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|0|NF0RHAT|68

computerited 4no/ysis
of 8io/oqico/ uoto
Cb[ect|ves
Introduct|on
ke|ated f|e|ds
n|story
AI1Lk 1nL kLSLN1 CCUkSL
W Lhe nuge data accumulaLed
W Us|ng the WWW
%%%%access Lhe daLa and Lhe meLhods for
Lhelr analysls
W App||cat|ons of 8I Lo
%%%%%molecular blology medlclne
bloLechnology agrlculLure forenslc sclence
anLhropology eLc
W
W the ro|e of computer sc|ence ln Lhe
%%%nalysls of Lhe daLa
%%% lnformaLlon reLrleval
%%%% and Lhe ablllLy Lo exLend Lhese
skllls by se/fdirected fie/d work on
the Web
W A sense of opt|m|sm
%%%% numan We|fare
AI1Lk 1nL kLSLN1 CCUkSL
1he Course Contents for 8|o|nformat|cs
W n lnslghL lnLo 8lolnformaLlcs
W 8lologlcal uaLabases
W 8lolnformaLlcs for Cene(s) alrwlse allgnmenL
W llgnmenL of MulLlple Sequences
W Searchlng sequence daLabases uslng 8LS1 lS1
W hylogeneLlc nalysls
W Pldden Markov models
W Cene redlcLlon Mlcro arrays
W 8lolnformaLlcs for roLeln(s) SLrucLure redlcLlon
W uynamlc programmlng appleL
W 8asmol hylogeny MulLlple allgnmenL
WnA1 IS 8ICINICkMA1ICS?
W 8ioinformotics is the unified discip/ine o
combinotion of bio/oqy computer
science ond informotion techno/oqy
W 1he computer bosed ono/ysis of
bio/oqico/ doto
A MCLLCULAk ALnA8L1
W MosL b|o|og|ca| macromo|ecu|e
are po|ymers chalns of mooomets
W ll monomers be|ong to the same
genera| c|ass
W the order|ng of monomers encodes
lnformaLlon llke Lhe leLLers of an
alphabeL
l1
lS
Slide 7
l1 THE SANE CENERAL CLASS, L!KE
NUCL!EC AC!DS: ATCC U
AND
AN!NOAC!DS: Leu, His, Ala ....... 20
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lS SO !T !S TH!S !NFORNAT!ON CODED !N NUCLE!C AC!DS AND PROTE!NS THAT THE B!O!NFORNAT!CS HELPS US ANALYSE
BUT BEFORE CO!NC TO FURTHER DETA!L LETS CETS NORE FAN!L!AR W!TH B! BY D!SSCUSS!NC !TS RELAATED F!ELDS
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kLLA1LD IILLDS
CCMU1A1ICNAL 8ICLCG
W appllcaLlon of compuLlng meLhods for
classlcal blology
W rlmarlly concerned wlLh
evoluLlonary populaLlon and
LheoreLlcal blology raLher Lhan Lhe
cellular or molecular level
kLLA1LD IILLDS
MLDICAL INICkMA1ICS
W appllcaLlon of compuLlng meLhods Lo
lmprove communlcaLlon
undersLandlng and managemenL of
medlcal daLa
kLLA1LD IILLDS
CnLMINICkMA1ICS
W 1he sLudy and appllcaLlon of compuLlng
meLhods along wlLh chemlcal and blologlcal
Lechnology for drug des|gn and deve|opment
kLLA1LD IILLDS
GLNCMICS
W nalysls and comparlson of Lhe
ent|re qenome of a slngle specles or
of mulLlple specles
W A qeoome set of oll qeoes possesseJ
by oo otqoolsm
kLLA1LD IILLDS
kC1LCMICS
W toJy of bow tbe qeoome ls
expressed in proteins ooJ of bow
tbese ptotelos fooctloo ooJ lotetoct
W oocetoeJ wltb tbe octuo/ stotes of
specific ce//s totbet tboo tbe
poteotlol stotes JesctlbeJ by tbe
qeoome
l2
Slide 13
l2 ie. CENONE !N ACT!ON, DYNAN!C STATE OF CELL
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kLLA1LD IILLDS
nAkMACCGLNL1ICS
W 1he use of genomlc meLhods Lo
deLermlne whaL causes var|at|ons |n
|nd|v|dua| response to drug
treatments
W 1he goal ls Lo ldenLlfy drugs LhaL may
only be effecLlve for subseLs of
paLlenLs or Lo ta||or drugs for spec|f|c
|nd|v|dua|s or groups
nIS1Ck CI
8ICINICkMA1ICS
W CeneLlcs
W CompuLers and CompuLer
Sclence
W 8lolnformaLlcs
l3
Slide 1S
l3 $U!CKLY PASS!NC THROUCH THESE H!STOR!ES
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nIS1Ck CI GLNL1ICS
W Cregor Mendel
W Chromosomes
W un
Gregor Mende| (18221884)
W Lheorles of PeredlLy
W Lhrough Lhe sLudy of pea pods
W SLudled Lhem
for Lhe fun of Lhe Lhlng"
l4
l6
Slide 17
l4 YOU CAN RECALL THE CLASS!CAL NENDEL!AN CROSSES
ROUND X WR!NKLED
ROUND
3 ROUND 1 WR!NKELD
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l6 SEE !F EvERY BODY UNDEERSTANDs NENDEL's CROSSES
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Mende|'s Lxper|ments
