IgE-mediated allergy is an immunoreaction that occurs when the immune system reacts improperly to otherwise innocuous proteins, designated allergens. Binding of an allergen to IgE attached to mast cells and basophils, stimulates the release of inflammatory substances, such as histamine, leading to disease reactions. Such reactions can involve a variety of symptoms, such as pins and needles, swelling of the oral cavity, alimentary canal and respiratory tract reactions or anaphylaxis. According to the American Academy of Allergy, Asthma and Immunology (AAAAI), there are about 40–50 million allergy sufferers in the USA, making it the sixth most common cause of chronic illness , and food allergies occur in 6%–8% of children under 4 years old  and in 4% of adults . Therefore, allergy has become a major clinical and public health issue.
Allergens occur in many foods, such as rice, hen's egg and peanut as well as in a number of non-food sources, typified by fungi, mites and insects. The Food and Agriculture Organization (FAO) and the World Health Organization (WHO) proposed that milk, seashell, egg, fish, peanut, soybean, nut and wheat are eight major sources of food allergens and the causes of most food allergies . These allergens have attracted much attention, and efforts have been made to determine the reasons for their allergenicity and what we can do to reduce it or to remove them. The arrival of genetically modified organisms (GMO) has made it even more urgent to find an accurate method for evaluating allergenicity as a part of the safety assessment of GMO before they are released commercially. Astwood et al. found that the main allergens of peanut and soybean were more stable in simulated gastric fluid (SGF) than nonallergenic proteins such as spinach ribulose bis-phosphate carboxylase/oxygenase, and proposed that the resistance of a protein to digestion is an important factor in its allergenicity . After that, assessment of the digestibility of a foreign protein in GM foods as a means of evaluating allergenicity was included not only in a decision tree approach proposed by FAO and WHO in January 2001 , but also in a weight-of-evidence approach proposed by The Codex Alimentarius Commission (Codex) in 2003 . Several ensuing studies have shown that allergenic proteins are more stable to pepsin digestion than those not connected with allergenic potential, but Yagami et al.  and Fu et al. [7, 8] found that the association between digestibility and allergenicity is not absolute. The disagreements may be attributed to variations in the amount of enzyme or protein, pH, temperature, ionic conditions etc. in the experiments. Computational simulation has the potential to substitute for manual experiments and will always achieve the same (simulated) conditions. However, there has been no report on computational simulation of gastric fluid digestion. Therefore, we have considered computer simulation of gastric fluid digestion to elucidate the relationship between the allergenicity and digestibility of proteins.
To date, about 256 food allergens have been included in the SDAP, including 121 allergens with known amino acid sequences and 10 with known allergenic determinants [9, 10]. The food and pollen allergen database in our laboratory also includes the amino acid sequences of major food and pollen allergens from eight species . These data make it possible to simulate gastric fluid digestion by a computer model. Food allergens can enter the human body either through ingestion or – when also occurring as airborne substances – by inhalation. Accordingly, these allergens can be divided into two groups as defined by the pathway of entrance leading to sensitization. Non-food allergens, however, mainly enter by the airborne pathway. Ingested allergens can be dubbed alimentary canal-sensitized (ACS), while others can be dubbed non-alimentary canal-sensitized (NACS). We propose that these two allergen groups would respond differently to gastric fluid digestion: the former is likely to be relatively resistant and the latter relatively labile. However, allergens are generally ingested along with nonallergenic proteins, so they must differ somewhat in biochemical properties. Proteins from SwissProt were collected into their respective species-origin protein sets (SOPS), and the digestibilities of allergens and SOPS were compared in an effort to derive an in silico model, which attempts to simulate protein susceptibility to gastric/intestinal protease activity.