We measure ROS production and stomatal aperture in cells treated with single and combined stimuli and develop an ordinary differential equation (ODE) model of stomatal closure based on biochemical pathway information.
BNICE (Biochemical Network Integrated Computational Explorer), a computational approach for the discovery of novel biochemical pathways that is based on biochemical transformations, overcomes many of the current limitations.
The KEGG database contains manually annotated pathways based on biochemical evidence from the literature, including metabolism, genetic information processing, environmental information processing and cellular processes.
The individual compounds and reactions of a pathway can also be assigned weights based on biochemical and network-based properties.
Mathematical descriptions of interactions of the mechanistic parts of the pathways were modeled based on biochemical reaction equations.
Secondly, an in silico validation analysis was performed using external and independently generated datasets with known pathway activation status based on biochemical measurements of protein knockdown (SIRT1, HDAC1), inhibitor treatment (HDAC1, DNMT2, EZH2), or activator treatment (HDAC4, SIRT1).
Based on biochemical and genetics studies, three alternative AsA biosynthetic pathways have been proposed (Figure 1A).
KEGG pathways, which are built based on biochemical reactions and may provide biological explanations for phenotype variation, present the order of 100 genes, which corresponds to roughly d = 0.01 in Figure 1E (9684 genes times 0.01).
A fermentation pathway has been proposed based on biochemical data [ 34].
The remaining human candidate genes listed in Table S2 are not associated with publications reporting a germline genetic polymorphism impacting MTX toxicity, although they are believed to be in the pathway that processes MTX, based on biochemical studies.
