Practical and predictive bioinformatics methods for the identification of potentially cross-reactive protein matches
Practical and predictive bioinformatics methods for the identification of potentially cross-reactive protein matches
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DOI：
10.1002/mnfr.200500277
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发表时间：
2006-07-01
影响因子：
5.2
通讯作者：
Goodman, Richard E.
中科院分区：
文献类型：
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作者：
Goodman, Richard E.
通过基因工程引入粮食作物的蛋白质的生物信息学比较提供了一种机制，以识别那些可能增加过敏反应风险的蛋白质。目标是鉴定已知是过敏原或与过敏原如此相似以至于可能诱导过敏交叉反应的蛋白质。安全性评价传统上使用或考虑了三种比较方法。一种是鉴定与已知过敏原序列完全匹配的蛋白质的任何短（6-8）氨基酸片段。第二种是使用基本局部比对搜索工具（BLAST）或FASTA进行总体一级序列比较，以找到超过80个氨基酸的大于35%同一性的匹配。第三种是基于3-D预测程序，以识别可能预测潜在交叉反应性的3-D相似性。生物信息学讲习班讨论了每种方法的效用。专家研讨会与会者一致认为，短段匹配（例如，6-8氨基酸）提供了不可接受的高假阳性匹配率和不确定的真阳性匹配率，并且对于在综合安全性评价的背景下进行的变应原性评价不是特别有用。关于最适当的生物信息学方法、在阳性匹配之后触发更仔细检查的可接受的评分标准或对研讨会期间讨论的各种三维方法的效用进行排序的可接受的评分机制，没有达成共识。然而，普遍的共识是，目前最实用的方法是使用FASTA或BLAST评价与已知过敏原的一级序列同一性。虽然在80个或更多个氨基酸上具有大于35%的同一性，（2003年由食品法典委员会推荐）是相当保守的，结论是，需要更多的数据或研究来证明改变这一标准的合理性，因为有一些证据表明，一些对进化上保守的蛋白质家族中的蛋白质敏感的个体可能会对共享大约40%身份
A bioinformatics comparison of proteins introduced into food crops through genetic engineering provides a mechanism to identify those proteins that may present an increased risk of allergic reactions for individuals with existing allergies. The goal is to identify proteins that are known to be allergens or are so similar to an allergen that they may induce allergic cross-reactions. Three comparative approaches have traditionally been used, or considered for safety evaluations. One identifies any short (6-8) amino acid segment of the protein that exactly matches a known allergen sequence. The second is an overall primary sequence comparison using Basic Local Alignment Search Tool (BLAST) or FASTA to find matches of greater than 35% identity over 80 amino acids. The third is based on 3-D prediction programs to identify 3-D similarities that might predict potential cross-reactivity. The utility of each of these approaches was debated in the bioinformatics workshop. The consensus agreement from the expert workshop participants was that the short-segment match (e.g., 6-8 amino acids) provides an unacceptably high rate of false positive matches and an uncertain rate of true positive matches, and was not particularly useful for an allergenicity evaluation performed in the context of comprehensive safety evaluation. There was no consensus regarding the most appropriate bioinformatics method, an acceptable scoring criteria for triggering closer examination subsequent to a positive match, or an acceptable scoring mechanism for ranking the utility of the various 3-D approaches that were discussed during the workshop. However, the general consensus was that the most practical approach at this time is to evaluate primary sequence identities to known allergens using either FASTA or BLAST. While there was good agreement that identities of greater than 35% over 80 or more amino acids (recommended by Codex in 2003) is quite conservative, the conclusion was that additional data or studies would be needed to justify changing this criterion as there is some evidence that some individuals sensitized to proteins in evolutionarily conserved protein families may experience cross-reactions to proteins sharing approximately 40% identity.