Immunoinformatics: bioinformatic strategies for better understanding of immune function

271 Pages·2003·2.664 MB·English

by  Novartis Foundation

Immunoinformatics:BioinformaticStrategiesforBetterUnderstandingofImmuneFunction:
NovartisFoundationSymposium254.Volume254
EditedbyGregoryBockandJamieGoode
CopyrightNovartisFoundation2003.ISBN:0-470-85356-5
IMMUNOINFORMATICS:
BIOINFORMATIC
STRATEGIES FOR BETTER
UNDERSTANDING OF
IMMUNE FUNCTION
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Novartis Foundation Symposium 254
IMMUNOINFORMATICS:
BIOINFORMATIC
STRATEGIES FOR BETTER
UNDERSTANDING OF
IMMUNE FUNCTION
2003
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NovartisFoundationSymposium254
viii+263pages,32¢gures,11tables
LibraryofCongressCataloging-in-PublicationData
Immunoformatics:bioinformaticstrategiesforbetterunderstandingofimmunefunction
/[editors,GregoryBockandJamieGoode].
p.cm.^(NovartisFoundationsymposium;254)
Includesbibliographicalreferencesandindex.
ISBN0-470-85356-5(alk.paper)
1.Immunoinformatics. I.Bock,Gregory. II.Goode,Jamie, III.Series.
QR182.2.I46I462003
571.9’6^dc22 2003057599
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Contents
SymposiumonImmunoinformatics:bioinformaticstrategiesforbetterunderstandingofimmune
function,heldattheNovartisFoundation,London,8^10October2002
Editors:GregoryBock(Organizer)andJamieGoode
ThissymposiumisbasedonaproposalmadebyNikolaiPetrovskyandVladimirBrusic
Hans-GeorgRammensee Chair’sintroduction 1
VladimirBrusicandNikolaiPetrovsky Immunoinformatics(cid:1)thenewkidin
town 3
Discussion 13
NikolaiPetrovsky,DiegoSilvaandVladimirBrusic Thefuturefor
computationalmodellingandpredictionsystemsinclinicalimmunology 23
Discussion 33
KamalakarGulukota Immunoinformaticsinpersonalizedmedicine 43
Discussion 50
AnneS.DeGrootandWilliamMartin Fromimmunometovaccine:
epitopemappingandvaccinedesigntools 57
Discussion 72
HanahMargalitandYaelAltuvia InsightsfromMHC-boundpeptides 77
Discussion 91
GeneraldiscussionI 98
DarrenR.Flower,HelenMcSparron,MartinJ.Blythe,ChristiannaZygouri,
DeborahTaylor,PingpingGuan,ShouzhanWan,PeterCoveney,
ValerieWalshe,PersephoneBorrowandIriniA.Doytchinova Computational
vaccinology:quantitativeapproaches 102
Discussion 120
Marie-PauleLefranc IMGT,theinternationalImMunoGeneTicsinformation
system1,http://imgt.cines.fr 126
Discussion 135
v
vi CONTENTS
StefanStevanovic¤,ClaudiaLemmel,MaikH(cid:1)ntschelandUteEberle
Generatingdatafordatabases(cid:1)thepeptiderepertoireofHLAmolecules 143
Discussion 155
StevenG.E.Marsh HLAnomenclatureandtheIMGT/HLASequence
Database 165
Discussion 173
ChristianSch˛nbach Fromimmunogeneticstoimmunomics:functional
prospectingofgenesandtranscripts 177
Discussion 189
DominikWodarz MathematicalmodelsofHIVandtheimmunesystem 193
Discussion 207
GeneraldiscussionII 216
StephanBeck Immunogenomics:towardsadigitalimmunesystem 223
Discussion 230
PaulKellam,RiaHolzerlandt,EvaGramoustianou,RichardJennerand
AntoniaKwan Viralbioinformatics:computationalviewsofhostand
pathogen 234
Discussion 247
Finalgeneraldiscussion 250
Hans-GeorgRammensee Closingremarks 253
Indexofcontributors 254
Subjectindex 256
Participants
StephanBeck WellcomeTrustSangerInstitute,WellcomeTrustGenome
Campus,Hinxton,CambridgeCB101SA,UK
MassimoBernaschi IAC‘MauroPicone’(C.N.R.),VialedelPoliclinico137,
I-00161Rome,Italy
FranciscoBorras-Cuesta DepartmentofInternalMedicine,Schoolof
