AllerML - Markup Language for Allergens

The Allergen Markup Language, AllerML, that we describe here is a first step in developing automated tools to access data on allergens in multiple databases. AllerML is based on IUIS nomenclature and consists of a hierarchical set of tags that describe the most important information normally contained in allergen databases, including common names, sources, sequence, structure, IgE and T-cell epitopes, and cross-reactivity. AllerML also includes tags for attributes, such as Pfam classifications, that link allergen-specific databases to other general purpose biological data sets. In its current form, AllerML can be used to automate the dynamic exchange of information on allergens, to incorporate data on new allergenic proteins as they are identified, and to support computational and bioinformatics studies of allergenicity and clinically significant cross-reactivity. Wide implementation of AllerML will simplify automatic exchange of data between allergen databases, and improve data access for integrated computational and bioinformatics analysis.

AllerML Tags

The AllerML tags proposed here encode all molecular information on allergens and IgE epitopes, as present in the major allergen databases. For each allergen in SDAP, the AllerML record can be obtained from the link “Translate to AllerML” located immediately below the title line with the allergen name in the SDAP page corresponding to an allergen.

Table 1. AllerML Tags (only the start tag is shown for each section)

Tag	Description
<AllerML_Allergen>	Allergen section
<AllerML_Allergen_Name>	Allergen name
<AllerML_Allergen_SDAP_ID>	Allergen SDAP ID
<AllerML_Isoallergen>	Isoallergen section
<AllerML_Isoallergen_Name>	Isoallergen name
<AllerML_Isoallergen_SDAP_ID>	Isoallergen SDAP ID
<AllerML_Allergen_Type>	Allergen type: IUIS or non-IUIS
<AllerML_Organism>	Allergen organism
<AllerML_Systematic_Name>	Systematic name
<AllerML_Taxonomy_ID>	Taxonomy ID
<AllerML_Common_Name>	Common name
<AllerML_Taxonomy>	Taxonomy
<AllerML_Comment>	Comment
<AllerML_Protein>	Protein section
<AllerML_Protein_Source>	Protein source: UniProt, GenBank, PubMed, or DOI
<AllerML_UniProt>	UniProt section
<AllerML_UniProt_ID>	UniProt ID
<AllerML_UniProt_Accession>	UniProt accession number
<AllerML_GenBank>	GenBank section
<AllerML_GenBank_Locus>	GenBank locus
<AllerML_GenBank_Accession>	GenBank accession number
<AllerML_GenBank_Version>	GenBank version
<AllerML_GenBank_GI>	GenBank GI
<AllerML_Protein_Length>	Protein length
<AllerML_Protein_Sequence>	Protein sequence
<AllerML_PDBML>	PDBML section
<AllerML_Epitopes>	Epitopes section
<AllerML_Epitope_Set>	Section for an epitope set, normally from a single publication
<AllerML_Epitope_Type>	Epitope type: IgE, T-cell
<AllerML_Epitope_Position>	Epitope position
<AllerML_Epitope_Sequence>	Epitope sequence
<AllerML_Epitope_Comment>	Epitope comment
<AllerML_MotifMate_Motifs>	Section for a collection of MotifMate motifs
<AllerML_MotifMate_Motif>	MotifMate motif
<AllerML_MotifMate_Motif_Position>	MotifMate motif position
<AllerML_MotifMate_Motif_Sequence>	MotifMate motif sequence
<AllerML_Cross-references>	Cross-references to other databases
<AllerML_EMBL>	EMBL (https://www.ebi.ac.uk/)
<AllerML_GenBank>	GenBank (https://www.ncbi.nlm.nih.gov)
<AllerML_DDBJ>	DDBJ (DNA Data Bank of Japan, https://www.ddbj.nig.ac.jp/)
<AllerML_HSSP>	HSSP (https://srs.ebi.ac.uk/srsbin/cgi-bin/wgetz?-page+LibInfo+-lib+HSSP)
<AllerML_PDB>	PDB (https://www.pdb.org)
<AllerML_IntAct>	IntAct (https://www.ebi.ac.uk/intact/site/index.jsf)
<AllerML_GO>	GO (https://www.geneontology.org/)
<AllerML_InterPro>	InterPro (https://www.ebi.ac.uk/interpro/)
<AllerML_Gene3D>	Gene3D (https://gene3d.biochem.ucl.ac.uk/Gene3D/)
<AllerML_Pfam>	Pfam (https://pfam.sanger.ac.uk/)
<AllerML_PRINTS>	PRINTS (https://www.bioinf.manchester.ac.uk/dbbrowser/PRINTS)
<AllerML_PROSITE>	PROSITE (https://www.expasy.org/prosite/)
<AllerML_References>	Set of references
<AllerML_Reference>	Reference
<AllerML_Reference_PubMed>	PubMed ID
<AllerML_Reference_Authors>	Set of authors
<AllerML_Author>	Author
<AllerML_Reference_Journal>	Journal
<AllerML_Reference_Title>	Title
<AllerML_Reference_Year>	Year
<AllerML_Reference_Volume>	Volume
<AllerML_Reference_Pages>	Pages

