Page 1
Programming and
Systems Biology
11.1 Programming in
Biology
11.2 Systems Biology
11.1 Programming in Biology From an era of manual computation, we are currently in a
phase of large scale (i.e., high-throughput) data generation,
automated analysis and prediction. Technological
advancements have proven to be a boon for generating
huge data, unthinkable a few decades ago. However,
the arrival of massive data has also thrown massive
challenges in the storage, visualisation, transfer, analysis
and interpretation of data.
The task that looked gigantic a decade back appears
trivial now.
The emergence of arti??cial intelligence (AI) and machine
learning (ML) techniques has changed research practices in
almost every ??eld. It is increasingly evident that, in future,
young biotechnology students working at the cutting edge
of science may require basic programming knowledge and
comfort with chemistry and statistical methods.
The purpose of this chapter is not to give an exhaustive
description of programming languages but to offer a
gentle introduction to some of the most popular high level
languages relevant to biologists.
Chapter 11
Chapte 11.indd 270 09/01/2025 15:18:04
Reprint 2025-26
Page 2
Programming and
Systems Biology
11.1 Programming in
Biology
11.2 Systems Biology
11.1 Programming in Biology From an era of manual computation, we are currently in a
phase of large scale (i.e., high-throughput) data generation,
automated analysis and prediction. Technological
advancements have proven to be a boon for generating
huge data, unthinkable a few decades ago. However,
the arrival of massive data has also thrown massive
challenges in the storage, visualisation, transfer, analysis
and interpretation of data.
The task that looked gigantic a decade back appears
trivial now.
The emergence of arti??cial intelligence (AI) and machine
learning (ML) techniques has changed research practices in
almost every ??eld. It is increasingly evident that, in future,
young biotechnology students working at the cutting edge
of science may require basic programming knowledge and
comfort with chemistry and statistical methods.
The purpose of this chapter is not to give an exhaustive
description of programming languages but to offer a
gentle introduction to some of the most popular high level
languages relevant to biologists.
Chapter 11
Chapte 11.indd 270 09/01/2025 15:18:04
Reprint 2025-26
Programming and Sy Stem S Biology 271
Although bioinformatics software is being developed
for all the available operating system (OS) platforms,
majority of successful application have been developed
on Linux platform. From the beginning of bioinformatics,
PERL is always at the core of sequence based large data
handling. Now a days these platforms are being enriched
with the advanced performing language, normally Python
and R provides strong facilities of statistical packages for
solving biological problems. Similarly, Python modules are
continuously being enriched with visualisation and analysis
modules for handling of large data set on standalone, web
server as well as cloud computing. Beyond these, MATLAB
also includes very good platform for bioinformatics data
analysis. Description of few of the most advanced languages,
active in the area of bioinformatics, is given below:
Python: It is a high level programming general purpose
language created by Guido van Rossum (1991). It is an object
oriented programming interactive language that can run
on unix, mac and windows. Python is very popular within
bioinformatics community largely because: (i) of the clear
meaning of terms used and the structure of statements (ii) it’s
expressivity and alignment to object-oriented programming,
and (iii) the availability of libraries and third-party toolkits.
Python has been successfully used for sequence and
structure analyses, phylogenetics and so on.
R: The name R has been derived from its inventors, Robert
Gentleman and Robert Ihaka, who developed this language.
R language has gained wide acceptance as a rapid and
reliable functional programming language that is ideal
for high volume analysis, visualisation and simulation of
biological data. The software is free and open source. The
R language has been used for analysis of genome sequence
and biomolecular pathways.
Moving from data analysis to designing the systems,
new programming languages have emerged. Among them
are—GEC (Genetic Engineering of living Cells), a rule
based language developed by Microsoft and Kera, an
object oriented knowledge based programming language
developed by Dr. Umesh P. of University of Kerala. Kera
(short form of Kerala, also means coconut) captures
information on the genome, proteins and the cell, using a
user edited biological library called Samhita.
