Table 1.
Output reactions of the ihsTLR v1.0 model.
Table 2.
Basic statistics about the MCS.
Figure 1.
Schematic representation of a signaling network.
The left part of the figure shows a toy model of a signaling network. Nodes and edges represent species and reactions, respectively. The network contains two inputs (top incoming arrows) and two outputs (bottom outgoing arrows). The set of reactions is partitioned in four modules (A, B, C, and D). Each crossed reaction belongs to an MCS for output (only 4 MCS are shown for simplicity). Each color denotes a different MCS. Targeting simultaneously the two red-crossed reactions disables
. This MCS describes an epistatic relation between modules A and B. The upper-right diagram represents the profile of output
, i.e. the collection of distinct signatures obtained from the MCS. The profile displays distributions showing the frequency of each signature (top) and how many times each module is hit by an MCS (right). In our example, the first signature is obtained twice (red and blue MCS). Module A is hit three times: twice by the first signature and once by the second one. The lower-right diagram represents the MCS Module Cardinality (MMC) distribution of
, which shows the number of MCS targeting
module(s) simultaneously (
). The targeted modules are color coded in relative proportion. Among all the MCS of cardinality 2, half of the targeted reactions belong to module A.
Table 3.
Modules of the TLR network.
Figure 2.
Profiles obtained for seven of the output reactions: AP-1, CREB, IRF3, IRF7, NF-B, ROS, and ROS(2).
Each vertical line represents a distinct signature, i.e. the list of modules hit by an MCS. The profiles also display distributions showing the number of times each signature is encountered (top) and how many times each module is hit by an MCS (right). These distributions emphasize the most frequent signatures and the most targeted modules, respectively (cf. Fig. 1). Profiles of AP-1(2) and NF-B(2) are omitted. The AP-1(2) profile is identical to the AP-1 one, minus the 7-th signature. The NF-
B(2) profile is composed of a single signature targeting the NF-
B module.
Figure 3.
Distributions of the MCS Module Cardinality (MMC).
Each reaction in a MCS belongs to a module and some of these reactions may belong to the same module. Hence, an MCS may target the same module through different reactions. The MMC represents the number of distinct modules an MCS hits. The bars in each plot represent the number of MCS targeting simultaneously modules (
). No MCS targets more than 4 modules at a time. The colors describe which modules are targeted, as well as their relative importance. The distributions enable to immediately identify modules that are targeted alone (e.g. Common metabolites, ROS production, TICAM) and the ones that are targeted with other modules (e.g. PDK1 for ROS, Early endosome for IFR7, or MyD88 for AP-1 and AP-1(2)). For
, the distributions do no show which combinations of modules are hit together (see Fig. 2).
Figure 4.
Identification of Essential Gene Sets.
Species is produced by two distinct reactions:
and
. These reactions require proteins
and
to be expressed, respectively. The proteins can be used as enzymes or substrates.
is a dimer coded by genes A and B, while
is coded by gene C. Species
is no longer produced if both
and
are absent. Hence, the deletion of genes A and C, or B and C renders reaction
non-producible.
Table 4.
EGS validation.