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Peanut Bioinformatics: Tools and Applications for Developing More Effective Immunotherapies for Peanut Allergy and Improving Food Safety

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Agricultural Bioinformatics

Abstract

Advanced tools of bioinformatics have been employed to assess the features critically required for allergenicity and cross-reactivity. A tremendous accumulation of data on plant proteins in recent years has made it possible to classify allergens in different protein families, with most food allergens grouped into four protein families. These families can be grouped together into superfamilies by comparing sequences and related structures. This information makes it possible to identify a wide range of related proteins that may result in the development of multiple food allergies that initiate the development of cross-reactive antibodies in susceptible individuals. Since peanut allergies are responsible for most episodes of food-induced anaphylaxis, a detailed immunological and molecular characterization of these allergenic components is essential to develop suitable immunotherapies. This would also allow us to screen transgenic plants for the possible development of allergens similar to those allergenic components in peanuts. Homology modeling in combination with residue-wise solvent accessibility of monomers and biological assemblies of allergens certainly gives valuable information about antigenic determinants on protein allergens. Through this review, we discuss the applications of bioinformatics tools toward the mitigation of peanut allergy.

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Abbreviations

BLAST:

Basic Local Alignment Search Tool

DNA:

Deoxyribonucleic acid

FARRP:

Food Allergy Research and Resource Program

FASTA:

Fast alignment

GM crops:

Genetically modified crops

IgE:

Immunoglobulin E

IUIS:

International Union of Immunological Societies

kDa:

Kilodalton

MW:

Molecular weight

ORF:

Open reading frames

PR:

Pathogenesis-related genes

SDAP:

Structural Database of Allergenic Proteins

URL:

Uniform resource locator

References

  • Aalberse RC (2000) Structural biology of allergens. J Allergy Clin Immunol 106:228–238

    Article  CAS  PubMed  Google Scholar 

  • Barre A, Sordet C, Culerrier R, Rance F, Didier A, Rouge P (2008) Vicilin allergens of peanut and tree nuts (walnut, hazelnut and cashew nut) share structurally related IgE-binding epitopes. Mol Immunol 45(5):1231–1240

    Article  CAS  PubMed  Google Scholar 

  • Berger B, Wilson DB, Wolf E, Tonchev T, Milla M, Kim PS (1995) Predicting coiled coils by use of pairwise residue correlations. Proc Natl Acad Sci U S A 92(18):8259–8263

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Bock SA, Muñoz-Furlong A, Sampson HA (2001) Fatalities due to anaphylactic reactions to foods. J Allergy Clin Immunol 107(1):191–193

    Article  CAS  PubMed  Google Scholar 

  • Boldt A, Fortunato D, Conti A, Petersen A, Ballmer-Weber B, Lepp U, Reese G, Becker WM (2005) Analysis of the composition of an immunoglobulin E reactive high molecular weight protein complex of peanut extract containing Ara h1 and Ara h3/4. Proteomics 5(3):675–686

    Article  CAS  PubMed  Google Scholar 

  • Bruinsma J (2009) The resource outlook to 2050: by how much do land, water, and crop yields need to increase by 2050? FAO expert meeting on ‘How to feed the world in 2050’. FAO, Rome, pp 24–26

    Google Scholar 

  • Brusic V, Petrovsky N, Gendel SM, Millot M, Gigonzac O, Stelman SJ (2003) Computational tools for the study of allergens. Allergy 58(11):1083–1092

    Article  CAS  PubMed  Google Scholar 

  • Burks W (2003) Peanut allergy: a growing phenomenon. J Clin Invest 111(7):950–952. doi:10.1172/JCI18233

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Burks AW, Cockrell G, Stanley JS, Helm RM, Bannon GA (1995a) Recombinant peanut allergen Ara h I expression and IgE binding in patients with peanut hypersensitivity. J Clin Invest 96(4):1715–1721

