venkatesh-deepinthebowel-2020.pdf (2.72 MB)
Deep in the bowel: highly interpretable neural encoder-decoder networks predict gut metabolites from gut microbiome
journal contribution
posted on 2020-07-20, 00:00 authored by Vuong Le, Thomas Quinn, Truyen TranTruyen Tran, Svetha VenkateshSvetha VenkateshBackground: Technological advances in next-generation sequencing (NGS) and chromatographic assays [e.g., liquid chromatography mass spectrometry (LC-MS)] have made it possible to identify thousands of microbe and metabolite species, and to measure their relative abundance. In this paper, we propose a sparse neural encoder-decoder network to predict metabolite abundances from microbe abundances. Results: Using paired data from a cohort of inflammatory bowel disease (IBD) patients, we show that our neural encoder-decoder model outperforms linear univariate and multivariate methods in terms of accuracy, sparsity, and stability. Importantly, we show that our neural encoder-decoder model is not simply a black box designed to maximize predictive accuracy. Rather, the network's hidden layer (i.e., the latent space, comprised only of sparsely weighted microbe counts) actually captures key microbe-metabolite relationships that are themselves clinically meaningful. Although this hidden layer is learned without any knowledge of the patient's diagnosis, we show that the learned latent features are structured in a way that predicts IBD and treatment status with high accuracy. Conclusions: By imposing a non-negative weights constraint, the network becomes a directed graph where each downstream node is interpretable as the additive combination of the upstream nodes. Here, the middle layer comprises distinct microbe-metabolite axes that relate key microbial biomarkers with metabolite biomarkers. By pre-processing the microbiome and metabolome data using compositional data analysis methods, we ensure that our proposed multi-omics workflow will generalize to any pair of -omics data. To the best of our knowledge, this work is the first application of neural encoder-decoders for the interpretable integration of multi-omics biological data.
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Journal
BMC GenomicsVolume
21Publisher
BioMed CentralLocation
London, Eng.Publisher DOI
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1471-2164Language
engPublication classification
C1 Refereed article in a scholarly journalCopyright notice
2020, The AuthorsUsage metrics
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