A method to quantify the biological impact of active substances on a biological system represented by a causally inconsistent network by determining a score for a degree of activation of the causally inconsistent network, the method comprising: (a) providing a causally inconsistent network representing a biological system composed of causal connections among a set of nodes, wherein the nodes represent biological entities, biological processes or other biological networks, the network having a reference node; (b) constructing, from the causally inconsistent network, a tree graph of tree-depth one comprising a root node and a set of child nodes, wherein the tree graph represents the biological entities, the biological processes, or the other biological networks represented by the network, the root node of the tree graph represents the network, and each child node in the tree graph represents a particular node in the set of nodes from the network and is connected to the root node by a respective signed, directed edge pointing from the root node to that child node; (c) determining, for each signed, directed edge connecting the root node to a respective child node in the tree graph, a respective sign based on one of a net sign of a respective shortest path connecting the first respective particular node in the network to the reference node in the network, a set of signed spanning trees based on the network, or a plurality of random walks over the network; (d) determining, for each child node in the tree graph, a respective weight based on one of a respective shortest path connecting the second respective particular node in the network to the reference node in the network, the set of signed spanning trees, or the plurality of random walks along the network; (e) scoring the tree graph based on a respective score and the respective weight assigned to each of the child nodes in the tree graph and the respective signs of each of the signed, directed edges; wherein the score represents the net activation of the network in response to the active substances; and wherein the steps of the method are implemented in software executing in a hardware element. (a) providing a causally inconsistent network representing a biological system composed of causal connections among a set of nodes, wherein the nodes represent biological entities, biological processes or other biological networks, the network having a reference node; (b) constructing, from the causally inconsistent network, a tree graph of tree-depth one comprising a root node and a set of child nodes, wherein the tree graph represents the biological entities, the biological processes, or the other biological networks represented by the network, the root node of the tree graph represents the network, and each child node in the tree graph represents a particular node in the set of nodes from the network and is connected to the root node by a respective signed, directed edge pointing from the root node to that child node; (c) determining, for each signed, directed edge connecting the root node to a respective child node in the tree graph, a respective sign based on one of a net sign of a respective shortest path connecting the first respective particular node in the network to the reference node in the network, a set of signed spanning trees based on the network, or a plurality of random walks over the network; (d) determining, for each child node in the tree graph, a respective weight based on one of a respective shortest path connecting the second respective particular node in the network to the reference node in the network, the set of signed spanning trees, or the plurality of random walks along the network; (e) scoring the tree graph based on a respective score and the respective weight assigned to each of the child nodes in the tree graph and the respective signs of each of the signed, directed edges;