D H D <A ??H  D 0d> 6 0  I? 2d   D 0AP   I? 2d   D 0E`  I? 2d  H D 0޽h ? f [f f3̙  `H0(  HH H 0޽h ? ̙33[#   ##"(    <O ( \ |95550 |95540 |95530 |95520 |95510 |95500 |95490 |95480 CAAGTTTATTTCTGTAGAGAGTGTAGAAGACAGTTCGATTTTAGCCTTTTCAGCGGCTTCTCTTATTCTTTGGACAGCC ||.|||:|||||:||::.::|::..::.||||.|||||||||.||.|||||.||.||||||.|.|::|:|||:|:|||| CAGGTTAATTTCGGTTTGCTGGCCGCTGGACAATTCGATTTTGGCTTTTTCGGCAGCTTCTTTCAGGCGTTGTAGAGCC |583630 |583640 |583650 |583660 |583670 |583680 |583690 |583700 |95470 |95460 |95450 |95440 |95430 |95420 |95410 |95400 ATACGGTCATTACTCAAATCGATACCGGTTTCTTTCTTGAAATGAGAAATAATTTCTTGCAACAAATAAATGTCAAAAT ||:::|||:|::.|||||||.||.||:::||||||.|||||:|:.|:.||.||:|::|::|::|....:::|||.||.| ATCACGTCTTGTTTCAAATCAATGCCTTGTTCTTTTTTGAACTCGGCGATGATGTGGTCGATGAGGCGTTGGTCGAAGT |583710 |583720 |583730 |583740 |583750 |583760 |583770 |95390 |95380 |95370 |95360 |95350 |95340 CTTCGCCACCCAAATGGGTGTCACCATTGGTAGATTTAACCTCAAA------GATACC------GTTATCGATGTCCAG ||||.||.|||||.:.|||.||.||.|||||:|:.:::||.||.|| |:..|| |||.:||||:||:|: CTTCACCGCCCAAGAAGGTATCGCCGTTGGTTGCCAATACTTCGAATTGTTTGTCGCCGTCGAGGTTGGCGATTTCGAT |583790 |583800 |583810 |583820 |583830 |583840 |583850 |95320 |95310 |95300 |95290 |95280 |95270 |95260 GATTGAAATATCGAAAGTACCACCGCCCAAGTCGAAAACAGCAAT------GACTTTTGGCTCTGATTTATCTAGACCG |||:|||||||||||||||||.|||||||||||.:|:||.||:|. |:||||::::||:::|||.||.|:|||| GATGGAAATATCGAAAGTACCGCCGCCCAAGTCATATACGGCTACTTTGCGGTCTTTGTTGTCGCCTTTGTCCATACCG |583870 |583880 |583890 |583900 |583910 |583920 |583930 |95250 |95240 |95230 |95220 |95210 |95200 |95190 TAAGCTAGGGCAGCAGCTGTTGGTTCGTTGACAACACGTAATACATTAAGCCCAATAATTTGTCCTGCGTCTTTAGTAG :|:||.|..||.||:||:||.||.|||||||..|..|||::.||.|.:|.:||....||:.|:|||.|||||||.||.| AATGCCAAAGCGGCTGCGGTCGGCTCGTTGATGATGCGTTTCACGTCCAAACCGGCGATACGGCCTACGTCTTTGGTGG |583950 |583960 |583970 |583980 |583990 |584000 |584010 |95170 |95160 |95150 |95140 |95130 |95120 |95110 CTTGTCTTTGGGCATCATTGAAGTAAGCAGGAACGGTGACAACAGCATTTTTGACGCTCTTCGCTAAGTAAGCCTCCGC ||||:|:||||:..||.||||||||.|||||.|||||.|.:||.||:|.::|:||:.|.|.::|.||||||||.||:|| CTTGACGTTGGCTGTCGTTGAAGTAGGCAGGGACGGTAATCACGGCTTCGGTTACTTTTTCGCCCAAGTAAGCTTCGGC |584030 |584040 |584050 |584060 |584070 |584080 |584090 |95090 |95080 |95070 |95060 |95050 |95040 |95030 TGTTTCCTTCATTTTATTTAAGATAAAACCTCCTATTTGGGCGGGGGAGTACGTTCTGTTTCTAGCCTCTACCCAGGCA :|.