Constructing and Analyzing a Gene Regulatory Network Siobhan Brady UC Davis How do we extract biologically important principles from thousands or millions of observations? How do we use genomics to understand how an organism works? Systems Theory The organization of variables Generalizable principles in the organization of a system Systems Biology Principles in the organization of a biological system Simplify a biological system study its basic building blocks Emergent properties A Framework for Systems Biology 1)Define all of the components of the system. Components in a Transcriptional Regulatory Network i) Define Nodes (variable in a system) Components in a Transcriptional Regulatory Network ii) Define Edges Interaction between nodes Edges can have mathematical descriptions Network Metrics In-Degree :The proportion of edges that go into a node (How many people know you?) Out-Degree : The proportion of edges that go out of a node (How many people do you know?) Calculate in-degree and out-degree for the classroom network 8,100 ORF clones (all against all) 2,754 Y2H interactions (CCSB-H1 - RED) 4,067 literature captured interactions (LC - BLUE) (Rual et al. 2005) Real-Life Networks Movie actors Node=actor, edge = same movei WWW Node=document, edge=link pointing from one document to another Power grid Node=generator/transformer/substation, edge=transmission lines between them (Barabasi and Albert, Science, 1999) Power Law Distribution P(k) = probability that a node in the network interacts with k other nodes = k - (Barabasi and Albert, Science, 1999) Network Motifs Patterns of interconnections that recur in many different parts of a network at frequencies much higher than those found in randomized networks 151 transcription factors 424 operons 577 interactions Randomized Network Nodes Edges Directions Degree Preservation Randomly switch pairs of edges repeating many times until randomized The identity of which TF regulates which gene is randomized 1000 Which network motifs can be found in the E. coli TRN? Three Node Loops 3 motifs found to be over-represented Do they perform a function that is advantageous to the organism? Coherent Type-1 FFL with an AND input function Dynamic Features of the Coherent FFL Do they perform a function that is advantageous to the organism? Coherent Type-1 FFL with an AND input function Dynamic Features of the Coherent FFL