Gathering Sequences: BLAST - T-CoffeeSelecting Diverse Sequences (Opus II) Selecting Diverse...

Gath

ering

Seq

uen

ces: BL

AS

TC

om

mo

n M

istake:S

equ

ences T

oo

Clo

sely Related

PRVA_MACFU SMTDLLNAEDIKKAVGAFSAIDSFDHKKFFQMVGLKKKSADDVKKVFHILDKDKSGFIEE

PRVA_HUMAN SMTDLLNAEDIKKAVGAFSATDSFDHKKFFQMVGLKKKSADDVKKVFHMLDKDKSGFIEE

PRVA_GERSP SMTDLLSAEDIKKAIGAFAAADSFDHKKFFQMVGLKKKTPDDVKKVFHILDKDKSGFIEE

PRVA_MOUSE SMTDVLSAEDIKKAIGAFAAADSFDHKKFFQMVGLKKKNPDEVKKVFHILDKDKSGFIEE

PRVA_RAT SMTDLLSAEDIKKAIGAFTAADSFDHKKFFQMVGLKKKSADDVKKVFHILDKDKSGFIEE

PRVA_RABIT AMTELLNAEDIKKAIGAFAAAESFDHKKFFQMVGLKKKSTEDVKKVFHILDKDKSGFIEE

:**::*.*******:***:* :****************..::******:***********

PRVA_MACFU DELGFILKGFSPDARDLSAKETKTLMAAGDKDGDGKIGVDEFSTLVAES

PRVA_HUMAN DELGFILKGFSPDARDLSAKETKMLMAAGDKDGDGKIGVDEFSTLVAES

PRVA_GERSP DELGFILKGFSSDARDLSAKETKTLLAAGDKDGDGKIGVEEFSTLVSES

PRVA_MOUSE DELGSILKGFSSDARDLSAKETKTLLAAGDKDGDGKIGVEEFSTLVAES

PRVA_RAT DELGSILKGFSSDARDLSAKETKTLMAAGDKDGDGKIGVEEFSTLVAES

PRVA_RABIT EELGFILKGFSPDARDLSVKETKTLMAAGDKDGDGKIGADEFSTLVSES

:*** ******.******.**** *:************.:******:**

-IDEN

TICAL SEQ

UEN

CES BRING

NO

INFO

RMA

TION

FOR TH

EM

ULTIPLE SEQ

UEN

CE ALIG

NM

ENT

-MU

LTIPLE SEQU

ENCE A

LIGN

MEN

TS THRIVE O

N D

IVERSITY…

Selectin

g D

iverse Seq

uen

ces (Op

us I)

Resp

ect Info

rmatio

n!

-This Alignm

ent Is not Informative about the relation

Betww

en TPCC MO

USE and the rest of the sequences.

-A better Spread of the Sequences is needed

PRVA_MACFU ------------------------------------------SMTDLLN----AEDIKKA

PRVA_HUMAN ------------------------------------------SMTDLLN----AEDIKKA

PRVA_GERSP ------------------------------------------SMTDLLS----AEDIKKA

PRVA_MOUSE ------------------------------------------SMTDVLS----AEDIKKA

PRVA_RAT ------------------------------------------SMTDLLS----AEDIKKA

PRVA_RABIT ------------------------------------------AMTELLN----AEDIKKA

TPCC_MOUSE MDDIYKAAVEQLTEEQKNEFKAAFDIFVLGAEDGCISTKELGKVMRMLGQNPTPEELQEM

: :*. .*::::