Allergen Name and Taxonomy

An example of the implementation of AllerML for Ara h 3 is shown in Scheme 1. The first part of the record indicates the IUIS allergen name and type (IUIS or non-IUIS). Other unique identifiers from each allergen database can be included (if available) using appropriate tags. The SDAP ID is given here as an example. The second part of the record contains source organism information including the accession number from the NCBI taxonomy database (https://www.ncbi.nlm.nih.gov/Taxonomy/). Comments may be included in any AllerML section under the tag <AllerML_Comment>, and may contain HTML tags used to format the text for display or to include other HTML elements such as tables or hyperlinks.

Scheme 1. Core information of Ara h 3 as an AllerML document

<AllerML_Allergen>

<AllerML_Allergen_Name>Ara h 3</AllerML_Allergen_Name>

<AllerML_Allergen_SDAP_ID>326</AllerML_Allergen_SDAP_ID>

<AllerML_Allergen_Type>IUIS</AllerML_Allergen_Type>

<AllerML_Organism>

<AllerML_Systematic_Name>Arachis hypogaea</AllerML_Systematic_Name>

<AllerML_Taxonomy_ID>3818</AllerML_Taxonomy_ID>

<AllerML_Common_Name>peanut</AllerML_Common_Name>

<AllerML_Taxonomy>Eukaryota; Viridiplantae; Streptophyta; Embryophyta;

Tracheophyta; Spermatophyta; Magnoliophyta; eudicotyledons;

core eudicotyledons; rosids; eurosids I; Fabales; Fabaceae;

Papilionoideae; Aeschynomeneae; Arachis

</AllerML_Taxonomy>

</AllerML_Organism>

<AllerML_Comment>glycinin</AllerML_Comment>

<AllerML_References>

<AllerML_Reference>

<AllerML_Reference_PubMed>10021462</AllerML_Reference_PubMed>

</AllerML_Reference>

<AllerML_Reference>

<AllerML_Reference_PubMed>11146387</AllerML_Reference_PubMed>

</AllerML_Reference>

</AllerML_References>

...

</AllerML_Allergen>

Cross-references to Other Web Databases

Other protein databases also contain relevant information about allergenic proteins, and we propose the following set of AllerML tags to link to the most relevant such services:

EMBL (https://www.ebi.ac.uk/), tag <AllerML_EMBL>
GenBank (https://www.ncbi.nlm.nih.gov), tag <AllerML_GenBank>
DDBJ (DNA Data Bank of Japan, https://www.ddbj.nig.ac.jp/), tag <AllerML_DDBJ>
HSSP (https://srs.ebi.ac.uk/srsbin/cgi-bin/wgetz?-page+LibInfo+-lib+HSSP), tag <AllerML_HSSP>
PDB (https://www.pdb.org), tag <AllerML_PDB>
IntAct (https://www.ebi.ac.uk/intact/site/index.jsf), tag <AllerML_IntAct>
GO (https://www.geneontology.org/), tag <AllerML_GO>
InterPro (https://www.ebi.ac.uk/interpro/), tag <AllerML_InterPro>
Gene3D, tag <AllerML_Gene3D>
Pfam (https://pfam.sanger.ac.uk/), tag <AllerML_Pfam>
PRINTS (https://www.bioinf.manchester.ac.uk/dbbrowser/PRINTS), tag <AllerML_PRINTS>
PROSITE (https://www.expasy.org/prosite/), tag <AllerML_PROSITE>