Chapte 11.indd 271 09/01/2025 15:18:04
Reprint 2025-26
Page 3
Programming and
Systems Biology
11.1 Programming in
Biology
11.2 Systems Biology
11.1 Programming in Biology From an era of manual computation, we are currently in a
phase of large scale (i.e., high-throughput) data generation,
automated analysis and prediction. Technological
advancements have proven to be a boon for generating
huge data, unthinkable a few decades ago. However,
the arrival of massive data has also thrown massive
challenges in the storage, visualisation, transfer, analysis
and interpretation of data.
The task that looked gigantic a decade back appears
trivial now.
The emergence of arti??cial intelligence (AI) and machine
learning (ML) techniques has changed research practices in
almost every ??eld. It is increasingly evident that, in future,
young biotechnology students working at the cutting edge
of science may require basic programming knowledge and
comfort with chemistry and statistical methods.
The purpose of this chapter is not to give an exhaustive
description of programming languages but to offer a
gentle introduction to some of the most popular high level
languages relevant to biologists.
Chapter 11
Chapte 11.indd 270 09/01/2025 15:18:04
Reprint 2025-26
Programming and Sy Stem S Biology 271
Although bioinformatics software is being developed
for all the available operating system (OS) platforms,
majority of successful application have been developed
on Linux platform. From the beginning of bioinformatics,
PERL is always at the core of sequence based large data
handling. Now a days these platforms are being enriched
with the advanced performing language, normally Python
and R provides strong facilities of statistical packages for
solving biological problems. Similarly, Python modules are
continuously being enriched with visualisation and analysis
modules for handling of large data set on standalone, web
server as well as cloud computing. Beyond these, MATLAB
also includes very good platform for bioinformatics data
analysis. Description of few of the most advanced languages,
active in the area of bioinformatics, is given below:
Python: It is a high level programming general purpose
language created by Guido van Rossum (1991). It is an object
oriented programming interactive language that can run
on unix, mac and windows. Python is very popular within
bioinformatics community largely because: (i) of the clear
meaning of terms used and the structure of statements (ii) it’s
expressivity and alignment to object-oriented programming,
and (iii) the availability of libraries and third-party toolkits.
Python has been successfully used for sequence and
structure analyses, phylogenetics and so on.
R: The name R has been derived from its inventors, Robert
Gentleman and Robert Ihaka, who developed this language.
R language has gained wide acceptance as a rapid and
reliable functional programming language that is ideal
for high volume analysis, visualisation and simulation of
biological data. The software is free and open source. The
R language has been used for analysis of genome sequence
and biomolecular pathways.
Moving from data analysis to designing the systems,
new programming languages have emerged. Among them
are—GEC (Genetic Engineering of living Cells), a rule
based language developed by Microsoft and Kera, an
object oriented knowledge based programming language
developed by Dr. Umesh P. of University of Kerala. Kera
(short form of Kerala, also means coconut) captures
information on the genome, proteins and the cell, using a
user edited biological library called Samhita.
Chapte 11.indd 271 09/01/2025 15:18:04
Reprint 2025-26
Biotechnology 272
11.2 Sy Stem S Biology 11.2.1 Introduction
In order to understand the mysteries of nature, scientists
are performing experiments since long. Findings of these
experiments are recorded in the form of data in the
literature. Starting from small bit of data to large ones, data
are being collected from decades of experimental efforts.
Presently, a large size of biological data is being generated
and stored in the digital format in a variety of storehouses
called databases. These digital data are the resources
which make the foundation for researchers to develop such
computational models which can perform tasks similar to
our complex biological systems, i.e., those we observe in
real in-vitro/in-vivo experiments or real life. Implementation
of such ideas is being performed with mathematical and
computational models to mimic complex biological systems.
These models are called system models. Therefore, you
can visualise the systems biology as the representation of
system models. Now-a-days systems biology has become
an area for intensive research with potent application.
Thus, it is an interdisciplinary ??eld of study that focuses
on complex biological interactions within biological systems
(Fig. 11.1). The concept of systems biology is being adopted
in a variety of biological contexts, particularly from last two
decades onwards. The human genome project is one of the
most glorious seedings of a thought of systems biology,
which led to new avenues of today’s form of systems biology.
