Computational Approach to Identifying Universal Macrophage Biomarkers.

Dharanidhar Dang,Pradipta Ghosh,Sahar Taheri,Lawrence S. Prince,Debashis Sahoo,Soumita Das

doi:10.3389/fphys.2020.00275

Abstract

Macrophages engulf and digest microbes, cellular debris, and various disease-associated cells throughout the body. Understanding the dynamics of macrophage gene expression is crucial for studying human diseases. As both bulk RNAseq and single cell RNAseq datasets become more numerous and complex, identifying a universal and reliable marker of macrophage cell becomes paramount. Traditional approaches have relied upon tissue specific expression patterns. To identify universal biomarkers of macrophage, we used a previously published computational approach called BECC (Boolean Equivalent Correlated Clusters) that was originally used to identify conserved cell cycle genes. We performed BECC analysis using the known macrophage marker CD14 as a seed gene. The main idea behind BECC is that it uses massive database of public gene expression dataset to establish robust co-expression patterns identified using a combination of correlation, linear regression and Boolean equivalences. Our analysis identified and validated FCER1G and TYROBP as novel universal biomarkers for macrophages in human and mouse tissues.

Highlights

Macrophages are specialized cells involved in the detection, phagocytosis and destruction of bacteria and other harmful organisms
Available microarray databases in Human U133 Plus 2.0 (n = 25,955, GSE119087), Mouse 430 2.0 (n = 11,758, GSE119085) Affymetrix platform were downloaded from National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) website (Edgar et al, 2002; Barrett et al, 2005, 2013)
To use Boolean Equivalent Correlated Clusters (BECC) to identify potential macrophage-specific genes, we identified CD14 as a seed gene as it is expressed in most macrophage populations (Figure 1B) (Griffin et al, 1981; Passlick et al, 1989)

Summary

Introduction

Macrophages are specialized cells involved in the detection, phagocytosis and destruction of bacteria and other harmful organisms. Disruption of normal macrophage biology is a hallmark of many diseases, including diabetes (Huang et al, 2010; Eguchi et al, 2012), asthma (Gordon, 2003), metastatic cancer (Qian and Pollard, 2010), tissue fibrosis (Murray and Wynn, 2011), and chronic inflammation (Kamada et al, 2008; Hansson and Hermansson, 2011; Murray and Wynn, 2011) These characteristics make understanding macrophage biology vital for studying disease pathogenesis. Macrophages function in both tissue repair during homeostasis and in the innate immune response

Methods

Results

Conclusion