Protein familiarity is a fundamental but rarely operationalized concept in the safety assessment of genetically modified crops: example of phosphomannose isomerase (PMI).

Fundamental to the safety assessment of genetically modified (GM) crops is the concept of negligible risk for newly expressed proteins for which there is a history of safe use. Although this simple concept has been stated in international and regional guidance for assessing the risk of newly expressed proteins in GM crops, its full implementation by regulatory authorities has been lacking. As a result, safety studies are often repeated at a significant expenditure of resources by developers, study results are repeatedly reviewed by regulators, and animals are sacrificed needlessly to complete redundant animal toxicity studies.

Evidence-based regulations for bioinformatic prediction of allergen cross-reactivity are needed.

The bioinformatic criteria adopted by regulatory agencies to predict the potential cross reactivity between newly expressed proteins in genetically engineered crops and known allergens involves amino acid identity thresholds and was formulated nearly two decades ago based on the opinion of allergy experts. Over the subsequent years, empirical evidence has been developed indicating that better bioinformatic tools based on amino acid similarity are available to detect real allergen cross-reactive risk while substantially reducing false-positive detections. Although the formulation of safety regulations, in the absence of empirical evidence, may require reliance on expert opinion, such expert opinion should not trump empirical evidence once it becomes available.

Trypsin cleavage sites are highly unlikely to occur in celiac-causing restricted epitopes.

To assess risk, the European Food Safety Authority requires that the amino-acid sequences of newly expressed proteins in genetically engineered (GE) crops should be searched for partial matches with 9-mer restricted epitopes known to cause celiac disease. None of the 26 known celiac-causing 9-mer epitopes contain an predicted trypsin cleavage site. The probability of this occurring by chance alone is 0.

Safety assessment of coleopteran active IPD072Aa protein from Psuedomonas chlororaphis.

The ipd072Aa gene from Pseudomonas chlororaphis encodes the IPD072Aa protein which confers protection against certain coleopteran pests when expressed in genetically modified (GM) plants. A weight of evidence approach was used to assess the safety of the IPD072Aa protein. This approach considered the history of safe use of the source organism and bioinformatic comparison of the protein sequence with known allergenic and toxic proteins.

Comparative assessment of multiple criteria for the in silico prediction of cross-reactivity of proteins to known allergens.

Genetically modified crops are becoming important components of a sustainable food supply and must be brought to market efficiently while also safeguarding the public from cross-reactivity of novel proteins to known allergens. Bioinformatic assessments can help to identify proteins warranting further experimental checks for cross-reactivity. This study is a large-scale in silico evaluation of assessment criteria, including searches for: alignments between a query and an allergen having ≥ 35% identity over a length ≥ 80; any sequence (of some minimum length) found in both a query and an allergen; any alignment between a query and an allergen with an E-value below some threshold.

Assessment of possible allergenicity of hypothetical ORFs in common food crops using current bioinformatic guidelines and its implications for the safety assessment of GM crops.

Before a genetically modified (GM) crop can be commercialized it must pass through a rigorous regulatory process to verify that it is safe for human and animal consumption, and to the environment. One particular area of focus is the potential introduction of a known or cross-reactive allergen not previously present within the crop. The assessment of possible allergenicity uses the guidelines outlined by the Food and Agriculture Organization (FAO) and World Health Organization's (WHO) Codex Alimentarius Commission (Codex) to evaluate all newly expressed proteins.

Systems biology approaches for understanding cellular mechanisms of immunity in lymph nodes during infection.

Adaptive immunity is initiated in secondary lymphoid tissues when naive T cells recognize foreign antigen presented as MHC-bound peptide on the surface of dendritic cells. Only a small fraction of T cells in the naive repertoire will express T cell receptors specific for a given epitope, but antigen recognition triggers T cell activation and proliferation, thus greatly expanding antigen-specific clones. Expanded T cells can serve a helper function for B cell responses or traffic to sites of infection to secrete cytokines or kill infected cells.

A model of the cell-autonomous mammalian circadian clock.

Circadian timekeeping by intracellular molecular clocks is evident widely in prokaryotes and eukaryotes. The clockworks are driven by autoregulatory feedback loops that lead to oscillating levels of components whose maxima are in fixed phase relationships with one another. These phase relationships are the key metric characterizing the operation of the clocks.