1. Predicting Host Immune Cell Dynamics and Key Disease-Associated Genes Using Tissue Transcriptional Profiles
- Author
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Jason E. Shoemaker, Yoshihiro Kawaoka, Muying Wang, and Satoshi Fukuyama
- Subjects
0301 basic medicine ,Cell type ,immune cell quantities ,tissue gene expression ,Cell ,Bioengineering ,Computational biology ,influenza infection ,Biology ,lcsh:Chemical technology ,lcsh:Chemistry ,03 medical and health sciences ,Immunopathology ,Gene expression ,medicine ,Chemical Engineering (miscellaneous) ,lcsh:TP1-1185 ,Gene ,030102 biochemistry & molecular biology ,Microarray analysis techniques ,Process Chemistry and Technology ,Cell migration ,Cell Fraction ,030104 developmental biology ,medicine.anatomical_structure ,deconvolution algorithm ,lcsh:QD1-999 ,disease-associated gene - Abstract
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.
- Published
- 2019