PRVA_MACFU VGAFSAIDS--FDHKKFFQMVG------LKKKSADDVKKVFHILDKDKSGFIEEDELGFI

PRVA_HUMAN VGAFSATDS--FDHKKFFQMVG------LKKKSADDVKKVFHMLDKDKSGFIEEDELGFI

PRVA_GERSP IGAFAAADS--FDHKKFFQMVG------LKKKTPDDVKKVFHILDKDKSGFIEEDELGFI

PRVA_MOUSE IGAFAAADS--FDHKKFFQMVG------LKKKNPDEVKKVFHILDKDKSGFIEEDELGSI

PRVA_RAT IGAFTAADS--FDHKKFFQMVG------LKKKSADDVKKVFHILDKDKSGFIEEDELGSI

PRVA_RABIT IGAFAAAES--FDHKKFFQMVG------LKKKSTEDVKKVFHILDKDKSGFIEEEELGFI

TPCC_MOUSE IDEVDEDGSGTVDFDEFLVMMVRCMKDDSKGKSEEELSDLFRMFDKNADGYIDLDELKMM

:. . * .*..:*: *: * *. :::..:*:::**: .*:*: :** :

PRVA_MACFU LKGFSPDARDLSAKETKTLMAAGDKDGDGKIGVDEFSTLVAES-

PRVA_HUMAN LKGFSPDARDLSAKETKMLMAAGDKDGDGKIGVDEFSTLVAES-

PRVA_GERSP LKGFSSDARDLSAKETKTLLAAGDKDGDGKIGVEEFSTLVSES-

PRVA_MOUSE LKGFSSDARDLSAKETKTLLAAGDKDGDGKIGVEEFSTLVAES-

PRVA_RAT LKGFSSDARDLSAKETKTLMAAGDKDGDGKIGVEEFSTLVAES-

PRVA_RABIT LKGFSPDARDLSVKETKTLMAAGDKDGDGKIGADEFSTLVSES-

TPCC_MOUSE LQ---ATGETITEDDIEELMKDGDKNNDGRIDYDEFLEFMKGVE

*: . .. :: .: : *: ***:.**:*. :** ::

Selectin

g D

iverse Seq

uen

ces (Op

us II)

Selectin

g D

iverse Seq

uen

ces (Op

us II)

PRVB_CYPCA -AFAGVLNDADIAAALEACKAADSFNHKAFFAKVGLTSKSADDVKKAFAIIDQDKSGFIE

PRVB_BOACO -AFAGILSDADIAAGLQSCQAADSFSCKTFFAKSGLHSKSKDQLTKVFGVIDRDKSGYIE

PRV1_SALSA MACAHLCKEADIKTALEACKAADTFSFKTFFHTIGFASKSADDVKKAFKVIDQDASGFIE

PRVB_LATCH -AVAKLLAAADVTAALEGCKADDSFNHKVFFQKTGLAKKSNEELEAIFKILDQDKSGFIE

PRVB_RANES -SITDIVSEKDIDAALESVKAAGSFNYKIFFQKVGLAGKSAADAKKVFEILDRDKSGFIE

PRVA_MACFU -SMTDLLNAEDIKKAVGAFSAIDSFDHKKFFQMVGLKKKSADDVKKVFHILDKDKSGFIE

PRVA_ESOLU --AKDLLKADDIKKALDAVKAEGSFNHKKFFALVGLKAMSANDVKKVFKAIDADASGFIE

: *: .: . .* .:*. * ** *: * : * :* * **:**

PRVB_CYPCA EDELKLFLQNFKADARALTDGETKTFLKAGDSDGDGKIGVDEFTALVKA-

PRVB_BOACO EDELKKFLQNFDGKARDLTDKETAEFLKEGDTDGDGKIGVEEFVVLVTKG

PRV1_SALSA VEELKLFLQNFCPKARELTDAETKAFLKAGDADGDGMIGIDEFAVLVKQ-

PRVB_LATCH DEELELFLQNFSAGARTLTKTETETFLKAGDSDGDGKIGVDEFQKLVKA-

PRVB_RANES QDELGLFLQNFRASARVLSDAETSAFLKAGDSDGDGKIGVEEFQALVKA-

PRVA_MACFU EDELGFILKGFSPDARDLSAKETKTLMAAGDKDGDGKIGVDEFSTLVAES

PRVA_ESOLU EEELKFVLKSFAADGRDLTDAETKAFLKAADKDGDGKIGIDEFETLVHEA

:** .*:.* .* *: ** :: .* **** **::** **

-A REA

SON

ABLE M

odel Now

Exists.

