A new ensemble-based algorithm for identifying breath gas marker candidates in liver disease using ion molecule reaction mass spectrometry.
BACKGROUND
Alcoholic fatty liver disease (AFLD) and non-AFLD (NAFLD) can progress to severe liver diseases such as steatohepatitis, cirrhosis and cancer. Thus, the detection of early liver disease is essential; however, minimal invasive diagnostic methods in clinical hepatology still lack specificity.


RESULTS
Ion molecule reaction mass spectrometry (IMR-MS) was applied to a total of 126 human breath gas samples comprising 91 cases (AFLD, NAFLD and cirrhosis) and 35 healthy controls. A new feature selection modality termed Stacked Feature Ranking (SFR) was developed to identify potential liver disease marker candidates in breath gas samples, relying on the combination of different entropy- and correlation-based feature ranking methods including statistical hypothesis testing using a two-level architecture with a suggestion and a decision layer. We benchmarked SFR against four single feature selection methods, a wrapper and a recently described ensemble method, indicating a significantly higher discriminatory ability of up to 10-15% for the SFR selected gas compounds expressed by the area under the ROC curve (AUC) of 0.85-0.95. Using this approach, we were able to identify unexpected breath gas marker candidates in liver disease of high predictive value. A literature study further supports top-ranked markers to be associated with liver disease. We propose SFR as a powerful tool for biomarker search in breath gas and other biological samples using mass spectrometry.


BACKGROUND
The algorithm SFR and IMR-MS datasets are available under http://biomed.umit.at/page.cfm?pageid=526.
Netzer
M
M
Research Group for Clinical Bioinformatics, Institute of Biomedical Engineering, University for Health Sciences, Medical Informatics and Technology (UMIT), Innsbruck Medical University, Innsbruck, Austria. michalel.netzer@umit.at
Millonig
G
G
Osl
M
M
Pfeifer
B
B
Praun
S
S
Villinger
J
J
Vogel
W
W
Baumgartner
C
C
D000465:Algorithms; D015415:Biomarkers / Q000032:analysis; D001944:Breath Tests; D015331:Cohort Studies; D006801:Humans; D008107:Liver Diseases / Q000175:diagnosis* / Q000378:metabolism; D013058:Mass Spectrometry / Q000379:methods*; D008875:Middle Aged
D015415:Biomarkers