Scheme 2. Cross-references section of Ara h 3

<AllerML_Cross-references>

<AllerML_Protein_Source>UniProt</AllerML_Protein_Source>

<AllerML_UniProt>

<AllerML_UniProt_ID>O82580_ARAHY</AllerML_UniProt_ID>

<AllerML_UniProt_Accession>O82580</AllerML_UniProt_Accession>

</AllerML_UniProt>

<AllerML_EMBL>AF093541</AllerML_EMBL>

<AllerML_EMBL>AAC63045.1</AllerML_EMBL>

<AllerML_GenBank>AF093541</AllerML_GenBank>

<AllerML_DDBJ>AF093541</AllerML_DDBJ>

<AllerML_HSSP>P04776</AllerML_HSSP>

<AllerML_PDB>1UD1</AllerML_PDB>

<AllerML_IntAct>O82580</AllerML_IntAct>

<AllerML_GO>0045735</AllerML_GO>

<AllerML_InterPro>IPR006045</AllerML_InterPro>

<AllerML_InterPro>IPR014710</AllerML_InterPro>

<AllerML_InterPro>IPR006044</AllerML_InterPro>

<AllerML_Gene3D>G3DSA:2.60.120.10</AllerML_Gene3D>

<AllerML_Pfam>PF00190</AllerML_Pfam>

<AllerML_PRINTS>PR00439</AllerML_PRINTS>

<AllerML_PROSITE>PS00305</AllerML_PROSITE>

</AllerML_Cross-references>

Protein Sequence

Scheme 3. Protein section of Ara h 3

<AllerML_Protein>

<AllerML_Protein_Source>UniProt</AllerML_Protein_Source>

<AllerML_UniProt>

<AllerML_UniProt_ID>O82580_ARAHY</AllerML_UniProt_ID>

<AllerML_UniProt_Accession>O82580</AllerML_UniProt_Accession>

</AllerML_UniProt>

<AllerML_Protein_Source>GenBank</AllerML_Protein_Source>

<AllerML_GenBank>

<AllerML_GenBank_Locus>AAC63045</AllerML_GenBank_Locus>

<AllerML_GenBank_Accession>AAC63045</AllerML_GenBank_Accession>

<AllerML_GenBank_Version>AAC63045.1</AllerML_GenBank_Version>

<AllerML_GenBank_GI>3703107</AllerML_GenBank_GI>

<AllerML_Protein_Length>510</AllerML_Protein_Length>

<AllerML_Protein_Sequence>

ISFRQQPEENACQFQRLNAQRPDNRIESEGGYIETWNPNNQEFECAGVAL

SRLVLRRNALRRPFYSNAPQEIFIQQGRGYFGLIFPGCPRHYEEPHTQGR

RSQSQRPPRRLQGEDQSQQQRDSHQKVHRFDEGDLIAVPTGVAFWLYNDH

DTDVVAVSLTDTNNNDNQLDQFPRRFNLAGNTEQEFLRYQQQSRQSRRRS

LPYSPYSPQSQPRQEEREFSPRGQHSRRERAGQEEENEGGNIFSGFTPEF

LEQAFQVDDRQIVQNLRGETESEEEGAIVTVRGGLRILSPDRKRRADEEE

EYDEDEYEYDEEDRRRGRGSRGRGNGIEETICTASAKKNIGRNRSPDIYN

PQAGSLKTANDLNLLILRWLGPSAEYGNLYRNALFVAHYNTNAHSIIYRL

RGRAHVQVVDSNGNRVYDEELQEGHVLVVPQNFAVAGKSQSENFEYVAFK

TDSRPSIANLAGENSVIDNLPEEVVANSYGLQREQARQLKNNNPFKFFVP

PSQQSPRAVA

</AllerML_Protein_Sequence>

</AllerML_GenBank>

</AllerML_Protein>

Epitopes Section

Scheme 4. Epitope section of Ara h 3

<AllerML_Epitopes>

<AllerML_Epitope_Set>

<AllerML_Epitope_Type>IgE</AllerML_Epitope_Type>

<AllerML_Epitope_Position>33-47</AllerML_Epitope_Position>

<AllerML_Epitope_Sequence>IETWNPNNQEFECAG</AllerML_Epitope_Sequence>

<AllerML_Epitope_Comment>

When altered, amino acids shown in red lead to a decrease of IgE binding: IETWNPNNQEFECAG

</AllerML_Epitope_Comment>

<AllerML_Epitope_Position>237-251</AllerML_Epitope_Position>

<AllerML_Epitope_Sequence>GNIFSGFTPEFLEQA</AllerML_Epitope_Sequence>

<AllerML_Epitope_Comment>

When altered, amino acids shown in red lead to a decrease of IgE binding: GNIFSGFTPEFLEQA

