My masters presentation demonstrating Icarus and DNA walking

1. Genome exploration in A-T G-C space introducing Icarus a DNA walking program Jonathan Blakes MSc Biotechnology and Computation Department of Biosciences Faculty of Science, Technology and Medical Studies

2. Problem too much information!

3. EnsEMBL UCSC Genome Browsers

4. Hypothesis Can DNA sequences be plotted in such a way that long sequences can be easily interpreted by humans without a prior i knowledge? “ It seems that the simplest method of visualizing some properties of genomes is to send a virtual walker for a genomic walk, ask "it" to talk about what it has seen and note its observations. If our walker doesn't move with a Brownian-like motion, it is possible to extract from its walk a lot of information . ” Stanislaw Cebrat , the principal Polish proponent of DNA walks Assigning a cardinal coordinate ( north , south , east or west ) to each of the four nucleotide bases ( A , T , G , C ) and taking steps in those directions as a sequence is read sequentially will produce a ‘walk’ of the sequence in which repetitive DNA elements will be seen as repetitive 2-dimensional ‘structures’.

5. DNA walks are plots of DNA or RNA sequences where each of the four nucleotide bases is assigned a direction and distance, the sequence is read off one nucleotide at a time and for each nucleotide the virtual walker takes a step in the designated direction creating a 'walk' of the sequence that reveals elements of structure in the nucleotide composition. DNA walking From Comparative Genometrics website, L'Université de Lausanne

6. Icarus Live Demonstration Could someone please suggest a mammalian gene to walk?

7. Mapping 24 possible combinations of cardinal vectors: 4 rotations for each of the 3 above mappings, and 4 rotations of each of their reflections about the x or y plane. Choosing which 3 ‘unique’ mappings of those 24 is a matter of parsimony.

8. A-T G-C

9. A-G C-T

10. A-C G-T

11. A-T G-C

12. A-T G-C is consistently smallest Smaller pictures can contain more information in less space and are therefore more amenable to publication, hence Genome Exploration in A-T G-C space

13. Duplications exons introns a 7 fold contiguous duplication in the male Y chromosome. Members of the TSPY (Testis-specific Y-encoded proteins) family identified by Skaletsky et al 1 using a combination of a whole chromosome dotplot with a 2-kb window and a custom Perl script running BLAST alignments of all 5-kb sequence segments, in 2-kb steps, of the entire MSY (Male Specific Y). In contrast I stumbled upon this purely by accident. 1. Skaletsky et al. Nature 2003 423.

15. Phylogeny algorithms neighbour joining Icarus’ UPGMA Distance Matrix

16. Phylogeny Demonstration

17. Newick format  Distance Matrix Output Newick format string representation of a tree: (Bovine:0.69395, (Gibbon:0.36079, (Orang:0.33636, (Gorilla:0.17147, (Chimp:0.19268, Human:0.11927) :0.08386):0.06124):0.15057):0.54939, Mouse:1.21460);

18. Phylogenies with DNA walks

19. Does summing distances from 3 mappings eliminate bias and produce a better phylogeny? NO. A better distance measure is needed.

21. Acknowledgements I would like to thank: Dr. Gary Robinson Dr. Colin Johnson Dr. Anthony Baines And everyone I have met during the Biotechnology and Computation MSc.