|||.|||||||||.:.|.||.:::::|::::|||||.|:.||.||::.|:.|.||..|.::||.|.||||||:||. GGCTTCTTTCATTTTACGCAGGACTTCTGCGGAAATTTGAGGAGGAGACAGCTCTTTGCCTTGTGCTTTTACCCATGCG |584110 |584120 |584130 |584140 |584150 |584160 |584170 |95010 |95000 |94990 |94980 |94970 |94960 |94950 TCTCCATTAGAATGCTTGACGATTTTGAAAGGAACCTGATTAATATCTCTTTGGACTTCAGCGTCCTCGAAACGGCGGC ||:||.||.::.::.||||.|||||.||||||:|.::.:|..||.||:|:|||||||||::.|||.||.||:.:|.||| TCGCCGTTGTTGGCTTTGATGATTTCGAAAGGCATAGATTCGATGTCGCGTTGGACTTCTTTGTCTTCAAATTTGTGGC |584190 |584200 |584210 |584220 |584230 |584240 |584250 |94930 |94920 |94910 |94900 |94890 |94880 |94870 CGATTAAACGCTTAGTAGCAAACAAAGTGTTTTCTGAGTTTATGACGGATTGTCGTTTGGCTGGCTCACCAACTAAACG ||||.|||||.||.|..||.:|:|:||||||||.:|:|||:.|:||:|:|||:||||||||:|||:||||.||:|..:: CGATCAAACGTTTGGCGGCGTAAATAGTGTTTTTGGCGTTGGTTACCGCTTGGCGTTTGGCAGGCGCACCGACGAGGAT |584260 |584270 |584280 |584290 |584300 |584310 |584320 |584330 |94850 |94840 |94830 |94820 |94810 |94800 |94790 TTCTCCGTCTTTAGTGAAAGCCACTACAGACGGAGTAGTTCTTGAGCCTTCTGCATTTTCGATAATTCTCGGAACTTTA |||:|||.|:|.:.:.:||||:|.:||.|||||:||.||:|:||:|||||||||.||||||||:|.|.|:|:::::... TTCGCCGCCGTCCAAATAAGCGATAACGGACGGCGTGGTGCGTGCGCCTTCTGCGTTTTCGATCACTTTGGTTTGACCG |584340 |584350 |584360 |584370 |584380 |584390 |584400 |584410 |94780 |94770 |94760 |94750 |94740 CCTTCCATAATAGCTACCGCAGAATTGGTAGTACCTAAATCAATACCGATAAC ..|||:.:|||.||.|::::|||.|||||:||||||||.||.||||||||:|| TTTTCGGAAATGGCCAAACAAGAGTTGGTTGTACCTAAGTCGATACCGATTAC |584420 |584430 |584440 |584450 |584460 T0Z0Z0' O =   <Dgp  '*(96264-94728)(582917-584471) Ev: 0 s: 1537/1555 r * S.cerevisiae.V (reverse complementary strand) / gi|12057208|(forward strand) * score = 1073 : bitscore = 491.92 * mutations per triplet 347, 108, 152 (1.79e-36) | ts : 272 tv : 335 |96260 |96250 |96240 |96230 |96220 |96210 |96200 |96190 TTCCGCTTCATTAACCATTCGATCAATCTCCGTATCAGATAGCCCAGACGCTCCGGCAACAGTGATGGAAGAGTCTTTG |||:||:||:||:|||||:||:||.||.||.:.:||.::.|.:||:||:|::||:::.|..||||||::.|:::||||. TTCGGCATCTTTCACCATGCGTTCGATTTCTTCTTCGCTCAAACCTGAAGAACCTTGGATGGTGATGTTGGCTGCTTTA |582920 |582930 |582940 |582950 |582960 |582970 |582980 |96180 |96170 |96160 |96150 |96140 |96130 |96120 TGGCTGGCGAGATCTTTTGCTGAAACGTTGATGATGCCGTTCGCATCGATATCAAAAGTGACTTCAATTTGTGGGGTAC .:|:||:|:::.|||||:||:|||||||::|:|||||||||:||.|||||.||.||.||:|||||.