LAPSE:2019.0874
Published Article
LAPSE:2019.0874
Predicting Host Immune Cell Dynamics and Key Disease-Associated Genes Using Tissue Transcriptional Profiles
Muying Wang, Satoshi Fukuyama, Yoshihiro Kawaoka, Jason E. Shoemaker
July 31, 2019
Motivation: Immune cell dynamics is a critical factor of disease-associated pathology (immunopathology) that also impacts the levels of mRNAs in diseased tissue. Deconvolution algorithms attempt to infer cell quantities in a tissue/organ sample based on gene expression profiles and are often evaluated using artificial, non-complex samples. Their accuracy on estimating cell counts given temporal tissue gene expression data remains not well characterized and has never been characterized when using diseased lung. Further, how to remove the effects of cell migration on transcript counts to improve discovery of disease factors is an open question. Results: Four cell count inference (i.e., deconvolution) tools are evaluated using microarray data from influenza-infected lung sampled at several time points post-infection. The analysis finds that inferred cell quantities are accurate only for select cell types and there is a tendency for algorithms to have a good relative fit (R 2 ) but a poor absolute fit (normalized mean squared error; NMSE), which suggests systemic biases exist. Nonetheless, using cell fraction estimates to adjust gene expression data, we show that genes associated with influenza virus replication and increased infection pathology are more likely to be identified as significant than when applying traditional statistical tests.
Keywords
deconvolution algorithm, disease-associated gene, immune cell quantities, influenza infection, tissue gene expression
Subject
Suggested Citation
Wang M, Fukuyama S, Kawaoka Y, Shoemaker JE. Predicting Host Immune Cell Dynamics and Key Disease-Associated Genes Using Tissue Transcriptional Profiles. (2019). LAPSE:2019.0874
Author Affiliations
Wang M: Department of Chemical and Petroleum Engineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA 15261, USA
Fukuyama S: Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan
Kawaoka Y: Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan; Department of Pathobiological Sciences, School of Veterinary Medicine, Influenza Research Institute, University of W
Shoemaker JE: Department of Chemical and Petroleum Engineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA 15261, USA; Department of Computational and Systems Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15260, USA; [ORCID]
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Journal Name
Processes
Volume
7
Issue
5
Article Number
E301
Year
2019
Publication Date
2019-05-21
Published Version
ISSN
2227-9717
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Original Submission
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PII: pr7050301, Publication Type: Journal Article
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LAPSE:2019.0874
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doi:10.3390/pr7050301
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Jul 31, 2019
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CC BY 4.0
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Jul 31, 2019
 
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Original Submitter
Calvin Tsay
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