Le SOMAscan, une approche innovante pour le dosage simultané de 1 305 protéines : application à l’étude du cancer et des maladies cardio-vasculaires

Genopole - Séminaire "Sciences & Techno" - Biomarqueurs et Protéomique
LeSOMAscan,uneapprocheinnovantepourledosagesimultanéde1305protéines:
applicationàl’étudeducanceretdesmaladiescardio-vasculaires
Jeudi27/04/2017auLAMBE(UEVE)
10h00-10h30:Useofmodifiedaptamersasanewproteomicstoolforunprecedented
multiplexassay-theSOMAscan
NicolasAutret,PhD–SomaLogic–[email protected]
Eventhoughproteinsarethetargetsof95%ofallknowndrugs,anddownstreamofboth
genetics and the environment, proteomics has failed to generate even a fraction of the
excitement that drives the genomics revolution. This has been justifiable until now because
largescale,highthroughput,highlymultiplexedproteinmeasurementshavenotbeenpossible.
With the availability of the SOMAscan 1.3k assay, using modified DNA-based reagents which form highly specific
complexes with proteins, we have re-purposed genetic technologies to measure proteins at unprecedented scale and
performance:sub-picogramdetectionofthousandsofproteinswithhighprecisionandtinyvolumesofsample.
Examples from cancer, neurological disorders up to cardiovascular diseases will be shown of how the individual novel
reagents as well as the SOMAscan assay are being used to uncover new biology, validate new targets, compliment
genomicsfindingsanddeliveractionableinformationformedicalpracticeanddrugdevelopment.
10h40-11h10- Predictive biomarkers for the response to treatments in triple-negative breast cancer: use of the
SOMAscaninadditiontothereverse-phaseproteinarray(RPPA)technology.
LeannedeKoning,PhD–InstitutCurie–[email protected]
Triplenegativebreastcancer(TNBC),characterizedbytheabsenceofhormonereceptorsandnoHER2overexpression,is
aheterogeneousgroupofbreastcancerswithbadprognosisduetoearlyrelapse.Notargetedtherapyoptionscurrently
exist.Here,wewantedtoestablishthetumorproteinprofileofourtriplenegativecellmodelsgrownin2Dand3D,in
orderto(i)refinetheclassificationofthisveryheterogeneoussubgroup,(ii)identifypredictivebiomarkersorsignatures
tobetteradapttreatments,and(iii)toproposenewtherapeuticstrategiesviathediscoveryoftargetproteins.
Somascantechnologyhasallowedustoprobe1305differentproteinsinawidescreenandthuspointoutthesignaling
pathwaysthatcanbederegulatedinthetriplenegativecelllinesgrownin3D.Theresultsarethenvalidatedandfurther
developedwiththeReversePhaseProteinArray(RPPA)technology,whichallowsnotonlytoquantifythetotalamountof
proteinbutalsotheirpost-translationalmodificationssuchasphosphorylationtobestudied.
UnlikeSomascan,RPPArequiresapreciseselectionoftheproteinstobeanalyzed,butitallowstostudy550samplesona
singlechip.Thetwotechnologiesarethuscomplementary:theSomascanallowsustoselectfromaboutthirtysamples
theproteinsandsignalingpathwaysofinterestwhicharethenstudiedmorefinelyinRPPAonalargeseriesofsamples,
includingnotonlycelllinesbutalsoxenograftsandpatienttumors.
11h20-11h50:Interestofmulti-markerapproachforpredictingearlymortalityinheartfailurepatientswithreduced
ejectionfraction
FlorencePinet,M.D.,PhD–InstitutPasteurdeLille–[email protected]
Ourobjectiveistofindnewbiomarkersassociatedwithearlycardiovascularmortalityinheartfailurebyamulti-marker
approach. For that purpose we used a prospective register (INCA study) including consecutively heart failure patients
(systolicHFwithLVEF≤45%),clinicallystable(nodecompensation,nohospitalizationintheprevious2months)withan
optimalmedicaltherapy.
The patients undergo a prognostic evaluation (NYHA class, BNP levels, LVEF measurement, Peak VO2 obtained during
cardiopulmonaryexercisetesting).Allpatientshadacoronarographyfordeterminingetiologyofcardiopathy.
WecompareproteinsignalsinplasmafromINCAstudyheartfailureparticipantswhowerealive(n=84)ordead(n=84)
within3yearsafterstudyenrollmentwithSOMAscan1.3kassay,measuring1,305proteins.4samples(allcontrols)failed
SOMAscanQCcriteriaandwereexcludedfromtheanalysis.WefoundacorrelationbetweenthelevelsofBNPquantified
byBNPSOMAmerwithClinicalBNP.345proteinsand2clinicalvariablesweresignificantatKStestFDRp<0.05.
Thenextstepisanintegrativeanalysisofmolecularandclinicaldatainordertobuildamolecularinteractionnetwork
undercytoscape.