TITLE:
A Comparison of Various Normalization Methods for LC/MS Metabolomics Data
AUTHORS:
Jacob E. Wulff, Matthew W. Mitchell
KEYWORDS:
Metabolomics, Normalization, Liquid Chromatography, Mass Spectrometry, TIC
JOURNAL NAME:
Advances in Bioscience and Biotechnology,
Vol.9 No.8,
August
13,
2018
ABSTRACT: In metabolomics data, like other -omics data,
normalization is an important part of the data processing. The goal of
normalization is to reduce the variation from non-biological sources (such as
instrument batch effects), while maintaining the biological variation. Many
normalization techniques make adjustments to each sample. One common method is
to adjust each sample by its Total Ion Current (TIC), i.e. for each feature in the sample, divide its intensity value by
the total for the sample. Because many of the assumptions of these methods are
dubious in metabolomics data sets, we compare these methods to two methods that
make adjustments separately for each metabolite, rather than for each sample.
These two methods are the following: 1) for each metabolite, divide its value
by the median level in bridge samples (BRDG); 2) for each metabolite divide its
value by the median across the experimental samples (MED). These methods were
assessed by comparing the correlation of the normalized values to the values
from targeted assays for a subset of metabolites in a large human plasma data
set. The BRDG and MED normalization techniques greatly outperformed the other
methods, which often performed worse than performing no normalization at all.