|||||.||:.||| CCGGTGCCTTTGTCTTTGGCGGAAACGTGCAGGATGCCGTTGGCGTCGATGTCGAAGGTTACTTCGATTTGCGGCATAC |583000 |583010 |583020 |583030 |583040 |583050 |583060 |96100 |96090 |96080 |96070 |96060 |96050 |96040 CTTTTGGAGCTGGAGGAATGCCCGCAAGAGTAAAATTACCTATTAATTTGTTATCCTTGACTAACTCCCTCTCACCTTG |:.:.||:||:||:|:.|||.|::|:|..:|.||:|:|||.|::.|||||||.:|:::..|::..||:|:.||.||||| CGCGCGGTGCAGGTGCGATGTCGCCCAAGTTGAACTGACCCAAAGATTTGTTGGCAGAAGCGCGTTCGCGTTCGCCTTG |583080 |583090 |583100 |583110 |583120 |583130 |583140 |96020 |96010 |96000 |95990 |95980 |95970 |95960 GAAAACTTTAACTTCCACCGATGTTTGACCTGATGCCGCAGTTGAAAAAATTTGAGATTTCTTATTGGGAATTGTAGAA :|.:||:|:.|.::..||.|:::||||...:::|:|:||.||:||.||:|.|||:||.:..||.:|:||.||:||.|:. CAGTACGTGGATGGTTACTGCGCTTTGGTTGTCTTCGGCGGTAGAGAACACTTGCGACGCTTTGGTCGGGATGGTGGTG |583160 |583170 |583180 |583190 |583200 |583210 |583220 |95940 |95930 |95920 |95910 |95900 |95890 |95880 TTTCTTGGGATTAATTTTGTAAAAACTCCTCCTAAAGTTTCAATACCCAATGATAGGGGAGTGACATCTAGCAACAAAA ||..|.:|.||.|.|||:||:|::||:||:||.|:.|||||.||||||||:||.||.|||||:||.||.||.|.|||:| TTCTTCTGAATCAGTTTGGTCATCACGCCGCCCATGGTTTCGATACCCAAAGACAGAGGAGTTACGTCCAGTAGCAATA |583240 |583250 |583260 |583270 |583280 |583290 |583300 |95860 |95850 |95840 |95830 |95820 |95810 |95800 CATCGGTAACTTCACCAGACAAGACCGCAGCCTGTATAGCGGCCCCTAAAGCGACTGCTTCATCAGGGTTAACAGCTTT |.|||:|.:::.|.||.::|||:||.:|.:|.||:||:||:||:||||:.||.||:|||||.||||||||:||.:|||| CGTCGCTGCGGCCGCCGCTCAATACTTCGCCTTGGATCGCTGCGCCTACGGCAACGGCTTCGTCAGGGTTCACGTCTTT |583320 |583330 |583340 |583350 |583360 |583370 |583380 |95780 |95770 |95760 |95750 |95740 |95730 |95720 TGATGCATCCTTACCGAATAATTTCTTTACAGTATCTGCAACCTTGGGCATCCTTGACATACCACCAACTAATAAAACA ::..|::||.||.|||||:||::..||:||.|.:|||:::||.||:|||||:|::|||:::||.||.||.||:|::||. GCGCGGTTCTTTGCCGAAGAAGGCTTTAACGGCTTCTTGTACTTTCGGCATACGGGACTGCCCGCCGACCAAGATTACG |583400 |583410 |583420 |583430 |583440 |583450 |583460 |95710 |95700 |95690 |95680 |95670 |95660 |95650 |95640 TCCGATATATCTGAGGCGGTAATTCTTGCGTCTTTCAGTGCTTTTTTGACAGGATCAACCGTTCTATCAATCAATGGGG ||::::||.||:::||.|:|:|::|.:||.|||||||.|||::|||||::|||:||.|.:|::|:.:.|||||.::::: TCGTCGATGTCGCCGGTGCTCAAGCCGGCATCTTTCAATGCAATTTTGCAAGGTTCGATAGAGCGGGTAATCAGGTCTT |583470 |583480 |583490 |583500 |583510 |583520 |583530 |583540 |95630 |95620 |95610 |95600 |95590 |95580 |95570 |95560 CGGTTATATTCTCAAGCTGAACCCTAGAAAAGGGCATACGAATATGCTTTGGGCCTGCAGCATCAGCAGTTATGAAAGG |....