Results
2,179 unique allergen entries were collected from WHO/IUIS and
AllergenOnline databases and subjected to the analysis of significant
literature co-mentions with 21,380 pathological terms. Remarkably, 1,143
of these allergens (52.45%) were not significantly correlated with any
pathological term (p-val≤1E-2), suggesting that these allergens could
have a weak or inexistent clinical relevance based on the lack of
significant information on their biological activity found in the
literature. Indeed, a large fraction of those allergens without any
significant correlation with symptoms is never mentioned in PubMed
according with our searches, i.e., 1,064 out of 1,143 allergens
(93.1%), being 760 of them retrieved from AllergenOnline and 304 from
WHO/IUIS database. In almost half of the remaining 79 allergens with
retrieved articles but no significant co-mentions with symptoms (38) had
only one article gathered from PubMed, whereas other 38 were quoted only
between 2 and 7 times. These observations indicate that most allergens
not statistically associated to any type of clinical symptoms were due
to the insufficient number of scientific articles available for them in
PubMed. Regarding the 3 allergens with no associated symptoms but
reported in 9 or more articles retrieved from PubMed, they belong to
uncommon food sources (i.e., fungi allergens Asp o 13, Asp o 21
and Pen ch 35). The rest of annotated allergen entries (1,036) were
associated with a great variety of clinical signs and symptoms (i.e.,
1,180) via 14,009 relationships.
Figure 1A shows the distribution of number of symptoms for the
allergens associated to 50 or more. The allergen associated to the
largest number of symptoms is Can f 3 (serum albumin of domestic
dog), associated to 313 terms. Some of these relationships for Can
f 3 could be artifacts due to the use of that protein and/or the animalper se in biomedical studies.
Overall, the symptomatology associated to allergens makes sense
considering the knowledge we have on them. For example, well-known food
allergens such as peanut Ara h 1 or birch pollen allergen Bet v 1 were
associated to a large variety of well-described clinical symptoms,
whereas gluten proteins were correlated to celiac disease, and
infections like anisakiasis and aspergillosis were exclusively
associated to parasites from Anisakis simplex (and related worm
parasites) and fungi allergens, respectively. Likewise, aeroallergens
were predominantly correlated to symptoms involving the respiratory
system (e.g., rhinitis, asthma, wheezing, sneezing,
conjunctivitis, bronchial disorders). There are also trivial
associations with general terms such as “allergy” or
“hypersensitivity”, as well as some “artifacts” such as the
relationship between “decrease circulating IgE” and several allergens.
This association was inferred from articles describing structural
modifications of allergens in their native form, through processing or
chemical/enzymatic approaches, to reduce their allergenic potential.
Figure 1B shows the distribution of number of allergens
associated to the symptoms with 50 or more. As expected, the generic
term “allergy” is associated to almost all allergens (824 out of
1,036).
Figure 2 shows, as an example, the symptomatology retrieved by
our system for Bet v 1 (major birch pollen allergen). The terms
include the very general allergy , as well as the typicalrhinitis, conjunctivitis, pruritus/itching , and the rareranaphylactic shock . That list of terms nicely recapitulates those
manually compiled for this allergen in dedicated resources and provide a
clear picture of the symptomatology of this pollen allergen.