2. 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 Lab RGBI @ ( IMIM – UPF – CRG )

3. Introduction Visualization of Genomic Annotations Comparative Genomics Human and Mouse Genomes Exon Structural Selection BIOINFORMÀTICA UPF T23 – 2003/03/06 – J.F. Abril and G. Parra @ Genome BioInformatics Lab – RGBI (IMIM-UPF-CRG) SUMMARY

4. Computational Analysis of Genomic Sequences 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)

5. From Genes to Genomes: Single Genes BIOINFORMÀTICA UPF T23 – 2003/03/06 – J.F. Abril and G. Parra @ Genome BioInformatics Lab – RGBI (IMIM-UPF-CRG)

6. From Genes to Genomes: Chromosomes BIOINFORMÀTICA UPF T23 – 2003/03/06 – J.F. Abril and G. Parra @ Genome BioInformatics Lab – RGBI (IMIM-UPF-CRG)

7. From Genes to Genomes: Whole Genomes BIOINFORMÀTICA UPF T23 – 2003/03/06 – J.F. Abril and G. Parra @ Genome BioInformatics Lab – RGBI (IMIM-UPF-CRG)

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

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

10. Programming in P OST S CRIPT (I) BIOINFORMÀTICA UPF T23 – 2003/03/06 – J.F. Abril and G. Parra @ Genome BioInformatics Lab – RGBI (IMIM-UPF-CRG) %!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

11. % % 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 P OST S CRIPT (II) BIOINFORMÀTICA UPF T23 – 2003/03/06 – J.F. Abril and G. Parra @ Genome BioInformatics Lab – RGBI (IMIM-UPF-CRG) % % 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%

12. GFF2PS and GFF2APLOT BIOINFORMÀTICA UPF T23 – 2003/03/06 – J.F. Abril and G. Parra @ Genome BioInformatics Lab – RGBI (IMIM-UPF-CRG)

13. Visualizing 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). BIOINFORMÀTICA UPF T23 – 2003/03/06 – J.F. Abril and G. Parra @ Genome BioInformatics Lab – RGBI (IMIM-UPF-CRG) http://genome.imim.es/software/gfftools/GFF2PS.html

14. Whole Genome Gene-Finding Homo sapiens GENES ab initio DATABASE homology BIOINFORMÀTICA UPF T23 – 2003/03/06 – J.F. Abril and G. Parra @ Genome BioInformatics Lab – RGBI (IMIM-UPF-CRG)

15. Whole Genome Gene-Finding: Comparative Approach BIOINFORMÀTICA UPF T23 – 2003/03/06 – J.F. Abril and G. Parra @ Genome BioInformatics Lab – RGBI (IMIM-UPF-CRG)

16. Whole Genome Gene-Finding: Comparative Approach GENES Homo sapiens Mus musculus GENES homology gene prediction gene prediction homology BIOINFORMÀTICA UPF T23 – 2003/03/06 – J.F. Abril and G. Parra @ Genome BioInformatics Lab – RGBI (IMIM-UPF-CRG)

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

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

19. Predicting “Novel” Genes in the Mouse Genome (I) golden path annotations additional blastn matches to ENSEMBL + REFSEQ BIOINFORMÀTICA UPF T23 – 2003/03/06 – J.F. Abril and G. Parra @ Genome BioInformatics Lab – RGBI (IMIM-UPF-CRG)

20. Predicting “Novel” Genes in the Mouse Genome (II) tblastx geneid exons tblastx sgp genes BIOINFORMÀTICA UPF T23 – 2003/03/06 – J.F. Abril and G. Parra @ Genome BioInformatics Lab – RGBI (IMIM-UPF-CRG) additional blastn matches to ENSEMBL + REFSEQ

21. Homo sapiens Predictions Mus musculus Predictions GENES Enriched Pool Structural Alignment Exstral BIOINFORMÀTICA UPF T23 – 2003/03/06 – J.F. Abril and G. Parra @ Genome BioInformatics Lab – RGBI (IMIM-UPF-CRG) Homology Blastp Homology and Gene Structure Filtering

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

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

24. Number of predictions TestedSuccess Rate Enriched142821462.15% Similar21253810.53% Other3659633.17% BIOINFORMÀTICA UPF T23 – 2003/03/06 – J.F. Abril and G. Parra @ Genome BioInformatics Lab – RGBI (IMIM-UPF-CRG) Results of the Experimental Validation

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

26. http://genome.imim.es/