|:..|.||.|..|:..|:|:.|:||::::|||::::|:.||.||.|||||:|.:||.||:...||:|||:|:|| CAACCAGGCTTTCGAATTTGGCGCGGGTAATTTTCATCGCCAAGTGTTTCGGGCCGGTTGCGTCCATGGTGATGTACGG |583550 |583560 |583570 |583580 |583590 |583600 |583610 |583620 T0ZZ -#H  0޽h ? ̙33$  K$C$#(    <d (  |95550 |95540 |95530 |95520 |95510 |95500 |95490 |95480 CAAGTTTATTTCTGTAGAGAGTGTAGAAGACAGTTCGATTTTAGCCTTTTCAGCGGCTTCTCTTATTCTTTGGACAGCC ||.|||:|||||:||::.::|::..::.||||.|||||||||.||.|||||.||.||||||.|.|::|:|||:|:|||| CAGGTTAATTTCGGTTTGCTGGCCGCTGGACAATTCGATTTTGGCTTTTTCGGCAGCTTCTTTCAGGCGTTGTAGAGCC |583630 |583640 |583650 |583660 |583670 |583680 |583690 |583700 |95470 |95460 |95450 |95440 |95430 |95420 |95410 |95400 ATACGGTCATTACTCAAATCGATACCGGTTTCTTTCTTGAAATGAGAAATAATTTCTTGCAACAAATAAATGTCAAAAT ||:::|||:|::.|||||||.||.||:::||||||.|||||:|:.|:.||.||:|::|::|::|....:::|||.||.| ATCACGTCTTGTTTCAAATCAATGCCTTGTTCTTTTTTGAACTCGGCGATGATGTGGTCGATGAGGCGTTGGTCGAAGT |583710 |583720 |583730 |583740 |583750 |583760 |583770 |95390 |95380 |95370 |95360 |95350 |95340 CTTCGCCACCCAAATGGGTGTCACCATTGGTAGATTTAACCTCAAA------GATACC------GTTATCGATGTCCAG ||||.||.|||||.:.|||.||.||.|||||:|:.:::||.||.|| |:..|| |||.:||||:||:|: CTTCACCGCCCAAGAAGGTATCGCCGTTGGTTGCCAATACTTCGAATTGTTTGTCGCCGTCGAGGTTGGCGATTTCGAT |583790 |583800 |583810 |583820 |583830 |583840 |583850 |95320 |95310 |95300 |95290 |95280 |95270 |95260 GATTGAAATATCGAAAGTACCACCGCCCAAGTCGAAAACAGCAAT------GACTTTTGGCTCTGATTTATCTAGACCG |||:|||||||||||||||||.|||||||||||.:|:||.||:|. |:||||::::||:::|||.||.|:|||| GATGGAAATATCGAAAGTACCGCCGCCCAAGTCATATACGGCTACTTTGCGGTCTTTGTTGTCGCCTTTGTCCATACCG |583870 |583880 |583890 |583900 |583910 |583920 |583930 |95250 |95240 |95230 |95220 |95210 |95200 |95190 TAAGCTAGGGCAGCAGCTGTTGGTTCGTTGACAACACGTAATACATTAAGCCCAATAATTTGTCCTGCGTCTTTAGTAG :|:||.|..||.||:||:||.||.|||||||..|..|||::.||.|.:|.:||....||:.|:|||.|||||||.||.| AATGCCAAAGCGGCTGCGGTCGGCTCGTTGATGATGCGTTTCACGTCCAAACCGGCGATACGGCCTACGTCTTTGGTGG |583950 |583960 |583970 |583980 |583990 |584000 |584010 |95170 |95160 |95150 |95140 |95130 |95120 |95110 CTTGTCTTTGGGCATCATTGAAGTAAGCAGGAACGGTGACAACAGCATTTTTGACGCTCTTCGCTAAGTAAGCCTCCGC ||||:|:||||:..||.||||||||.|||||.|||||.|.:||.||:|.::|:||:.|.|.::|.||||||||.