Approaches for integrating heterogeneous RNA-seq data reveal cross-talk between microbes and genes in asthmatic patients

Author:

Spakowicz Daniel,Lou Shaoke,Barron Brian,Gomez Jose L.,Li Tianxiao,Liu Qing,Grant Nicole,Yan Xiting,Hoyd Rebecca,Weinstock George,Chupp Geoffrey L.,Gerstein MarkORCID

Abstract

AbstractSputum induction is a non-invasive method to evaluate the airway environment, particularly for asthma. RNA sequencing (RNA-seq) of sputum samples can be challenging to interpret due to the complex and heterogeneous mixtures of human cells and exogenous (microbial) material. In this study, we develop a pipeline that integrates dimensionality reduction and statistical modeling to grapple with the heterogeneity. LDA(Latent Dirichlet allocation)-link connects microbes to genes using reduced-dimensionality LDA topics. We validate our method with single-cell RNA-seq and microscopy and then apply it to the sputum of asthmatic patients to find known and novel relationships between microbes and genes.

Funder

U.S. National Library of Medicine

National Heart, Lung, and Blood Institute

Publisher

Springer Science and Business Media LLC

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