-Going Further:Rem

ote Hom

ologues.

Alig

nin

g R

emo

te Ho

mo

log

ues

PRVA_MACFU ------------------------------------------SMTDLLNA----EDIKKA

PRVA_ESOLU -------------------------------------------AKDLLKA----DDIKKA

PRVB_CYPCA ------------------------------------------AFAGVLND----ADIAAA

PRVB_BOACO ------------------------------------------AFAGILSD----ADIAAG

PRV1_SALSA -----------------------------------------MACAHLCKE----ADIKTA

PRVB_LATCH ------------------------------------------AVAKLLAA----ADVTAA

PRVB_RANES ------------------------------------------SITDIVSE----KDIDAA

TPCS_RABIT -TDQQAEARSYLSEEMIAEFKAAFDMFDADGG-GDISVKELGTVMRMLGQTPTKEELDAI

TPCS_PIG -TDQQAEARSYLSEEMIAEFKAAFDMFDADGG-GDISVKELGTVMRMLGQTPTKEELDAI

TPCC_MOUSE MDDIYKAAVEQLTEEQKNEFKAAFDIFVLGAEDGCISTKELGKVMRMLGQNPTPEELQEM

: ::


PRVA_ESOLU LDAVKAEGS--FNHKKFFALVG------LKAMSANDVKKVFKAIDADASGFIEEEELKFV

PRVB_CYPCA LEACKAADS--FNHKAFFAKVG------LTSKSADDVKKAFAIIDQDKSGFIEEDELKLF

PRVB_BOACO LQSCQAADS--FSCKTFFAKSG------LHSKSKDQLTKVFGVIDRDKSGYIEEDELKKF

PRV1_SALSA LEACKAADT--FSFKTFFHTIG------FASKSADDVKKAFKVIDQDASGFIEVEELKLF

PRVB_LATCH LEGCKADDS--FNHKVFFQKTG------LAKKSNEELEAIFKILDQDKSGFIEDEELELF

PRVB_RANES LESVKAAGS--FNYKIFFQKVG------LAGKSAADAKKVFEILDRDKSGFIEQDELGLF

TPCS_RABIT IEEVDEDGSGTIDFEEFLVMMVRQMKEDAKGKSEEELAECFRIFDRNADGYIDAEELAEI

TPCS_PIG IEEVDEDGSGTIDFEEFLVMMVRQMKEDAKGKSEEELAECFRIFDRNMDGYIDAEELAEI


: . .: .. . *: * : * :* : .*:*: :** .

PRVA_MACFU LKGFSPDARDLSAKETKTLMAAGDKDGDGKIGVDEFSTLVAES-

PRVA_ESOLU LKSFAADGRDLTDAETKAFLKAADKDGDGKIGIDEFETLVHEA-

PRVB_CYPCA LQNFKADARALTDGETKTFLKAGDSDGDGKIGVDEFTALVKA--

PRVB_BOACO LQNFDGKARDLTDKETAEFLKEGDTDGDGKIGVEEFVVLVTKG-

PRV1_SALSA LQNFCPKARELTDAETKAFLKAGDADGDGMIGIDEFAVLVKQ--

PRVB_LATCH LQNFSAGARTLTKTETETFLKAGDSDGDGKIGVDEFQKLVKA--

PRVB_RANES LQNFRASARVLSDAETSAFLKAGDSDGDGKIGVEEFQALVKA--

TPCS_RABIT FR---ASGEHVTDEEIESLMKDGDKNNDGRIDFDEFLKMMEGVQ

TPCS_PIG FR---ASGEHVTDEEIESIMKDGDKNNDGRIDFDEFLKMMEGVQ

TPCC_MOUSE LQ---ATGETITEDDIEELMKDGDKNNDGRIDYDEFLEFMKGVE

:: .. :: : :: .* :.** *. :** ::