||:|| CTTGACGTTGGCTGTCGTTGAAGTAGGCAGGGACGGTAATCACGGCTTCGGTTACTTTTTCGCCCAAGTAAGCTTCGGC |584030 |584040 |584050 |584060 |584070 |584080 |584090 |95090 |95080 |95070 |95060 |95050 |95040 |95030 TGTTTCCTTCATTTTATTTAAGATAAAACCTCCTATTTGGGCGGGGGAGTACGTTCTGTTTCTAGCCTCTACCCAGGCA :|.|||.|||||||||.:.|.||.:::::|::::|||||.|:.||.||::.|:.|.||..|.::||.|.||||||:||. GGCTTCTTTCATTTTACGCAGGACTTCTGCGGAAATTTGAGGAGGAGACAGCTCTTTGCCTTGTGCTTTTACCCATGCG |584110 |584120 |584130 |584140 |584150 |584160 |584170 |95010 |95000 |94990 |94980 |94970 |94960 |94950 TCTCCATTAGAATGCTTGACGATTTTGAAAGGAACCTGATTAATATCTCTTTGGACTTCAGCGTCCTCGAAACGGCGGC ||:||.||.::.::.||||.|||||.||||||:|.::.:|..||.||:|:|||||||||::.|||.||.||:.:|.||| TCGCCGTTGTTGGCTTTGATGATTTCGAAAGGCATAGATTCGATGTCGCGTTGGACTTCTTTGTCTTCAAATTTGTGGC |584190 |584200 |584210 |584220 |584230 |584240 |584250 |94930 |94920 |94910 |94900 |94890 |94880 |94870 CGATTAAACGCTTAGTAGCAAACAAAGTGTTTTCTGAGTTTATGACGGATTGTCGTTTGGCTGGCTCACCAACTAAACG ||||.|||||.||.|..||.:|:|:||||||||.:|:|||:.|:||:|:|||:||||||||:|||:||||.||:|..:: CGATCAAACGTTTGGCGGCGTAAATAGTGTTTTTGGCGTTGGTTACCGCTTGGCGTTTGGCAGGCGCACCGACGAGGAT |584260 |584270 |584280 |584290 |584300 |584310 |584320 |584330 |94850 |94840 |94830 |94820 |94810 |94800 |94790 TTCTCCGTCTTTAGTGAAAGCCACTACAGACGGAGTAGTTCTTGAGCCTTCTGCATTTTCGATAATTCTCGGAACTTTA |||:|||.|:|.:.:.:||||:|.:||.|||||:||.||:|:||:|||||||||.||||||||:|.|.|:|:::::... TTCGCCGCCGTCCAAATAAGCGATAACGGACGGCGTGGTGCGTGCGCCTTCTGCGTTTTCGATCACTTTGGTTTGACCG |584340 |584350 |584360 |584370 |584380 |584390 |584400 |584410 |94780 |94770 |94760 |94750 |94740 CCTTCCATAATAGCTACCGCAGAATTGGTAGTACCTAAATCAATACCGATAAC ..|||:.:|||.||.|::::|||.|||||:||||||||.||.||||||||:|| TTTTCGGAAATGGCCAAACAAGAGTTGGTTGTACCTAAGTCGATACCGATTAC |584420 |584430 |584440 |584450 |584460 0Z0ZeH@@@ +%,$,$,$* 0' O =   <p  '*(96264-94728)(582917-584471) Ev: 0 s: 1537/1555 r * S.cerevisiae.V (reverse complementary strand) / gi|12057208|(forward strand) * score = 1073 : bitscore = 491.92 * mutations per triplet 347, 108, 152 (1.79e-36) | ts : 272 tv : 335 |96260 |96250 |96240 |96230 |96220 |96210 |96200 |96190 TTCCGCTTCATTAACCATTCGATCAATCTCCGTATCAGATAGCCCAGACGCTCCGGCAACAGTGATGGAAGAGTCTTTG |||:||:||:||:|||||:||:||.||.||.:.:||.::.|.:||:||:|::||:::.|..||||||::.