Figure
2. Screenshots of the web interface when used for retrieving the
symptoms associated to the major birch pollen allergen (Bet v 1 ).
The left panel shows the query form where the user can enter the
allergen or symptoms to search for (in this case the name of the
allergen) and the type of relationships. The right panel shows the
results of the query, in this case the list of symptoms for Bet v
1 .
To identify those allergens potentially causing life-threatening, we
selected a series of severe symptoms which are disclosed in decreasing
order of frequency:
- anaphylactic shock (HP:0100845) or anaphylaxis (D000707) associated to
210 individual allergens;
- exercise induced anaphylaxis (HP:0410139) associated to 34 individual
allergens;
- food-induced anaphylaxis (HP:0500095) associated to 27 individual
allergens;
- dyspnea (HP:0002094) associated to 10 individual allergens;
- idiopathic anaphylaxis (HP:0410148) associated to 6 individual
allergens;
- loss of consciousness (HP:0007185) associated to 5 individual
allergens;
- hypotension (HP:0002615) associated to 4 individual allergens;
- Collapse associated to 3 individual allergens;
Overall, 222 allergens could be significantly correlated with
life-threatening severe allergic reaction symptoms (Supplementary Table
1), whereas 814 allergens were statistically correlated to a wide range
of less severe symptoms.
Regarding the main exposure route of those allergens correlated with
life-threatening severe allergic reaction symptoms, 121 allergens were
related to ingestion, 51 to insect venom allergies, 44 were classified
as aeroallergens (23 of them being derived from plants, 10 to cats,
dogs, horses or guinea pigs, 9 derived from dust mites, 2 corresponding
to american cockroach) and 6 related to dermal contact (mostly to latex
allergens) (Supplementary Table 1).
This list of 222 allergens was further manually refined based on the
following prioritization criteria:
i) consideration of ingestion, contact and airway exposure routes of
allergens related to food sources. This criterium served to disregard,
mainly, insect venom allergens, and some aeroallergens from sources
without any food relevance;
ii) consideration of allergens belonging to sources recognised as the
most common causing food allergies and intolerances based on European
Regulation[21] and the reviewed Codex priority
allergen list by an ad hoc Joint FAO/WHO Expert Consultation
Committee[22].
iii) consideration of allergens belonging to well-known allergen protein
families or subfamilies (e.g ., tropomyosins, parvalbumins,
non-specific lipid-transfer proteins, 2S albumins, vicilins, legumins)
regardless of the food relevance of the source; or
iv) consideration of allergens not included in any of the above criteria
but unequivocally associated to life-threatening severe allergic
symptoms. This last criterium served to disregard a few allergens
included in the initial list as they could not be directly linked to
severe symptoms. This was due to several reasons, such as:
- some of the significant co-mentions retrieved in certain articles were
based on the correlation of anaphylaxis with the whole food source
instead of specific allergens,
- some articles compared allergens associated with a wide range of
symptoms and the text-mining approach could not automatically
differentiate among those allergens associated to severe symptoms and
those related to mild symptoms,
- some articles dealt with allergens and/or derived peptides used for
immunotherapy but these proteins were not identified as responsible for
triggering severe symptoms.
Overall, a refined list
containing 137 food allergens resulted from applying above criteria
(Table 1 ). This set of allergens could be further considered
for a more target allergenicity RA of novel proteins as will be
discussed below.