1 / 32

Immunological databases on the web

Immunological databases on the web. Ole Lund Center for Biological Sequence Analysis BioCentrum-DTU Technical University of Denmark lund@cbs.dtu.dk. Vaccines have been made for 36 of >400 human pathogens. +HPV & Rotavirus. Immunological Bioinformatics, The MIT press.

mandy
Download Presentation

Immunological databases on the web

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Immunological databases on the web Ole Lund Center for Biological Sequence Analysis BioCentrum-DTU Technical University of Denmark lund@cbs.dtu.dk

  2. Vaccines have been made for 36 of >400 human pathogens +HPV & Rotavirus Immunological Bioinformatics, The MIT press.

  3. Deaths from infectious diseases in the world in 2002 www.who.int/entity/whr/2004/annex/topic/en/annex_2_en.pdf

  4. Pathogenic Viruses 1st column: log10 of the number of deaths caused by the pathogen per year2nd column: DNA Advisory Committee (RAC) classificationDNA Advisory Committee guidelines [RAC, 2002] which includes those biological agents known to infect humans, as well as selected animal agents that may pose theoretical risks if inoculated into humans. RAC divides pathogens intofour classes.Risk group 1 (RG1). Agents that are not associated with disease in healthy adult humansRisk group 2 (RG2). Agents that are associated with human disease which is rarely serious and for which preventive or therapeutic interventions are often availableRisk group 3 (RG3). Agents that are associated with serious or lethal human disease for which preventive or therapeutic interventions may be available (high individual risk but low community risk)Risk group 4 (RG4). Agents that are likely to cause serious or lethal human disease for which preventive or therapeutic interventions are not usually available (high individual risk and high community risk)3rd column: CDC/NIAID bioterror classificationclassification of the pathogens according to the Centers for Disease Control and Prevention (CDC) bioterror categories A–C, where category A pathogens are considered the worst bioterror threats4th column: Vaccines availableA letter indicating the type of vaccine if one is available (A: acellular/adsorbet; C: conjugate; I: inactivated; L: live; P: polysaccharide; R: recombinant; S staphage lysate; T: toxoid). Lower case indicates that the vaccine is released as an investigational new drug (IND)).5th column: G: Complete genome is sequenced Data derived from /www.cbs.dtu.dk/databases/Dodo.

  5. Need for new vaccine technologies • The classical way of making vaccines have in many cases been tried for the pathogens for which no vaccines exist • Need for new ways for making vaccines

  6. Databases Used for Vaccine Design • Sequence databases • General • Sequences of proteins of the immune system • Epitope databases • Pathogen centered databases • HIV • mTB • Malaria

  7. Sequence Databases • Used to study sequence variability of microbes • Sequence conservation • Positive/negative selection • Examples • Swissprot http://expasy.org/sprot/ • GenBank http://www.ncbi.nlm.nih.gov/Genbank/

  8. MHC Class I pathway Figure by Eric A.J. Reits

  9. The binding of an immunodominant 9-mer Vaccinia CTL epitope, HRP2 (KVDDTFYYV) to HLA-A*0201. Position 2 and 9 of the epitopes are buried deeply in the HLA class I molecule. Figure by Anne Mølgaard, peptide (KVDDTFYYV) used as vaccine by Snyder et al. J Virol 78, 7052-60 (2004).

  10. Expression of HLA is codominant

  11. Polymorphism and polygeny

  12. The MHC gene region http://www.ncbi.nlm.nih.gov/mhc/MHC.fcgi?cmd=init&user_id=0&probe_id=0&source_id=0&locus_id=0&locus_group=0&proto_id=0&banner=1&kit_id=0&graphview=0

  13. Human Leukocyte antigen (HLA=MHC in humans) polymorphism - alleles http://www.anthonynolan.com/HIG/index.html

  14. Logos of HLA-A alleles O Lund et al., Immunogenetics. 2004 55:797-810

  15. Clustering of HLA alleles O Lund et al., Immunogenetics. 2004 55:797-810

  16. Databases of Sequences of Proteins of Immune system • Used to study variability of the human genome • Anthony Nolan Database (IMGT/HLA sequences) • http://www.anthonynolan.com/HIG/ • IMmunoGeneTics HLA (IMGT/HLA) database • Sequences of HLA, antibody and other molecules • http://imgt.cines.fr/ • dbMHC • Clinical data and sequences related to the immune system • http://www.ncbi.nlm.nih.gov/gv/mhc/main.cgi?cmd=init

  17. Peptide-MHC complex Incubation Development Determination of peptide-HLA binding • Step I: Folding of MHC class I molecules in solution b2m Heavy chain peptide • Step II: Detection of de novo folded MHC class I molecules by ELISA C Sylvester-Hvid et al., Tissue Antigens. 2002 59:251-8

