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IGAUNA (IMPROVED GLOBAL SEQUENCE
ALIGNMENT USING NON-EXACT ANCHORS)
All rigI11s r ( ~ s ( ~ \ w I . ' l l~ is work U I I I J ~ uol. I)(!
~ ( ~ ~ ) L o ( I ~ L ( ~ I Y I 111 \vliol(! or i l l st,, l)y ~ ) l ~ o t o ( ~ i ) ~ ) y
or o t . l ~ c ~ rllcwrls, w i tho~~t 1 1 1 ( ~ ~wr~llissioil o f tlw i ~ ~ ~ t , l l ~ ) r .
APPROVAL
Name: IlIwsoutl H i ~ r i ~ ti
Dcgrce: M A S T E R OF SCIENCE
Titlc of thesis: IC;i\UMA (Irtlyrovctl Global Soquc!~ice Aligrmlc~~t IJsing NOII-
cXsac:t A11c:llors)
Datc Approved: l o ~ + I ~ / Z ~ C - F
2% SIMON FRASER @ ,,,,,,,l~Iibrary &.g
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Simon Fraser University Library Burnaby, BC, Canada
Revised: Spring 2007
Abstract
Contents
. . Approval 11
... Abstract 111
Quotation v
Contents vii
List of Tables x
List of Figurcs xi
1 Introduction 1
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.1 I\[olivnl.iotls 2
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.2 01tr Cont.ril)ut,ions 3
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.3 Tl~clsis Orgarri./,ill.iott 3
2 Background 4
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1 Biolngic:nlB;~c:l<gror~tltl 5
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2 Biologic.al 'li.rlr~s 6
. . . . . . . . . . . . . . . . . . . . . . . . . . 2.3 Cot~tp~ttt!~. Scic~~c:c. Ri~(:kgl.o~t~ld S
3 P r e v i o u s W o r k 0 1 1 Globa l S c q u e n c c Alignment 15
3.1 Scorillg hdct. l ids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
3.2 L). y t~ i~ t l l i~ . l'rogral~ll~ling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
3.3 ~ \ ~ l ~ l ~ o r - E i ~ s c ~ t l / I I i t . Mel.hotls . . . . . . . . . . . . . . . . . . . . . . . . . . . . lr3
3.3.1 FAST!\ . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
3.3.2 BLAST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . I!)
3.3.3 CI.IAOS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
3.3.4 1,ACAN . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
9') . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.3.5 GLASS ,,
3.3.6 htIlJh1111o1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 . 7 C111sf aI\Y 23
3.3.8 AVID . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 4
13 . X . (3 h. l C: i\ . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1
4 Gc~wt.ic. Algor i t l~n~ . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
3.5 I l i t l t lc~~ .\ 1ilrk0~ l ~ l ~ t l ~ l . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
4 Gcrlcra l A l g o r i t h m s F o r A n c h o r - B a s e d R4etl iods 27
'1.1 U~~ilcling S ~ ~ f f i s '1'1.1~ . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
4.1.1 High Lc.vcl Ukl~mc!t~'s Algorit.lin-1 . . . . . . . . . . . . . . . . . . . . . 28
4.1.2 S~wc: t lu~~ Tecl~l~icl~~c., Part 1 . . . . . . . . . . . . . . . . . . . . . . . . 2'3
. . . . . . . . . . . . . . . . . . . . . . . . 4.1.:3 S p c x ~ l r ~ p T d m i c p ~ c , Pi1l.t. 2 33
4.2 Fincliug hlaxili~~~lr~-\Iic:igl~L At~cllor Set. . . . . . . . . . . . . . . . . . . . . . . 34
5 G A U N A 37
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.1 kIc:t. llotl tlesc.ript. ioll 37
5.2 Finding h;I:~xiln;d Il~cx;~c:t Mat~c l~ i s . . . . . . . . . . . . . . . . . . . . . . . . 39
5.3 Sc lcc t i~~g A ~ r l l o r s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44
5.3.1 Fitltlit~g 1, i ~ r g ( > ~ t rli)t. i l l \l.?\igI~t . No~~-c.rossit~g A1lc11o1.s . . . . . . . . . . 44
5.4 C:losillg Thc. GILI)S . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 .5 C;I\UNI\ I ' ~ I ~ ; I I I ~ o ~ . o ~ . s 45
7 IGATJNA 50
7.1 h.Io.~sul.illg 1\11 Alig11111~11 1. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50
7.2 I ~ n l ) r i ) \ ~ c ~ ~ i c ~ ~ ~ t s to CAUNA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51 5') 7.2.1 Esoll \Akigl~t. Aclj~lstlrlclll . . . . . . . . . . . . . . . . . . . . . . . . . .
7.2.2 13ri111(:11illg . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
7.2.9 Pwri~lllctcr O p t h i z i l t i o ~ ~ . . . . . . . . . . . . . . . . . . . . . . . . . . 54
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.3 Optillla1 Alignlll~'l~t. 57
7.4 1GAlJX.A Pi~ran~c:t.nrs. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58
8 IGAUNA Results and Conclusion 50
1 Eq)c~ri lno~~t;d Settiligs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5!)
5.2 I'i~r.l.lll(!t.(:l. Scttiligs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30
8.2.1 I<-valr~cSet. s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60
8.3 A l i g l ~ ~ ~ ~ ~ l l t . R.esrllts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62
8 . 1 hI(w~ory U s q y . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62
8.3.2 Spcctl . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64
8.3.13 Qrli11it.y Of A l i g l ~ ~ l ~ c l ~ t s . . . . . . . . . . . . . . . . . . . . . . . . . . . 65
8 .. %.4 IGi\I!NA I ~ n [ ) r o \ ~ c ~ ~ ~ ~ c ~ l ~ t s CC)III~):L~(:(I 'Ii) GAUNA . . . . . . . . . . . . . 68
8.3.5 S I I I I I I I I ~ I ~ Y of r~osults . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71
8.4 Co~~cllwiori nlltl l7ilt3r~re LVork . . . . . . . . . . . . . . . . . . . . . . . . . . . 71
Bibliography 73
List of Tables
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6.1 GAUNA Specificity 47
6.2 GAUNA Global Aligurl~oiit llctsults . . . . . . . . . . . . . . . . . . . . . . . . 4!J
8.1 I<-valrw ERwt . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 1
8.2 R'Iousc Dog Al i l ? ;~~ni (~n t r t (~11 ( . s . . . . . . . . . . . . . . . . . . . . . . . . . . 6:)
8.3 h~louso C11ic:kw Aligritilciit Rrsu1t.s . . . . . . . . . . . . . . . . . . . . . . . . ti3
8.4 I I u r i i ; ~ ~ i Dog ~-\ l i : l ; l i r l le~~t I l e s ~ ~ l t s . . . . . . . . . . . . . . . . . . . . . . . . . . 6.: 1
5.5 IIuinmr Cliickcri Aligliiiic~it . Rrs111t.s . . . . . . . . . . . . . . . . . . . . . . . . 64
3.6 I l ~ ~ ~ i l i i - l ~ MOUSC i ? \ l i g ~ l r ~ ~ c ~ ~ t . R ~ s l ~ l f . ~ . . . . . . . . . . . . . . . . . . . . . . . . . 6 5
S.7 H \ I ~ I I ; ~ I ~ R.i~t. A l i g l ~ l ~ ( . i ~ t . R(w1Ifs . . . . . . . . . . . . . . . . . . . . . . . . . . 6:)
List of Figures
sii
Introduction
Aft or tlw cliscovcry of DNA ill 1953 [5], our liriomlctlgc: of orgal~is~l is ant1 t h i r I )~~ i l t l i~ ig st.riic:- 7 .
I rlws 1 i i ~ v;istly growll, I his 1~1s i l l t,urli ros~ilLo(I i l l 1 . 1 ~ c:reat,iol~ ol' 1 1 c w I ~ t x ~ ~ c : l ~ c s of scicincc
tl(!tli(:ill.(ltl to s t d y i n g t.hc ~li;iili b u i l d i ~ ~ g I)loc:l<s of' life. bIolec111;ir 1)iology: gc!~lc:tics i i ~ i ( l KC-
~loliiics ilrc-: silc.11 llcw fioltls bra~icliilig from biology ulitl \vit,l~ t,lio c v c ~ groniil~g iilvolvc?nio~it, of
111ilI I i~ l l~i l l . i ( :~ a.nd c:oll~pr~l.cr sc:ic:licc in I.kicsc! fic:ltls? ilisc:il)lincs s l ~ c h ;is c:ornput,i~t i o l d 1)iology
hilvc~ I ) c ~ l i croiltctl. Gclictic:~ is t,ho a r w of Ihlogical st,~lcly c'onc:erllotl \vit , l i licwtlily alitl
wit.11 t . 1 ~ vilriatiolis lx!t.wc:el~ nrgai~isl~is t11a.t rcs111t fro111 it.. G~!llotliics is i L rcc(~~it . sci(:ntil-i(:
disci1)lilic wit,11 the i l i l i l of (Idini~ig :ln(l (:Ii;~rii~t,(:rizil~g t l i ~ (~)1111)1(>t,c gc~~cbtic 11iiaIw111) of i l l 1
orgialiis111.
Tllc i~ll icrmt ~~li~tllol~i;~t,ic:;\l s t , r \ ~ < : t . ~ ~ r ~ of DNA i111~ l t I ~ c i \ lgori t . l i~~~ic E)~O(:CSSPS 11scd t,o cx-
prrss prot,cins hiis Ictl t,o ii claw cx)llal~ori~tio~l I)c!l.\vecrl n~olec~llilr I~iology, comput,i?r sc:iellc:o,
~ i ~ i ( l i ili~tlloi~~iit,i(~s. 11s il. rcsillt.~ cc)l~il)l~t,i~t.io~ii~l biology I ~ ~ I s I ) N ! I ~ (,rc~ilt,o(I wliicli is [ i l l ~ I I ~ W -
tlist.iplirl:~ry ficlrl thnl i11)l)lic:s thc~ t,cx:ll~liclric:s o f c-:c-mpr~t,or sric.~icc: i11ltl applic!tl ~niltlhcni;~t.ic:s
to prol~lolus i~lspirccl Iy biology. As i t tlisciplilw, c,oiill)lit,iit.io~l;II biology is H rc!lat,i\~c!ly I I C W
ficlcl l)111, I ,II(w 1i;ls I ) W I ~ i~ virlmu;~l ( q > l o s i o ~ ~ o f work i l l 1111iwmiI,ics, g o v c r ~ ~ ~ w ~ i t , r(:smrch l;~.l>s
:\IICI 1 . 1 ~ : pl'i\,i~t(! S W ~ O ~ .
Tllis l iv I ( l is r c l ~ ~ t , i v d ~ . yo1111g i l l l t l l . ( ' ~ t ! i l l , ~ l ~ i l l tllis I i & l 111ili11Iy ~tilrt(!(l i\l't('~. <,st;~l)-
lisllnlerll, of Tlw IIluiiarl Gcliollle Pro,jc.c:t. (IIGP) ill 1990. 111 1!)W the U.S. I)('~)ilrt.lll(!t~t,
of E~icrgy (DOE) o s t , ~ ~ l ~ l i s l ~ ~ d t,Iic Microl~i;ll G C ~ W I I I P I'rogri1111 (MGP) ;IS a c o ~ ~ ~ p a ~ ~ i o u t,o
I IGP ~ I K I s inw 1.hc11 I ~ I ~ L I ~ J ~ ~ I C W cliscovcrivs llil.~(! I)(Y:II ~u i~c lc ill this fidd. A I ~ . l i o ~ ~ g h l'ro~ii l h
c :o l i i~)~~tor sc,ic!l~cc:/llliit,I~(\r~lilticill 1)oint of vicw, a I:w algoritlll~ls \vit , l l rcq)ec.t t.o sc?cluc~lc:c
a Ions 1.1 Mot iv t '
01, livillg O r g i ~ l l ~ s l l ~ ~ , (!ill1 11~?11) 11s l l l l ( ~ ( ! r s ~ ~ l l ~ ( ~ Illor(! i 1 ~ ) 0 1 1 ~ , t~iscxsos i l l l ( I (~~!sigll i l~g b(!t,t(!r (\rllgs.
Thcreforc mc ~~c:ccl sc:cluc:l~c-:o i ~ l i g ~ l i ~ ~ ~ ~ ~ t , ~ll(>t,llo(ls tl~ilt give 11s Iligl~ quillil,y ;~ligilnl(:~~ki 1 0 I ) ( '
u s ~ l L o cxl rilcl, l)iologic:i~lly vd11i11)Ic~ i ~ ~ f o r i ~ ~ i ~ t , i c ) ~ ~ i l l ) c ) ~ ~ t , l i v i ~ ~ g o r g ; ~ ~ ~ i s ~ ~ ~ s .
Wit11 L11(, o v ~ r g r o w i ~ ~ g 1)iologicxl tl;~ti~l);~sc:s s11c.11 as NCBI (N;~t , i (>~~i l l R~:SOII~CC for I3iot~rli-
110Iogy T~~Soxx~~iitiol~) l ~ I I I ( I I'D13 (I'r0t~i11 DaI,it B;I I I I<)~? ~ I I C I Y ! is 21 I I I I ~ : ~ I I I I ~ I I ~ I ~ of I ) ~ O ( Y S S C ( I
nlld 11111)rocc~ss~tl tl;~t,;l i~vi~ilablc lo sc:icntist,s. Solnctin~cs to l i ~ ~ t l a gootl st,;irt.ing point t,o
lhttp://www.ncbi.nlm.nih.gov/
' h t t p : //www . umass. edu/rnicrobio/rasmol/pdblite . htm
1.2 Our Contributions
on R ty1)ical tlt!skt.ol)/lal)tol) C O I I I ~ L I ~ , ~ ~ i l ~ l t,llcir c:sc.c:~ltion t , i r~~os is ~ ~ s r ~ d l y too long to l)c
11sc~1 frc:quc~t.ly. T h r ot,l~c:r o ~ l r s t h t rccl~~irc: less ti111e to c!sec:ulc, prucluc:c: lcss rdiiiblc
r~s111 ts wit11 IO\V(T, :iil(l s o ~ n c ~ t i ~ ~ i w I K J ~ , i l ( ' (X?])~; i lkJ](! q ~ d i t its.
