Joel Correa da Rosa, Jose O. Aleman, Jason Mohabir, Yupu Liang, Jan L. Breslow, Peter R. Holt

Obesity has reached epidemic proportions in the United States, but little is known about the mechanisms of weight gain and weight loss. Integration of omics data is becoming a popular tool to increase understanding in such complex phenotypes. Biomarkers come in abundance, but small sample size remains a serious limitation in clinical trials. In the present study, we developed a strategy to screen predictors from a multiomics, high-dimensional, and longitudinal dataset from a small cohort of 10 women with obesity who were provided an identical very-low calorie diet. Our proposal explores the combinatorial space of potential predictors from transcriptomics, microbiome, metabolome, fecal bile acids, and clinical data with the application of the first-order Spearman partial correlation coefficient. Two statistics are proposed for screening predictors, the partial association score, and the persistent significance. We applied our strategy to predict rates of weight loss in our sample of participants in a hospital metabolic facility. Our method reduced an initial set of 42,000 biomarker candidates to 61 robust predictors. The results show baseline fecal bile acids and regulation in RT-polymerase chain reaction as the most predictive data sources in forecasting the rate of weight-loss. In summary, the present study proposes a strategy based on nonparametric statistics for ranking and screening predictors of weight loss from a multiomics study. The proposed biomarker screening strategy warrants further translational clinical investigation in obesity and other complex clinical phenotypes.