Advances in top-down proteomics for disease biomarker discovery

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1、JOURNALOFPROTEOMICS74(2011)920–934availableatwww.sciencedirect.comwww.elsevier.com/locate/jprotReviewAdvancesintop-downproteomicsfordiseasebiomarkerdiscoveryDavidCalligaris,ClaudeVillard,DanielLafitte⁎INSERMUMR911,CentredeRechercheenOncologiebiologiqueetenO

2、ncopharmacologie,Aix-MarseilleUniversité,PlateformeProtéomiqueetInnovationTechnologiqueTimone,FacultédePharmacie,27BoulevardJeanMoulin,13385MarseilleCedex5,FranceARTICLEINFOABSTRACTArticlehistory:Top-downmassspectrometrystrategiesallowidentificationandchara

3、cterizationofReceived19January2011proteinsandproteinnetworksbydirectfragmentation.TheseanalyticalprocessesAccepted29March2011involveapaneloffragmentationmechanisms,someofwhichpreserveproteinpost-Availableonline6April2011translationalmodifications.Thustop-do

4、wnisofspecialinterestinclinicalbiochemistrytoprobemodifiedproteinsaspotentialdiseasebiomarkers.ThisreviewdescribesseparatingKeywords:methods,massspectrometryinstrumentation,bioinformatics,andtheoreticalaspectsofTop-downfragmentationmechanismsusedfortop-down

5、analysis.ThebiologicalinterestofthisFragmentationstrategyisextensivelyreportedregardingthecharacterizationofpost-translationalProteomicsmodificationsinbiochemicalpathwaysandthediscoveryofbiomarkers.OnehastobearBiomarkersinmindthatquantitativeaspectsthatareb

6、eyondthefocusofthisreviewarealsoofcriticalPost-translationalmodificationsimportantforbiomarkerdiscovery.Theconstantevolutionoftechnologiesmakestop-downstrategiescrucialplayersinclinicalandbasicproteomics.©2011ElsevierB.V.Allrightsreserved.Contents1.Introduc

7、tion..........................................................9212.Top-downworkflow......................................................9212.1.Separationandsamplehandling...........................................9212.2.Massspectrometry....................

8、..............................9232.3.Dedicatedsearchenginesfortop-downanalysis..................................9233.Fragmentationmechanismsforprimarysequenceanalysisobservedduringtop-downanalysis.....