Presently, systems biology models can provide theoretical
description for discovery of emergent functional properties
of cells, tissues and organisms, similar to those which
were only possible through experiments. Examples of most
ef??cient system models are metabolic or signaling network.
Along with fundamental understanding of the mechanism
of action of biological systems, systems biology is intensely
being utilized into potent applicability, e.g., in the areas of
health and diseases from biological networks to modern
therapeutics.
11.2.2 Historical perspective
Before the emergence of systems biology, the scenario
of research in biological sciences (e.g.,1900–1970) was
wondering around physiology, population dynamics,
Chapte 11.indd 272 09/01/2025 15:18:04
Reprint 2025-26
Page 4
Programming and
Systems Biology
11.1 Programming in
Biology
11.2 Systems Biology
11.1 Programming in Biology From an era of manual computation, we are currently in a
phase of large scale (i.e., high-throughput) data generation,
automated analysis and prediction. Technological
advancements have proven to be a boon for generating
huge data, unthinkable a few decades ago. However,
the arrival of massive data has also thrown massive
challenges in the storage, visualisation, transfer, analysis
and interpretation of data.
The task that looked gigantic a decade back appears
trivial now.
The emergence of arti??cial intelligence (AI) and machine
learning (ML) techniques has changed research practices in
almost every ??eld. It is increasingly evident that, in future,
young biotechnology students working at the cutting edge
of science may require basic programming knowledge and
comfort with chemistry and statistical methods.
The purpose of this chapter is not to give an exhaustive
description of programming languages but to offer a
gentle introduction to some of the most popular high level
languages relevant to biologists.
Chapter 11
Chapte 11.indd 270 09/01/2025 15:18:04
Reprint 2025-26
Programming and Sy Stem S Biology 271
Although bioinformatics software is being developed
for all the available operating system (OS) platforms,
majority of successful application have been developed
on Linux platform. From the beginning of bioinformatics,
PERL is always at the core of sequence based large data
handling. Now a days these platforms are being enriched
with the advanced performing language, normally Python
and R provides strong facilities of statistical packages for
solving biological problems. Similarly, Python modules are
continuously being enriched with visualisation and analysis
modules for handling of large data set on standalone, web
server as well as cloud computing. Beyond these, MATLAB
also includes very good platform for bioinformatics data
analysis. Description of few of the most advanced languages,
active in the area of bioinformatics, is given below:
Python: It is a high level programming general purpose
language created by Guido van Rossum (1991). It is an object
oriented programming interactive language that can run
on unix, mac and windows. Python is very popular within
bioinformatics community largely because: (i) of the clear
meaning of terms used and the structure of statements (ii) it’s
expressivity and alignment to object-oriented programming,
and (iii) the availability of libraries and third-party toolkits.
Python has been successfully used for sequence and
structure analyses, phylogenetics and so on.
R: The name R has been derived from its inventors, Robert
Gentleman and Robert Ihaka, who developed this language.
R language has gained wide acceptance as a rapid and
reliable functional programming language that is ideal
for high volume analysis, visualisation and simulation of
biological data. The software is free and open source. The
R language has been used for analysis of genome sequence
and biomolecular pathways.
Moving from data analysis to designing the systems,
new programming languages have emerged. Among them
are—GEC (Genetic Engineering of living Cells), a rule
based language developed by Microsoft and Kera, an
object oriented knowledge based programming language
developed by Dr. Umesh P. of University of Kerala. Kera
(short form of Kerala, also means coconut) captures
information on the genome, proteins and the cell, using a
user edited biological library called Samhita.
Chapte 11.indd 271 09/01/2025 15:18:04
Reprint 2025-26
Biotechnology 272
11.2 Sy Stem S Biology 11.2.1 Introduction
In order to understand the mysteries of nature, scientists
are performing experiments since long. Findings of these
experiments are recorded in the form of data in the
literature. Starting from small bit of data to large ones, data
are being collected from decades of experimental efforts.
Presently, a large size of biological data is being generated
and stored in the digital format in a variety of storehouses
called databases. These digital data are the resources
which make the foundation for researchers to develop such
computational models which can perform tasks similar to
our complex biological systems, i.e., those we observe in
real in-vitro/in-vivo experiments or real life. Implementation
of such ideas is being performed with mathematical and
computational models to mimic complex biological systems.
