Correlating High-dimensional longitudinal microbial features with time-varying outcomes with FLORAL.

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Tác giả: Mirae Baichoo, Francesca Castro, Anqi Dai, Victoria Donovan, Teng Fei, Tyler Funnell, Ana Gradissimo, Jennifer Haber, Alexander M Lesokhin, Jenny Paredes, Jonathan U Peled, Sandeep S Raj, Urvi A Shah, Marcel R M van den Brink, Nicholas R Waters

Ngôn ngữ: eng

Ký hiệu phân loại:

Thông tin xuất bản: United States : bioRxiv : the preprint server for biology , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 692481

Correlating time-dependent patient characteristics and matched microbiome samples can be helpful to identify biomarkers in longitudinal microbiome studies. Existing approaches typically repeat a pre-specified modeling approach for all taxonomic features, followed by a multiple testing adjustment step for false discovery rate (FDR) control. In this work, we develop an alternative strategy of using log-ratio penalized generalized estimating equations, which directly models the longitudinal patient characteristic of interest as the outcome variable and treats microbial features as high-dimensional compositional covariates. A cross validation procedure is developed for variable selection and model selection among different working correlation structures. In extensive simulations, the proposed method achieved superior sensitivity over the state-of-the-art methods with robustly controlled FDR. In the analyses of correlating longitudinal dietary intake and microbial features from matched samples of cancer patients, the proposed method effectively identified gut health indicators and clinically relevant microbial markers, showing robust utilities in real-world applications. The method is implemented under the open-source R package FLORAL, which is available at (https://vdblab.github.io/FLORAL/).
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