IV(: i~~t,uoduc,l: IGAUNA, a ncw algorif I I I I I ~ I I I C ~ progri1111 t,o f i 1 ~ 1 glol~al l~;~irwist! a l i g ~ ~ ~ ~ ~ c - : r ~ t - s
wil.l~ w r y I~igli q11a1il.j. results ant1 ill ;i very oIIicic:nt lllilnncr, cwxl csc:c:~~I.i~ldc: otl a typic:;d
lal)t,op for large? s c ~ l ~ ~ o ~ m ! s .
\V(! ;tlso il~troclr~cc: il I ICW way of' ~ ~ l c a s u r i ~ ~ g the qlliility o f scquc:~~cc!s i ~ ~ ~ t l i~~t.ro(l~lc:c ;L
so-c:;dl(:tl opti7rin.l glob;~l wlign~llcwt I.)c:t,\vc:c:l~ t,\vo soqucwcc-s \rrhic:l~ c;ui I)(? ~lso(l 1.0 ~lloi~surr!
tllc i lwli ty of a givc11 i ~ l i g n ~ l ~ c ~ ~ l , .
1.3 Thesis Organization
Background
2.1 Biological Background
obtw.iiwtl from 21 t.llcwct.ic:id p o i ~ ~ t of view s l~o~ i l t l l)c c!sha~~st.ivc:ly tt?st;cd in t 11e liilxi to ~nillic'
s~lrc: it tloes llut ~ I ; L V C illly ~ i l i \ j ~ ) ~ . side (:fr(:ct.s.
11i1vi11g t . 1 ~ almvc p o i ~ ~ t s ~ I I 111i11c1, t IIP ~ C ; ~ S O I I S why 011c s l i c ~ ~ ~ l ( l I)(! f i~~i i i l i i~r wit.11 thv liolog-
difl'orc~~t, (losiigo ~ I K I tIr11gs ~ I I X ! prwxil)wl for ~IifI'crc~~t, 1)cc)pI~ ~ic~cordillg t,o t,I~c>ir ~CIIOIIIC: ,
i.c. t h wholr hc~ .~d i t , a ry i l ~ f o r ~ ~ l i a t i x ~ o f ~ I I C o r g i u l i s ~ ~ ~ cnc:oclcd ill DNA, wl~ic:l~ ~ n i t b ~ t heir
r w l ) o ~ ~ ! s to tl~c:riq),y (I issimil~~r; i ( l c~~ t , i f i ( :~~ t , i (>~~ of (1r11g Lnrgcts w11id1 arc l)rot,cins \vl~os(!
h111(:t,io11s G L I I h! 111odifim1 scl~!ct,ivdy L I I I C I l l t ~ l l ) t,o m r o i~ disoasc; ; 1 1 d Iilst, 1)11t 11ot l(~ist ,
itlc11tihc:;tt,io11 of m i s s i ~ ~ g or clc:f(:c:t.iv(-: gc~~c!s ant1 rcplacw~~cwt o r s r ~ p l ) l y i ~ ~ g 01' its protl~~c:t.s
2 .2 Biological Terms
CHAPTER. 2. BACKGROUND
r 7 1 I I V t , t : r ~ ~ ~ i:xoI1 WilS coinctl I)y t l ~ : i\rwric:a~i I,ioc:I.lc~~ilist. MTalt,rr Gill)c>rt in 1978 5 TTl ccsolis
arc t,yl)ic:iilly multiples of thrcc nuclaotitlcs (cvcry triplet of I m c s callctl a c:otlon is t r i~ns la t td
illto ccrr;;~ili amino ;~c:itl [2(i]). But, ~ i o t all ~ l i c inforuiat,ion irisi(lc t l ~ c D N A is cxpresscd ;is
prot,cins or IZNA, some regions of the DNA SO(~L~CI~( :O ilr(? (levo(;(:tl t,o c:ont.roI ~n(!c:li;xnis~~~s. -- - - - --
' h t t p : //en. wikipedia. org/wiki/Talk: Exon
2.3 Computer Science Background
:q)pro;~clies to solve t,l~is prohlo~n.
Exact string I I I ; I ~ C ~ I ~ I I ~ ~ I I I ~ S(?(111011(:(? a l i g m l c ~ ~ t ar(> 1.(!li~t.i\'t!l3: old topics O F (:0111p11t,~r
sc:icnc:c brrt tlwir rcw!r~t ctxt.e~~sivo ilpl)lic:;lt,ioris in bioil~ti.)r~ll;~t,i(:~ l l i ~ ~ r ~ s ~ ~ l t , ( x l in r (~n~w(x1
;~l , tc : l~ t , io~~ t,o t,11cw problclrls.
2.4 Computer Science Terms
W I I ( ~ ~ I l>~~i l ( l i~ ig ii suflix t,rw for a. st,ri~ig, soi~wt.ii~ics a. suffix of' tlii! s t , r i i~g ('ill1 Oc 1)iIrt. o['
i\ l o i i g ~ i ~ s~illix :11i(1 t,l~c:r(!Sor(~, its ~ ( 1 l)osit,ioi~ iiiiglil, I N , oti i l l1 i:(lgc o r k111 iiit(w1n1 I N N I P of
t11(, ti,ce. l b t11lsrlre t11a1. c!;1(:11 s ~ ~ l l i s i~ct,rii~lly c:ritls at. ;I I w f , a r ~ i ~ i c l r l c ! <:l~i~ri~<.t.('r \vlii(:lt is I I O ~
l);l.~'t. Of L ~ c ~~~)~ l :Lb( ! t , is ~ t ( ~ d ( : ( ~ ti) LhC Vll(1 of Lll(! ~ h % l g . l ' l l i ~ (IliIril(:t('r 1 l ~ l l ; l ~ ~ ~ ~ d(!llOk!(l 1 ) ~
S i ~ i l c l is c:all(:tl tlto t c r - inr id s!jitr601. I-Iciicc, t,lle s11f1-ix t rcc is ac-:t,tii~lly built oil ,S$. Figuro
2.1 sl~o\vs ;I suflix t,rc:c 1)uilt oil 111~ sc:c111~11c:c ATTATC:.
r ; ~ ~ ~ ( l o i ~ i l y g o i ~ c r a l ~ ( l c ;~~ i ( l i ( l ;~ l ,w , of' ( :o l i rs~ , iimsl, \vill 1101 get, i l r ( ! ;~so~~i~l) l ( ! s(:orc, :11i(1 thy
will IJC tlclrt,etl. IIowcvcr! ;I fow of tllc inst.i~nc:c:s rr~igl~t. gct ;I roaso~~nl)lc scoro (sl~ow nc:l.ivit,y)
a t d I.h(:sc citll I)c 11sctl Iowil~.tl Curt.hor solvil~g Lh(: p ~ ~ l ) l c ~ ~ i . T~ICSC c~111t1id;~tc:s arc Itc,pL i l11~1
Previous Work On Global Sequence
3.1 Scoring Methods
i\ 111oro gc:~~rr;d i \ ~ ~ d st,ill ( : ~ S ~ : - ~ , ~ - V ; I I ( : I I I ~ I ~ ~ C ~ 111(>t 1 1 0 ~ 1 OF i~ssig~~ilig S(:OIW~ is t i ) IISC ~~latxicvs
this c:oi~t,aiii t l ~ ! sc:orc of ~)ilit'-misc' illigl~l~l(!llt,s I)(:~\\Y!(:II (:\'Cry pair of t.110 ilIl)IlilI)(!l. ])('il~g 11s('(I.
Srl(:li CSRI I~ I ) IC!S ; I ~ O PAM [I21 i i i i ( l BLOSUR4 [l5] whic,ii ar(? witlcly rlsc:tl in prot,oin aligilinorll,
algorithnis. \:Vc IM: a s i~i~i lar nlatrix for pairwisc ~u~c:loot,itle scorc?s i l l IGAUNA.
Tlio c:l~oic-.o of scoring ftinctio~i (:;111 I~nvc? a grwl ii1il)ac:l; 011 t,ho cp~alil-y of thc fiml ;1lig11-
3.2 Dynamic Programming
d i ( w rr( : l : . ! I ) giws 1.he s w r o o f aIigni11g (d~;~ri~<:t,t>r :c with (:l~i~.ra(:t~cr :y.
U s i ~ ~ g this rcx:rirsivc! cquat,io~l, wo call clyri;~nlicillly l)uilcl ;L ta1)lc a~ l t l LM: 1 1 ~ ; values s t ,o rc~ l
i n 111~ l ) r ( :v io~~s r o ~ v s / ( ~ ~ I ~ ~ ~ l ~ ~ l s I,o ~ ~ l t i ~ ~ l i ~ t , ( ~ l > ~ (,;il(:~~lat,(! V 1 1 ) + 1 ~ 1 1 + 11. [Jsii~g I llis f;tl)l(!. \v(,
ci111 t.rt1c.e Imck ; L ~ ~ c I 1)uilcl tlic, nct,linl i ~ l i g l l i l l ( ~ 1 1 t .
B;lsc~I o i l t,hc N(~cc.lloiria~i-M'r~~liscti i i l go~ i t l i~ i~ , 1 1 1 ~ illit,llors i n [33] ~ I I I ~ I ~ V C t l ~ c SI);L(:C co111-
pI(.sit,y of N ( ! ( ~ ~ I ~ C I I I ~ I I ~ - \ V L ~ I I S C I ~ i t l p r i t l l ~ ~ l 11~1 11si11g ii 1 1 i w t,rirl< i n t .11~ LIP t.i~1>1~: II~sLcw(I O F
I<(!(.l)illg tllo \\l!lol(! h l )h! , t>llc!y Ollly h : l ) t,llc! hist ro\v a.ld c:ohlllll i l l l (I t.h0r(!f01Y! t.ll(!y lIS(!
l i~~c i i r sp;lc:r? ill t,hc Ic~igt,h o f tho i l~puts , i w t l l.her(! is no c l l i~ .~~go in t,l.~cl r i ~ r ~ u i l ~ g I . ~ I I I C . If 1 . 1 1 ~
il(:t,l~i~I o p t i ~ l ~ i ~ l idignnwlt is (Iosiml ( i ~ ~ ~ t . ~ i l ( l o f , ~ L I s ~ , tl~e! score of ~ I I C o p t , i ~ ~ i i ~ l a l i g i l i i ~ ~ ~ ( ; ) , tell(!
r1111ni11g t,iiuc will i l~c rwsc , l)ut, t,lic 11iag11it11dc will slily t,lic S ~ I I X (i.c. q ~ l a ( l r a t , i ~ ) .
Witli il sliglit. c:l~;~llgo to t,llc' for~~llilil (Iw(:ril)td ;1.1)0\~:, t l i ~ Sliiit,li-\li;lt,(:rllia.11 algorit,i~ln for
h :d il l igl l l l l ( ! l l t~~ (2111 I)(' O\)ti\ill(!c1 [ S G ] . I t 1lil.S (~llil(Il.ilti(: l.llllllilll?; tilll(! ;111(.1 SI)ilC(f ( : 0 1 1 l ~ ~ ~ ~ ' ~ i t ~ ~ ' ~
3.3 Anchor-Based/Hit Met hods
3.3.1 FASTA
3.3.2 BLAST
\vllorc li is i1 (:om~)l~till,lc I ' u ~ l c t i o ~ ~ of S i111tl 7) is tllo prol)i~l,ilit,y of l i ~ ~ t l i ~ ~ g a11 LISP wil.ll
scoro grvat,r!r or (~111:il l.o S [?:%I. r 7 1 t~is rosi~lt giws ~~l(!iu~il lgfi~l SCIIIRII~.~(:S t.0 S: C;ivcm sin: 01' 1Ii1! (I;lt.i~l);ls~ 1111d i ~ . scorilig
syst(!111> t,110 rw111t d c t c r ~ ~ ~ i l ~ c s wl~at, I I I ~ I I ~ I I I ~ I I SCOIW \vc IW(-XI look for i 1 1 O I Y I W to 11ot gct,
r i~ndo~rl I~it,s.
'Tl~c g ~ ~ ~ c r a l i1lg0rit.tl111 of BLAST call I>(: s u l ~ u ~ ~ a r i z c d iis li)llo\\rs:
Step 1:
b'ind all S L I ~ ~ S ~ ~ ~ ~ I I ~ ~ ~ I ~ ~ ~ ~ S of IPII$II I V , S I I C I I t11at tllcir score ; l g i ~ i ~ ~ s t , t 1 1 ~ q ~ ~ c r y (2 is ut h ~ s t
7'(< '7). I V is t.vl)icillly cclual to 3-5 i111d 11-12 for proleius i111tl DNA scc111c:llc~:s rcspcctivcly.