Go

ing

Fu

rther…


PRVB_BOACO LQSCQAADS--FSCKTFFAKSG------LHSKSKDQLTKVFGVIDRDKSGYIEEDELKKF

PRV1_SALSA LEACKAADT--FSFKTFFHTIG------FASKSADDVKKAFKVIDQDASGFIEVEELKLF

TPCS_RABIT IEEVDEDGSGTIDFEEFLVMMVRQMKEDAKGKSEEELAECFRIFDRNADGYIDAEELAEI

TPCS_PIG IEEVDEDGSGTIDFEEFLVMMVRQMKEDAKGKSEEELAECFRIFDRNMDGYIDAEELAEI


TPC_PATYE SDEMDEEATGRLNCDAWIQLFER---KLKEDLDERELKEAFRVLDKEKKGVIKVDVLRWI

. : .. . :: . : * :* : .* *. : * .

PRVA_MACFU LKGFSPDARDLSAKETKTLMAAGDKDGDGKIGVDEFSTLVAES--

PRVB_BOACO LQNFDGKARDLTDKETAEFLKEGDTDGDGKIGVEEFVVLVTKG--

PRV1_SALSA LQNFCPKARELTDAETKAFLKAGDADGDGMIGIDEFAVLVKQ---

TPCS_RABIT FR---ASGEHVTDEEIESLMKDGDKNNDGRIDFDEFLKMMEGVQ-

TPCS_PIG FR---ASGEHVTDEEIESIMKDGDKNNDGRIDFDEFLKMMEGVQ-

TPCC_MOUSE LQ---ATGETITEDDIEELMKDGDKNNDGRIDYDEFLEFMKGVE-

TPC_PATYE LS---SLGDELTEEEIENMIAETDTDGSGTVDYEEFKCLMMSSDA

: . :: : :: * :..* :. :** ::

WH

AT

MA

KE

S A

GO

OD

AL

IGN

ME

NT

…

-THE M

ORE D

IVERGEA

NT TH

E SEQU

ENCES, TH

E BETTER

-THE FEW

ER IND

ELS, THE BETTER

-NICE U

NG

APPED

BLOCKS SEPA

RATED

WITH

IND

ELS

-DIFFEREN

T CLASSES O

F RESIDU

ES WITH

IN A

BLOCK:

•Completely Conserved

•Conserved For Size and Hydropathy

•Conserved For Size or Hydropathy

-THE U

LTIMA

TE EVALU

ATIO

N IS A

MA

TTER OF PERSO

NN

AL JU

DG

EMEN

TA

ND

KNO

WLED

GE.

DO

NO

T O

VE

RT

UN

E!!!

chite ---ADKPKRPLSAYMLWLNSARESIKRENPDFK-VTEVAKKGGELWRGLKD

wheat --DPNKPKRAPSA

FFVFMGEFREEFKQKNPKNKSVAAVGKAAGERWKSLSE

trybr KKDSNAPKRAMTSFMFFSSDFRS----KHSDLS-IVEMSKAAGAAWKELGP

mouse -----KPKRPRSAYNIYVSESFQ----EAKDDS-AQGKLKLVNEAWKNLSP

***. ::: .: .. . : . . * . *: *

chite AATAKQNYIRALQEYERNGG-

wheat ANKLKGEYNKAIAAYNKGESA

trybr AEKDKERYKREM---------

mouse AKDDRIRYDNEMKSWEEQMAE

* : .* . :

DO

NO

T PLAY W

ITH

PARA

METERS IF YO

U KN

OW

THE A

LIGN

MEN

TYO

U W

AN

T: MA

KE IT YOU

RSELF!

chite ---ADKPKRPL-SAYMLWLNSARESIKRENPDFK-VTEVAKKGGELWRGLKD

wheat --DPNKPKRAP-SAFFVFMGEFREEFKQKNPKNKSVAAVGKAAGERWKSLSE


mouse -----KPKRPR-SAYNIYVSESFQ----EAKDDS-AQGKLKLVNEAWKNLSP

***. :*: .: .. . : . . * . *: *





* : .* . :

TU

NIN

G o

r NO

T T

UN

ING

?

