The Expanded Central Dogma

1. DNA • RNA • mRNA • tRNA • rRNA • hnRNA • Etc. Protein The Expanded Central Dogma Protein Regulate Degradation /Activation Protein/RNA Regulate Modification transcription translation Protein/RNA Regulate Initiation Protein/RNA/AA’s Regulate Ribosome

2. cDNA Microarrays • Takes “snapshot” of cellular mRNA levels under chosen experimental conditions • Two current representations: • General un-weighted graph (enumerate maximalcliques, neighborhood search, dominating set) • Bipartite graph (biclique) • Goal: Group genes that exhibit similar responses to stimuli – co-regulation

3. Microarrays and General Graphs Normalized Data Correlation Adjacency Matrix Calc. Correlation Coefficient Correlation coefficient range: -1 to 1 1: Perfectly correlated 0: No correlation -1: Perfectly anti-correlated Take Abs. Value, then Threshold Filter (ex. 0.7) Un-weighted Adjacency Matrix

4. Clique Enumeration Algorithm • Choose ‘well-selected’ vertex (no pre-processing) • Add selected vertex to set compsub (potential clique) • Create sets candidate and not from old sets by removing all vertices not connected to the selected candidate (keeping old intact) • Call function recursively on new sets • On return, remove selected vertex from set compsub and add to set not • Clique is found when sets candidate and not are empty

5. Genes Experiments Exp. A: Extreme temp. Exp. C: Heavy metal exposure Gene 3 Microarrays and Bipartite Graphs Normalized Data Exp. A: Extreme temp. Gene 1 Exp. B: High glucose level Gene 2 After Threshold Filter (3) Exp. C: Heavy metal exposure Gene 3

6. Promoter Transcription Factor Binding Sites (Motifs) Transcription Regulation Upstream Region Downstream Region yfg

7. Module Detection • Presence of common motifs indicates co-ordinate regulation – a module • Sequence of motifs in module rarely important • Position of a motif relative to other motifs can be important

8. Genes Motifs Module Bipartite Graph Gene 1 Gene 2 Gene 3 Gene 1 Gene 2 Gene 3