title: Discrimination of ischemic and hemorrhagic strokes using a multiplexed, mass spectrometry-based assay for serum apolipoproteins coupled to multi-marker ROC algorithm.
abstract: OBJECTIVE
  Typically, apolipoproteins are individually measured in blood by immunoassay. In this report, we describe the development of a multiplexed selected reaction monitoring (SRM) based assay for a panel of apolipoproteins and its application to a clinical cohort of samples derived from acute stroke patients.
  
  
  METHODS
  An SRM assay for a panel of nine apolipoproteins was developed on a triple quadrupole mass spectrometer. Quantitative data for each apolipoprotein were analyzed to determine expression ratio and receiver operating characteristic (ROC) values for ischemic versus hemorrhagic stroke.
  
  
  RESULTS
  The optimized SRM assay was used to interrogate a small cohort of well-characterized plasma samples obtained from patients with acute ischemic and hemorrhagic strokes. The ROC analyses demonstrated good classification power for several single apolipoproteins, most notably apoC-III and apoC-I. When a novel multi-marker ROC algorithm was applied, the ischemic versus hemorrhagic groups were best differentiated by a combination of apoC-III and apoA-I with an area under the curve (AUC) value of 0.92.
  
  
  CONCLUSIONS
  This proof-of-concept study provides interesting and provocative data for distinguishing ischemic versus hemorrhage within first week of symptom onset. However, the observations are based on one cohort of patient samples and further confirmation will be required.
authors.affiliation: ThermoFisher Scientific BRIMS, Cambridge, MA, USA. mary.lopez@thermofisher.com
authors.forename: Mary F
authors.initials: MF
authors.lastname: Lopez
authors.forename: David A
authors.initials: DA
authors.lastname: Sarracino
authors.forename: Amol
authors.initials: A
authors.lastname: Prakash
authors.forename: Michael
authors.initials: M
authors.lastname: Athanas
authors.forename: Bryan
authors.initials: B
authors.lastname: Krastins
authors.forename: Taha
authors.initials: T
authors.lastname: Rezai
authors.forename: Jennifer N
authors.initials: JN
authors.lastname: Sutton
authors.forename: Scott
authors.initials: S
authors.lastname: Peterman
authors.forename: Oksana
authors.initials: O
authors.lastname: Gvozdyak
authors.forename: Sherry
authors.initials: S
authors.lastname: Chou
authors.forename: Eng
authors.initials: E
authors.lastname: Lo
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Buonanno
authors.forename: MingMing
authors.initials: M
authors.lastname: Ning
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D000595:Amino Acid Sequence; D001053:Apolipoproteins / Q000097:blood* / Q000145:classification; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins / Q000032:analysis*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D006474:Hemorrhagic Disorders / Q000175:diagnosis* / Q000473:pathology; D006801:Humans; D007511:Ischemia / Q000175:diagnosis / Q000473:pathology; D057230:Limit of Detection; D008297:Male; D013058:Mass Spectrometry / Q000379:methods* / Q000592:standards; D008875:Middle Aged; D008969:Molecular Sequence Data; D012372:ROC Curve; D020521:Stroke / Q000175:diagnosis* / Q000473:pathology; D055815:Young Adult
chemical_list: D001053:Apolipoproteins; D015415:Biomarkers; D001798:Blood Proteins