Application of an End-to-End Biomarker Discovery Platform to Identify Target Engagement Markers in Cerebrospinal Fluid by High Resolution Differential Mass Spectrometry

2010 ◽  
Vol 9 (3) ◽  
pp. 1392-1401 ◽  
Author(s):  
Cloud P. Paweletz ◽  
Matthew C. Wiener ◽  
Andrey Y. Bondarenko ◽  
Nathan A. Yates ◽  
Qinghua Song ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Cerebrospinal Fluid ◽  
High Resolution ◽  
Biomarker Discovery ◽  
Target Engagement ◽  
End To End

scholarly journals High-Resolution Serum Proteomic Profiling of Alzheimer Disease Samples Reveals Disease-Specific, Carrier-Protein–Bound Mass Signatures

2005 ◽  
Vol 51 (10) ◽  
pp. 1946-1954 ◽  
Author(s):  
Mary F Lopez ◽  
Alvydas Mikulskis ◽  
Scott Kuzdzal ◽  
David A Bennett ◽  
Jeremiah Kelly ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
High Resolution ◽  
Alzheimer Disease ◽  
Mass Spectra ◽  
Biomarker Discovery ◽  
High Resolution Mass Spectrometry ◽  
Carrier Protein ◽  
High Resolution Mass ◽  
Peptide Mass ◽  
Resolution Mass

Abstract Background: Researchers typically search for disease markers using a “targeted” approach in which a hypothesis about the disease mechanism is tested and experimental results either confirm or disprove the involvement of a particular gene or protein in the disease. Recently, there has been interest in developing disease diagnostics based on unbiased quantification of differences in global patterns of protein and peptide masses, typically in blood from individuals with and without disease. We combined a suite of methods and technologies, including novel sample preparation based on carrier-protein capture and biomarker enrichment, high-resolution mass spectrometry, a unique cohort of well-characterized persons with and without Alzheimer disease (AD), and powerful bioinformatic analysis, that add statistical and procedural robustness to biomarker discovery from blood. Methods: Carrier-protein–bound peptides were isolated from serum samples by affinity chromatography, and peptide mass spectra were acquired by a matrix-assisted laser desorption/ionization (MALDI) orthogonal time-of-flight (O-TOF) mass spectrometer capable of collecting data over a broad mass range (100 to >300 000 Da) in a single acquisition. Discriminatory analysis of mass spectra was used to process and analyze the raw mass spectral data. Results: Coupled with the biomarker enrichment protocol, the high-resolution MALDI O-TOF mass spectra provided informative, reproducible peptide signatures. The raw mass spectra were analyzed and used to build discriminant disease models that were challenged with blinded samples for classification. Conclusions: Carrier-protein enrichment of disease biomarkers coupled with high-resolution mass spectrometry and discriminant pattern analysis is a powerful technology for diagnostics and population screening. The mass fingerprint model successfully classified blinded AD patient and control samples with high sensitivity and specificity.

Biomarker Discovery by Mass Spectrometry in Cerebrospinal Fluid and Plasma after Global Hypoxia-Ischemia in Newborn Piglets

Neonatology ◽  
2018 ◽  
Vol 114 (4) ◽  
pp. 307-314
Author(s):  
Kasper Jacobsen Kyng ◽  
Anders Valdemar Edhager ◽  
Tine Brink Henriksen ◽  
Christer Zøylner Swan ◽  
Niels Gregersen ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Cerebrospinal Fluid ◽  
Biomarker Discovery ◽  
Newborn Piglets ◽  
Hypoxia Ischemia
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