Medicine,UniversityofNavarra,Irunlarrea1,31008Pamplona,Spain
VladimirBrusic KnowledgeDiscoveryDepartment,InstituteforInfocomm
Research,21HengMuiKengTerrace,119613,Singapore
AnnieDeGroot BrownUniversity,TB/HIVResearchLaboratory,
BrownUniversity,BoxG,Providence,RI 02912 ,USA
CharlesDeLisi CenterforAdvancedGenomicTechnology,BostonUniversity,
1stFloor,Room102,48CummingtonStreet,Boston,MA02215,USA
DarrenR.Flower BioinformaticsGroup,TheEdwardJennerInstitutefor
VaccineResearch,Compton,Newbury,BerkshireRG207NN,UK
KamalakarGulukota gvkbioSciencesPrivateLimited,#210,‘MyHome
Tycoon’,6-3-1192,Begumpet,Hyderabad500016, India
PaulKellam VirusGenomicsandBioinformaticsGroup,Departmentof
Immunology&MolecularPathologyandDepartmentofVirology,
WindeyerInstituteofMedicalSciences,WindeyerBuilding,46ClevelandStreet,
LondonW1T4JF,UK
CanKesmir DepartmentofTheoreticalBiology,UtrechtUniversity,
Padualaan8,3584CH,Utrecht,Netherlands
Marie-PauleLefranc IMGT,theinternationalImMunoGeneTicsinformation
system1,Universite¤ MontpellierII,Laboratoired’ImmunoGe¤ne¤tique
vii
viii PARTICIPANTS
Mole¤culaire,LIGM,UPRCNRS1142,InstitutdeGe¤ne¤tiqueHumaine,
141ruedelaCardonille,F-34396MontpellierCedex5,France
TimLittlejohn Biolateral,POBoxA51,En¢eldSouth,NSW,2133,Australia
TerryLybrand DepartmentofChemistry,VanderbiltUniversity,Centerfor
StructuralBiology,5142Biosci/MRBIII,Nashville,TN37232-8725,USA
HanahMargalit DepartmentofMolecularGenetics&Biotechnology,
HebrewUniversityHadassahMedicalSchool,POBox12272,EinKerem,
Jerusalem91120,Israel
StevenG.E.Marsh AnthonyNolanResearchInstitute,RoyalFreeHospital,
PondStreet,Hampstead,LondonNW32QG,UK
AlanS.Perelson MSK710,T-10,TheoreticalDivision,LosAlamosNational
Laboratory,POBox1663,LosAlamos,NM87545,USA
NikolaiPetrovsky CanberraHospital,AutoimmunityResearchUnit,
POBox11,2606Woden,ACT,Australia
Hans-GeorgRammensee(Chair) Interfakult(cid:1)resInstitutfˇrZellbiologie,
AbteilungImmunologie,Universit(cid:1)tTˇbingen,AufderMorgenstelle15,
D-72076Tˇbingen,Germany
LukasRoth NovartisPharma,TransplantationResearch,WSJ-386.9.26,
CH-4002Basel,Switzerland
DiegoSilva(NovartisFoundationBursar) AutoimmunityResearchUnit,
TheCanberraHospital,Canberra,ACT2065,Australia
ChristianSch˛nbach RIKENGenomicSciencesCenter,Biomedical
KnowledgeDiscoveryTeam,E-209,1-7-22Suehiro-cho,Tsurumi,
Yokohama,Kanagawa,230-0045,Japan
StefanStevanovic¤ Interfakult(cid:1)resInstitutfˇrZellbiologie,Abteilung
Immunologie,Universit(cid:1)tTˇbingen,AufderMorgenstelle15,D-72076
Tˇbingen,Germany
EdgarWingender GBF-Braunschweig,GenomeAnalysis,MascheroderWeg1,
D-38124Braunschweig,Germany
DominikWodarz FredHutchinsonCancerResearchCenter,1100Fairview
AvenueNorth,MP-655,Seattle,WA98109-1024,USA
Immunoinformatics:BioinformaticStrategiesforBetterUnderstandingofImmuneFunction:
NovartisFoundationSymposium254.Volume254
EditedbyGregoryBockandJamieGoode
CopyrightNovartisFoundation2003.ISBN:0-470-85356-5
Chair’s introduction
Hans-GeorgRammensee
Interfakult(cid:1)res Institut fˇr Zellbiologie, Abteilung Immunologie, Universit(cid:1)t Tˇbingen,
AufderMorgenstelle15,D-72076Tˇbingen,Germany
This is a timely meeting. Although Vladimir Brusic’s opening paper is titled
‘Immunoinformatics(cid:1)thenewkidintown’,thisisactuallya¢eldthathasbeen
aroundforawhile,althoughunderadi¡erentname.Atleastpartofwhatweknow
of as immunoinformatics was previously known as ‘theoretical immunology’.
