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

Abstract

Sputum 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.

A topic modeling approach reveals the dynamic T cell composition of peripheral blood during cancer immunotherapy

“… 31 Spatial information can be incorporated into the model to investigate the tumor and immune cell interactions. Moreover, LDA can also be applied for multi-omics data analysis, 32 , 33 integrating data from multiple assays to better understand cancer heterogeneity and predict patient clinical outcomes.…”

Single-cell RNA-sequencing in asthma research

“…Daniel Spakowicz et al developed an integrated dimensionality reduction and statistical modeling approach, linking human genes, cells as well as microbes and identified their relationships. They validated the method with scRNA-seq and studied sputum from asthmatics and found unknown interactions between microbes and genes, such as mast cells responding to Haemophilus and Pasteurella via IL1B, while eosinophils responding to Candida via GCSAML (38).…”

Faculty Opinions recommendation of Approaches for integrating heterogeneous RNA-seq data reveal cross-talk between microbes and genes in asthmatic patients.

“…Sputum bulk and single-cell RNA-seq data are available through dbGaP under the NCBI BioProject PRJNA611097 [58]. Code for LDA-link and to regenerate all figures is available at https://github.com/gersteinlab/decoasthma [59] Ethics approval and consent to participate This study was approved by the Yale Institutional Review Board Human Investigation Committee (0102012268). All study participants gave written informed consent.…”