W Crossbred Lwo dlfferenL Lypes of pea seads
Sperlcal
Wrlnkled
W fLer Lhe 2
nd
generaLlon of pea seeds were
crossbred Mendel noLlced LhaL alLhough all
of Lhe 2
nd
generaLlon seeds were spherlcal
abouL 1/4
Lh
of Lhe 3
rd
generaLlon seeds were
wrlnkled
Mende|'s Lxper|ments (cont)
W Mendel developed Lhe concepL of
#d|screte un|ts of |nher|tance" and
W LhaL each lndlvldual pea planL had
two vetsloos ot olleles of a LralL
deLermlnlng gene
Wa|ther I|emm|ng (18431903)
W SLudled Lhe cells of salamanders
W lmproved flxlng and sLalnlng
meLhods
W ueveloped Lhe concept of mitosis
(1882)
n|story of Chromosomes
August We|smann (18341914)
W Soma ce||s and germ ce||s
W Lheory of Lhe conLlnulLy of germ
plasm
W Lhe concept of meiosis
W S Sutton (18771916)
W sLudled germ cells of Lhe
tocbystolo moqoo (grasshopper)
W uiscovered thot chromosomes
corried the ce//s units of
inheritonce
1 n Morgan (18661943)
W SLudled Lhe tosopblloe Lo deLermlne
wheLher heredlLy deLermlned
uarwlnlsL evoluLlon
W lound LhaL qenes cou/d be mopped ln
order along Lhe lengLh of a
chromosome
n|story of DNA
W CrlfflLh
W very MacLeod and McCarLy
W Pershey and Chase
W WaLson and Crlck
I Gr|ff|th
W ln 1928 Lhe effecLs of bacLerla on
mlce
ueLermlned LhaL some klnd of
transform|ng factor" exlsLed ln
Lhe heredlLy of cells
Avery MacLeod (187719SS)
W 1hrough Lhelr work ln bacLerla showed
LhaL DNA was the transform|ng factor
W DNA Lransferrlng geneLlc lnformaLlon
revlously LhoughL Lo be a proLeln
A|fred nershey (19081997)
Martha Chase (1930 )
W 1932 SLudled Lhe bacLerlophage 12
and lLs hosL bacLerlum scbetlcblo
coll
W lound LhaL un acLually
ls Lhe geneLlc maLerlal
LhaL ls Lransferred
ames Watson (1928)
Iranc|s Cr|ck (1916)
W 1931 CollaboraLed Lo gaLher all avallable
daLa abouL un ln order Lo deLermlne lLs
sLrucLure
W 1933 ueveloped
1he double hellx model for un sLrucLure
1he 1CC sLrands LhaL Lhe hellx ls conslsLed of
@be sttoctote wos too ptetty oot to be
ttoe
!MLS u W1SCn
W rogramable Mechanlcal CompuLer
n|story of Computers
Computer 1|me||ne
W 10008C 1he abacus
W 1623 Wllhelm Schlckards mechan|ca| ca|cu|ator
W 1926 llrsL paLenL for a semlconducLor trans|stor
W 1939 Atanasoff8erry Computer created at Iowa
State
the wor|ds f|rst e|ectron|c d|g|ta| computer
W 1939 Lhe l8M SCC)
W 1943 Collossus 8rlLlsh vacuum tube computer
W 1944 Crace Popper rogrammer
W 1943 llrsL Computer 8ug
l7
Slide 36
l7 An analogy can be conceived between the monomerspolymers and small simplle wires and complex physical strucutres(used in the
makeing of transisters etc RECARD!NC THE STORACE AND/OR PROCESS!NC OF !NFORNAT
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W 1948 Lo 1931 1he flrsL commerclal compuLer
W 1932 CW uummer concelves lnLegraLed clrculLs
W 1934 lC818n language developed
W 1963 Mouse lnvenLed by uouglas LnglebarL
W 1969 UNIk CS developed by kenneLh 1hompson
W 1970 llrsL sLaLlc and dynamlc 8Ms
W 1971 llrsL mlcroprocessor Lhe 4004
W 197S M|crosoft founded by 8||| Gates and au| A||en
W 1976 pple mlcrocompuLers released
W 1981 llrsL l8M C wlLh uCS
W 198S M|crosoft W|ndows
W 1992 ent|um processor
Genom|cs
W Cenome
compleLe seL of geneLlc lnsLrucLlons for maklng an
organlsm
W Cenomlcs
Lo analyze CLnCML
Wa|ter G||bert and Ireder|ck Sanger won the
Nobe| r|ze |n 1980 for the |nvent|on of DNA
sequenc|ng |n 1977
Larly genomlcs was mosLly recordlng genome
sequences
PlsLory of Cenomlcs
W 1980
llrsL compleLe genome sequence for
adenovlrus ls publlshed
W lx174 3386 base palrs codlng 9 proLelns
W 3kb
W 1993
oemopbllos lofloeozeo genome sequenced (flu bacLerla 18
Mb)
W 1996
occbotomyces cetevlsloe (bakers yeasL 121 Mbp)
W 1997
coll (47 Mbp)
W 2000
9seoJomooos oetoqlooso (63 Mbp)
u melanogasLer genome (180Mb)
2001 1he 8lg Cne
W 1he Puman Cenome sequence ls publlshed
3 Cb
WhaL nexL?