These models are called system models. Therefore, you
can visualise the systems biology as the representation of
system models. Now-a-days systems biology has become
an area for intensive research with potent application.
Thus, it is an interdisciplinary ??eld of study that focuses
on complex biological interactions within biological systems
(Fig. 11.1). The concept of systems biology is being adopted
in a variety of biological contexts, particularly from last two
decades onwards. The human genome project is one of the
most glorious seedings of a thought of systems biology,
which led to new avenues of today’s form of systems biology.
Presently, systems biology models can provide theoretical
description for discovery of emergent functional properties
of cells, tissues and organisms, similar to those which
were only possible through experiments. Examples of most
ef??cient system models are metabolic or signaling network.
Along with fundamental understanding of the mechanism
of action of biological systems, systems biology is intensely
being utilized into potent applicability, e.g., in the areas of
health and diseases from biological networks to modern
therapeutics.
11.2.2 Historical perspective
Before the emergence of systems biology, the scenario
of research in biological sciences (e.g.,1900–1970) was
wondering around physiology, population dynamics,
Chapte 11.indd 272 09/01/2025 15:18:04
Reprint 2025-26
Programming and Sy Stem S Biology 273
enzyme kinetics, control theory, cybernetics, etc. as the
segmental components of research. The systems biology
has been mapped to be evolved from a physiological
description, when in 1952 Alan Lloyd Hodgkin and Andrew
Fielding Huxley (Nobel laureates) described a mathematical
model for action potential propagation along the axon of
a neuronal cell. More evolved implementation of theory
emerged in 1960 when the ??rst computer model of the
heart pacemaker was developed by Denis Noble [PMID
13729365]. The systems biology was formally launched
by systems theorist Mihajlo Mesarovic in 1966 at the
Case Institute of Technology in Cleveland, Ohio, titled
“Systems Theory and Biology”. In 1968, ??rst theory about
systems biology was published by Ludwig von Bertalanffy,
which is considered as precursor of this discipline. The
duration betwen 1960s and 1970s was the decade of
development of multiple aspects of complex molecular
systems, such as the metabolic control analysis and the
biochemical systems theory. Furthermore, skepticism
of systems theory with molecular biology was broken by
the development of theoretical biology, which includes
the quantitative modelling of biological processes. Since
1990s, functional genomics is generating large quantities
of high-quality biological data, which are helping in the
development of more realistic models. In continuation of
these developments in the area of systems biology, National
Science Foundation (NSF) put forward a challenge to
mathematically model the whole cell. In this direction, in
2003, Massachusetts Institute of Technology (MIT) started
search of solution of this challenge in association with
CytoSolve. Finally, in 2012 whole cell model of Mycoplasma
genitalium (cell wall less bacterium), for prediction of
cell viability in response to the genetic mutations, was
developed by Mount Sinai School of Medicine, New York.
Presently, a big systems biology project, namely ‘Physiome’
is available (http://physiomeproject.org/). This project is
aimed at developing a multi-scale modelling framework
for understanding the physiological function that allows
models to be combined and linked in a hierarchical
fashion. For example, electromechanical models of the
heart, need to be combined with models of ion channels,
myo??lament mechanics and signal transduction pathways
at the subcellular level and then to link these processes
Chapte 11.indd 273 09/01/2025 15:18:04
Reprint 2025-26
Page 5
Programming and
Systems Biology
11.1 Programming in
Biology
11.2 Systems Biology
11.1 Programming in Biology From an era of manual computation, we are currently in a
phase of large scale (i.e., high-throughput) data generation,
automated analysis and prediction. Technological
advancements have proven to be a boon for generating
huge data, unthinkable a few decades ago. However,
the arrival of massive data has also thrown massive
challenges in the storage, visualisation, transfer, analysis
and interpretation of data.
The task that looked gigantic a decade back appears
trivial now.
The emergence of arti??cial intelligence (AI) and machine
learning (ML) techniques has changed research practices in
almost every ??eld. It is increasingly evident that, in future,
young biotechnology students working at the cutting edge
of science may require basic programming knowledge and
comfort with chemistry and statistical methods.
