The use of E-scores to determine the quality of protein alignments

Approaches to assess IgE mediated allergy risks (sensitization and cross-reactivity) from new or modified dietary proteins

“…There is however little solid scientific basis for a general application of this rule, which has not been formally validated, as far as we know. The conservatism of the greater than 35% identity over 80 amino acids approaches and applicability to all protein families has been questioned (Herman et al, 2015;Silvanovich et al, 2009). The 80 amino acid sliding window approach is thought to be selected to correspond to the typical size of a protein domain containing IgE epitopes (Herman et al, 2009).…”

“…Alignment of the whole sequence of the novel protein and allergens in the database, without the restriction of the length of the sliding window has been proposed as a relevant alternative approach (Herman et al, 2015;Silvanovich et al, 2009). However, although the literature referenced above suggests a greater scientific basis for E-score than for the greater than 35% identity/80 AA sliding window (Herman et al, 2015;Silvanovich et al, 2009), more detailed studies concerning the relevance of using E-score (E-value) for predicting allergenic cross-reactivity would be of benefit. One possibility would be hypothesis-driven investigations with relevant human serum samples.…”

Percent amino-acid identity thresholds are not necessarily conservative for predicting allergenic cross-reactivity

“…Specifically, a threshold of >35% identity over a stretch of ≥80 amino acids is considered a cross-reactive risk under this guidance (Codex Alimentarius Commission, 2007). The main argument against the Codex approach has been the high false-positive rate; this method identifies many sequences with no allergenic cross reactivity (Cressman and Ladics, 2009;Ladics et al, 2007;Silvanovich et al, 2009;Song et al, 2014). For this reason, most researchers have suggested using well established bioinformatic tools, like the local alignment tool FASTA, in combination with a statistical measure of alignment significance (e.g.…”

Peanut Bioinformatics: Tools and Applications for Developing More Effective Immunotherapies for Peanut Allergy and Improving Food Safety

“…Water scarcity, energy resources, and food have become a matter of concern with the growing population (Bruinsma 2009;Gregory and George 2011). To avoid confusion with expressed or predicted protein-coding sequence, open reading frames (ORFs) are referred to as novel polypeptides, even though at times the novel polypeptide sequence may overlap with an expressed or protein-coding sequence (Vrtala 2008;Silvanovich et al 2009). Translation of stop-to-stop frames, alignments to the allergen online database using FASTA, and search for eight residue identical matches were used (Silvanovich et al 2009).…”

“…To avoid confusion with expressed or predicted protein-coding sequence, open reading frames (ORFs) are referred to as novel polypeptides, even though at times the novel polypeptide sequence may overlap with an expressed or protein-coding sequence (Vrtala 2008;Silvanovich et al 2009). Translation of stop-to-stop frames, alignments to the allergen online database using FASTA, and search for eight residue identical matches were used (Silvanovich et al 2009). The novel polypeptide sequences were created by scanning all six DNA reading frames (starting at base 1, 2, or 3 of each DNA sequence and translating each nonoverlapping nucleotide triplet into an amino acid using the standard genetic codon table and then reversing the sequence and repeating the process).…”