There was an important meeting on this subject in New Mexico in 1988, which
resultedinatwo-volumebook(Perelson1988).
Thesubjectofimmunoinformaticsasweseeittodaycanroughlybedividedinto
threeareas:the hard, thesoftand thesemi-soft.Achallengefor this group isto
decidebytheendofthemeetingwhetherIamcorrectwiththisclassi¢cation!Let
mestartwithadescriptionofhardimmunoinformatics.ThiscontainswhatIwill
call‘hardfacts’:DNA,RNAandpeptidesequencesthatwecanwritedown.This
partofimmunoinformaticscanbeusedforagrowingnumberofapplicationsthat
will have a direct impact on biomedicine. One example is peptides for T cell
recognition, working out which peptides are recognized by the T cell receptor
during an infection. Hard immunoinformatics is one of the newest parts of the
¢eld and is only a few years old. The amount of information in this realm is
growingexponentially.15yearsagoallwehadwereafewDNAsequences,but
nowwehaveatremendousamountofdatastoredinvariousdatabases.
Semi-softimmunoinformaticscomprisesalgorithmsandparameterswhichwe
usetocreatethe‘hard’part.ItincludesallthepredictionalgorithmsweuseinDNA
or peptide sequences: we say that a particular DNA sequence will interact with
some regulatory protein or this piece of protein sequence will interact with the
MHC. The one hallmark of this semi-soft area is that all the predictions can be
tested accurately. You can predict the peptide sequence to bind to HLA, and
thengo onandtestwhether thisistrue.Some ofthepredictionswillbecorrect
and others won’t. At one point, though, we may get to a stage where we can
omittheveri¢cationofthepredictionbyexperiment.Ipersonallythinkthiswill
neverbethecase,andwewillalwayshavetoverifyourpredictions,butothersmay
disagree.
Thenwecometothesoftpartofimmunoinformatics.ThisisIwouldtode¢neas
something that can never be tested with hard facts. This may raise some
1
2 RAMMENSEE
controversy. I would classify this part of immunoinformatics as what has
previouslybeenknownas‘theoreticalimmunology’.Thisincludesmathematical
descriptions of the behaviour of populations, whether this is at the level of the
individual, or at cellular or antibody levels. It involves interactions between
antibodies,infectiousagentsandTcells.Iwouldliketoproposethatthesekinds
of models will stay soft because it is not possible to verify the predictions
experimentally. If you predict that you need 30 T cells in a human to start an
e⁄cientimmuneresponseagainstaviralinfectionusingmathematicalmodelling,
youwillneverbeabletoprovethis.Ontheotherhand,whilethesepredictions
cannotbetestedaccurately,theycancertainlybeofhelp.Forexample,ifonecan
calculate in a mathematical model the percentage of people that need to be
immunizedagainstmeaslestoavoidanepidemic,thiswillbeofgreatuse.
SoIproposethatitisusefultobreakdownimmunoinformaticsintothesethree
categories of hard, semi-soft and soft. At the end of the meeting we can discuss
whether or not my proposal is correct. Two important questions related to this
are whether soft immunoinformatics can ever be tested accurately, and whether
the predictions from semi-soft immunoinformatics can stand alone without
experimentalveri¢cation.Let’snowmovetothe¢rstpresentation.
Reference
PerelsonAS(ed)1988Theoreticalimmunology.ProceedingsoftheTheoreticalImmunology
Workshop,June1987,SantaFe,NewMexico.Addison-Wesley,Reading,MA