< 2.5%. Roughly one-third (858 to 1092) of these genes are found in the most variable gene set in the brain dataset used for the network reconstruction. The PFC variant of the human immune/microglia module was highly enriched for genes which are differentially expressed in the full length or truncated Tyrobp experiments (P < 1e-15) (Figure 6A). We projected results of RNA sequencing experiments onto a large Bayesian brain network of ~8000 nodes that contains the microglia module as well as many other modules. In this large network, we could track differential expression of genes which are predicted to be downstream of TYROBP at various network path distances (Figure 6B). The highest predictive power for differential expression is in the primary neighborhood of the perturbed gene, and this power decreases for genes which are farther away in the network. The enrichment for differentially expressed genes in the network neighborhood of TYROBP and strong negative correlation between the fraction of confirmed targets and path distance (r= −0.82, P=4.e-07) (Figure 6B), show that our causal network structure is a significant and useful predictor of response to gene perturbations, even in a challenging cross-species setting. Thus both the structure and direction of links
