1. Romain Rivière AReNa – 28.03.2007

2.  Characterise RNA families  Improve non-coding RNA identification in genomic data  Determine the RNA players in regulatory networks  Identify potential RNA drug targets

5. Yeast tRNA-Phe crystal structure (pdb 4TNA)

6. 1. Enumerate all the motifs 2. Regroup by similarity 3. Find the building blocks

8. A motif is a set of connected nucleotides together with their interactions

10. …

11. 1. Enumerate all the motifs 2. Regroup by similarity 3. Find the building blocks

12. 12 54 3 0 1 0 0 1 1 0 1 1 0 0 1 0 1 0 0 1 1 0 1 1 0 0 1 0 12 54 3 0 1 0 1 1 1 0 1 1 0 0 1 0 0 1 1 1 0 0 0 1 0 1 0 0 24 13 5 0 1 0 0 1 1 0 1 1 0 0 1 0 1 0 0 1 1 0 1 1 0 0 1 0 Matrix representation of the graph : 2 1 ≠ = = Scan through all permutations to decide if two graphs are isomorphic !

13. ? ? ? ? ? ? ? ?

14. 12 54 3 0 1 0 0 1 1 0 1 1 0 0 1 0 1 0 0 1 1 0 1 1 0 0 1 0 12 54 3 0 1 0 1 1 1 0 1 1 0 0 1 0 0 1 1 1 0 0 0 1 0 1 0 0 24 13 5 0 1 0 0 1 1 0 1 1 0 0 1 0 1 0 0 1 1 0 1 1 0 0 1 0 Matrix representation of the graph : 2 1 ≠ = = Take the minimum through all permutations of the matrix representation

15. 1821183321

16. 1. Enumerate all the motifs 2. Regroup by similarity 3. Find the building blocks

18. Type of motifsEdges … … 7 7 7 10 5 6 4 4 30 Find a small set of types of motifs that covers the most edges

19. … General graphs are not compact enough Not usable for modelling

20. …

24.  Motif discovery Biological relevance of block-function relationships?  RNA folding Practical usability?

25. François Major Sébastien Lemieux Véronique Lisi Karine St-Onge Philippe Thibault Patrick Gendron Martin Larose All other lab members

27.  We applied the method to the large ribosomal subunit  We restrict the graphs allowed for the base to cycles  We found 334 cycles that covers 90% of the structure.

28.  Canonical label of a graph : Take the minimum of the matrices over all the permutations  Property : 2 graphs have the same canonical label if and only if they are isomorphic

29.  Group together motifs which are identical  Done with canonical labelling Idea : associate a string to each graph such that two graphs are associated with the same string if and only if they are identical (isomorphic). Difficult problem well studied Potentially highly computation time.

31.  3^n. 10^n where n is the size of the structure  10^14 op/s world fastest computer

37.  RNA is a very important medium in the transfer of genetic information  Convey information through its structure in addition to its sequence  Example : miRNA

39. Similar secondary structure But, only one miRNA functional !

40.  3 main types of molecular interactions : Phosphodiester link Base pairing Base stacking