The purpose of this chapter is not to give an exhaustive
description of programming languages but to offer a
gentle introduction to some of the most popular high level
languages relevant to biologists.
Chapter 11
Chapte 11.indd 270 09/01/2025 15:18:04
Reprint 2025-26
Programming and Sy Stem S Biology 271
Although bioinformatics software is being developed
for all the available operating system (OS) platforms,
majority of successful application have been developed
on Linux platform. From the beginning of bioinformatics,
PERL is always at the core of sequence based large data
handling. Now a days these platforms are being enriched
with the advanced performing language, normally Python
and R provides strong facilities of statistical packages for
solving biological problems. Similarly, Python modules are
continuously being enriched with visualisation and analysis
modules for handling of large data set on standalone, web
server as well as cloud computing. Beyond these, MATLAB
also includes very good platform for bioinformatics data
analysis. Description of few of the most advanced languages,
active in the area of bioinformatics, is given below:
Python: It is a high level programming general purpose
language created by Guido van Rossum (1991). It is an object
oriented programming interactive language that can run
on unix, mac and windows. Python is very popular within
bioinformatics community largely because: (i) of the clear
meaning of terms used and the structure of statements (ii) it’s
expressivity and alignment to object-oriented programming,
and (iii) the availability of libraries and third-party toolkits.
Python has been successfully used for sequence and
structure analyses, phylogenetics and so on.
R: The name R has been derived from its inventors, Robert
Gentleman and Robert Ihaka, who developed this language.
R language has gained wide acceptance as a rapid and
reliable functional programming language that is ideal
for high volume analysis, visualisation and simulation of
biological data. The software is free and open source. The
R language has been used for analysis of genome sequence
and biomolecular pathways.
Moving from data analysis to designing the systems,
new programming languages have emerged. Among them
are—GEC (Genetic Engineering of living Cells), a rule
based language developed by Microsoft and Kera, an
object oriented knowledge based programming language
developed by Dr. Umesh P. of University of Kerala. Kera
(short form of Kerala, also means coconut) captures
information on the genome, proteins and the cell, using a
user edited biological library called Samhita.
Chapte 11.indd 271 09/01/2025 15:18:04
Reprint 2025-26
Biotechnology 272
11.2 Sy Stem S Biology 11.2.1 Introduction
In order to understand the mysteries of nature, scientists
are performing experiments since long. Findings of these
experiments are recorded in the form of data in the
literature. Starting from small bit of data to large ones, data
are being collected from decades of experimental efforts.
Presently, a large size of biological data is being generated
and stored in the digital format in a variety of storehouses
called databases. These digital data are the resources
which make the foundation for researchers to develop such
computational models which can perform tasks similar to
our complex biological systems, i.e., those we observe in
real in-vitro/in-vivo experiments or real life. Implementation
of such ideas is being performed with mathematical and
computational models to mimic complex biological systems.
These models are called system models. Therefore, you
can visualise the systems biology as the representation of
system models. Now-a-days systems biology has become
an area for intensive research with potent application.
Thus, it is an interdisciplinary ??eld of study that focuses
on complex biological interactions within biological systems
(Fig. 11.1). The concept of systems biology is being adopted
in a variety of biological contexts, particularly from last two
decades onwards. The human genome project is one of the
most glorious seedings of a thought of systems biology,
which led to new avenues of today’s form of systems biology.
Presently, systems biology models can provide theoretical
description for discovery of emergent functional properties
of cells, tissues and organisms, similar to those which
were only possible through experiments. Examples of most
ef??cient system models are metabolic or signaling network.
Along with fundamental understanding of the mechanism
of action of biological systems, systems biology is intensely
being utilized into potent applicability, e.g., in the areas of
health and diseases from biological networks to modern
therapeutics.
