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

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

Microarrays and General Graphs Gene 1Gene 2Gene 3 Gene Gene Gene Correlation coefficient range: -1 to 1 1: Perfectly correlated 0: No correlation -1: Perfectly anti-correlated Exp. AExp. BExp. C Gene 1612 Gene 2083 Gene 3914 Gene 1Gene 2Gene 3 Gene 101 Gene 201 Gene 311 Calc. Correlation Coefficient Take Abs. Value, then Threshold Filter (ex. 0.7) Normalized DataCorrelation Adjacency Matrix Un-weighted Adjacency Matrix

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

Microarrays and Bipartite Graphs Exp. AExp. BExp. C Gene 1612 Gene 2083 Gene 3914 Normalized Data ExperimentsGenes Gene 1 Gene 2 Gene 3 Exp. C: Heavy metal exposure Exp. B: High glucose level Exp. A: Extreme temp. Exp. AExp. BExp. C Gene 1100 Gene 2011 Gene 3101 After Threshold Filter (3) Exp. C: Heavy metal exposure Exp. A: Extreme temp. Gene 3

Transcription Regulation yfg Upstream RegionDownstream Region Transcription Factor Binding Sites (Motifs) Promoter

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

Module Bipartite Graph GenesMotifs Gene 1 Gene 2 Gene 3 Gene 1 Gene 2 Gene 3