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Burks AW, Cockrell G, Stanley JS, Helm RM, Bannon GA (1995b) Recombinant peanut allergen Ara h I expression and IgE binding in patients with peanut hypersensitivity. J Clin Invest 96(4):1715–1721. doi:10.1172/JCI118216

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Burks AW, Sampson HA, Bannon GA (1998) Peanut allergens. Allergy 53(8):725–730. doi:10.1111/j.1398-9995.1998.tb03967.x

    Article  CAS  PubMed  Google Scholar 

  • Buschmann L, Petersen A, Schlaak M, Becker WM (1996) Reinvestigation of the major peanut allergen Ara h 1 on molecular level. Monogr Allergy 32:92–98

    CAS  PubMed  Google Scholar 

  • Chandra RK (2003) Food hypersensitivity and allergic disease: a new threat in India. Indian Pediatr 40(2):99–101

    CAS  PubMed  Google Scholar 

  • Chatel JM, Bernard H, Orson FM (2003) Isolation and characterization of two complete Ara h 2 isoforms cDNA. Int Arch Allergy Immunol 131(1):14–18

    Article  CAS  PubMed  Google Scholar 

  • Christensen LH, Riise E, Bang L, Zhang C, Lund K (2010) Isoallergen variations contribute to the overall complexity of effector cell degranulation: effect mediated through differentiated IgE affinity. J Immunol 184(9):4966–4972. doi:10.4049/jimmunol.0904038

    Article  CAS  PubMed  Google Scholar 

  • Cuff JA, Barton GJ (2000) Application of multiple sequence alignment profiles to improve protein secondary structure prediction. Proteins 40(3):502–511

    Article  CAS  PubMed  Google Scholar 

  • Ferreira F, Hawranek T, Gruber P, Wopfner N, Mari A (2004) Allergic cross-reactivity: from gene to the clinic. Allergy 59(3):243–267. doi:10.1046/j.1398-9995.2003.00407.x

    Article  CAS  PubMed  Google Scholar 

  • Gregory PJ, George TS (2011) Feeding nine billion: the challenge to sustainable crop production. J Exp Bot 62(15):5233–5239

    Article  CAS  PubMed  Google Scholar 

  • Grundy J, Matthews S, Bateman B, Dean T, Arshad SH (2002) Rising prevalence of allergy to peanut in children: data from 2 sequential cohorts. J Allergy Clin Immunol 110(5):784–789

    Article  PubMed  Google Scholar 

  • Hales BJ, Bosco A, Mills KL, Hazell LA, Loh R, Holt PG, Thomas WR (2004) Isoforms of the major peanut allergen ara h 2: IgE binding in children with peanut allergy. Int Arch Allergy Immunol 135(2):101–107

    Article  CAS  PubMed  Google Scholar 

  • Helm RM, Burks AW (2000) Mechanisms of food allergy. Curr Opin Immunol 12(6):647–653

    Article  CAS  PubMed  Google Scholar 

  • Hileman RE, Silvanovich A, Goodman RE, Rice EA, Holleschak G, Astwood JD, Hefle SL (2002) Bioinformatic methods for allergenicity assessment using a comprehensive allergen database. Int Arch Allergy Immunol 128(4):280–291. doi:10.1159/000063861

    Article  CAS  PubMed  Google Scholar 

  • Hoffman M, Arnoldi C, Chuang I (2005) The clinical bioinformatics ontology: a curated semantic network utilizing RefSeq information. Pac Symp Biocomput:139–150

    Google Scholar 

  • Ivanciuc O, Mathura V, Midoro-Horiuti T, Braun W, Goldblum RM, Schein CH (2003) Detecting potential IgE-reactive sites on food proteins using a sequence and structure database, SDAP-food. J Agric Food Chem 51(16):4830–4837

    Article  CAS  PubMed  Google Scholar 

  • Ivanciuc O, Gendel SM, Power TD, Schein CH, Braun W (2011) AllerML: markup language for allergens. Regul Toxicol Pharmacol 60(1):151–160. doi:10.1016/j.yrtph.2011.03.006

