TWN Info Service on Biosafety
18 May 2023
Third World Network
www.twn.my
Dear Friends and Colleagues
A systems biology approach to assessing potential unintended effects in GM crops
A recent study proposes a more advanced and thorough means to evaluate potential changes to the compositional profile of genetically modified (GM) crops, in order assess unintended effects with potential food safety implications.
Using advanced molecular ‘omics’ profiling techniques that can assess global changes to levels of RNA, protein and metabolites in a plant, the study on a GM soybean revealed a range of unintended changes in compositional profile, including increased levels of allergens and 70 proteins that were differentially expressed compared to the conventional counterpart. The scientists concluded that these changes have potential biological significance, with alteration to several metabolic pathways (related to protein synthesis and processing).
Current risk assessment processes generally use a ‘targeted’ approach for assessing potential changes to nutrient and anti-nutrient profiles of GM crops, where a limited number of components are assessed. Even if significant changes are detected compared to its non-GM counterpart, regulators usually deem the difference ‘not biologically meaningful’, if the levels are within those seen in other crops.
This concept of ‘substantial equivalence’ has long been criticised as inadequate and arbitrary. Indeed, in practice, this principle allows comparison of the transgenic line to any variety within the species, and even to an abstract entity made up of the composite of selected characteristics from all varieties.
The alternative ‘systems biology’ approach undertaken by the study authors with the use of global profiling techniques instead provides an untargeted and unsupervised analysis that reduces bias, allows for an additional chance to detect unintended changes such as new toxins or allergens, and allows for comparison of compounds or molecule relevant to each GM crop, rather than to a pre-determined list of compounds. Increasing the range of compounds also allows risk assessment to keep abreast of changes in technical progress for GM crops that may involve deeper levels of intervention and thus increased complexities of potential changes.
As the authors conclude, “Based on the results generated by the approach proposed in our study, we conclude that the comparative assessment according to the current EFSA guidance is not fit for purpose and needs to be improved.”
Instead, a “systems biology approach based on a holistic perspective can be more informative in risk assessment than the currently employed endpoint-by-endpoint analysis for the assessment of potential unintended effects in a GM plant.”
With best wishes,
Third World Network
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Integration of omics analyses into GMO risk assessment in Europe: a case study from soybean field trials
Benevenuto, R.F., Zanatta, C.B., Waßmann, F. et al.
Environ Sci Eur 35, 14 (2023)
https://doi.org/10.1186/s12302-023-00715-6
Abstract
In Europe, genetically modified organisms (GMOs) are subject to an authorization process including a mandatory risk assessment. According to the respective guidance by the European Food Safety Authority (EFSA), one of the pillars of this GMO risk assessment is a comparative analysis of the compositional and agronomic characteristics. This targeted approach has been criticized for its limitations, as it only considers pre-determined compounds, being insufficient to assess a comprehensive range of relevant compounds, including toxins and anti-nutrients, on a case-specific basis. Strategies based on advanced untargeted omics technologies have been proposed as a potential broader approach to be implemented into the initial step of the risk assessment framework. Here, we provide an example of a step-by-step omics analysis based on systems biology approach to fit into the context of European GMO regulation. We have performed field trial experiments with genetically modified (GM) Intacta™ Roundup Ready™ 2 Pro soybean containing both cry1Ac and cp4epsps transgenic inserts and analyzed its proteomic profile against the non-GM counterpart and reference varieties. Based on EFSA’s comparative endpoint-by-endpoint approach, the proteomics analysis revealed six proteins from the GMO outside the 99% tolerance intervals of reference varieties (RVs) in the equivalence test. Interestingly, from the near-isogenic (non-GM) comparator we found as many as ten proteins to be outside of the said RVs’ equivalence limits. According to EFSA’s statistical guidelines, differences found in metabolite abundance between a GMO and its non-GM comparator would not be considered biologically relevant as all compounds of concern remained within the equivalence limits of commercial RVs. By assessing the proteomic and metabolomic data through our proposed systems biology approach, we found 70 proteins, and the metabolite xylobiose as differentially expressed between the GMO and its non-GM comparator. Biological relevance of such results was revealed through a functional biological network analysis, where we found alterations in several metabolic pathways related to protein synthesis and protein processing. Moreover, the allergenicity analysis identified 43 proteins with allergenic potential being differentially expressed in the GM soybean variety. Our results demonstrate that implementation of advanced untargeted omics technologies in the risk assessment of GMOs will enable early and holistic assessment of possible adverse effects. The proposed approach can provide a better understanding of the specific unintended effects of the genetic modification on the plant’s metabolism, the involved biological networks, and their interactions, and allows to formulate and investigate dedicated risk hypotheses in the first place. We draw conclusions on a detailed comparison with the comparative assessment according to EFSA and provide scientific arguments and examples on how the current comparative approach is not fit for purpose.