The next step in their study justifies the method’s title (CRAFT: “Causal Reasoning Analytical Framework for Target Discovery”) and is what separates their approach from previous efforts. Their goal was to identify a surface receptor whose activity would change the transcription levels of the entire inflammation genetic module from the “epileptic” version back to the “healthy” version. To do this, they built a computer model of how different membrane receptors influence changes in gene transcription using published databases of membrane receptor function. Put another way, if one considers the set of genes that is altered in TLE as a set of dominoes that has toppled, the authors asked which one was pushed first? This insight led them to identify the gene Csf1R, which encodes the macrophage-colony stimulating factor (M-CSF) receptor expressed by microglia. In their computational model, reducing the activity of the M-CSF receptor changed the expression of a wide range of genes and ultimately pushed the network back to the expression level of genes seen in the healthy samples. After an exhaustive modeling study, they had finally arrived at the testable hypothesis that the microglial M-CSF receptor was overactivated in TLE and that this was producing a wide range of downstream transcriptional changes to promote seizures.