    Article  PubMed Central  PubMed  Google Scholar 

  • Kleber-Janke T, Crameri R, Appenzeller U, Schlaak M, Becker WM (1999) Selective cloning of peanut allergens, including profilin and 2S albumins, by phage display technology. Int Arch Allergy Immunol 119(4):265–274

    Article  CAS  PubMed  Google Scholar 

  • Koh LYJ, Brusic V, Krishnan SPT, Seah SH, Tan PTJ, Khan AM, Li ML (2004) BioWare: a framework for bioinformatics data retrieval, annotation, and publishing. In: Proceedings of the symposium model analysis and simulation of computer and telecommunication systems. The University of Sheffield, Sheffield, 25–29 July 2004

    Google Scholar 

  • Koppelman SJ, Vlooswijk RA, Knippels LM, Hessing M, Knol EF, van Reijsen FC, Bruijnzeel-Koomen CA (2001) Quantification of major peanut allergens Ara h 1 and Ara h 2 in the peanut varieties Runner, Spanish, Virginia and Valencia, bred in different parts of the world. Allergy 56(2):132–137

    Article  CAS  PubMed  Google Scholar 

  • Koppelman SJ, Knol EF, Vlooswijk RA, Wensing M, Knulst AC, Hefle SL, Gruppen H, Piersma S (2003) Peanut allergens Ara h 3: isolation from peanut and biochemical characterisation. Allergy 58(11):1144–1151

    Article  CAS  PubMed  Google Scholar 

  • Krause S, Reese G, Randow S, Zennaro D, Quaratino D, Palazzo P, Ciardiello MA, Petersen A, Becker WM, Mari A (2009) Lipid transfer protein (Ara h 9) as a new peanut allergen relevant for a Mediterranean allergic population. J Allergy Clin Immunol 124(4):771–778

    Article  CAS  PubMed  Google Scholar 

  • Lupas A (1996) Prediction and the analysis of coiled-coil structures. Methods Enzymol 266:513–525

    Article  CAS  PubMed  Google Scholar 

  • Matsuda T, Nakamura R (1993) Molecular structure and immunological properties of food allergens. Trends Food Sci Technol 4(9):289–293. doi:10.1016/0924-2244(93)90072-I

    Article  CAS  Google Scholar 

  • Midoro-Horiuti T, Goldblum RM, Brooks EG (2001) Identification of mutations in the genes for the pollen allergens of eastern red cedar (Juniperus virginiana). Clin Exp Allergy 31(5):771–778

    Article  CAS  PubMed  Google Scholar 

  • Mills EN, Jenkins J, Marigheto N, Belton PS, Gunning AP, Morris VJ (2002) Allergens of the cupin superfamily. Biochem Soc Trans 30(Pt 6):925–929

    CAS  PubMed  Google Scholar 

  • Mills EN, Jenkins JA, Alcocer MJ, Shewry PR (2004) Structural, biological, and evolutionary relationships of plant food allergens sensitizing via the gastrointestinal tract. Crit Rev Food Sci Nutr 44(5):379–407

    Article  CAS  PubMed  Google Scholar 

  • Mishra A, Gaur S, Singh BP, Arora N (2012) In silico assessment of the potential allergenicity of transgenes used for the development of GM food crops. Food Chem Toxicol 50(5):1334–1339

    Article  CAS  PubMed  Google Scholar 

  • Mittag D, Akkerdaas J, Ballmer-Weber BK, Vogel L, Wensing M, Becker WM, Koppelman SJ, Knulst AC, Helbling A, Hefle SL, Van Ree R, Vieths S (2004) Ara h 8, a Bet v 1-homologous allergen from peanut, is a major allergen in patients with combined birch pollen and peanut allergy. J Allergy Clin Immunol 114(6):1410–1417