S t e p 2:
. '~;~l . ion; t l C:cw(c!r ti)r Iliof.c:c.l~~~ology I n l ' o r ~ t ~ ; ~ t . i o ~ ~ (o) http: //www . ncbi . nlm. nih .gov/ 4 r
I ' l l( ' ~ I I I ~ I I ( > ivc!1) ; ~ l ) l ) l i c , ; ~ l i o 1 1 V ; U I I N . t ' o l~~ ld i l l http: //www. n c b i .nlm. nih. gov/Education/BLASTinfo/ information3.html
"http://en.wikipedia.org/wiki/BLAST
111 ortior to c:ol~q)ut,e t.he co~~lplcxi ty o f ULAST, wt! 11aw t.o kuow "w11;lt. is ;I c l ~ a ~ ~ c c li oL'
;I S-swriug sccl~~!l~c.c\ lmf. Ilnving a T-scorillg ~ror(1 OC size I/\/ ?". lSx1)(!1.ill1(:lll.;II rohl11l.s SI IOW
f llnt givcl~ T ~ I H I 1V, ~ I I P ca11 f i d n ;~ntl h sudl t,l~i~f 1; = e-("S+b). I3;1scc1 on t.llis, Int 14: IN.
;I nwd)c r of nlorcls gcncrat.cd 1'01. an i r ~ p u t (Illcry ill Step 1 a ~ d iU I)(: a 11111nl)or of rc!sid~~(:s
i l l t,l~c: tlat,i~l.)asc. T l m l colnylesit,y of BLAST is O(rrN7 + 6.n. + -). Aftw illt,rotluct,io~l of t,llr o r i g i ~ d BLAST, lllarljr tliffcret~t versiorls i ~ i ~ ~ ~ t : ( l a t ( l i f l iw~~f ,
t,yl)c:s of s o c l ~ ~ c ~ ~ ~ c c ~ s (i.v. nmil~o-acitls, protc!ins, otc..) ; ~ r l t l for (lill'(:rc~~t. pl;~l.for~ils w(>ro tlcv(!I-
opctl. Solrlc: of 1 . l 1 c w arc DLASI'N, I'RLAS'T. Ul,i\S'l'S, PSI-IJLAST, C:I\PPISD-I~LI\S'L',
J,IEC,A-DI,AST, 17St\-UI,t\S'T. MJ1J-I)L!\Srr, 711,1\'1', cst,c:.
PSI-Blnst (Posit,ion-Si)rc:ific Iterative BLAST) ;ml GAPPED 13LAST are int.rotlucrtl ill
(121. The idea. I ) c l ~ i ~ ~ t l GAPPED-BLAST is as hllo\vs: TIN: o r i g i ~ ~ a l BLAST Iillt1.s i1 si~lglo
\vc-)rtl of Icl~gt,ll u~ t,llnt scorcs a.t, loi~st ?' against tho clrlc:~,~;. B11t i f wc lir~tl t,nw n.ol.11~ ()I'
le11gt~11 6: ant1 sc:orc: T t ,hi~t lic O I I t l ~ e S ~ I I I C tliagonal wit.11i11 tlist,anc:e /1 fro111 each o t l m , t.11(:11
if 7' si~.t,islic:s cc,rt,ain criteria, mc just. c ~ ~ t c l ~ t l T i ~ l l o w i ~ ~ g gaps too, to rc;lc:h 7'. Usi~ig t.llis
mc:t,lloti, nv c>ntl 111) wit11 rilorc hits: l)ut, sillct: we (:over 111orc of thc: st,ring (1)y c:on~lcc:t,illg ?'
3.3.3 CHAOS
3.3.5 GLASS
1. For a n i~~i t iwl k , find all n ~ a t c l ~ i n g k - r ~ ~ c r s (k-long \vortls).
~\dlJ!l/lrri.c:r. ; I roliit.ively f ~ s t g l o l ~ l alig~l~ricnt. algi)rit,li~~i ~ ) Y ( ~ ~ L ' I ~ ~ , C ( I i l l [13] 7 . It. ~ I S C S s~il[ ix
trees t,o fild 111ilt,c11c!s I)ctt,\vc:c:~~ t.wo s t , r i~~gs .
hlUi\,Ii~ic?r usc,s ~ i ~ i l ~ i ~ l l i ~ l ~ ~ r l i q ~ w cxit(.t I I I R ~ C ~ I C S callctl 1\4 lil\%q as a~lcliors. The, ~iriicluc~lic~ss
Ol' a 1lliltdl i l l t,llc t.WO scclll('llcW 1llc:lllS t,lli~t tll(\l'e> 11~s t O h! Ollly 011(! (:OpV Of t ]I(' ~ l l t l t ~ ~ l i l l g
3.3.7 ClustalW
111cnt.s '. It, is 111orc scwsit.ivr! tl1il11 tlic: ol.li(:r col-~~rriorily-~lsctI global i l l i g ~ l l ~ i ~ ~ i t ~iiot,l~~(.ls by
llsilig tJic followil~g ~~~ct l ioc l !':
*[I. is i\\viiliil)lr ; \ I http: //www. e b i . ac .uk/clustalv/\#
"http: //bimas. dcrt .nih.govjclustalv/clustalw. html
3.3.8 AVID
011cc tllo rclc:r~rsio~l is c~)~~iplc:t~ctl, AVID nligl~u t , l lc \ rcrni~i~~ing ur~alig~lctl rcgio~is 1lsi11g fllc
N ~ ~ ~ I I I I I ; I I I - M ~ I I I I s ( : I I i ~ l g ~ r i l . l ~ ~ ~ ~ [34] i f ~ , I I c , v ill.(> s~~ fF ic i~~~ t , l y ~ l ~ r t . i111(l 01 hcrwisc I C ~ I V W I . ~ I ( ~ s c
regiolls rlnalignocl. h/IAVID [Ci] is a. progrcssivc: ~llnll.iple i~lig~~m(:~lt . t,ool t.hi~t il.lc:orl)orittc:s
AVID.
3.3.9 MGA
3.4 Genetic Algorithm
3.5 Hidden Markov Model
problcn~, t,Ilcu t,rans~ilissio~i a ~ d cniissior~ ~)rol>iil~ilit,ics slinultl I,(: tlccitloil I)y tra.ir~ir~g using
I~ 'o~ .n~c~r-r l / l l i i~(~k '~~~n~~~( l i ~ l g o r i t ~ h ~ ~ ~ s . Thew 121~ Vitcrhi ; ~ l g o ~ - i l , l ~ ~ n (:an I)c ~lsctl to itlig11 SC~IICII(:( \S.
O n e gootl Li.ilt,u~<! of H1\?1\'Ih is that they can l x rlsctl to itlrntXy dictlic!r ;I s c ~ l ~ ~ c ~ ~ c c .
I ) e lo~~gs t.o il piu.ti(:ulur Sa~~iily 01' s(:q~ie~lt:(:s (i.c. ~ ~ O ~ C ~ I I S ) [X ) ] . 1 1 o ~ v ~ ~ w r . this apl)roac11
is not as popr11;lr a s other nlethotls, I)cc:iiusc? tlic t.ol)ology o f t,lw IIMhI 1110t1ol is I~igl~ly
tk:pc~~tlant on t l ~ c ~)ilrti(:uliir ~ ) r o b l c n ~ ilncl t.hc sc:q~~c!~~cc!s I~cing stutlictl. Wc idso 1iwi1 a
largo 11urnl)cr of squc~~c:c:s in o r t l ( ~ t,o / , ~ . n i r s t . 1 1 ~ III\/I.\,I i ~ 1 1 ~ 1 find tlw ~ ~ ; ~ I I s I ~ ~ ~ s s ~ ~ I I / ~ ~ ~ I I ~ s s ~ ~ I I
prol)rll)ili t,ic!s.
General Algorithliis For Anchor-Based
4.1 Building Suffix Tree
Using >I 11i)ivt: ;~pl)roacdi to I)uiltl a suKis two O I I ;I s h i ~ l g S[l..ll], tak(!s O(.r,,'') ti111o a~ l t l sI,ilct?.
\IT(! ~ . ; L I I tlo t , l ~ ; ~ t i l l ; I I I if,c:rat,ivc: \vay ils Sollonrs: 111akc tllc: t r w l),y 111aki11g a ~.oot, ;111d i l l 1 ctlgt:
t111d Ii1l)cl t,hc edge: wit11 t11c lor~gwt suffix of S, i.c. .S itself. 'I'11(:n talw 1 . 1 ~ : ~lc?st. s ~ ~ f l i s l)y
d i ~ ~ ~ i ~ ~ a t i ~ ~ g thc first, ch i r ac t , c~ of t h p e v i o t ~ s s t~f l i s ~ I I I C I l , r a \ w x t11e t r w s t a r t i~ tg f1.0111 tllc
root,. As long c:har;lc:tkrs nrc fo~u~c-l t l i i~ t rnatcl~ tllc (:11rr(wt s111Iix 011 thv t.rtx?, follow 1 . 1 1 ~
cxlgos ilrl t l l)ra~ich(ts. \VI~CII ;I cl~i~.rac:t,c.r that. tloc?s lot. ~l~atc:ll tl1c nest cl~ari~c(.er 011 the ~ N Y !
is c :~~c~or~~~t t : ro ( l~ crcatc a 11cw hri111(:11 a ~ ~ t l a11 ctlgo al~cl laI)t!l tllc ctlgc: with tllc rcl l l i l i~~i~lg
c.llim~c:t.t:rs o f t.110 ( : I I ~ I . C I I ~ s ~ ~ t f i s . An a.11 ~ I ~ I I R ~ ; ~ V ( I 1 1 1 c h ( l using t,hc S;LIIW i t l ( , ; ~ is I,o s t ~ r t frolll
tlw sllortc~st sufiis i ~ r l c l i~ t ld l o l l g ( ~ sulliscs in (wt:11 il.eri~t,ioll. Figuro 4.1 sllows t.l~is 1)rocc:ss.
1<i1(:11 s111Iis o f lc!~igt,l~ I I L , tci~n 1)c i ~ d ( l ( d i t , 1,o [lit: t,ro(~ in O( t i 1 , ) 1,i111c ;~ncI ll~crt:Sort> t,l~t> t,oIi~l
4.1.1 High Levcl Ukkoncn's Algorithm
Definition AII h p l z c i t S,u[Jix 7i~f: 011 s txi~lg S, is a. tru: Ol>t,i~i~l~cl I'I'UIII the S I I I ~ X t r ~ c li)r
S l ~ y r(!lnovil~g (vor,y (O~>JJ of t I N > t(mlli11a1 syni1)oI !i fro111 t,11r (:(lg,~ lal)(,ls oc t,lw 1 r(x?, t lmi
l'('lllO~i11.g ;Lily cYlg(? tlli\L 1 1 W 110 Ii~h('1, iill(1 t I l P l 1 ~(2lllO~illg i\lly 110(1(: f.,ll:lt, ( 1 0 ~ ~ l l ~ t , 11ilv~ 1L.t
lcirst Iwo c11iltlrc.11. W r ! tl(:~~ot,c: t,lw iml)li(.it. sl~llix t,rw of t11(: s t r i l ~ g S[l..i] I)y Ii.
/ \]I il11pli(4t, s u l h t,r(:(! 011 S i l ~ d u l w all t,lw s ~ ~ f f i s e s of S, I)ut S O I ~ I C sulfixw ~ l ~ i g l ~ f , 11ot~
( : I I ( ~ at. i l h f . l2ig11rc 4,2(;1) sh)\vs ;UI i~x;11111)1(! o f i1.11 ilnpli(:il. s111lix t.ro(:.
Uku1111c:n's a lgor i t l~ l l~ is tlivicl(:tl i~lt,o 1ri ~)lii~sc>s. In phi~sc i + 1, trc:c: I , + L is c:onstn~ct,c>tl
flx,l11 I , . Eil(:Il l j l ~ i ~ ~ ( ; i + 1 is f l~rt ,I~(>r (livicl(:(l il~t,o ,i + 1 ( ~ x t , w ~ s i o ~ ~ s ~ O I I C for (lil(:ll of t,11(! L -I- I
s ~ ~ f t i x c ~ of S[l. . i + 1) . 111 clxt,rnsio~~ , j of pl~iisr i + 1, t h algorit,l~rn first h d s tlw c m l of tJlc!
1,i~Lll S ~ O I I I 1.11(! root laI)~le(I wit.11 s111>stri11g S[,j..i]. It. t11e11 C S ~ . C I I ~ S t 1 1 ~ S I I ~ S ~ ~ I I ~ l)y i ~ ( l ( l i ~ ~ g
Ill(! chi\racl.c!r .S[i + 11 t,o it.s cntl, I I I I I ( M .S[i. + 11 alrcwljr i~.l)lw;\rs I.11c:rc:. I I is jllst I,h: sil~glv
c(la~? li\l.)cl~tl 1 ) ~ ' ~ : l \ i l r i ~ ( : t ~ r S[1].
I : Collst~rllc:t II 2: for i fsolll 1 Lo 711 - 1 do : I : {pcrformilig plli~sc~ i + I } 4: for j from 1 to I. + 1 do (7: {p(~rfoslnillg o s t , o ~ ~ s i o ~ ~ j) (i: E'intl t . l~e clld of the pat,ll fro111 the soot. lal)clc?cl S[j..i] ill tho currc!nt tmo. If ncetl(d,
est,c!l~cl t,lli~t I ) ; I ~ . I I I)y iltltlil~g cllilri\(:tcr S[ i + 11 t,o mit,kc SIIIY: Llli~t, S[:j..i. + 11 is i l l tall(: trcc,.
7 : end for 8: end for
4.1.2 Speedup Techniquc, Part 1
i + 1 \\wr1<s.