</AllerML_Epitope_Comment>

<AllerML_Epitope_Position>276-290</AllerML_Epitope_Position>

<AllerML_Epitope_Sequence>VTVRGGLRILSPDRK</AllerML_Epitope_Sequence>

<AllerML_Epitope_Comment>

When altered, amino acids shown in red lead to a decrease of IgE binding: VTVRGGLRILSPDRK

</AllerML_Epitope_Comment>

<AllerML_Epitope_Position>303-317</AllerML_Epitope_Position>

<AllerML_Epitope_Sequence>DEDEYEYDEEDRRRG</AllerML_Epitope_Sequence>

<AllerML_Epitope_Comment>

When altered, amino acids shown in red lead to a decrease of IgE binding: DEDEYEYDEEDRRRG

</AllerML_Epitope_Comment>

<AllerML_Reference_PubMed>10021462</AllerML_Reference_PubMed>

</AllerML_Epitope_Reference>

</AllerML_Epitope_Set>

</AllerML_Epitopes>

Allergen INSCH Motifs

Scheme 5. AllerML encoding for the INSCH motif section of Ara h 3.

<AllerML_INSCH_Motif>

<AllerML_INSCH_Motif_ID>INSCH011</AllerML_INSCH_Motif_ID>

<AllerML_INSCH_Motif_Sequence>

VNSLKLPQLQDLDLSAEYVVLYEGALLLPHYNSNAHSIVYVTRGEGRVQV

</AllerML_INSCH_Motif_Sequence>

</AllerML_INSCH_Motif>

Allergen MotifMate Motifs

Scheme 6. AllerML encoding for the MotifMate motifs section of Ara h 3.

<AllerML_MotifMate_Motifs>

<AllerML_MotifMate_Motif>

<AllerML_MotifMate_Motif_Position>127-138</AllerML_MotifMate_Motif_Position>

<AllerML_MotifMate_Motif_Sequence>FdeGDlIavPtG</AllerML_MotifMate_Motif_Sequence>

</AllerML_MotifMate_Motif>

<AllerML_MotifMate_Motif>

<AllerML_MotifMate_Motif_Position>65-76</AllerML_MotifMate_Motif_Position>

<AllerML_MotifMate_Motif_Sequence>ApqEiFIqqGrG</AllerML_MotifMate_Motif_Sequence>

</AllerML_MotifMate_Motif>

…

<AllerML_MotifMate_Motif>

<AllerML_MotifMate_Motif_Position>173-178</AllerML_MotifMate_Motif_Position>

<AllerML_MotifMate_Motif_Sequence>FnLaGN</AllerML_MotifMate_Motif_Sequence>

</AllerML_MotifMate_Motif>

…

</AllerML_MotifMate_Motifs>

IgE Cross-reactive Peptides

Scheme 7. AllerML encoding of quantitative data regarding allergen cross-reactivity with peptides for Jun a 1

<AllerML_Epitope_Reference>

<AllerML_Epitope_Sequence>MPRARYGL</AllerML_Epitope_Sequence>

<AllerML_Epitope_PD>0</AllerML_Epitope_PD>

<AllerML_Epitope_RWT>1</AllerML_Epitope_RWT>

</AllerML_Epitope_Reference>

<AllerML_Peptide>

<AllerML_Peptide_Sequence>MPRARYGF</AllerML_Peptide_Sequence>

<AllerML_Peptide_PD>1.19</AllerML_Peptide_PD>

<AllerML_Peptide_RWT>0.74</AllerML_Peptide_RWT>

</AllerML_Peptide>

<AllerML_Peptide>

<AllerML_Peptide_Sequence>MPRARYGM</AllerML_Peptide_Sequence>

<AllerML_Peptide_PD>1.43</AllerML_Peptide_PD>

<AllerML_Peptide_RWT>0.65</AllerML_Peptide_RWT>

</AllerML_Peptide>

<AllerML_Peptide>

<AllerML_Peptide_Sequence>MPRARFGL</AllerML_Peptide_Sequence>

<AllerML_Peptide_PD>1.59</AllerML_Peptide_PD>

<AllerML_Peptide_RWT>1.08</AllerML_Peptide_RWT>

</AllerML_Peptide>