    Article  CAS  PubMed  Google Scholar 

  • Oezguen N, Zhou B, Negi SS, Ivanciuc O, Schein CH, Labesse G, Braun W (2008) Comprehensive 3D-modeling of allergenic proteins and amino acid composition of potential conformational IgE epitopes. Mol Immunol 45(14):3740–3747. doi:10.1016/j.molimm.2008.05.026

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ortolani C, Ispano M, Scibilia J, Pastorello EA (2001) Introducing chemists to food allergy. Allergy 56(67):5–8

    Article  PubMed  Google Scholar 

  • Piersma SR, Gaspari M, Hefle SL, Koppelman SJ (2005) Proteolytic processing of the peanut allergen Ara h 3. Mol Nutr Food Res 49(8):744–755

    Article  CAS  PubMed  Google Scholar 

  • Pons L, Olszewski A, Gueant JL (1998) Characterization of the oligomeric behavior of a 16.5 kDa peanut oleosin by chromatography and electrophoresis of the iodinated form. J Chromatogr B Biomed Sci Appl 706(1):131–140

    Article  CAS  PubMed  Google Scholar 

  • Pons L, Chery C, Romano A, Namour F, Artesan MC, Guéant JL (2002) The 18 kDa peanut oleosin is a candidate allergen for IgE-mediated reactions to peanuts. Allergy 57(Suppl 72):88–93

    Article  PubMed  Google Scholar 

  • Power TD, Ivanciuc O, Schein CH, Braun W (2013) Assessment of 3D models for allergen research. Proteins 81(4):545–554. doi:10.1002/prot.24239

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Rabjohn P, Helm EM, Stanle JS, West CM, Sampson HA, Burks AW, Bannon GA (1999) Molecular cloning and epitope analysis of the peanut allergen Ara h 3. J Clin Invest 103(4):535–542

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Restani P, Ballabio C, Corsini E, Fiocchi A, Isoardi P, Magni C, Poiesi C, Terracciano L, Duranti M (2005) Identification of the basic subunit of Ara h 3 as the major allergen in a group of children allergic to peanuts. Ann Allergy Asthma Immunol 94(2):262–266

    Article  CAS  PubMed  Google Scholar 

  • Riaz T, Hor HL, Krishnan A, Tang F, Li KB (2005) WebAllergen: a web server for predicting allergenic proteins. Bioinformatics. 21(10):2570–2571

    Google Scholar 

  • Sampson HA (2004) Update on food allergy. J Allergy Clin Immunol 113(5):805–819

    Article  CAS  PubMed  Google Scholar 

  • Schein CH, Ivanciuc O, Braun W (2007) Bioinformatics approaches to classifying allergens and predicting cross-reactivity. Immunol Allergy Clin North Am 27(1):1–27

    Article  PubMed Central  PubMed  Google Scholar 

  • Scheurer S, Son DY, Boehm M, Karamloo F, Franke S, Hoffmann A, Haustein D, Vieths S (1999) Cross-reactivity and epitope analysis of Pru a 1, the major cherry allergen. Mol Immunol 36(3):155–167

    Article  CAS  PubMed  Google Scholar 

  • Sharma P, Singh AK, Singh BP, Gaur SN, Arora N (2011) Allergenicity assessment of osmotin, a pathogenesis-related protein, used for transgenic crops. J Agric Food Chem 59(18):9990–9995. doi:10.1021/jf202265d

    Article  CAS  PubMed  Google Scholar 

  • Shin DS, Compadre CM, Maleki SJ, Kopper RA, Sampson H, Huang SK, Burks AW, Bannon GA (1998) Biochemical and structural analysis of the IgE binding sites on ara h1, an abundant and highly allergenic peanut protein. J Biol Chem 273(22):13753–13759

    Article  CAS  PubMed  Google Scholar 

  • Sicherer SH, Munoz-Furlong A, Sampson HA (2003) Prevalence of peanut and tree nut allergy in the United States determined by means of a random digit dial telephone survey: a 5-year follow up study. J Allergy Clin Immunol 112(6):1203–1207