Now, \\Y: (.i111 i ~ ~ t rotl~~c:t> a toc~l~t~icluc~ t.I~i\t will rc~luc:c: t,l~o \\:o~,st c:i~sc r ~ ~ l ~ l ~ i l i g l i 1 1 1 ( 1 of t l ~ ( '
i~ lgor i t l~ l t~ t .0 O(II ').
I P 4 GEIVERA L A LCX)RI?'R.\.lS FOR ANCHOR-BASED I\.I/,:?'IIODS 3 1
Algorithm 2 Sirlglc 12xtc1lsio11 Algorit11111 (SEA)
( :11;11 . i l ( ' f ( '~ g 0 1 1 t11(' ( ? d g ( ' i l l l t l C l l l i t s , 1 1 1 i ~ k i l l g S111.(' t , l l ; l t t.110 7 ~ ) i l t l l f1.0111 . ' i ( l l ) ( : 1 1 ( 1 ~ 0 1 1 t .11 i i t (?(Ip,(?
( ! ~ i i < : t , I y /J c : I l ; \ r ~ [ ~ r s ( I O I V I ~ its l ; i b ( ! I .
4.1.3 Speedup Techniclue, Part 2
0 1 1 ~ 1)~01)1~111 t . 0 1)1.0(:(!(1(1 SIII.I.~ICI. il.11(1 I.OCII~CC t . 1 1 ~ r l l n n i ~ ~ g (.i~iic OC U ~ ~ O I W I I ' S i11gOrith111 10
O ( n 3 is 1l1o fact t l ~ i ~ t it ' we rcc:ortl ill1 thc? c41;irac.tcw 011 t11c etigcs of 1 . 1 1 ~ t r c x ~ , t11c i~lg:)ri t , l l~~~
will rt:cluirc, T)(ri.') space and tIicrc!fore O(ir) r l m n i ~ ~ g time will 11ot I)e ac:llirvirblc. To over-
csoi~~c. this l)rol)1(:111, i11stt;d of roc:ortling c:l~ar;~c:ters, A:(: la1x:l tllo ctlgils l)y ;t pair oS i~itlicc's
i ( l (~~~t , i fy ing f.he st.irrt and (211d irr(liccs of t h c s~~I ) s t , r i r~g on that. edge. This wily, oldy 1n.o
1 1 1 1 l l l t W ~ ~ ari! writ t.(lll 011 ibllY (:(lg(! illl(1 S ~ I I C C : t,ll(! 1 1 1 1 1 1 1 ~ ) ( ' ~ o f C ( ~ ~ C S is ilf. 111ost. 271. - 1, t,llc: t,r(Y1
will o~ i ly IISP ~ ( I I ) S ~ I U : .
Observation 1: 111 ally l)hi~s(?, if sufIis c x t e l ~ s i o ~ ~ rul(: 3 ap1)lic:s ill cxt .cus io~~ j : it will
i l I ~ i 3 i1.pl)ly i l l f'llrt,Il~r (~xt ,e~~sioi is 1111t,iI t.11(: (? l l ( l of t,lli~t 1)IliI~i'. 'rll(? ri!;ls011 is t,lli~t, \V~IC! I I 1'111(!
3 i~.ppli(!~, t.11(: l)iltl~ Iiil~clntl S[j . . i ] i l l tlre currt:~lt. trcc ~rrust, c :o~~ t i~~uc : with cl~ar;tc:tcr S[.i + 1 1
i l l l t l SO 1.110 pi~f~11 181)(:1t!d c?[,j + L..i,] (Io( 's i l I ~ 0 , i l l l ( l I'll!(: :: ilgilil~ a ~ ) l ) l i ( ' ~ i l l t . 1 1 ~ lI('S1. (~xt.(!l~siolls.
It is a.lso I)cric?fic~i;d to ol)sc?rvc: that. a ~lc?n. s u f h l i d t ~ l w c l s t.o l)c ntltlctl to I.l~c t.rcc: o~ i ly idtor
it11 c s t c ~ ~ s i o ~ ~ i l l ml~ic:l~ c s t c ~ l s i o ~ ~ rulc 2 a.pplic:s. Now we ~:;III stat,(! t.110 I I ~ X L t~.ic:lt.
T c c h n i q u c 2: K ~ t l ally plinsci i + 1 tllo first I,i111r Li~i~t, cxf.c~~ision r111c 3 iq)l)lios. If Illis
I ~ a p l ) o ~ ~ s i l l ostmsioii j : t11c11 111(:re is 110 ~lectl to t:xplir:it.ly h l 1.11~: e ~ ~ ( l of' ally s t r i ~ ~ g S[X:..i]
I'OI' k > , j . id1(: ( : i l l ] t l l(! (~xt,cllsiolls i l l l ) l l i l ~ ( ' i+l I , I I i l [ , ill'(' (1011(: ;lfk!l' t , l lC [irst ~ ! s ~ Y ~ ~ l L i o l ~ of rIl](!
3, . i 7 ~ 1 p l j ( : % t (-*x1~11sioris.
Observation 2: I f ;it so111c: poi l~t i l l Ult l to~~c.~~'s illp0rit11111 i~ 10i1.f is ~~.(:ilt~(:(l i111(l li\l)c:lctl ,j
(for 1 lie s11Uis st , ;~rt , i~ig ilt, p o s i f h ~ i , j of S ) : t , l i c~~ t,lli~f., lvaf will rcmri11 ;I h f i l l i l l1 s~~(xx!ssi\:c
Lrccs c:rc:atetl (Iuriug the illg0~.itl1111. TIIC r c a s o ~ ~ is t l~ i i t t l ~ e r ~ is 110 I I I C ( : ~ I H I ~ I I I ill t.11~ algo1.itl1111
I;o c ~ s t , o ~ ~ t l ;I. Ical' c~lgc? l)c~,yi)l~il il-s c,rirrc?~it, I w S , i.c wl i r~i ;I IcilT is Ii~bcl(:tl , j . c!sl- i!~~sio~~ nil(> 1
Wil l ill\Vnys ii])[)IJ' (,o (Xk!rl~i(>II ill illly SIIC(~C~SS~V(! pllasc!.
I,ct j , tl(:~~otc, the lilst, extc~i~s io~i i l l this scq~lc~~c:c~. Now \vo (::III proscut t l ~ c last trick.
Technique 3: In ~ ) l~ i i sc i + 1: wlioli u Ioirf ctlgc' is first croi~t.c!tl and n,ol~l(l 11or111;111y I)('
1al)cletl wit11 sul)stxi~ig S[l)..i + 11, i~~st,c!ad of writ i l~g i~~tliccbs ( p , [+ 1) O I I the ctlge, writ(: ( p , o ) ,
w l ~ ~ r c (, is s,v~nl)ol tlci~ot,ing "t,Ilo crirrcwt cr~tl". Sy11il)ol P is $1. glob;~l illtlex t h t is sct, tao
i + 1 once in c!acl~ phasr. 111 phas(-: i + 1: sin(:(: tho idgoritlm k~lows I llitt riilo 1 will i11)pIy in
c:sto~rsio~ls 1 L11l.ol1gl1 , j , i ~ t l(\i~st,, it I ICC(I (10 110 il(l(litio11i11 cxl)li(:il ivork t o i~~l l ) lc i i~( :~r l t.I~os(~
j ; cst,c?~lsio~~s. Inst-xwl, it. only tlocs c o ~ ~ s t a ~ ~ l , work t.o ~ I I ( :~CI I ICI I~ , v i ~ r i i ~ I ) I ~ C! ~ I I I ( I t h 1 (!OW
oq)lic:it, work I'or (so111~) c:xtcusio~~s st nrt.ii~g wit11 c:xt,clisior~ , j l + 1.
L s i ~ i g tc>c:l~niq~~c?s 2 i ~ l d 3, csplicit, c~st ,m~sio~ls in plii~sc i + 1 using 2 iLrc. o ~ ~ l y r c q ~ ~ i r c d
A l g o r i t h m 3 Si~igl(, I'hilscl Algoritlm (SI'A)
I : Inci~oii~ciil, iiitlw e t.o i + 1 (By X?c:hniq~ic 3, t l ~ i s correctly irnplctncnts all ill~l)licit. c.xtc:~~sions I t,hroug11 j , ) .
2: Explicitly coull)utt succcssivc cxtciisior~s (usiug i~ lgor i t l l l~~ 2) ~t i~rf . i l lg a t j , + 1 u~it i l r c x - l i i ~ ~ g tlic first, oxl.c~isioii J ~vlierc r~ i l c 3 applies or until 2111 (xtc~iisio~is ilrc ( I O I L C in this l)ll;~so (13y 7'ric:lc 2, t liis c~orroctly i ~ n l ) l ~ w ~ c i ~ t , s ill1 ( . I N > :~tl( l i t io~~ill iiril)lit,it, cstcwsiolis :j + 1 t , l ~ r o ~ ~ g l i .i + 1).
:%: To prcparc for thc nest step, set; 3, + 1 to j - 1.
Thcorci r r 2: Usiug s u l h l i ~ ~ k s a i d triclts 1, 2 a ~ d 3, IJkkoi~c!~i's ;~lgorit,luii 1)liiltls i~~~l ) l i ( : i t
sldfis t,rc!c!s Il t.llro11g11 I,, i l l O(n.) ti111o.
4.2 Fincling Maxilnum- Weight Anchor Set
C4ivc1i u set of ~ n a t c : h s , we would liltc t,o scloct sct of 11011-crossing niatcklc:~, also r(\forrcd L o
13i1s(~l on t11is d e f i ~ ~ i t i o ~ ~ , a givc11 111;1t(:h :\I = (.il, i2.11,!2) c o r r c s p o ~ i d i ~ ~ g to a ~ l ~ l i ~ . t . ( ~ k ~
h?t\\.e(?ll Sl[bl..i2] and S2[ll..12], dofillf!~ poillts Of il ~.(Y:ti~llgIC 7. in t h ~ (.ill.l.(&Ul [)Iilll(' with
f IN: I)ot.t.o~~i Icft. c o r ~ ~ c r I ) c i ~ ~ g thc p o i ~ ~ t . (61, L 1 ) i111tl I.lie top rigl~t, c o r ~ ~ c r l)c!i~~g ( i2 , 12). Ilcfino
thch wc+ght, of r. to 1w its tlrca. T l ~ c ~ ) r o l h l ~ ~ of fincling i~ scl. of 11lnsi111n.l ~rintc:hos, rc(ll~ccs to
filldillg i L s(!t, 0l' llO~l-(:~O~~illg' ~~Y:l.illlglW Wit.11 l l l i l ~ i l l l l l l l l ilrCil COV(!l'HpC. L;IOl'C! fO~lllill1)':
Dcfinition Let.
I)LLS(?(I 011 t11cir XII IML:~ itii(1 \v(, s\v~c!1) I , I ~ O I I I f'ro~ri right t o lcff,. At, (>il,t:I~ st,:i.gt?; wl1(:11 \w are
1)roc:ossing rc>c:t;uiglc i, wc! ivarit to 1i11k it to t,llc I I I ~ I X ~ ~ ~ ~ I I I I weigl~t pi~tll i l l t h ilil.(:rviil
[ S I I , ~ : I : [ ~ ] , +x] x [Y~rma:[i], +DL] iintl storc i t i l l ii sot I I . \\'o [lsc1 Nc:i : t [ i ] to clor~oto t,licl ~icst
rcc:t.iu~glt: i ~ i tlic I)ost patli c o n t a i ~ ~ i ~ ~ g roct~a~~glo i ( t l~o piit11 witli 11iiisi11lu111 iveigl~t.).
Tllc! O ~ ) ( ~ ~ ~ l t ~ i O l l ~ l l ( ? ( ! ( ~ ( Y ~ t,0 ~)Ilild iLl l (1 lll~illipllh~:(~ sel, D i l W U [ I ( / ( L ~ C illl(1 DC5b. TllP OI)('riL-
t io~i Besb(D, y) rct.urus Mccttl( i) of a rcctt~ngle with ~ ~ ~ i ~ ~ i l n u l i i Y.tr~i.r~[i] 2 and ret11r11s O i f
I I O s rd i rc:c%ii.~iglc i exists. TJ~)tlatr:(L?, I ) ~~l)tlatcls t,lic sc:t I1 as I'ollows: It ii(lt1s 1 . 1 1 ~ Iwsl pa(,Ii
startir~g at; rwtat lgl~ i to D, hit. i t pr(!s(:rv(:s t l ~ c (:o~l~l)at.ibilit,y alliol~y II I ( : I I I~)C~S of D. 111
otlic:r worcls. Sor ally I\vo l)ii.t,lls p i i ~ i c l (1 swli t,li;it. J I 5 (1 i l l set. 11, wc: wol~l(l liko lo r o ~ ~ i o \ ~ c 1).
A l g o r i t h m 4 k' incli~~r klaxiniun~ \.\'cirlit Anc~i~ors
Now iv(! (.a11 I ' o r ~ ~ ; ~ l l y (l(:sc:silw t l ~ i s prowss i l l Algorit,l1111 4.
