Research Article
Correlation-Based Network Generation, Visualization, and
Analysis as a Powerful Tool in Biological Studies: A Case Study
in Cancer Cell Metabolism
Albert Batushansky,
1
David Toubiana,
2
and Aaron Fait
1
1
Te Jacob Blaustein Institutes for Desert Research, Ben-Gurion University of the Negev, 84990 Midreshet Ben-Gurion, Israel
2
Telekom Innovation Laboratories, Department of Information Systems Engineering, Ben-Gurion University of the Negev,
84105 Beer Sheva, Israel
Correspondence should be addressed to Albert Batushansky; batushanskya@missouri.edu
Received 11 May 2016; Revised 3 August 2016; Accepted 18 August 2016
Academic Editor: Shigehiko Kanaya
Copyright © 2016 Albert Batushansky et al. Tis is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
cited.
In the last decade vast data sets are being generated in biological and medical studies. Te challenge lies in their summary,
complexity reduction, and interpretation. Correlation-based networks and graph-theory based properties of this type of networks
can be successfully used during this process. However, the procedure has its pitfalls and requires specifc knowledge that ofen lays
beyond classical biology and includes many computational tools and sofware. Here we introduce one of a series of methods for
correlation-based network generation and analysis using freely available sofware. Te pipeline allows the user to control each step
of the network generation and provides fexibility in selection of correlation methods and thresholds. Te pipeline was implemented
on published metabolomics data of a population of human breast carcinoma cell lines MDA-MB-231 under two conditions: normal
and hypoxia. Te analysis revealed signifcant diferences between the metabolic networks in response to the tested conditions.
Te network under hypoxia had 1.7 times more signifcant correlations between metabolites, compared to normal conditions.
Unique metabolic interactions were identifed which could lead to the identifcation of improved markers or aid in elucidating
the mechanism of regulation between distantly related metabolites induced by the cancer growth.
1. Introduction
Advanced technology methods for high-throughput bio-
logical studies, such as metabolomics and transcriptomics
developed during the last decades, are successfully applied
in biomedical research [1], plant studies [2], and micro-
biology [3]. Te wide use of these technologies led to
the accumulation of data on biological processes at their
multiple levels (metabolic, genetic, enzymatic, physiological,
phenotypical, etc.) and called for the development of tools
to ease the visualization, analysis, and interpretation of an
ofen complex and multidimensional matrix. Furthermore,
the readily available “omics” technologies in biological lab-
oratories prompted biologists to enter a feld ofen needing
extensive computational knowhow and led to the increased
interest in biological interaction networks [4]. Tus, in the
recent decades networks describing cellular processes were
generated for human [5], yeast [6], and plants [7].
Networks can be presented as graphs, that is, a set of
vertices (V) connected by edges (E), and consequently can
be analyzed using graph theory, an approach that has been
increasingly implemented in biological studies during the
last decade. It is commonly accepted that graph theory as a
scientifc discipline was frst used by the Swiss mathematician
Leonhard Euler in 1735-1736, tackling the K¨ onigsberg bridge
problem. Later, in the 19th and 20th centuries, graph theory
was formulated and eventually introduced for applied felds,
such as physics, computer science, and biology [8]. Today,
graph theory consists of many tens of basic defnitions and
properties [9]. Te understanding of the biological networks
lies in the nature of the vertices and edges between them; that
is, the vertices may represent one of the components of the
Hindawi Publishing Corporation
BioMed Research International
Volume 2016, Article ID 8313272, 9 pages
http://dx.doi.org/10.1155/2016/8313272