Dysregulated Signal Propagation in a MYC-associated Boolean Gene Network in B-cell Lymphoma

By the modern molecular biological approaches that exploit the availability of high quality gene expression data, it is made clear that flexible and robust responses of cellular programs are encoded in the relations between gene expression values. These relations naturally define a network where they stand for edges between the nodes that stand for the genes. The wiring of these networks often found to be dysregulated in cancer. Different system biological approaches that rely on correlations, differential equations and logical analysis are used to probe these relations in gene expression data especially. In our work we investigated selected biological functions in aggressive germinal center B-cell lymphoma in terms of a logical analysis of gene-regulation in Boolean space and a signal propagation algorithm considering network topology based on gene expression data. We especially aimed at studying the activity of the MYC gene as a key player. It is shown that the functional output of a gene network is affected by the states of the genes and also by the wirings between them. Our results support the key function of MYC in lymphoma biology. In addition, we showed that genes can alter functional output of the network by alternative mechanisms like reducing the variance in propagating signal and locking it to a certain level.