-MO

ST METH

OD

S ARE TU

NED

FOR W

ORKIN

G W

ELL ON

AVERA

GE

-PARA

METERS BEH

AVIO

UR D

O N

OT N

ECESSARILY FO

LLOW

THE

THEO

RY (i.e. Substitution Matrices).

-A G

OO

D A

LIGN

MEN

T IS USU

ALLY RO

BUST(i.e. Changes little).

-TUN

E IF YOU

WA

NT TO

CON

VINCE YO

URSELF.

-PARA

METERS TO

TUN

E USU

ALLY IN

CLUD

E:•G

OP/ G

EP•M

ATRIX

•SENSITIVITY Vs SPEED

GO

P

GEP

Substitution Matrices

(Etzold and al. 1993)

Gonnet

61.7Blosum

5059.7

Pam250

59.2

KE

EP

A B

IOL

OG

ICA

L P

ER

SP

EC

TIV

E

chite ---ADKPKRPLSAYMLWLNSARESIKRENPDFK-VTEVAKKGGELWRGLKD

wheat --DPNKPKRAPSAFFVFMGEFREEFKQKNPKNKSVAAVGKAAGERWKSLSE


mouse -----KPKRPRSAYNIYVSESFQ----EAKDDS-AQGKLKLVNEAWKNLSP

***. ::: .: .. . : . . * . *: *





* : .* . :

chite AD--K----PKR-PLYMLWLNS-ARESIKRENPDFK-VT-EVAKKGGELWRGL-

wheat -DPNK----PKRAP-FFVFMGE-FREEFKQKNPKNKSVA-AVGKAAGERWKSLS

trybr -K--KDSNAPKR-AMT-MFFSSDFR-S-KH-S-DLS-IV-EMSKAAGAAWKELG

mouse ----K----PKR-PRYNIYVSESFQEA-K--D-D-S-AQGKL-KLVNEAWKNLS

* *** .:: ::... : * . . . : * . *: *

chite KSEWEAKAATAKQNY-I--RALQE-YERNG-G-

wheat KAPYVAKANKLKGEY-N--KAIAA-YNK-GESA

trybr RKVYEEMAEKDKERY----K--RE-M-------

mouse KQAYIQLAKDDRIRYDNEMKSWEEQMAE-----

: : * : .* :

DIFFEREN

T PARA

METERS

RE

PE

AT

S

THERE IS A

PROBLEM

WH

EN TW

O SEQ

UEN

CES DO

NO

T CON

TAIN

THE SA

ME N

UM

BER OF REPEA

TS

IT IS THEN

BETTER TO M

AN

UA

LLY EXTRACT TH

E REPEATS A

ND

TO A

LIGN

THEM

. IND

IVIDU

AL REPEA

TS CAN

BE RECOG

NIZED

USIN

G D

OTTER

Ch

oo

sing

Th

e Rig

ht M

etho

d

PROBLEM

PROG

RAM

ClustalW

ClustalW

MSA

DIA

LIGN

II

DIA

LIGN

II

METH

OD

Source: BaliBase, Thompson et al, N

AR, 1999

Exam

ples o

f Mistakes

Playin

g W

ith B

locks: M

bh

1

Playin

g W

ith B

locks: tR

NA

Syn

thases

Playin

g W

ith B

locks:R

Tase

Co

nclu

sion

The Best Alignm

ent Method:

•Your Brain•The Right D

ata

The Best Evaluation:•Your Eyes•Experim

ental Information (Sw

issProt)

What Can I Conclude:•H

omology=> Inform

ation Extrapolation

How

Can I go Further?:•PrositePatterns.•PrositeProfiles.

Gathering Sequences: BLAST - T-CoffeeSelecting Diverse Sequences (Opus II) Selecting Diverse...

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Transcript of Gathering Sequences: BLAST - T-CoffeeSelecting Diverse Sequences (Opus II) Selecting Diverse...