111 ortlor 1.0 i~c:liic\~! ;L ~ I I I ~ I I ~ I ~ ~ t i m : of 0 ( h g 1t), wo 1i(wI 1.0 cllic:icwl.ly i ~ ~ ~ p l ( : n ~ ~ l ~ t . sc1. 11 so
t-liat t 1 1 ~ Br:,s/. a l~ t l b'ptLrl.l,c opcnitiolis I.i~kc O(1og11) tillw. Tl~i~t, 11lci1ns \\re ~ ~ c ~ t l t,o Oc i ~ l ) l ( t
t,0 ~(~tll'(:Il, illscl't, joill allti split i l l C)(lOg 1 1 . ) tilll(:. \AT(! (:ill1 i l ~ ' ~ . O l l l ~ ) ~ i ~ ~ l tIlilt, 11sillg k i l I ) i l I i l l I (Y!( I
~ ( ' i ~ ~ c ' h t rw . S i ~ m cwc:h pal.11 i can bo u n i q ~ w l j ~ ic-lo~~tifiotl by i1.s Hmrl(i.) ( ~ L I I ~ t . 1 ~ rwt o f t . 1 1 ~
path (:;u1 bc const~ruct,cvl u s h g .Vc..ct[l] poi~lters) , cacll clenwiit i l l D (:iui I ) ( : sc~pr.c~srlit,ccl ly
; I 11111111)(~ w l~ id l is 1 1 1 ~ s~( : l .a l lg l~ n111riO~r 1 . l l i 1 ~ i l . ( Y ) S ~ ( ~ S ~ ) O ~ ~ ( I S lo. Eac:h r~l(:nic~l~l, of D Iias ;L
To/nll,Vci</lrt i111d a Ylttil?. ~ s s o c i i ~ t d wi1.h it. HOW~VCI. since all c!le~~~o~-it,s of 11 ill.'! n~ut.ually
cxm~pi~t . i lh i i l ~ t l Oc:c:al~se i l l t l ~ o for lool), wc: SGIII 1 . 1 1 ~ c1(:111o11t,s I);isetl 011 tl~c:ir .Y-c:oortli~~i~t,c~s
fro111 riglit, t,c) l ~ f t , , t,11c ou lw of i~scel~(lillg Tot.~~~lIV~~~t.,ql~t. is 1 , l l ~ silllic as t,Iw o r ( h of tl(w(~n(li11g
Yinirt . I'liorcforc: although nlc Ii;~vc t,wo k ~ y s associntc:tl nriLll tach clcmcnl, (i.c ?'o/.crlWr:~i~ylrL
;11i(I Yti~in)! if \vv sorl, t.11~ ~ ! I ( W I O I I ~ S i ll the L r o ~ OII OIW lwy~ 111ey will I ) ( ! sor~.(xl on t.11~ o t h
lwy i l l 1 . 1 ~ o1)positc ortlor.
GAUNA
In this c:l~apt,c:r wc will tlescrilx GAUNA (C:lul)al A l igm~~(mt Using ~ 'o I I - cx~~( ' [ , Al1~1m.s)
( l c l o j l i t S i I S J i i v i I l i e I l i o l ~ l ~ l l i s l ~ i t . I . 141) i l . t ~ t l sliow its
~)(:r l ;)r~~~ar~c-:(! c~oiu~);irc?cl t,o otlwr stat(.-of-t.hc!-i~rt, i~lgorit 11l11s. 111 ortlrr t.o (lo t l~ i s , n.(, will licit.
givc ;I Iligh-1ovc:l ovcrvicw of 11on: GrI l JNA works i ~ ~ i t l t l ~ ~ l l n ~ ! will ( ~ s ~ I w I I I I :V(>~JJ 1)il l . t) of' t l ~ c
algori~,lut~ in 111orc (Ict,ilil. GAIJNA is t l ~ r 1)asis for I(:I\UNI\ i111t1 t l~crcforc: r~~~il(!rst.;llitli~ig
5.1 Met hod description
G A U X A is i t rcutrsi\v a l g o r i t h ~ 11asc:tl 011 thca lollowing t , l ~ l w l r ~ a i r ~ s t ~ p h :
Algorithm 5 G A U S A H i ~ h Lewl
5.2 Finding Maxiilia1 Inexact Matches
~ i v ( ? l l t,\\W s(!(!U(!llc(!S ~ 1 . 1 1 ~ 1 .s2: ?I, ([llil(I~ll~)I(! ( i 1 , .i2. l l 1 2 ) is ('iIII<!(I ki rrt.(lk:/t . i f t.Il(! ol)l illli11
i ~ l i g l l ~ ~ ~ ( \ l ~ t s(:or(! o f t,11c t.\vo S I ~ ~ S ~ ( I I I ~ I I ( : ( ! SI [I1! i l + - I] i111tl S2[i2, i:! + 12 - I] is grcJiatc:r
tllilll 01. (YlllilI t0 W ~ ~ l . t ~ i l i l l tlll.(!~llOld. NO((! t.llilL i l l tile ~(X~llOl S [ i , j ] t lC l lO t ( !~ tllc ~ l l b~ ( ! c lU( ! l l ( ' ( ~
of 1 . 1 1 ~ sc!qiIcnc:c S sl ;~rt.il~g i ~ t p o s i l h i i i u ~ d cllding iil, 1)ositiol~ j . If Sl [ i l : i l + 11 - L ] =
S2[i2, i.2 + 1.2 - I! t.hc 111at~c:h is c:allecl an c m ~ : ~ ~ ~ i l k l i . , o t i ~ ~ r w i s c it is cidlocl a11 iiwxnc.1 711.(~t(,l~.
I;i)llowing t . 1 ~ t lc l i~l i t ion ol' Dc1cllc:r ct a]. , a 1uatc11 ( i l , 1 2 ! l l . 12) is c:all(d Y I L . U . X ~ ~ I L ~ ~ il' i t (.i111110t.
be cxtcwclctl at ctit.hw cwtlpoint [13]. For irlcxict, i ~ l ~ c h o r s wo p l c w l i x c t l ~ i s t l c f i l ~ i t i o ~ ~ 21s
f'oIloi\:~: AIL cxi~ct. I ~ I L L ~ . ~ I ( i l ! i2! 1 1 . 1 2 ) is I I L . K L L / I ~ . ~ if' t11erc is 110 o t l ~ ( ~ r 111ill ( i i . i h , 1; 1,;) stl(,l~
tlial. Sl [ i l . i l + l1 - 11 is il 1)ropc:r S I I ~ ~ S N ~ I ~ ( ! ~ I ( Y ! of Si [i', , b', + I', - 11 i111d S21i2, i2 + l2 - 11 is
21 l)ropcr S L ~ I M Y ~ ~ I ( ! ~ I C ~ o f S2[i$;i; + l b - 11. Wc w i l l 011ly (m~si( lcr i11wact ~ n i ~ t ( ~ l ~ c s for w11icl1
l 1 = l 2 ~ I I I ( I t , l ~ c l ~ f o ~ 011r l l l i ~ t c l ~ ~ s will I>(! S C ~ I ~ ( W ~ ~ I I , N I l)y il t,riple ( i l . i ,2 , 1 ) .
11s i l l ot,Il(!r ~ 1 c l 1 0 r I ) ~ I s ~ ( I ~ ~ I P ~ ~ I I O ( I S ! G A U K i i LISPS st~lt ix ~,NY!S to lilul : I I ~ ( ~ ~ I O W . 111 Scctio11
4.1 n.e Ila\:o tl(w:ril)c:tl i l l tlctail I ~ o w t.o 1)uiltl ;I suftis tree i l l lil~ctar L i l l x i111cl Sl)il(.('.
For ;I S ~ Y ~ I W U W S, t,llc: snlic,lll-, fcat.11l.c: we ~lc:ctl of a slllfix t r w for S is t,l~;lt, t,llc> ~.OII( , ;II ;(~-
11a1io11 of odgr-lnl)cls 011 t,hc ~ ) i ~ t , l l fro111 the: root t,o i111 i n t e r ~ ~ i l l ~ lo t lc is n ropci~t sul)scqt~c~lc:c~
i l l S \\:11(w tllc: 11u11l1)c.r of ~ , c l ) c ~ ~ t s c:orrc:sl)ol~cli~lg to all i ~ ~ t c w ~ a l ~ ~ o t l ( . is ( y 1 1 i 1 1 t,o t,llc I I I I ~ I I I ) ( T
o f I ( J ~ I v ( ' s of t,llc s111,t~rcc rootc:tl a1 L l ~ l t il~l.c:n~nl ~ ~ o t l ( : .
LC:(. SI i111d '5'2 IJC! t8 l lo ~, \vo il11)11t S(!CILI( : I I~~S to 0111. ;~lgori t , l l~n o f Ic11gf.11 / I / i111(1 71, ~ q w ~ t . i v ( ~ l , y .
\?To biiil(l i t st~ffis t,rc?c! for S1 :111(1 ~ , I I C I I s o ;~ rc l~ f;)r s~ l l ) s c~~ i~c~~~c :c s o f S:, o v ~ r t.his s~~Ili.u t,rocl. \\I('
\\'is11 t.0 f i l l t l ill1 lliil~illlill llli3I;CIl(!~ 0f illl(l & t.llat Ilil\r(? ~lifflllll(!ll~; S(:01.(! H ~ O V C il. t.lll.(~S110I(1
s . Tllc 11i1ivo ~nc:t,hotl is to h l . for onc:l~ slll-)scqi~cnc.c "ii o f thsc: pilths of 1 . l ~ si~tIix tr(:(,
st ,art , i~~g 21t. t,he root wliose Iiilx:l, ~niit,checl with SI,, has an n l i g ~ ~ n ~ o l ~ t scorc grcutvr t11al1 s .
Not,ic:c: t,l~c:ro (:i111 I)c ;I lilrgc: 11~1111)0r o f SU(:II 1)il.Lll~ a l t l cvc:l~ t,llc! 111ost d f ic ic~~t , i1lpprit.11111~
k l l o rn l~ fi)r t l~is ~)roblcrr~ have vc?ry 11igI1 ri l l~~li l lg 1.imc il11(1 Sl)il(.(! L . ( Y ~ ~ I ~ L . ( W ~ ( W ( ~ makillg ( . I I (> I I I
ill~lxiict.ic:i~l [:JOj. r 1 l o ovcrconlc I his prol)lcn~, no 11111~1 co11si(lvr t1w s ~ . ~ I I c ( . I ~ ~ ( : oE i ~ ~ p i l . S ( : ( ~ ~ I C I I C ( ~ S . \<\;II(:II
t11c i11p11t s(yi1(!11(:(:s iir(! w r y s i ~ ~ ~ i l a r , t,l~c:rc call I)(: 111) to O ( r r ~ 1 i . ) ~rluirriiil 111~1t.cl1cs ( W I I U I wt!
II;I\T s11ol.t ~ l ~ i l t c l ~ o s i l l o11c soquc1lc:e r(:l)ei~t(-?tl I I I ~ I ~ I Y ti111cs i n t . 1 1 ~ 0t.11cr S(~U(:II(:(:S) while 1 . 1 1 ~
null~lwr o f I . 1 1 ~ irrdlors is at rrlost O(lnin{//~,, 11.)) (since i~llc:llors arc ~lol~-c:rossillg ~llat,c:I~c's, 1,11('
11111i11)(~1. Of illl(:1101.~ ilt. I I I D S ~ . ~([llill 1.0 t , i l ~ 11111~1~)(!1. Of' ~:llill.il(:t.(!l'~ i l l 1 ~ I c ~1101'L(!~t. S(YILI( 'IIC:(~).
111 t . l l is rxso I I I O S ~ , of t l w n ~ i ~ x i l i ~ i d l ~ i ~ t ( h ( , s wo (lisc:~r~l(xl (111rillg t11c ~ . I I ( , I I O S s(~Iw1,ioll ~ ) I I ~ . W .
T h r ~ s i t s1i1iicc.s t,o l i i i t l ;I slili~ll i i ~ ~ r ~ i l x r of lil;~silrral riik~[.c.hc:s; wc: c:licosc! tlloscl \\;it11 Irigl~c>st,
scort:. 0 1 1 t,hc ot.llcr Ilalid if t.hc input sc?qucnt:c~s arc? tlissilnilar, thc 11unil)or of ~riilxilnal
III~L~(:II(?S is I ~ S I I ~ I ~ ~ J ~ CIOSC t,o t,lw nri~nlwr of f i l d i1.11~1iors i l l wllic11 case orir algorithrri will lint1
~liosl; of tlw rriasii~lal ~i~at,c:licxs.
Dofilio 1 1 1 ~ siriiil;\rity value: I)c:twow t,wo sr~l)scqrlcxic:c? rY i i l ~ t l Y . tS(X, Y ) : ;is tl~r: score, ol
1 1 1 ~ ol)Lilri;ll i i l i g~ i~ i i~ i i t tlivitlctl by t,lic leiigt.li of tJic s~il)scclrlc:licc~ (wc o111y ca~lsitlor ini~t(:1ics
with S I I ~ ) S C ( ~ ~ I I ~ : I I C C of the silni(l 1~11gth).
