title: Identification of targeted analyte clusters for studies of schizophrenia.
abstract: The search for biomarkers to diagnose psychiatric disorders such as schizophrenia has been underway for decades. Many molecular profiling studies in this field have focused on identifying individual marker signals that show significant differences in expression between patients and the normal population. However, signals for multiple analyte combinations that exhibit patterned behaviors have been less exploited. Here, we present a novel approach for identifying biomarkers of schizophrenia using expression of serum analytes from first onset, drug-naïve patients and normal controls. The strength of patterned signals was amplified by analyzing data in reproducing kernel spaces. This resulted in the identification of small sets of analytes referred to as targeted clusters that have discriminative power specifically for schizophrenia in both human and rat models. These clusters were associated with specific molecular signaling pathways and less strongly related to other neuropsychiatric disorders such as major depressive disorder and bipolar disorder. These results shed new light concerning how complex neuropsychiatric diseases behave at the pathway level and demonstrate the power of this approach in identification of disease-specific biomarkers and potential novel therapeutic strategies.
authors.affiliation: Department of Chemical Engineering and Biotechnology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QT, United Kingdom.
authors.forename: Tammy M K
authors.initials: TM
authors.lastname: Cheng
authors.forename: Yu-En
authors.initials: YE
authors.lastname: Lu
authors.forename: Paul C
authors.initials: PC
authors.lastname: Guest
authors.forename: Hassan
authors.initials: H
authors.lastname: Rahmoune
authors.forename: Laura W
authors.initials: LW
authors.lastname: Harris
authors.forename: Lan
authors.initials: L
authors.lastname: Wang
authors.forename: Dan
authors.initials: D
authors.lastname: Ma
authors.forename: Victoria
authors.initials: V
authors.lastname: Stelzhammer
authors.forename: Yagnesh
authors.initials: Y
authors.lastname: Umrania
authors.forename: Matt T
authors.initials: MT
authors.lastname: Wayland
authors.forename: Pietro
authors.initials: P
authors.lastname: Lió
authors.forename: Sabine
authors.initials: S
authors.lastname: Bahn
mesh_terms: D000328:Adult; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001714:Bipolar Disorder / Q000097:blood; D016000:Cluster Analysis; D003865:Major Depressive Disorder / Q000097:blood; D004195:Disease Models, Animal; D001330:Electronic Data Processing; D005260:Female; D006213:Hallucinogens; D006801:Humans; D008297:Male; D010622:Phencyclidine; D040901:Proteomics; D051381:Rats; D012559:Schizophrenia / Q000097:blood* / Q000139:chemically induced; D015398:Signal Transduction
chemical_list: D015415:Biomarkers; D006213:Hallucinogens; D010622:Phencyclidine