    Article  PubMed  Google Scholar 

  • Silvanovich A, Bannon G, McClain S (2009) The use of E-scores to determine the quality of protein alignments. Regul Toxicol Pharmacol 54(3l):S26–S31. doi:10.1016/j.yrtph.2009.02.004

    Article  CAS  PubMed  Google Scholar 

  • Simons FER (2008) Emergency treatment of anaphylaxis. BMJ 336:1141–1142. doi:10.1136/bmj.39547.452153.80

    Article  PubMed Central  PubMed  Google Scholar 

  • Singh H, Raghava GP (2001) ProPred: prediction of HLA-DR binding sites. Bioinformatics 17(12):1236–1237

    Article  CAS  PubMed  Google Scholar 

  • Singh AK, Mehta AK, Sridhara S, Gaur SN, Singh BP, Sarma PU, Arora N (2006) Allergenicity assessment of transgenic mustard (Brassica juncea) expressing bacterial codA gene. Allergy 61(4):491–497

    Article  CAS  PubMed  Google Scholar 

  • Sonika R, Anil J (2013) Molecular modelling: a new scaffold for drug design. Int J Pharm Pharm Sci 5(1):5–8

    Google Scholar 

  • Stadler MB, Stadler B (2003) Allergenicity prediction by protein sequence. FASEB J 17(9):1141–1143

    CAS  PubMed  Google Scholar 

  • Viquez OM, Konan KN, Dodo HW (2003) Structure and organization of the genomic clone of a major peanut allergen gene. Ara h 1. Mol Immunol 40(9):565–571

    Article  CAS  PubMed  Google Scholar 

  • Vrtala S (2008) From allergen genes to new forms of allergy diagnosis and treatment. Allergy 63(3):299–309. doi:10.1111/j.1398-9995.2007.01609.x

    Article  CAS  PubMed  Google Scholar 

  • Wichers HJ, De Beijer T, Savelkoul HF, Van Amerongen A (2004) The major peanut allergen Ara h 1 and its cleaved-off N-terminal peptide; possible implications for peanut allergen detection. J Agric Food Chem 52(15):4903–4907

    Article  CAS  PubMed  Google Scholar 

  • Woods RK, Stoney RM, Raven J, Walters EH, Abramson M, Thien FC (2002) Reported adverse food reactions overestimate true food allergy in the community. Eur J Clin Nutr 56(1):31–36

    Article  CAS  PubMed  Google Scholar 

  • Yang CY, Wu JD, Wu CH (2000) Sequence analysis of the first complete cDNA clone encoding an American cockroach Per a 1 allergen. Biochim Biophys Acta 1517(1):153–158

    Article  CAS  PubMed  Google Scholar 

  • Zhang ZH, Koh JL, Zhang GL, Choo KH, Tammi MT, Tong JC (2007) AllerTool: a web server for predicting allergenicity and allergic cross-reactivity in proteins. Bioinformatics. 23(4):504–506

    Google Scholar 

  • Zhang ZH, Tan SC, Koh JL, Falus A, Brusic V (2006) ALLERDB database and integrated bioinformatic tools for assessment of allergenicity and allergic cross-reactivity. Cell Immunol 244(2):90–96

    Article  CAS  PubMed  Google Scholar 

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Acknowledgment

Venkatesh K acknowledges CSIR, New Delhi, for the financial assistance.

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Correspondence to Ramesh Katam .

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Kandula, V., Gottschalk, V.A., Katam, R., Anupalli, R.R. (2014). Peanut Bioinformatics: Tools and Applications for Developing More Effective Immunotherapies for Peanut Allergy and Improving Food Safety. In: P.B., K., Bandopadhyay, R., Suravajhala, P. (eds) Agricultural Bioinformatics. Springer, New Delhi. https://doi.org/10.1007/978-81-322-1880-7_7

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