W osL Cenomlc era
ComparaLlve Cenomlcs
luncLlonal Cenomlcs and SLrucLural Cenomlcs
roLeomlcs
roteom|cs
W Lhe sLudy of Lhe proLeomeLhe
#kC1L|n comp|ement of the
genCML"
W Lhe quallLaLlve and quanLlLaLlve
comparlson of proLeomes under
dlfferenL condlLlons Lo furLher unravel
blologlcal processes
What Makes roteom|cs Important?
W cell's DNA|ts genomea b|uepr|nt for
Lhe ce||'s potent|a| all Lhe posslble forms
LhaL lL could concelvably Lake
W lL does not descr|be the ce||'s actua|
current form
What Makes roteom|cs Important?
W ll cells ln an organlsm conLaln Lhe same un
W 1hls un encodes every posslble cell Lype ln
LhaL organlsmmuscle bone nerve skln eLc
W lf we wanL Lo know abouL Lhe Lype and sLaLe
of a parLlcular cell Lhe DNA does not he|p us
W ln Lhe same way LhaL knowlng whaL language
a compuLer program was wrlLLen ln Lells us
noLhlng abouL whaL Lhe program does
W vlew a webpage and lLs source by 8lghL
CllcknL1 racLlceP88hLm
What Makes roteom|cs Important?
Cut of the thousands of genes on|y a handfu|
actua||y determ|ne that ce||'s structure
Many of the |nterest|ng th|ngs about a g|ven
ce||'s current state can be deduced from the
type and structure of the prote|ns |t expresses
Changes |n for examp|e t|ssue types carbon
sources temperature and stage |n ||fe of the
ce|| can be observed |n |ts prote|ns
roteom|cs In D|sease 1reatment
W large number of dlseases are caused by a
parLlcular paLLern ln a group of genes LC?
W lsolaLlng Lhls group by comparlng Lhe hundreds
of Lhousands of genes ln each of many
genomes would be very lmpracLlcal
W Look|ng at the proteomes of the ce||s
assoc|ated w|th the d|sease |s much more
eff|c|ent
roteom|cs In D|sease 1reatment
W Many human dlseases are
caused by a normal proLeln
belng modlfled lmproperly
W 1he LargeLs of almosL all
medlcal drugs are proLelns
Lxamp|es
W WhaL do Lhese have ln common?
lzhelmers dlsease
CysLlc flbrosls
Mad Cow dlsease
Stan|ey rus|ner
prion protein
ls a norma| proLeln frequenL ln llvlng organlsms
When some prlon change lLs shape by mlssfoldlng lL
becomes r|on%%% an lnfecLlous agenL
W un||ke other known lnfecLlous agenLs whlch musL
conLaln nuclelc aclds along wlLh proLeln
componenLs
W r|ons come ln dlfferenL sLralns each wlLh
a sllghLly dlfferenL sLrucLure and mosL
sLralns breed Lrue
W rlon repllcaLlon ls neverLheless sub[ecL Lo
occaslonal eplmuLaLlon and Lhen naLural
selecLlon [usL llke oLher forms of
repllcaLlon
W Lhe number of posslble dlsLlncL prlon
sLralns ls llkely far smaller Lhan Lhe number
of posslble un sequences so evo|ut|on
takes p|ace w|th|n a ||m|ted space