Our s~iffis tree ~ ( ~ i i r d ~ iilg~rilhili works ;IS follows. Lot 7' I ) ( ? t l l ~ siifiis t,rcc. of SI . A
locatioii i l l 'I' is c:itllcb~. ;L iiotlc of T or a l)oi~lt, 011 all c:tlgc of T tlli~t: splil,s tIw lal)(:l o f t.hc
cdgc intm t,wo s:il)soq~~rnc:c:s. For ci~c:h sulfix S$ of S2, wo ti ld iill locatiolrs 11 ill T sricli t.liiit,
tl~cb Iiil,rl o f tlio pat , l~ fro111 t,l1c: l,oot, of ?' 1.0 p Iias a Iiigh si~iiilwrit,y valuc: \\.it11 solric: ~)rc!iis of
S;. Algorit.hm 6 ricpid.s our sill-lix 1.rc.c scil.rc:li mc:t.llorl for a S I I ~ S; of &. Lct. S; = .S2[r1, rr] I)e il sul-Iis of Sz i ~ l i ( 1 l ~ t P 1 ) ~ tlic set of Iocat,iolis in 7' rct~irli(:(l 1))'
aIgorit,lilii 2 Sor S.1. \Vv ~ i o w filitl t l i ~ sc.1, of iricsact 11iatc41c:s I)ctn.coil tllc: 1)rctixc.s of S; al~t l
s~ll)sc?cl~~(~nt:(~s of Sl. I+r ~il(.ll 1~)(.ilt.i(.)11 71; ill P. 1 ~ t I)(! I.Iit-: l a i d OF the. 1)ilt.li frow root ~f
7 ' to 7);. L(8t R , I) ( ! t l ~ c sot of' oc~~r l , c : l l c . c~ of Y , i l l .Sl . Not.ic:o I Iiat oc:c~irl.c>licc~s ol' 1: i r i Sl
t:orrcspo~~rl Lo t l ~ c Ii lhls of lhc pill.11~ from t.11~ root. 1.0 p; t.o ;I lcilf of t h s~~ l ) l . r c~! mol,c!tl ill.
pi. Tllerof'orc! I?; (:art be com1)utc:tl efIicic:~~t,ly by travcwing t,he s~rl)t,rcc! of T root,ctl a t pi.
Orlc(> tlic sct R, is corlil)rlt.c:el, for cad1 sr~l)scclwlrc:c\ Sl[r.,. 7;. + (I:( - 11 i l l R, tJio i i l g o ~ ~ i t l ~ i ~ ~
o i ~ t p u t s t . h (5, .TI, IY, I) ;IS ill1 ir~txilct, 111atc11 (SW Figure 5.2) .
This p r 0 ~ : ~ ( 1 ~ 1 r c sig~iiiica~it,ly rcx111ccs s(!1~(4i t,iliic l),y l)ruiii~ig tlic s(:arcli spti.(:t!. Ilo\v~:vcr,
c:oi1i1)rit,irig t h o1)l,ii11;il idigrlrlcnt I)c~.\w(:II the: Y, i~ird SG 11si11g N(:(!(ll1iiil11-~4~1111~(:11 r(!quirt!s
qiiatlr;l.tic tillie a1ic.l t.oo slow for our 1)urposcs. To ovcl.colilc this, t h c t l y i a ~ r ~ i c progr~l i i~~ui l ig
is lilrrit,(xl LO il l,i111d of widtlr 11 i i . ~ ~ l i l ~ d L l i ~ l i l i i i l l (liiigo~li~l (Fig~rrc 5 . I ) L l i ~ rc111r(:ing r~lririilig
time to O(tllY,I). Not,ic.c t h t iulcllors found tliis way do )lot c.olita.ill lolig S(I~II(:II(:CS of i l d ~ l s ;
lolrg scclric:ric:c?s of ilitlcls i t r t . 1 ~ c~orrsc:rvcd rc!gio~~s will orrljr I,(: tlet,ec:t,c:cl nl11c:rl wc! c:losc. gal)s
I)~t\v(!(:rr the ;in(-Irors. ~\lgorithlri 7 (It!s('rilxs ~ I I C 1 ~ 1 i i ~ i 1 1 1 d ~~~ritt~lr-fintlirrg rnot,hotl.
A f h linclillg i ~ l e x x t n~atclres, tile algorit.hl11 nost i(hltiiic!s l l l ~ ~ i l l l d 111alch~s. li) (10
so, wc: sort t,lrc rllatc,lic~s wit,lr ~,c:sl)oct to t,lic'ir loc:atio~~s i r i o~rv of t,lic sc:cl~rcricos. thtoct 1 . 1 1 ~
~lon-nla.xilllal ~~iat.c.lics. RIKI ~ ( ? I I I O V ( ~ t,lr(w~ fro111 tile SO^ of I I I ; I ~ C ~ I ( I S .
Algorithm G Swrr l i i l~a 0 1 1 'I'll(, S~lffis 'I'rrc'
Fig~irv 3.1: To 11ii11w t8Iw Dl-) ro11ti11c f'ast,cr, o111y t11c iiwa ~ I I O W I I will Iw ~ ~ o i ~ ~ r ~ x l , Tllis r (w~l t , s is sliortcr sccplcwccw ol' ilitlcls i l l tlrc ~nat.chcs
Algorithm 7 l:ilitlinr$ h'liisi~nal Mat.c:hcs
CHAPTER 5 . G,4 IJNA
'I-
5.3 Selectsing Anchors
5.3.1 Filldi~lg Lnrgcst Total Wcight Non-crossing Anchors
Fig11rc 5.3: A sct oi' 1111c11ors is (lq)ict(!d. 1~cct;111glcs ~ O ~ ) I . C S ( : I I ~ t h : 111axi1ui11 t ~ ~ i ~ t , c l t ( ~ s a11(1 ;I
sot of gootl at~cllors is tl(~l)ic.tcd i l l \vltit,c rc:c:t.i~~~gl(,s c:ott~~cctc!tl 1)y t l ; ~ s l l c ~ l lillcs.
5.4 Closing The Gaps
5.5 GAUNA Parameters
11. \Vi t l t l l (1, of t,ll(. I)nlltl n r o l l ~ l t l t . 1 1 ~ l l l n i l l (liilg~llill O f the (lylalllic ~) l '~g~i~l l l l l l i l lg tiil)1(!.
To aligl~ t11o s~il)sccpcl~c:cs ol' S2 wit11 t l ~ : p t l i 1iil)c:ls of' tlic suffix tl.cv, tllc suffix t l w
sc:;~,c:ll nlgorit,l~ln rc.st,ric:ts t l i c (I>r~~ill l~i( . p r ~ g r i ~ l l ~ ~ ~ l i r i g t:11)1~ t,o :i 1.);111(1 of width IJ ~ I Y ) I I I I ( !
t , l~( ; 111i1i11 (liago~iid.
GAUNA Results
6.1 Exact vs. Inexact Anchors, Spccificity Evaluation
6.2 GAUNA Parameter Settings and Results
T a l ~ l r 6.1: GALJNA Spcc.ificity
S e c l w ~ ~ w s i\~lc.l~ors Specificity
co~~si ( l (wxl in 0111' I ( % L prorc!ss ar(: i ~ \ ~ i l i l ; ~ l ) l ( ! t ~ t . ~1f,l,~~://\\~\\:\\~.~>i111~.111;1t,~l.(:i1/gil1111~/.
For (:01111)itriso11 1)11rpos(!s all p r o g r t u ~ ~ s \v~r(! ~ I I I I 011 tl I h u x I I I ~ I ( ~ I ~ I I ( ~ \vith tl. 3.4 GI1
iutc4(R) Xcto~l('l'ibI) pl,oc:clssor ;m1 2 GI3 of RAM.
\V(+ 1 1 0 ~ ~ : t11;~t for illig11111(?1.1( of ~ I I I I ~ F L I I and (:1ii111p, G A U N A (:IIos(' ~ ~ i \ ( : t i l ~ ~ ( . h o r ~ ilS ~ I I ( : s ( >
c:o\~!rcd niorn t i i i l ~ ~ 50% of tliv SI-:(LII(:IIC(~S. 111 tllc ~ t h r C:ilSCx t,he 1):~ranic.l.cr s r t k i ~ ~ g s IVPIY!:
I( = {25, 10. 7): E = 1500', (1 = O.S> m c l .I,: = 7 (a clcwriptiol~ of ci~c:]~ par;u~lctor ( X I I)(!
fo1111c1 in S o c t i o ~ ~ 5 . 5 ) .
011r c:ol~~l)ariso~is of CAUNA, LAGAN: AVlL), h l U h [ ~ ~ ~ o r , ;ml MC;A arc: s ~ ~ ~ r ~ n l a r i z t x l in
'ri\l)l(: 6.2. CVo tclste(l f . 1 1 ~ o t l m tools ( n ~ h c ~ o ~)ossil)lc), to [ i ~ ~ c l t . 1 1 ~ parnrnc:tc:rs t , l~ i~t 111ilsi1nizc
tllcir pe~rfor~~~alic:('.
'li, Illcli~srlrc? t,llr! fl1l;llit.y 01' tllc! iihglllll~llt.~, lillcl 1 I IC illiglllll(:ll(. r(:giolls (llilt l i i l ~ i ' il
high ~ L ~ ~ ~ I I I I I ~ : I I ~ X . O ~ C :111i.1 C:OVPI. II IOY( ' t l ~ i ~ i 10% ~f iL l l ( 'soI~. TIIO t ~ t , i ~ l 101lgtI1 of ~ 1 1 < , 1 1 wgioi~s
cl(!tcrilii~ic~s t,lic\ cp ;~ l i t ,~ . of ail i \ l ig~l~~i( ' i i t i ~ l i ( l is sIiow11 I I I I ( ~ ( : ~ t110 C : ~ o ~ : r q j c ( : O ~ U I I I I ~ i l l ' l ' i l l ) l (~
6.2,
'li) l ~ i i ~ ~ ( l l ( : r o g i o ~ ~ s of (liffor~v~t. I c ' I I ~ ~ ~ I , \\T (Iof ~ I I ! t h ~~orli~iilin:cl s w r c for il l1 a l ig~l~ucut
region t,o bo $, wl~orc? s is tlic? score o f t,hc illig11111(:11t,, b is t,hc 1~1igt,h o f tllc i ~ l i g ~ ~ m ( : ~ ~ t , i l ~ ~ ( l P
is thc ~nasimrun value ill tho scoril~g 111at1.i~ (note that, nor~nalizc!d score is alwilys less t h ~
1). A 1.cgio11 t . l l i l t I~ils a 1lor111alizcc.l st:oi.cl al)o\.o 0.8 is co~~sitl(:rc>tl as a lligll i ~ l i g ~ i ~ ~ i ( ' ~ l t s(:or(>
29:%37=17 CiAUKA 1 l(i27Ci5 LAGAS
AVID IIlJhIillor Tvl G A
'lYw r(~111ts of global d i g n t ~ w ~ ~ t ~ s for (Iiff(w11t 1)rograms. Tinw is iu sc(:or~(ls i\11d 111(~1ory is in III(!~~II)J~~.c:s.
7.1 Measuring An Alignment
ils \IT lalorn !lot c:fIicir~~t,) t,o alqdy, for t,lic. (:i\scl o f I>iologi(:i~I soq~lc!~~c:os, it ilocs 11ot. provicle
11s \Vif 11 11111(~11 illf01.111ilf i011 ilI)~llfd t!lO illig'lllll~llt,. SO WC 1 1 ( ? ~ d 11101.(, sOl)llisti(:il(.(!(I \V;lys Of
tirfi~lccl a c:ol~se~,vr(l r e g i o ~ ~ to I) ( . all i~lip,l~lll(:l~t region t , h t 1~1s a h i g l ~ a l i g ~ ~ l ~ ~ c n t scol.c: i111(.l
covcw I I I O ~ C t1li111 10% of an c : so l~ . Tllc rc?i~sol~ w l ~ y csolls are i ~ ~ ~ p ~ ) r t . ; i ~ i t : is L11iit fro111 t h :
SOLLII(I t ,I l :~t, (lo ]lot, ov(:rl;tl) \vit,l~ i1llJl CYWII , \w t11i11k t,lt(!,y 111ig11t, still I ) ( > o f S O I ~ I C i l ~ ~ ~ ) o r t a ~ t ( x ! . , 7 1 IIC 1)ioIogicd ~ i i o l i v i ~ l k ) ~ ~ l w l ~ i ~ i d 1.11~ i r ~ ~ p o r t i i ~ ~ c c o f ct~11scrvcc1 r (y$o~~s (:i11(1 tlicrdorc (XOIIS)
is illkit i C i l 1,(:gio11 11ils ( : I I ~ I I I ~ ( Y ~ litt,lc over t,i111(:, i t IIIIIS(., I ) ( > rcsist.i1.111, t.o 11111t,;llio11s i111(l so
tllrrc is R gootl rl~allcc I.hal, if. has t m n of sonic! import i111cc lor the lifi: o S L I I C spc.cic.s.
'I'hcroforc?, i l l IGAIJNA 1)csitlcs looliil~g a t thc c:or~sc:rvod rcgio~ls ovorlappily, esolls, wc!
il.ls0 look ;it t-llc OWl'idl (:OVCrilg(! of cOllScI'Vt!tl I'(!giollS il.lld 0111. 111~il~111.~1ll0llki ill.(! I)a.S(!d 011
I)ot,ll t , l l c w fac:t,ors.
