BTD41 System Biology: Dr. Akhilesh Dubey Assistant Professor BSE Division

BTD41
System Biology
Dr. Akhilesh Dubey

Assistant Professor
BSE Division
WHAT IS “SYSTEM BIOLOGY” ?
The study of the mechanisms underlying complex biological processes as integrated systems of
many interacting components.
Systems biology involves

1. collection of large sets of experimental data
2. proposal of mathematical models that might account for at least some significant aspects of
this data set,
3. accurate computer solution of the mathematical equations to obtain numerical predictions, and
4. assessment of the quality of the model by comparing numerical simulations with the
experimental data.
-(Leroy Hood, 1999)
OVERVIEW OF SYSTEM BIOLOGY
● As a field of study, particularly, the study of the interactions between the components of
biological systems, and how these interactions give rise to the function and behavior of that
system
(for example, the enzymes and metabolites in a metabolic pathway).
● As a paradigm, usually defined in antithesis to the so-called reductionist paradigm (biological

organisation), although fully consistent with the scientific method. The distinction between the two
paradigms is referred to in these quotations:
"The reductionist approach has successfully identified most of the components and many of the
interactions but, unfortunately, offers no convincing concepts or methods to understand how
system properties emerge...the pluralism of causes and effects in biological networks is better
addressed by observing, through quantitative measures, multiple components simultaneously and
by rigorous data integration with mathematical models" Sauer et al
"Systems biology...is about putting together rather than taking apart, integration rather than
reduction. It requires that we develop ways of thinking about integration that are as rigorous as
our reductionist programmes, but different....It means changing our philosophy, in the full sense of
OVERVIEW OF SYSTEM BIOLOGY
● As a series of operational protocols used for performing research,

- a cycle composed of theory, analytic or computational modelling
1. to propose specific testable hypotheses about a biological system,

2. to experimentally validate the model
3. to utilize the newly acquired quantitative description of cells or cell processes in order to
further refine the computational model or theory.
Since the objective is a model of the interactions in a system, the experimental techniques that
most suit systems biology are those that are system-wide and attempt to be as complete as
possible. Therefore, transcriptomics, metabolomics, proteomics and high-throughput techniques
are used to collect quantitative data for the construction and validation of models.
● As a socioscientific phenomenon defined by the strategy of pursuing integration of complex data

about the interactions in biological systems from diverse experimental sources using
interdisciplinary tools and personnel.
● As the application of dynamical systems theory to molecular biology.

HISTORY
Systems biology finds its roots in:
● the quantitative modeling of enzyme kinetics, a discipline that flourished between 1900
and 1970,
● the mathematical modeling of population growth,
● the simulations developed to study neurophysiology, and
● control theory and cybernetics.

HISTORY
● One of the theorists who can be seen as one of the precursors of systems biology is
Ludwig von Bertalanffy with his General Systems Theory.
● One of the first numerical simulations in biology was published in 1952 by the British
neurophysiologists and Nobel prize winners Alan Lloyd Hodgkin and Andrew Fielding
Huxley, who constructed a mathematical model that explained the action potential
propagating along the axon of a neuronal cell.
● In 1960, Denis Noble developed the first computer model of the heart pacemaker.
● The 1960s and 1970s saw the development of several approaches to study complex
molecular systems, such as the Metabolic Control Analysis and the biochemical
systems theory.
The successes of molecular biology throughout the 1980s, coupled with a skepticism toward
theoretical biology, that then promised more than it achieved, caused the quantitative modelling of
biological processes to become a somewhat minor field.
HISTORY
● Birth of Functional Genomics in the 1990s meant that large quantities of high quality
data became available, while the computing power exploded, making more realistic
models possible. In 1997, the group of Masaru Tomita published the first quantitative
model of the metabolism of a whole (hypothetical) cell.
● Around the year 2000, after Institutes of Systems Biology were established in Seattle
and Tokyo, systems biology emerged as a movement in its own right, spurred on by the
completion of various genome projects, the large increase in data from the omics (e.g.
genomics and proteomics) and the accompanying advances in high-throughput
experiments and bioinformatics.
● Since then, various research institutes dedicated to systems biology have been
developed.
○ the NIGMS of NIH established a project grant that is currently supporting over ten
Systems Biology Centers in the United States.
○ In summer 2006, The National Science Foundation (NSF) put forward a grand
challenge for systems biology in the 21st century to build a mathematical model
of the whole cell.
DIFFERENT AREAS ASSOCIATED WITH SYSTEM BIOLOGY
According to the interpretation of Systems Biology as the ability to obtain, integrate and analyze
complex data sets from multiple experimental sources using interdisciplinary tools, some typical
technology platforms are:
● Phenomics: Organismal variation in phenotype as it changes during its life span.
● Genomics: Organismal deoxyribonucleic acid (DNA) sequence, including intra-organisamal

