Relationships between total, relative and absolute molecular abundance in aging genomics studies: Simple theoretical consideration.

Abstract

In most of the studies using Next Generation Sequencing, the normalization step is performed to adjust the total number of short reads to quantitate the expression of biomolecules such as mRNA. This preprocessing is based on the assumption that the total number of the sequenced reads is constant across different biological conditions and conducted to remove technical variability. Normalized expression values such as count per million are relative expression values, losing information on absolute amounts. However, in aging and cancer research, it has been reported the assumption that the total number of reads is constant across conditions does not hold. In this study, based on a simple theoretical analysis, we present that log fold-change in absolute abundance can be expressed by the observed log fold-change of relative abundance plus log fold-change of total abundance. The logic presented in this study focuses on the relationship between global and local change in omics research. It can be used as a quick check on how a differentially expressed gene in an omics study based on relative abundance should be interpreted in terms of absolute abundance.