11.2.2 Historical perspective
Before the emergence of systems biology, the scenario
of research in biological sciences (e.g.,1900–1970) was
wondering around physiology, population dynamics,
Chapte 11.indd 272 09/01/2025 15:18:04
Reprint 2025-26
Programming and Sy Stem S Biology 273
enzyme kinetics, control theory, cybernetics, etc. as the
segmental components of research. The systems biology
has been mapped to be evolved from a physiological
description, when in 1952 Alan Lloyd Hodgkin and Andrew
Fielding Huxley (Nobel laureates) described a mathematical
model for action potential propagation along the axon of
a neuronal cell. More evolved implementation of theory
emerged in 1960 when the ??rst computer model of the
heart pacemaker was developed by Denis Noble [PMID
13729365]. The systems biology was formally launched
by systems theorist Mihajlo Mesarovic in 1966 at the
Case Institute of Technology in Cleveland, Ohio, titled
“Systems Theory and Biology”. In 1968, ??rst theory about
systems biology was published by Ludwig von Bertalanffy,
which is considered as precursor of this discipline. The
duration betwen 1960s and 1970s was the decade of
development of multiple aspects of complex molecular
systems, such as the metabolic control analysis and the
biochemical systems theory. Furthermore, skepticism
of systems theory with molecular biology was broken by
the development of theoretical biology, which includes
the quantitative modelling of biological processes. Since
1990s, functional genomics is generating large quantities
of high-quality biological data, which are helping in the
development of more realistic models. In continuation of
these developments in the area of systems biology, National
Science Foundation (NSF) put forward a challenge to
mathematically model the whole cell. In this direction, in
2003, Massachusetts Institute of Technology (MIT) started
search of solution of this challenge in association with
CytoSolve. Finally, in 2012 whole cell model of Mycoplasma
genitalium (cell wall less bacterium), for prediction of
cell viability in response to the genetic mutations, was
developed by Mount Sinai School of Medicine, New York.
Presently, a big systems biology project, namely ‘Physiome’
is available (http://physiomeproject.org/). This project is
aimed at developing a multi-scale modelling framework
for understanding the physiological function that allows
models to be combined and linked in a hierarchical
fashion. For example, electromechanical models of the
heart, need to be combined with models of ion channels,
myo??lament mechanics and signal transduction pathways
at the subcellular level and then to link these processes
Chapte 11.indd 273 09/01/2025 15:18:04
Reprint 2025-26
Biotechnology 274
to models of tissue mechanics, wavefront propagation and
coronary blood ??ow—each of which may well have been
developed by a different group of researchers.
11.2.3 Theme behind the systems biology
To cover diverse disciplines of biology, systems biology has
been observed from different aspects. The reductionist
worked on identi??cation of components and interactions
of a system, but no convincing method
could be evolved to describe the
pluralism of system. Pluralism can be
better observed through quantitative
measures of multiple components
simultaneously and this can only
be possible by mathematical models
containing rigorous data integration.
In this way, it can be said that systems
biology is the observation of system
by integrating different components
together (Fig.11.1). Covering all the
individual components together at
the core of theme of systems biology
is: ‘Object network mapping and
its integration with interdependent
dynamic event—kinetics with partial
differential equations’.
11.2.4 Protocol for systems
biology experiments
To perform a standard systems biology experiment,
discrete steps, as shown in Fig.11.2, are followed.
The whole protocol basically involves de??nition of
problem, designing of experiment, execution of the
experiments to generate data, collection of the resultant
data and their arrangement in appropriate ??le formats
followed by the development of network interface. This is
followed by transfer of this network interface which should
be precise as well as mechanism based so that the model
can be developed accordingly. This is further followed by
analysis of discrepancies between model based simulation
results and experimental data and accordingly model the
hypothesis with reference to the discrepancies observed.
Finally, the simulation is repeated and tested again and
Fig. 11.1: Depiction of Systems Biology as an
interdisciplinary ??eld of study that fo -
cuses on complex biological interactions
within biological systems
SYSTEMS
BIOLOGY
- Synthesis
- Analysis
- Modelling
Concept
SYSTEM
SCIENCE
- Hypotheses
- Genetic
Modi?cation
- Quantitative
Measurement
LIFE
SCIENCE
INFORMATION
SCIENCE
- Data Bases
- Modelling Tools
- Visualisation
Tools
Chapte 11.indd 274 09/01/2025 15:18:04
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