7.2 Improvements to GAUNA
7.2.2 Branching
1: ~ ~ ~ O I I L ~ S ~ = C ; ~ : I I ~ S ( ~ ~ I I L (S2) {fil~rlir~g t11v pot,c,l~t,i:il scst o f esons i l l S 2 ) 2: lCiAUNl\(se(ll~c>r~(,(> '51; s ( ! t [ ~ ~ t ~ ~ ~ c e &, ;~rray I<[l , . . i~l(lt>x i . 11iatd1%1 111, 11o(lt: s11fhx-
r 7 Irtx~Rool., c:sol~s c ~ s o ~ ~ l i s l ) {I<[ l . . . 11: ;I list of l(mgt,l~ ~~lir~:sl iol~ls for a ~ i ( , l ~ o r s i l l (lifI'(w~tit r t , c~~rs io~ i s : I<[l] ;> K[2] -, . . . > I<[[] } { i : t,lw c.11rrr11t i ~ ~ t l c x for I<}
:$: if ( ~ S l ~ ~ S 2 ~ ) is s ~ ~ k : i t : ~ ~ t l , y s111;111 the11 /I: {c:so~lList is t . 1 1 ~ sct of poter~~ttul c w ~ ~ ~ s } ,;: Aligrl Sl i111t1 5'2 11si11g h~cc~llc111:111-\4~~111scl1 aIgorit11111. i : rcturli 7: crld if 8 : i f i > 1 then 1 : rc turr~
{L(YI\Y! ,Yl : I I I ( I S2 ~ ~ ~ ~ : i l i g ~ ~ o ( l } 10: crid if I I : Ch11 1~inclhIi1silir:tl (5'1 , S2. I<[i]! :\I, sl~flix'l'rc:c:l<oot.. tw)~lI,isl,) . 12: A(l,j~lst, 111;1tkti wigtl ts of 111at,t,Iles i11 111 lx~se(l 011 t~xous i l l cxo11List ;11i(1 t,lle ~ ) ; I I ~ I I I P ~ P ~
z41~lI'LIFYING_Ri\TI0 1:s. S(:l(:c*t. a s111xwt of n~~c : l~or s wit11 I I I ~ ~ S ~ ~ I I I I I I I t,oti~l wt'igl~t, ; I I I ~ 1)11t t l l t : ~ ~ ~ ~ I I tlic li11a1 alig~l-
I I I O I I ~ ()I' S 1 i l ~ l t l S 2 . 1.1: for cuc.11 1);1il. of itltcr-ar~c:l~or s c c l ~ ~ c ~ r ~ c ~ ~ s , .Si i ~ r ~ l .S,i do I . ~ , , C:111 IGALrKA(.5'{, S i . I<; i 4- 1, :\I. s~~f l ix ' l ' r (~t~I~oof , ! (lsol~List,) itlig11 S{ i11i(I S;. i ( i : end ~ O I .
17: reL11ru
As cliscussetl in Socl i o t ~ 5.2, tjlrc: trl;lilr p ;~r . ;~~l~otcrs 11sc~1 in GAUNA (wl~icli are kept t,llc Sill l l( '
i l l ICALJNA ;IS wvll) ;II .C K - v ; ~ l ~ ~ c ~ s . :, sill~ili~ril,!; t,llrc~sl~oltl .s. a ~ ~ t l tllc cliagol~al wi(lt,l~ ( I i l l 1.11(:
U P 1 ill)l(~.
' ~ I I ( > i~~t,cl .-al~c,l~or 1(!11g:11 I11r(:s11oItl E ! is ;L llll~osl~old t l ~ t ( ~ ~ I . ~ : ~ I I I ~ I I c s \ Y ~ I C I I t o us(: N ~ W I I ~ ~ I I ~ I ~ I -
WIIIIS(.II i ~ l g o ~ . i t l ~ ~ u i l l i~ wgion i l~s lwt l of fi~itlil~g III:I( . ( . I ICS. I t is sv1. st1(.11 l . l ~ t , I.110 0 ( 1 1 ~ )
1 : FinelMasirn;~lh~I;~t~cl~crs ( S C ~ L I ~ I I ( : C St, S ( Y ~ L I ~ I I C C S2 , irit li: set A / , 110i1c S I I I I ~ X T ~ P C ~ ~ O O ~ , c~solis c\xonList) { A t will lioltl ~.l.~:it.c:l~c?s}
2: J'=(ij
:{: for t/' sulfixc~s .$ of S2 do ,1:
: if S? h;ls ; ~ n o\;c:rlap wit11 ;MI (XOII i l l (~01i1,ist then (i: CMl S(:iir(:lirrr(!(:Bri~~~(:l~i~~g ( ~ ~ ~ I l i ~ ' T r ( ~ ( ~ r < o o t , , .S2, I ) , Vj, k , (>xo~~I , i s t ) 7: clsc 8. C h l l Sc;irc.IiTrcc. (s~~liisTrc~c~Root,! &, I ) , 0, k ) : e n c l i f
10:
I 1 : for Vp; E I' do 12: 1%1(l oc.c:urrcw:es of p, ill SI ~ I . I I ( ~ i ~ t l t l t h n i to A.I 1 : cncl for 1.1: cnd for 15: R(wlo\,t! I Y ! ~ ~ I I I ~ ~ ~ I I I ~ , ~ u a t d ~ c s
rn i~tdws i111tl h d p s us c:ont,rol tIi(* r~lllning the I)y lilnililig tlic spilcc t l l i~t Dl' (:o\~cPs. AS
;I sitdc-('lf(!ct, i t iilso lilllits t,il(: i~liglllllC'lll, I > ( > Of' il ~ l ) ( Y ' i i l l (,YI)C tll;lt, (1O('s llot ilIIO\\ ' 11101.(!
t.lli411 d c:or~scuttivo gaps i l l tlw ~ l ~ ; ~ t , c l ~ o s . 'rllis is ~~c.c.ol)t;~l)lc~ l)i:causr! for ~l~at,cl~c:s c:ol~l.ail~illg
long c:ol~scx:~~t.ivo gill) il~t,cwi~ls, wc (:ill1 view t,h~sc! ;IS two sq)arat,c\ I I ~ ~ I ~ ( : I I ( > S i ~ l d i(lu~tiI'y tll(w!
i l ~ c l ( ~ ~ ) ( ? r ~ ( l c ~ ~ ~ t , l j ~ .
IJifi(!d 011 our c*sl)cril~lc:llts, I<-values grc?al.ly ;lfi!ct ttlc sl)c7c!tl all(] quiilil,)f of tllc! illig11111~11t.
i111(1 ('i1li 1 1 1 d i ~ 21 111i1,jor ( l i h w ~ c ( ~ in t IIC: q ~ ~ : ~ l i l ~ y of t,Iiv solutio~i, \VP l)(~rfor111(~1 (~xt(!r~sivc t(>st,-
illg 1.0 (l(:tcrlili~~(! I II(! qui~li ly of t,Iw i~ I ig l~ l l~<? l~ t I ) H S O ~ 011 tlifl'erc:tlt sets of lC-ixlllcs. rutuitivcly,
the I I IO~Y: 1 ~ ~ ~ ~ 1 s t , l ~ ~ r c arc. t,11c 1011gcr IGAUNA t :~ l i~s t,o ~ I I I I . l'lic l)iggx>r tlw K - \ ~ I I P . t110
longer tho nlatdtes wc f i ld shoultl bc aid tllrrc?forc if w: clloosc too largo ;I K-vi~luc.: \\I(!
llligl~t lil~(l ,jl~st, ;I fc\v I I L I I I I I ) C ~ of' I I I ~ I . ~ C ~ I ( ; S t , l~;it (lo I I O ~ ( :o\T~ 11111c~l1 of' tIl(5 two S(Y~I ICI IC( :S ill111
CXIAI'7'ER 7. IGA CJNA 57
7.3 Optimal Alignment
a l i g i ~ ~ i ~ c ~ ~ r l s .
7 .
Ill(: r c ~ i ~ i l i ~ ~ i ~ ~ g rcgio~is hot\vm~i~ CSOIIS. ; t r ~ iilig~~(!(l 11si11g rog111;1r IGAtJN.4 routirws~ I l l ( !
w y wc! have! t1i:sc:rilxxI t h i ~ i l l t hc prcviuus srct ions (as opl,oscd t,o using ULAST). 'I'IIc
hi id r ~ s u l t is i1.n illiglllllc?l~t wil.11 ~l l lp l l i~s is 011 1 1 1 ~ illig11111(:1lt. of O X O I ~ regions i ~ ~ i ( l iti \vc will
sot: 1i~1.s a lliglicr scorc! wki(!n w: col~sicler colisorvrtl regiolls ovcrli lppi~~g csolis.
r 7 1 [I(! acIvt \~~Li~g(> CIS \iilvilig t l i i > s O - ( ' ~ I I I C X I opL'iv~(~d (I&!JIL,IIL(Y~,~, is t,liill-l i t , giws 11s a 1 1 w t , i ~ ~ i i l t , t ! ol'
I lOW 11111('11 il ~.('jillIill. ~.liglllll('rlt, l l i l~ t,ll(! pOt.(?llt,i;ll t ,O i1?11)1.0\'0i1 i l l tP1~111s Of c!xorl digl l l l l ( !nt~.
If t l ~ c optinlal iiliglll~~ont has il sc:orc I I I I I C ~ I Ilighcr t,lian ii giwn ;digrllll(mf., wc h1ow LI1i1t.
tlltrre is still 11111('11 1.00111 for i~nprov(m(wt i l l t.110 Loo1 Li~ilL procI~c:(~l tlic illigl~~~i(:lil.. IIOLV(IV(II,:
il' t,ili! givP11 illiglllll~llt S(:orCS VF1.y c~OS(!~\; t 0 tall(! 01)t.illlill ;lliglllll~llt: \\I(! kll0W tllklt t.hV ( l l l i l l i ! ,~ '
ol' tlic: i \ l i g ~ i ~ ~ ~ ( ' l ~ t ( , i i l ~ i o t I ) ( > i l l~l)ro\:~~(l 1 1 i u d 1 . 111 t.liis c:;~s(>: 0111. foc11s will 1 ) ~ ' 011 i l ~ i p l . o v i ~ ~ g
t l w spctcd of t l . 1 ~ tool antl how 1nuc11 sp;1w i t IISCS. So 1)asically if t\4V (liffcrmt 111~111oiIs
protlucc t.wo a l i g l~~ l~c l~ t s with scores very (:loso tu tllc opt i l~l i~l a l ig l l~~l~l l t , , t.lli:l~ t 1 1 ~ o11e w11ic.h
1)rotlucx:s tlic idignl~lont f;~stc?r ; u ~ l with lcss mcluory, has I.hc ;~.tlva~ithgc! o w r t l lo o t h c ~ OII~!.
7.4 IGAUNA Parameters
Usillg tlill'c:rc~it pari111ic:tcw gives IGATJNA t , l ~ c . Il(~sil)ilil,y to IN' L I ~ for tliffcrcnt cxsc:s casil!..
By 1)r01)crly sc?t,l.i~g t.llrw l)arn~~lc?t.c:rs, IC:I\UNI\ call il(.tl~;llly 1.1111 (:x;~c:t.ly lilit: G A U S A o r i t
call I)c c:sc:c:ut,ccl t.o Iiilcl t.he opt-i111al ~ I I ~ ~ I I I I I C I I L . Bc!siclc,s t,lx o~ lcs nrc 11;lvc. ;~lro~~.cly clc~scril)otl
IGAUNA Results and Conclusion
8.1 Experimental Settings
8.2 Parameter Settings
(20: 7) { 'LO, 10) (25, 10) (25, 7 ) ( 3 0 , 15) (20, 10, 7) (25, 10, 7) (35, 10, 7 ) (35, 20, 7) (50, 30, 12) (40, 20, 10, 7) (45, 25, 10: 7) (50, 30, 10. 7)
c:o~~sitl(!rctl 1.11~ followi~~g I<-v;ill~c srt.s: (20: 7 ) , (20, 10): (25, 10}, (25, 71, (30 , 15): ('20,
10; 71, { 2 5 : 10, 7). (35, 10: 7): (35, 20, 71, (50. 30, 12) , (40, 20. 10, 7): (45. 25, 10: 7): (50:
30, 10: 7 ) . Wit.11 e w r y ~:Iiiu~g(: ill the sct of' I<-values. 1GAUNA's yerl'orm;i~ic:o coi~sisl.c~il lp
cha~igc!tl in ;ill t . 1 ~ sl)cc:ic:s, t21~c!rt?l:orc t.o s l ~ o w tllv c l~iu~gcs , \vc! will olily s l ~ o w t,lic: rcs111l.s for
U I I C 1)ilir of sl)v(:ics ( I I I I I ~ I I - D ~ ~ i ~ l i p i ~ ~ ~ e n t ) .
As call 1)c sc!c:11 fro^^^ TaI)Ic 8.1, c l ~ a ~ ~ g i ~ ~ g I<-valuc: scts (wi t J~ i i~ rcaso11u1)lc values) tloc's
not ~ f k c t scnsitivitv an(/ spcc:ifil.y sig~~ilicant,ly. Howewr t,he r u n l ~ i l ~ g the (:iin j~ii l ip at S O I I ~ F
p o i ~ ~ t ~ s . The S ~ I I I W 1)at,tcr11 of j u ~ ~ ~ p s i l l tinlc: applies to ot,licr specic:s a s wdl, hut witli wrying
i~~tc:i~sit.ic?s from 1.5 t,o 4 tinics inc:rcilse i l l t i~iic.
Loolci~~g at 'I';ibl(: 8.1 reveals t,lliit si~lcc: tlw ruli~iiug t,ii~ic? (low ~iot , ( : l i i l i i ~ ( ~ 1 1 1 1 i ~ l i ((:x(:q)t
for 111(! ~ I I I I I ~ ) p o i ~ i t . ~ ) , 1.0 gel. 1.lic lu;i.uiir~~~rn scnsil.ivit,g ; i ~ i t l spcx:ilil,y: wc: sho111tl c:lioost? l , l ~ >
I\'-wlue sct (25, 10: 7 ) .