|:::||||. TTCGGCATCTTTCACCATGCGTTCGATTTCTTCTTCGCTCAAACCTGAAGAACCTTGGATGGTGATGTTGGCTGCTTTA |582920 |582930 |582940 |582950 |582960 |582970 |582980 |96180 |96170 |96160 |96150 |96140 |96130 |96120 TGGCTGGCGAGATCTTTTGCTGAAACGTTGATGATGCCGTTCGCATCGATATCAAAAGTGACTTCAATTTGTGGGGTAC .:|:||:|:::.|||||:||:|||||||::|:|||||||||:||.|||||.||.||.||:|||||.|||||.||:.||| CCGGTGCCTTTGTCTTTGGCGGAAACGTGCAGGATGCCGTTGGCGTCGATGTCGAAGGTTACTTCGATTTGCGGCATAC |583000 |583010 |583020 |583030 |583040 |583050 |583060 |96100 |96090 |96080 |96070 |96060 |96050 |96040 CTTTTGGAGCTGGAGGAATGCCCGCAAGAGTAAAATTACCTATTAATTTGTTATCCTTGACTAACTCCCTCTCACCTTG |:.:.||:||:||:|:.|||.|::|:|..:|.||:|:|||.|::.|||||||.:|:::..|::..||:|:.||.||||| CGCGCGGTGCAGGTGCGATGTCGCCCAAGTTGAACTGACCCAAAGATTTGTTGGCAGAAGCGCGTTCGCGTTCGCCTTG |583080 |583090 |583100 |583110 |583120 |583130 |583140 |96020 |96010 |96000 |95990 |95980 |95970 |95960 GAAAACTTTAACTTCCACCGATGTTTGACCTGATGCCGCAGTTGAAAAAATTTGAGATTTCTTATTGGGAATTGTAGAA :|.:||:|:.|.::..||.|:::||||...:::|:|:||.||:||.||:|.|||:||.:..||.:|:||.||:||.|:. CAGTACGTGGATGGTTACTGCGCTTTGGTTGTCTTCGGCGGTAGAGAACACTTGCGACGCTTTGGTCGGGATGGTGGTG |583160 |583170 |583180 |583190 |583200 |583210 |583220 |95940 |95930 |95920 |95910 |95900 |95890 |95880 TTTCTTGGGATTAATTTTGTAAAAACTCCTCCTAAAGTTTCAATACCCAATGATAGGGGAGTGACATCTAGCAACAAAA ||..|.:|.||.|.|||:||:|::||:||:||.|:.|||||.||||||||:||.||.|||||:||.||.||.|.|||:| TTCTTCTGAATCAGTTTGGTCATCACGCCGCCCATGGTTTCGATACCCAAAGACAGAGGAGTTACGTCCAGTAGCAATA |583240 |583250 |583260 |583270 |583280 |583290 |583300 |95860 |95850 |95840 |95830 |95820 |95810 |95800 CATCGGTAACTTCACCAGACAAGACCGCAGCCTGTATAGCGGCCCCTAAAGCGACTGCTTCATCAGGGTTAACAGCTTT |.|||:|.:::.|.||.::|||:||.:|.:|.||:||:||:||:||||:.||.||:|||||.||||||||:||.:|||| CGTCGCTGCGGCCGCCGCTCAATACTTCGCCTTGGATCGCTGCGCCTACGGCAACGGCTTCGTCAGGGTTCACGTCTTT |583320 |583330 |583340 |583350 |583360 |583370 |583380 |95780 |95770 |95760 |95750 |95740 |95730 |95720 TGATGCATCCTTACCGAATAATTTCTTTACAGTATCTGCAACCTTGGGCATCCTTGACATACCACCAACTAATAAAACA ::..|::||.||.|||||:||::..||:||.|.:|||:::||.||:|||||:|::|||:::||.||.||.||:|::||. GCGCGGTTCTTTGCCGAAGAAGGCTTTAACGGCTTCTTGTACTTTCGGCATACGGGACTGCCCGCCGACCAAGATTACG |583400 |583410 |583420 |583430 |583440 |583450 |583460 |95710 |95700 |95690 |95680 |95670 |95660 |95650 |95640 TCCGATATATCTGAGGCGGTAATTCTTGCGTCTTTCAGTGCTTTTTTGACAGGATCAACCGTTCTATCAATCAATGGGG ||::::||.||:::||.|:|:|::|.:||.|||||||.|||::|||||::|||:||.|.:|::|:.:.