R ESEARCH G ENOME B IOINFORMATICS L AB R ESEARCH at G ENOME B IOINFORMATICS L AB Josep F. Abril Ferrando and Genís Parra Farré Genome BioInformatics Research

RRESEARCHESEARCHat

GGENOMEENOME BBIOINFORMATICSIOINFORMATICS LLABAB

Josep F. Abril Ferrandoand

Genís Parra Farré

Genome BioInformatics Research Lab

RGBI @ ( IMIM – UPF – CRG )

Introduction

Visualization of Genomic

Annotations

Comparative Genomics

Human and Mouse Genomes

Exon Structural SelectionBIOINFORMÀTICA UPF T23 – 2003/03/06 – J.F. Abril and G. Parra @ Genome BioInformatics Lab – RGBI (IMIM-UPF-

CRG)

SUMMARYSUMMARY

Computational Analysis of Genomic Computational Analysis of Genomic SequencesSequences

DNA SEQUENCE

Sequencing

ASSEMBLED SEQUENCE

Assembling

ANNOTATED SEQUENCE

Analyzing

BIOINFORMÀTICA UPF T23 – 2003/03/06 – J.F. Abril and G. Parra @ Genome BioInformatics Lab – RGBI (IMIM-UPF-CRG)

From Genes to Genomes: Single GenesFrom Genes to Genomes: Single Genes


From Genes to Genomes: ChromosomesFrom Genes to Genomes: Chromosomes


From Genes to Genomes: Whole GenomesFrom Genes to Genomes: Whole Genomes


Comparative Genomics: Single GenesComparative Genomics: Single Genes


Comparative Genomics: Syntenic RegionsComparative Genomics: Syntenic Regions


Programming in PProgramming in POSTOSTSSCRIPT (I)CRIPT (I)


%!PS

%

%% Variable Definition: $counter = 0

/counter 0 def

%

%% Function Definition: sub box(x,y) {...}

/box { %%% y x box

gsave %

20 mul % y X

0 % y X 0

moveto % y

20 mul % Y

dup % Y Y

10 0 % Y Y 10 0

rlineto % Y Y

0 % Y Y 0

exch % Y 0 Y

rlineto % Y

-10 0 % Y -10 0

rlineto % Y

neg % -Y

0 % -Y 0

exch % 0 -Y

rlineto %

closepath %

0 1 0 % 0 1 0

setrgbcolor % "green-color"

fill %

grestore %

} def %

Vector Graphics

Language

Prefix Notation

Stacks:

exec, paths, dicts, ...

Dictionaries:

Identifier Object

%

%% Initialization

100 100 translate % New Coords Origin

2 5 scale % Re-scaling x-axes*2

% % y-axes*5

%

%% BaseLine

gsave %

0 0 moveto %

90 0 lineto %

0 setgray %

1 setlinewidth %

stroke %

grestore %

Programming in PProgramming in POSTOSTSSCRIPT (II)CRIPT (II)


%

%% Main Loop

mark % mark

0.25 0.35 0.15 % mark 0.25 0.35 0.15

counttomark % mark 0.25 0.35 0.15 3

{ %%%%%%%%%%%%%% begin loop (x3)

/counter %%

counter %%

1 add %%

def %% $counter = $counter + 1

counter %

% 1st loop: mark 0.25 0.35 0.15 counter==1

% 2nd loop: mark 0.25 0.35 counter==2

% 2nd loop: mark 0.25 counter==3

box % mark ...

} repeat %%%%%%%%%%%%%% finish loop (x3)

pop % clean up stack (removes "mark")

%

showpage

%%EOF%%

GFF2PS and GFF2APLOTGFF2PS and GFF2APLOT


Visualizing Genomic AnnotationsVisualizing Genomic Annotations

J.F. Abril and R. Guigó.

" gff2ps: visualizing genomic annotations "

Bioinformatics 16(8):743-744 (2000).

M.G. Reese, G. Hartzell, N.L. Harris, U. Ohler, J.F. Abril and S.E. Lewis.

" Genome Annotation Assessment in Drosophila melanogaster "

Genome Research 10(4):483-501 (2000).M.D. Adams et al (including J.F. Abril).

" The Genome Sequence of Drosophila melanogaster "

Science 287(5461):2185-2195 (2000).

J.C. Venter et al (including J.F. Abril and R. Guigó).

" The Sequence of the Human Genome "

Science 291(5507):1304-1351 (2001).

R.A. Holt et al (including J.F. Abril and R. Guigó).

" The Genome Sequence of the Malaria Mosquito Anopheles gambiae "

Science 298(5591):129-149 (2002).


http://genome.imim.es/software/gfftools/GFF2PS.html

Whole Genome Gene-FindingWhole Genome Gene-Finding

Homosapiens

GENES

abinitio

DATABASE

homology


Whole Genome Gene-Finding: Comparative Whole Genome Gene-Finding: Comparative ApproachApproach


Whole Genome Gene-Finding: Comparative Whole Genome Gene-Finding: Comparative ApproachApproach

GENES

Homosapiens

Musmusculus

GENES

homology

geneprediction

geneprediction

homology


Whole Genome Gene-Finding Results Whole Genome Gene-Finding Results AnalysisAnalysis


Human and Mouse Comparative GenomicsHuman and Mouse Comparative Genomics


Mouse Genome Sequencing Consortium (including J.F. Abril, G. Parra and R. Guigó).

" Initial sequencing and comparative analysis of the mouse genome "

Nature 420(6915):520-562 (2002).

G. Parra, P. Agarwal, J.F. Abril, T. Wiehe, J.W. Fickett and R. Guigó.

" Comparative gene prediction in human and mouse "

Genome Research 13(1):108-117 (2003).

R. Guigó, E.T. Dermitzakis, P. Agarwal, C.P. Ponting, G. Parra, A. Reymond, J.F. Abril, E. Keibler, R. Lyle, C. Ucla, S.E. Antonarakis and M.R. Brent.

" Comparison of mouse and human genomes followed by experimental verification yields an estimated 1,019 additional genes "

PNAS 100(3):1140-1145 (2003).

Predicting “Novel” Genes in the Mouse Predicting “Novel” Genes in the Mouse Genome (I)Genome (I)

golden path annotations

golden path annotations

additional blastn matches to ENSEMBL + REFSEQ



Predicting “Novel” Genes in the Mouse Predicting “Novel” Genes in the Mouse Genome (II)Genome (II)

tblastx

geneidexons

tblastx

sgpgenes



Homosapiens

Predictions

Musmusculus

Predictions

GENESEnriched Pool

StructuralAlignment Exstral


HomologyBlastp

Homology and Gene Structure FilteringHomology and Gene Structure Filtering


Exon Structure over an AlignmentExon Structure over an Alignment


RT-PCR ValidationRT-PCR Validation

Number of predictions

Tested Success Rate

Enriched 1428 214 62.15%

Similar 2125 38 10.53%

Other 3659 63 3.17%


Results of the Experimental ValidationResults of the Experimental Validation


Example of a Bash ScriptExample of a Bash Script

http://genome.imim.es/

Documents

R ESEARCH G ENOME B IOINFORMATICS L AB R ESEARCH at G ENOME B IOINFORMATICS L AB Josep F. Abril Ferrando and Genís Parra Farré Genome BioInformatics Research