  18. HLA Binding Results KD\PathogenInfluenza Marburg Pox F. tularensis Dengue Hantaan Lassa West Nile Yellow Fever KD<50 42 45 97 45 67 59 27 52 50 50<KD<500 63 39 42 21 44 20 21 41 52 KD>500 87 29 38 6 30 11 22 29 35 in progress 9 1 1 4 6 4 12 31 33 Total 201 114 178 76 147 94 82 153 170 • 1215 peptides received • 1114 tested for binding • 827 (74%) bind with KD better than 500nM • 484 (43%) bind with KD better han 50 nM Søren Buus Lab

  19. ELISPOT assay • Measure number of white blood cells that in vitro produce interferon-g in response to a peptide • A positive result means that the immune system has earlier reacted to the peptide (during a response to a vaccine/natural infection) SLFNTVATL SLFNTVATL SLFNTVATL SLFNTVATL SLFNTVATL SLFNTVATL Two spots

  20. Influenza Peptides positive in ELISPOT Mingjun Wang et al., submitted

  21. Peters B, et al. Immunogenetics. 2005 57:326-36, PLoS Biol. 2005 3:e91.

  22. Epitope Databases • Used to find regions that can be recognized by the immune system • General Epitope Databases • IEDB General epitope database • http://immuneepitope.org/home.do • AntiJen (MHC Ligand, TCR-MHC Complexes, T Cell Epitope, TAP , B Cell Epitope molecules and immunological Protein-Protein interactions) • http://www.jenner.ac.uk/AntiJen/ • FIMM (MHC, antigens, epitopes, and diseases) • http://research.i2r.a-star.edu.sg/fimm/

  23. More Epitope Databases • SYFPEITHI • Natural ligands: sequences of peptides eluded from MHC molecules on the surface of cells • http://www.syfpeithi.de/ • MHCBN: Immune related databases and predictors • http://www.imtech.res.in/raghava/mhcbn/ • http://bioinformatics.uams.edu/mirror/mhcbn/ • HLA Ligand/Motif Database: Discontinued • MHCPep: Static since 1998, replaced by FIMM

  24. Prediction of HLA binding • Many methods available, including: • bimas, syfpeithi, Hlaligand, libscore, mapppB, mapppS,mhcpred, netmhc, pepdist, predbalbc, predep, rankpep, svmhc • See links at: • http://immuneepitope.org/hyperlinks.do?dispatch=loadLinks • Recent benchmark: • http://mhcbindingpredictions.immuneepitope.org/internal_allele.html

  25. B cell Epitope Databases • Linear • IEDB, Bcipep, Jenner, FIMM, BepiPred • HIV specific database • http://www.hiv.lanl.gov/content/immunology/ab_search • Conformational • CED: Conformational B cell epitopes • http://web.kuicr.kyoto-u.ac.jp/~ced/

  26. MHC class II pathway Figure by Eric A.J. Reits

  27. Pathogen Centered Databases • HIV • http://www.hiv.lanl.gov/content/index • Influenza • http://www.flu.lanl.gov/ • Tuberculosis • http://www.sanger.ac.uk/Projects/M_tuberculosis/ • POX • http://www.poxvirus.org/

  28. Reviews • Tong JC, Tan TW, Ranganathan S. Methods and protocols for prediction of immunogenic epitopes. Brief Bioinform. 2006 Oct 31 • Web based Tools for Vaccine Design (Lund et al, 2002) • http://www.cbs.dtu.dk/researchgroups/immunology/webreview.html

  29. Other Resources • Gene expression data • Localization prediction • SignalP

  30. Immunological resources at CBS • Web servers • CTL epitopes • http://www.cbs.dtu.dk/services/NetCTL/ • MHC binding • http://www.cbs.dtu.dk/services/NetMHC/ • http://www.cbs.dtu.dk/services/NetMHCII/ • http://www.cbs.dtu.dk/services/NetMHCpan/ • Proteasome processing • http://www.cbs.dtu.dk/services/NetChop-3.0/ • B-cell epitopes • http://www.cbs.dtu.dk/services/BepiPred/ • http://www.cbs.dtu.dk/services/DiscoTope/ • Plotting of epitopes relative to reference sequence • http://www.cbs.dtu.dk/services/EpiPlot-1.0/ • Analysis of human immunoglobulin VDJ recombination • http://www.cbs.dtu.dk/services/VDJsolver/ • Geno-pheno type association based mapping of binding sites • http://www.cbs.dtu.dk/services/SigniSite/ • PhD/master course in Immunological Bioinformatics, June, 2008 • http://www.cbs.dtu.dk/courses/27685.imm/

  31. Other Predictions at CBS • Training matrix and neural network methods • Training of Gibbs sampler

  32. Links to links • IEDB’s Links • http://immuneepitope.org/hyperlinks.do?dispatch=loadLinks

More Related