Abstract
Sequence variation can affect the physiological state of the immune system. Major experimental efforts targeted at understanding the genetic control of the abundance of immune cell subpopulations. However, these studies are typically focused on a limited number of immune cell types, mainly due to the use of relatively low throughput cell-sorting technologies. Here we present an algorithm that can reveal the genetic basis of inter-individual variation in the abundance of immune cell types using only gene expression and genotyping measurements as input. Our algorithm predicts the abundance of immune cell subpopulations based on the RNA levels of informative marker genes within a complex tissue, and then provides the genetic control on these predicted immune traits as output. A key feature of the approach is the integration of predictions from various sets of marker genes and refinement of these sets to avoid spurious signals. Our evaluation of both synthetic and real biological data shows the significant benefits of the new approach. Our method, VoCAL, is implemented in the freely available R package ComICS.
Highlights
The immune system consists of a remarkable collection of immune cell subpopulations with complex interconnections
Quantitative trait locus (QTL) studies have identified a plethora of genetic variants that lead to inter-individual variation in the abundance of immune cell subpopulations, both in normal and disease states
Cell sorting is an effective method of monitoring immune cell type quantities; owing to the large number of possible immune cell subsets, it can be difficult to apply this method to each cell type over multiple individuals
Summary
The immune system consists of a remarkable collection of immune cell subpopulations with complex interconnections. To gain a better understanding of immune processes at the cellular level, such as cell proliferation, differentiation, activation and migration, researchers have systematically quantified the abundance of particular immune cell types in health and disease. This approach has provided insights into the role of immune cells during both homeostasis and disease progression; for example, recruitment and accumulation of macrophages in adipose tissue are associated with obesity [1]; the presence of eosinophils in the airway lumen and lung tissues is considered a defining feature of asthmatic disease [2]; recruitment of monocytes to arterial vessel walls is an early step in the development of atherosclerosis [3]; and an increase in CD4+CD28null T cells is detectable in patients with complications of rheumatoid arthritis [4].
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