8.3 Alignment Results
8.3.1 Memory Usage
Progrim TCL ECL KEG' TCLE Tirr~c (s) k I ( m (t~tl))
tlie scqucwces a~ i t l feetling t1lc111 L o GeiicScan, ~ v c can s o l v ~ t , l ~ i ~ t prol)lcl~i. Figuiv 8.1 sl~ows
CHAPTER 8. 1G24 UNA RESIJLTS A N D CO,VCL USION
In terms of specxi, the overl~cntl t h l . GCI.I~S(.~LII (:;LIISCS, is the I)igg:.~st. f'a(:li)r ill rc(Iu(:itig
IGAUNA's spertl co~upiircd t,o GAUNA. Honrc!vc:r: it is possible to c?s tract t,ho c+so~is I)y
IGAUNA ,111ow tllis convc~~ie~ l t ly ) . Bri~nchi~i:, lias it11 i~iflrlc\~~cc on ( h c s p c ~ ~ 1 its wcll. h t
paramel;c!rs. Ovc~ri~ll, illt.hol~gl~ b r a r d ~ i n g cloos rc:tlllce the spectl, it, docs not retlr~ce i t 11111(:11.
Table 8.6: EIurnan Mor~so Aligr~tr~rnt. Rrsulth
P I ~ ~ I ~ I I I TCL ECL E 'ELI3 T i l ~ w (s) M(w1 (11~1))
0ptirn;d 110875 5957 63 7568 97 9 1 IGAUNA 141853 5928 6 7431 130 90 G U N 12G716 5922 62 7451 5 2 S ,5 I 123425 5862 Cil 7351 14 1 205 I\V I L) 2 5777 (i0 6081 60 4!1S
Prograrli I ECL NEC T C 3 X T ~ I I I ~ . (s) kIc111 (1111))
O p t h a l 381350 11237 60 17505 394 2% IGAUNA 405007 10891 5 l(;9!)1 4 1 0 280 GAUNA 997121 lOS(i5 55 165.54 382 27 1 LAGAN :365457 104j9 56 16284 659 76 1 AVID 231496 1082 7 1929 238 1'307
8.3.3 Quality Of Aligrlrrierlts
111 ortlcr to 1)ctl:c.r cso~l~p;u.cx IGAGNA wsults wit11 i,llc other tools nicwt,ionctI, it \\.ill I)(:
I~clpful t.o c:o~~sitlcr g rap l~s sl~o\\w ill F igr~ws 8.2 I,o 8.5.
14s wc can SOP in E'igrlrcs 8.2 m t l 8.3, IGAUNA ~)crforms clrlit,c w ~ l l whcn it co~l~cts t.o
csoli cowrage. \\'11on t :ol~sit leri~~g moll (!o\lt'ri1fi(! (o~i ly cco~~sit lori~~g CXOIIS t , l~at I~avc: Iwt~11
c:ovc:rctl ~ n o r o t h n 50%) imtl also t o l ~ l cxon c:o\lcra.go ( co r~s idor i~~g all f . 1 1 ~ c:onsc:rvc!d r c g i o ~ ~ s
that fkll i ~ ~ s i t i c c so~ l s ) , IC4AUNA perfornis l)ctt,er tI1a11 d l t J ~ c o i . h tools; wcll, c:sc:cpt [or
ClIAPY'ER 8. IGAUNA RESULTS AND CONCLUSION
Menwry Usage
Human-Rat Hmar i - H~~ran- Hurren-Dog Mouse-Dog Mouse-
Exon Coverage Length
I kl ouse.Dug lul ouse-Chc ken
Figure 8.2: E x o ~ Covor;igc? Lol~gt l~ for Mousc-Dog ant1 h?ousc!-Cliickc~l
CHAPTER S. IC;AIJNi\ RESlJLTS A N D CONCLUSION
Exon Coverage Length
Figorc. 5.3: Ex011 Coveragc Length for H~~man-Ritt , , IIwmiin-Mo~~sc. 111i1nall-Chic~kcr1. 1Ium~il1-Dog
Total Exon Coverage
Total Exon Coverage
6 000 0
I IiumafkRat HunianM iruse Hurnat~Ch~r: ken HumanDug
tlle Hutuil~l-Dog (:ils(!. Mi(: c:otisitlcr t,liis (:;IS(: ill tl(:t,ail:
S~lrl)risit~gly, 1,AC:AN scorctl cvcll Iliglicr I.ll;ln o ~ ~ r nptilili~l aligtitriollt,, i l t ~ l \vo i~i\wt, i-
giltcxl c?xl)l i~~li:~t , in~l~ fbr 1,liis "inriclclit,". Aftcr aligliing tlic Hurllati-Dog socl~~otlc:es, \vc> 01)-
sc~rvctl that. LAGAN is not usi~lg tllc c:olrlplct,c scc1uclic:cs i l l it,s fitlal n.ligtlnwt~t,: Wo (!stri~(:Lctl
t,llc: origit~al S C ( ~ I I ( ? I ~ C O S fro~ti tllc ;~lig~iccI S C C I U C ~ I ~ C C S i11ic1 fo~lllcl t,llitt the Ictigth of tl~c:. sciclrlc5~~cc~s
usccl by LAGAX \wc?rt? (j/lTjllK3 for soclt~c:~~c:c: OIL(: (as oppostxl to &l!)GI)OO of tlio u~,igitiid) ii l l (1
5033G45 for scqllc:nc:o t,wo (;IS ol)posc:tl t o 6424515 of t . 1 ~ origitml). 111 chssctlcc, LAGAN
is "tlmnvil~g away" parts of thc scxlool~co that could not I)(! i-lligl~(!d p r o p ~ r l y (i.e 1% of
tllc first scqllcncc? and 16% of the s(!(:o11(1 s ~ ~ I I c I ~ ( : ( : ) . This rcs~dt,s in i i higlicr c1cnsit.y of
conscrvc!tl rcgio~ls (eit l~er in tol.al or just in t.hc cxons, tlcpcncling on wltcre tlie t , l lro\\~~-
il\vil;lr scg111~11ts I~il\r(! I)c:ct~) a.ud t,llercforc 1,AGAN will score h i g h nrllo11 ~ ~ ~ o a s u r i ~ ~ g t l ~ c
co~tscrvc?tl rc?gions. T l ~ t c:xplailis thc huge tlifferelice ill our Exo~l-Covc.r;lgc:-Lo~~gtll ;ultl
7i)tirl-Cot1sc:rvc.tl-Lc1lgt,l1-i11-Ex cstiillat,cs 1)cl.wcc:ri LAGAN i111t1 even the opt,i~~t;ll itligll-
8.3.4 IGAUlVA Improvements Compared To GAUNA
to scc: how IGAIJNA hm inil)rovcd, \vc bast our con~parisu~ls o n GAUNA m t l (:01111)arillg Lo
1 1 1 ~ opl i~rial i~ l i g l l l~ l~~ l t , \VC sco how n111(:11 room Lllcrc is fur i~ripro\wnrnt. 'I'ho11 wo scc liovi
Total Exon Coverage Length Improvenient (Compared to GAUNA)
We call sec I.hat IGAUNA has i~~iprovetl wtmut. 5C)X comparctl t,o GAUNA, ~ncal~ing
l:lii~.t. it. has cowl-ctl aho111, 50% of t.hr pot,mthlly c:o\:c!ra.l>lc rogiolis 1101. prwio~lsly c:o\w.cc-l
by G A I J N A . Thc only csccpt,iol~ is hIolwx~-Cliic.kel~ i~lig~~rncnt, , Altho~igll I G A U N A Ilits
iliiprowd i l l t,l~is case as \vclll it, SNXIIS t,liat, Llicre is st,ill 11iuc11 11ior~ I , O O I I I Lor i~i i~)ro\rcl i~o~~t~
(i I . l l ( I id1 t l l ~ Ot,hCl' ~ O I S ill'(' fil~~illg hhill(1 i l l Illis (C?lsC ;IS \vCll),
In tornis of' total c.o~iservc?d rcsgions: as 11m1tio11c:cl earlier, we ( : i ~ l l l l ~ t I ~ S C 1 . 1 1 ~ opti~ili-11
;~lig~l~r~crlt, for cotnpariso~~, bc!c:i~~~sc it 1)iascs c x o ~ ~ s too 1nuc1i ant1 t.li;it 1iiig11t. i ~ ~ t ~ r f c r c wit11
t,he alig~r~~lcirlt of ot.lwr potcrit,ii~.lIj: good r~gions. Thcrdoro we colupare IGAUNA o ~ l y t,o
GAUNA alid ;IS wc cull see fro111 F ig~~ros 8.7 itlld 8.8 a.11tl the t.a.l)l(~s in Scct.io11 8.3. IGAUNA
has i~nl)rovc!tl from 5 t.o 12 1wrc:cnt.. Thc o ~ l y esc:ciptioll is Hlmm-Rat itlig11111e1lt. whew \v(\
s w c-mly i~l)o~ll. 3% i l~~pro \ :e~ l~c i~ t (\vliick is t , l ~ c s lo~igcst scqtiencc. in our tc3st sot.).
Mouse- k g htlnusc-itwken
I Total Conserved Region
Human-Ral Human41 ouse Human Ch~c kerl Human-Dog
CIIA PTER 3'. IGA IJNA RESIJL'LY A N D CONCIL CJSION
8.3.5 Summary of Results
8.4 Conclusion and Future Work
it. is oflic:iciit lmth ill tinlo al~cl space. Depcnding on wlictl~er spcctl or q~~ ; i l i t y nec~ls to I)(!
opt,in~izc:d, IGAIJNA's pirsit~~~rt,t!rs (:a11 I)(! fl(!xibly set t,o suit cach ir~tlivitluiil cils(!. 1 1 0 ~ -
cvcr t,hcrc is sl,ill 1iirrc41 roonl t,o i~ lcn r~)o ra te more biological Iicv~sistks illto it, in or(lcr to
iic~l~icvc-: l)t:tt,t!r ~xwdts . 111 t J ~ e salllo way tJint G A U N A is capal)lt: of p e r l ' o s l ~ ~ i ~ ~ g 11111ltiplv
scqllrmcx: ~ l i g ~ ~ ~ n ( : ~ i t , , w (:a11 l'l~rt,llor (!xt(>11(1 t,lit, (:;~pabilit,iw 01' IGAUNA t,n I ) ( ? used or1 111111-
roo111 for rcLilli~~g tllc (lcfillition u i d LlSilg(! of an opti111a1 aligtl l im~t wIiic11 rcquircs il l)ctt(:r
untlcrstantling of biological scqucllccs U K I scorillg nlc~lhorls. 'I'hc:rc is also ;I polcntial Lo
illcorporate p;iri~llelism int,o IGAUNA 1)y divitlirig t,lle query st ,r i l~g iirld feeding (>ilt.ll 1 ) i ~ I .
ir~t,o a separate 1)roc:essor. M'c i l r ( : i\.lsu worki~lg 011 d(:vc:lopitl;: a user frielltlly i~lt,c!l.filct: for
IGAUNA alicl 111aIw it: avaiI;~l)lc: as i~ s t ~ ~ ~ ~ ~ l - a l o ~ ~ c progrml ii11(1 >11so >is >I \wl) i~l)l)li(:i~tio~l.
[!)I C . I ~ l l I ' g e a l l t l S. I(ill ' lil1. P l . (Yl i ( : t io l l Or ( U l l l p l e t . ~ g(!IlC ~ t I . l l ~ t l 1 1 . ~ : ~ i l l I l l l l l l i l l l g( : l lOll l i ( . ( I l l i l .
,I. ~Llol. I? Io l . , 2G8:78-!)4, 1!)!)7.
L3113LIoC:I?ll PI-IY 74
[14] D ~ I I I Gusfic:ltl. Al!lor.itliiris oil. St~.irr!~s, fi.cc.s (md S C ~ ~ L C ~ L C P S : C O ~ I L ~ , U ~ C I . SC~CYICC ( i d
G'orry).~~lnliontd Biolopy. USA: Chlnl)ritlgc! Univcrsit.y I'rws, [19!)7] (19!)9).
[l(i] C:il)son T . T l ~ o n ~ p s o ~ ~ J.D. Higgins D.G. Gillson T.J. Higgius D.; T ~ O I I I ~ S O I I .l. Clustd w: inlprovil~g the swsit,ivity of progrcssivcl~~ultiplc scqucmx alignnlct~~t tl~rougl-I secluel~cx: wc!igl~lil~g:positio~l-s~)ecific gal) peualtics mt l w i g h t rria.t,rix choico. Nucdcir Acids Rcs., 2'2:4673-4680, 199-1.
[24] Gcrolcl I<arp. G'dl c~ntl ~r~olrv:~rlnr. biolotpy : concr~pts arul cxpe~irne7its. C:l~icl~est,er : John \YiI(:y, 2005.
[:32] C r ~ g o r y h'l. C:oo~)cr h,lic:l~iwl F. I(il11 El~fi( '~io I ) i ~ \ l ~ t I t ) ~ NISCJ Co1111):trativc Stxjli(~i~ci~tg l'rogri~nl Eric D. C:rcon Arcrd Sitlow h1ic:llacl Urrltll~o. Chllo~lg U. L)o il11~1 S~ri11il.11 Bi~t:zoglou. Lagan :trltl r r ~ ~ l t i - h g m : Efficic~~t. f:ools for lar~e-scalc ~ r ~ ~ ~ l t , i p l ~ i~liglllt~(:nt. of' gclloli~ic d l l i~ . G ~ ~ r m r ~ i ( , RI : s~ (L~( , / I . , 13(4):721-731, 2003.
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1351 .J.P, h/Icsirov B. Bcrgc:r S. J3atzoglou, I,. Puclltc:~ a ~ ~ t l E.S. I ,a~~tl( :r . Hu111al1 ; t l l t l ~ilouso g t ~ l c str11cA11rc: Ch~ipa ra t ivo u ~ i ~ l y s i s a l~ t l applicaliol~ to cxon protlictiol~. Geriorrcc! Rc:stwr(:lr, .Jr~ly 1 2000.
