Aside from the non-supervised approach, the supervised multivari-
ate technique is utilized to identify interested metabolites directly.
Partial Least Squares-Discriminant Analyses (PLS-DA) and
Orthogonal Partial Least Squares-Discriminant Analyses (OPLS-
DA) are regress methods with a binary “dummy” response variable,
which are used to extract meaningful metabolites from expression
matrix table directly.6 Mechanism Interpretation and Hypothesis Generation
After interested metabolites are identified and quantified, the inter-
pretation of complex interaction between genes, proteins, and
metabolites is one important goal of metabolomics study. Func-
tional annotations to metabolites can give meaningful biological
information and provide mechanistic insights into a living system
[119]. In general, an enrichment analysis is conducted to reveal
biological pathways of target metabolites, which describe function
of these metabolites and can help understand their physiological
roles in a living system. Recently, some software packages and
databases are developed for mechanism interpretation and hypoth-
esis generation in metabolomics (seeTable1 for details). The
KEGG, BioCyc, iPath, KaPPA-View, MapMan, MetPA, MetScape,
MGV, Paintomics, Pathos, PathVisio, ProMeTra, Reactome, and
VANTED resources provide mapping and visualizing tools of meta-
bolites correlated to biological pathways, while the MSEA,
MBRole, MPEA, and IMPaLA tools can carry out enrichment
analysis [120, 121]. In detail, the KEGG’s pathway browser is
created and maintained by the Kanehisa Laboratories, which pro-
vides a list of pathways and compounds within these pathways.
Biocyc.orgresource is developed and managed by SRI Interna-
tional, which present mapping and visualizing tools for metabolites.
The visualization tools of Reactome website can provide integrative
pathway information retrieving from multi-data source (such as
VANTED, iPath, and MetScape). Specially, experimental data can
be mapped to correlated metabolism graphs quickly in VANTED
website. iPath offers an “interactive” mode for biological pathways
visualization. Users can visualize and operate biological networks
with customized mode in MetScape website. In addition, a lot of
tools of omics data visualization are presented recently, such as
ProMeTra, Paintomics, PathVisio, and MGV. Specially, the
KaPPA-View and MapMan are developed for plant metabolomics.
Currently, some pathway visualization tools are integrated into
general analytical software to facilitate data analysis of metabolo-
mics, for example, the MetPA and the Pathos tool have been
integrated in the Metabo and MeltDB platform, respectively.
MSEA, MBRole, MPEA, and IMPaLA are enrichment analysis
tools, which are utilized for human and mammalian metabolomicsMetabolomics: A High-Throughput Platform for Metabolite Profile Exploration 283