Integration of transcriptomic and proteomic data identifies biological functions in cell populations from human infant lung

Author:

Du Yina1ORCID,Clair Geremy C.2ORCID,Al Alam Denise34,Danopoulos Soula34,Schnell Daniel56,Kitzmiller Joseph A.1,Misra Ravi S.7,Bhattacharya Soumyaroop78ORCID,Warburton David34,Mariani Thomas J.78,Pryhuber Gloria S.7,Whitsett Jeffrey A.1,Ansong Charles2,Xu Yan15ORCID

Affiliation:

1. The Perinatal Institute and Section of Neonatology, Perinatal and Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio

2. Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington

3. Developmental Biology and Regenerative Medicine Program, Department of Pediatric Surgery, The Saban Research Institute, Children’s Hospital Los Angeles, Los Angeles, California

4. Keck School of Medicine, University of Southern California, Los Angeles, California

5. Division of Biomedical Informatics, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio

6. Heart Institute and Center for Translational Fibrosis Research, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio

7. Department of Pediatrics, University of Rochester Medical Center, Rochester, New York

8. Division of Neonatology and Program in Pediatric Molecular and Personalized Medicine, University of Rochester Medical Center, Rochester, New York

Abstract

Systems biology uses computational approaches to integrate diverse data types to understand cell and organ behavior. Data derived from complementary technologies, for example transcriptomic and proteomic analyses, are providing new insights into development and disease. We compared mRNA and protein profiles from purified endothelial, epithelial, immune, and mesenchymal cells from normal human infant lung tissue. Signatures for each cell type were identified and compared at both mRNA and protein levels. Cell-specific biological processes and pathways were predicted by analysis of concordant and discordant RNA-protein pairs. Cell clustering and gene set enrichment comparisons identified shared versus unique processes associated with transcriptomic and/or proteomic data. Clear cell-cell correlations between mRNA and protein data were obtained from each cell type. Approximately 40% of RNA-protein pairs were coherently expressed. While the correlation between RNA and their protein products was relatively low (Spearman rank coefficient rs ~0.4), cell-specific signature genes involved in functional processes characteristic of each cell type were more highly correlated with their protein products. Consistency of cell-specific RNA-protein signatures indicated an essential framework for the function of each cell type. Visualization and reutilization of the protein and RNA profiles are supported by a new web application, “LungProteomics,” which is freely accessible to the public.

Funder

HHS | NIH | National Heart, Lung, and Blood Institute (NHBLI)

Publisher

American Physiological Society

Subject

Cell Biology,Physiology (medical),Pulmonary and Respiratory Medicine,Physiology

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