We have reviewed the manuscript:(Ayyadurai and Deonikar, 2015), which we understand is based on earlier work by ( Deonikar et al., 2015 Mohan et al., 2015 ). The methodology in these papers employs a promising computational systems biology approach to model the effects of genetic modification (GM) on critical molecular pathways affecting plant physiology. The computational results suggestin concentrations of formaldehyde and glutathione in the genetically engineered soybean (GMO) tissues. These significant changes in key biomarker concentrations could cause deleterious biological impacts. The computational systems biology results reveal how a “small,” single recombinant DNA event may create “large,” unpredictable, systemic perturbations to molecular systems equilibria. In light of such changes, it is clear to say that GMOs and non-GMOS may not always be “substantially equivalent.” This research acknowledges the complexity of biological organisms and indicates how systems biology can enable modeling and prediction of potential unexpected perturbations from GM. Thesepredictions should motivate regulatory agencies, in conjunction with stakeholders from industry and public interest groups, to develop objectivefor measuring and comparing biomarker concentrationsandacross GMOs and their non-GMO counterparts as criteria for assessing substantial equivalence. Until such Standards are developed for testing, we believe it premature to approve GMOs and to consider them safe.