|||||.::::: TCGTCGATGTCGCCGGTGCTCAAGCCGGCATCTTTCAATGCAATTTTGCAAGGTTCGATAGAGCGGGTAATCAGGTCTT |583470 |583480 |583490 |583500 |583510 |583520 |583530 |583540 |95630 |95620 |95610 |95600 |95590 |95580 |95570 |95560 CGGTTATATTCTCAAGCTGAACCCTAGAAAAGGGCATACGAATATGCTTTGGGCCTGCAGCATCAGCAGTTATGAAAGG |....|:..|.||.|..|:..|:|:.|:||::::|||::::|:.||.||.|||||:|.:||.||:...||:|||:|:|| CAACCAGGCTTTCGAATTTGGCGCGGGTAATTTTCATCGCCAAGTGTTTCGGGCCGGTTGCGTCCATGGTGATGTACGG |583550 |583560 |583570 |583580 |583590 |583600 |583610 |583620 T0ZZ -#H  0޽h ? ̙33r 0 2* (   d  c $     s * @   Une methode utilise par plusieurs outils d alignement local est base sur la recherche de court fragments conserv appels graines. Une deuxime tape implique une extension des graines en possibles alignements.                  H  0޽h ? ̙33, 0 ||(  |X | C     | S l @   ~Pourquoi s interesser l amlioration : D un point de vue materiel : constatation suivante. Il existe un algorithme exact depuis plus de 20 ans, mais il est quadratique, et mme avec ses dernires optimisations le cout reste trop lev pour tre applicable de trs longues squences. Depuis les annes 80 des algorithmes heuristiques ont t mis en place afin de rpondre la demande.T                                      %          H | 0޽h ? ̙33  0 B : (  d c $   . s * @   A model proposed by PatternHunter to detect similarities is called spaced seed. .. Beacoup d article sur les graines espaces ces dernires annes (Karkainne & patern matchin exact & The seed pattern searched is composed of matches letters (sharp) but also joker position ( don t care which means that we do not care about the column of the alignment under this similarity.) Two quantities can be measured on a spaced seed& On the following example I want the previous seed to detect this similarity. if i try to match the seed at the 4th position, then I will align an error with the second matching element: the seed does not detect the similarity at this position. But if I shift the seed by one position on the left, all possible errors in my seed are under joker positions. It implies that the seed will detect the similarity at this position. D--@   2   &       H  0޽h ? ̙331 0 X(  XX X C     X S  @   ' Critre de detection des alignements @     H X 0޽h ? ̙33u4x`EÆc{ػ+GW{G#bH& E! 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