Machine Learning Analysis of Volatolomic Profiles in Breath Can Identify Non-invasive Biomarkers of Liver Disease

Abstract Disease-related effects on hepatic metabolism can alter the composition of chemicals in the circulation and subsequently in breath. The presence of disease related alterations in exhaled volatile organic compounds (VOC) could provide a basis for non-invasive biomarkers of hepatic disease. This study examined the feasibility of combining global VOC (volatolomic) profiles from breath analysis and machine learning to develop signature pattern-based biomarkers for cirrhosis. Breath samples were analyzed using thermal desorption-gas chromatography-field asymmetric ion mobility spectroscopy to generate volatolomic profiles. Samples were collected from 35 persons with cirrhosis, 4 with non-cirrhotic portal hypertension, and 11 healthy participants. Molecular features of interest were identified to determine their ability to classify cirrhosis or portal hypertension. A molecular feature score was derived that increased with the stage of cirrhosis and had an AUC of 0.78 for detection. Chromatographic breath profiles were utilized to generate machine learning-based classifiers. Algorithmic models could discriminate presence or stage of cirrhosis with a sensitivity of 88-92% and specificity of 75%. These results demonstrate the feasibility of volatolomic profiling to classify clinical phenotypes without identifying specific compounds. These studies will pave the way in developing non-invasive biomarkers of liver disease based on volatolomic signatures found in breath.