Complex Systems Biology of Networks: The Riddle and the Challenge - Systems Biology of Metabolic and Signaling Networks - page 18

NETWORKS

Metabolome

Mass-Energy transformaon

Signaling FLUXOME

Genome

Informaon carrying-transformaon

Transcriptome
Proteome & PTMs

Fig. 2.1 The fluxome and the overall integration of mass-energy/information and signaling
networks. Signaling networks connect and modulate the mass-energy-information networks.
The fluxome represents the complete ensemble of fluxes in a cell, and as such it provides a true
dynamic picture of the phenotype because it captures, in response to the environment, the
metabolome (mass-energy) in its functional interactions with the information (genome,
transcriptome, proteome, and posttranslational modifications, PTMs) and signaling networks
(Cortassa et al. 2012 ). As a result of this integration between several cellular processes, the
fluxome represents a unique phenotypic signature of cells (Cascante and Marin 2008 ).
The double sense of the arrows denote reciprocal interactions and an overall cyclic topology and
connectivity that results in circular causality. Thus, an output from a network (metabolome, e.g.,
ROS or AMP:ATP ratio) is the input of the next network (signaling, e.g., AMPK network), which
after processing will feedback on the same network that produced the initial triggers (e.g., ROS,
AMP), thus modulating their levels.

circuitry is not fixed: it is dynamic rather than static, a structure that is itself changing over
the course of the developmental cycle. It is just this dynamic system that I am calling the
developmental program.” (Fox Keller 2000 )
If regulatory state (transcription factors, signaling pathways, etc.) is accepted to control
metabolic state, is it not also unconditionally certain that metabolic state will reciprocally
control the regulatorystate itself? Understanding this reciprocity, and digging to the bottom
of it, is where the future lies (McKnight 2010 )

Cell function can be visualized as the outcome resulting from the unfolding
in space and time of three different kind of interacting networks: mass-energy,
information, and signaling (Fig. 2.1 ). Mass - energy transformation networks
comprise metabolic and transport processes, e.g., metabolic pathways and electro-
chemical gradients, that give rise to the metabolome. Information - carrying networks
include the genome, transcriptome, and proteome, which account for the whole
set of genes, transcripts, proteins, and their posttranslational modifications,
respectively. Signaling networks , distinct in composition, dynamics, and topology,
modulate by activating or repressing the function in space and time of the
mass-energy/information networks to which they relate, e.g., metabolome, genome.
The overall outcome of this process is the phenotype represented by the fluxome,
which accounts for the whole set of fluxes sustained by a diverse range of processes