title: Surface enhanced laser desorption ionization spectrometry reveals biomarkers for drug treatment but not dose.
abstract: Here we describe the use of SELDI-MS to detect dose-dependent peptide changes in plasma from mice treated with vehicle or rosiglitazone at one of two doses (10 and 30 mg/kg). SELDI features differentiating spectra from the three conditions were found and used to train classifiers. Samples treated with vehicle could be reliably distinguished from samples treated with either dose, but samples treated with the different doses could not be reliably distinguished from one another. We conclude that while SELDI-TOF mass spectra can be used to distinguish treated from untreated samples, the reproducibility and information content of SELDI-TOF are currently not sufficient as a pharmacodynamic readout to distinguish between mice treated with 10 or 30 mg/kg of rosiglitazone. This raises more general questions about whether SELDI's sensitivity is sufficient for detecting dose-dependent changes in plasma.
authors.affiliation: Department of Molecular Profiling Proteomics, Merck Research Laboratories, Rahway, NJ, USA. cloud_paweletz@merck.com
authors.forename: Cloud P
authors.initials: CP
authors.lastname: Paweletz
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Wiener
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Sachs
authors.forename: Roger
authors.initials: R
authors.lastname: Meurer
authors.forename: Margaret S
authors.initials: MS
authors.lastname: Wu
authors.forename: Kenney K
authors.initials: KK
authors.lastname: Wong
authors.forename: Nathan A
authors.initials: NA
authors.lastname: Yates
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Hendrickson
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008954:Models, Biological; D010455:Peptides / Q000032:analysis / Q000097:blood* / Q000737:chemistry; D015203:Reproducibility of Results; D000077154:Rosiglitazone; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*; D045162:Thiazolidinediones / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D015415:Biomarkers; D010455:Peptides; D045162:Thiazolidinediones; D000077154:Rosiglitazone