cell specific variation. (i.e. Telomere length variation etc.).
● Epigenomics/Epigenetics: Organismal and corresponding cell specific transcriptomic

regulating factors not empirically coded in the genomic sequence. (i.e. DNA methylation,
Histone Acetylation etc.).
● Transcriptomics: Organismal, tissue or whole cell gene expression measurements by DNA

microarrays or serial analysis of gene expression
● Interferomics: Organismal, tissue, or cell level transcript correcting factors (i.e. RNA
interference)
● Translatomics / Proteomics: Organismal, tissue, or cell level measurements of proteins and

peptides via two-dimensional gel electrophoresis, mass spectrometry or multi-dimensional
protein identification techniques (advanced HPLC systems coupled with mass
spectrometry). Sub disciplines include phosphoproteomics, glycoproteomics and other
methods to detect chemically modified proteins.
● Metabolomics: Organismal, tissue, or cell level measurements of all small-molecules

known as metabolites.
● Glycomics: Organismal, tissue, or cell level measurements of carbohydrates. •
● Lipidomics: Organismal, tissue, or cell level measurements of lipids

In addition to the identification and quantification of the biological molecules further techniques
analyze the dynamics and interactions within a cell. This includes:
● Interactomics: Organismal, tissue, or cell level study of interactions between molecules.

Currently the authoritative molecular discipline in this field of study is protein-protein
interactions (PPI), although the working definition does not preclude inclusion of other
molecular disciplines such as those defined here.
● NeuroElectroDynamics: Organismal, brain computing function as a dynamic system,

underlying biophysical mechanisms and emerging computation by electrical interactions.
● Fluxomics: Organismal, tissue, or cell level measurements of molecular dynamic changes

over time.
● Biomics: systems analysis of the biome.

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BTD41

Dr. Akhilesh Dubey

Systems biology involves

● As a paradigm, usually defined in antithesis to the so-called reductionist paradigm (biological

● As a series of operational protocols used for performing research,

1. to propose specific testable hypotheses about a biological system,

● As a socioscientific phenomenon defined by the strategy of pursuing integration of complex data

● As the application of dynamical systems theory to molecular biology.

Systems biology finds its roots in:

● the mathematical modeling of population growth,

● the simulations developed to study neurophysiology, and

● control theory and cybernetics.

● Phenomics: Organismal variation in phenotype as it changes during its life span.

● Genomics: Organismal deoxyribonucleic acid (DNA) sequence, including intra-organisamal

● Epigenomics/Epigenetics: Organismal and corresponding cell specific transcriptomic

● Transcriptomics: Organismal, tissue or whole cell gene expression measurements by DNA

● Translatomics / Proteomics: Organismal, tissue, or cell level measurements of proteins and

● Metabolomics: Organismal, tissue, or cell level measurements of all small-molecules

● Glycomics: Organismal, tissue, or cell level measurements of carbohydrates. •

● Lipidomics: Organismal, tissue, or cell level measurements of lipids

● Interactomics: Organismal, tissue, or cell level study of interactions between molecules.

● NeuroElectroDynamics: Organismal, brain computing function as a dynamic system,

● Fluxomics: Organismal, tissue, or cell level measurements of molecular dynamic changes

● Biomics: systems analysis of the biome.

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