Seralogix Mechanistic Model Interrogation and
The resulting Bayesian network models that are trained and scored provide considerable insight into the gene-to-gene or protein-to-protein relationships. Interrogation of these models provides valuable insight into which biological function and genes are most likely governed by the treatment or disease being studied. An intermediate (and often iterative) step requires the involvement of the research biologist/scientist to examine the resulting models for clues that help explain the host response. Working with the Seralogix's bioinformaticians, the interpretation of the initial results help select groups of pathways and gene ontology categories that are of high interest. These high interest biological processes form the initial building blocks for creating a biological system model.
Figure 1 shows a typical network model for the MAPK signaling pathway. Figure 2 shows the DBGGA gene scores as a heatmap for the MAPK pathway. Gene/protein nodes on the network model (Fig 1) have the same color coding as on the gene score heatmap. Orange highlighted nodes on the model are those defined as mechanistic genes that surpass a user selected threshold which for this cases is |Bayesian z-score| > 2.24. The model can be visually inspected (static or animated) at any selected time point to view the status of gene/protein expression and correlation between gene relationships. Arcs having thicker lines in the network (Fig. 1) have high positive or negative correlations. A selected set of highly correlated arcs for this model is shown in Figure 3. Interpretation of the arcs and state of gene perturbations provide evidence of pathway points of disruptions or alterations due to the experimental condition.
Such interrogation guides the biologist to identify potential malfunctions and is especially powerful when employed for comparative analysis between multiple experimental conditions. For example, arcs that are reversed in correlation between two conditions may suggest likely candidate genes that are being manipulated as a result of the stimuli/conditions being compared.