Immunological databases on the web
This presentation is the property of its rightful owner.
Sponsored Links
1 / 32

Immunological databases on the web PowerPoint PPT Presentation


  • 161 Views
  • Uploaded on
  • Presentation posted in: General

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

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.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -

Presentation Transcript


Immunological databases on the web

Immunological databases on the web

Ole Lund

Center for Biological Sequence Analysis

BioCentrum-DTU

Technical University of Denmark

[email protected]


Vaccines have been made for 36 of 400 human pathogens

Vaccines have been made for 36 of >400 human pathogens

+HPV & Rotavirus

Immunological Bioinformatics, The MIT press.


Deaths from infectious diseases in the world in 2002

Deaths from infectious diseases in the world in 2002

www.who.int/entity/whr/2004/annex/topic/en/annex_2_en.pdf


Pathogenic viruses

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.


Immunological databases on the web

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


Databases used for vaccine design

Databases Used for Vaccine Design

  • Sequence databases

    • General

    • Sequences of proteins of the immune system

  • Epitope databases

  • Pathogen centered databases

    • HIV

    • mTB

    • Malaria


Sequence databases

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/


Mhc class i pathway

MHC Class I pathway

Figure by Eric A.J. Reits


Immunological databases on the web

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).


Immunological databases on the web

Expression of HLA is codominant


Immunological databases on the web

Polymorphism and polygeny


Immunological databases on the web

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


Immunological databases on the web

Human Leukocyte antigen (HLA=MHC in humans) polymorphism - alleles

http://www.anthonynolan.com/HIG/index.html


Logos of hla a alleles

Logos of HLA-A alleles

O Lund et al., Immunogenetics. 2004 55:797-810


Clustering of hla alleles

Clustering of HLA alleles

O Lund et al., Immunogenetics. 2004 55:797-810


Databases of sequences of proteins of immune system

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


Immunological databases on the web

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


Hla binding results

HLA Binding Results

KD\PathogenInfluenzaMarburgPoxF. tularensisDengueHantaanLassaWest NileYellow Fever

KD<50424597456759275250

50<KD<500 633942214420214152

KD>50087293863011222935

in progress911464123133

Total201114178761479482153170

  • 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


Elispot assay

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


Influenza peptides positive in elispot

Influenza Peptides positive in ELISPOT

Mingjun Wang et al., submitted


Immunological databases on the web

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


Epitope databases

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/


More epitope databases

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


Prediction of hla binding

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


B cell epitope databases

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/


Mhc class ii pathway

MHC class II pathway

Figure by Eric A.J. Reits


Pathogen centered databases

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/


Reviews

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


Other resources

Other Resources

  • Gene expression data

  • Localization prediction

    • SignalP


Immunological databases on the web

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/


Other predictions at cbs

Other Predictions at CBS

  • Training matrix and neural network methods

  • Training of Gibbs sampler


Links to links

Links to links

  • IEDB’s Links

    • http://immuneepitope.org/hyperlinks.do?dispatch=loadLinks


  • Login