I HISTORY OF BIOINFORMATICS Bioinformatics is an interdisciplinary field that develops methods

and software tools for understanding biologicaldata. As an interdisciplinary field of science,

bioinformatics combines computer science, statistics, mathematics, and engineering to analyze and
interpret biological data. Bioinformatics has been used for in silico analyses of biological queries
using mathematical and statistical techniques. Bioinformatics derives knowledge from computer
analysis of biological data. These can consist of the information stored in the genetic code, but also
experimental results from various sources, patient statistics, and scientific literature. Research in
bioinformatics includes method development for storage, retrieval, and analysis of the data.
Bioinformatics is a rapidly developing branch of biology and is highly interdisciplinary, using
techniques and concepts from informatics, statistics, mathematics, chemistry, biochemistry, physics,
and linguistics. It has many practical applications in different areas of biology and medicine.
Bioinformatics: Research, development, or application of computational tools and approaches for
expanding the use of biological, medical, behavioral or health data, including those to acquire, store,
organize, archive, analyze, or visualize such data. Computational Biology: The development and
application of data-analytical and theoretical methods, mathematical modeling and computational
simulation techniques to the study of biological, behavioral, and social systems. "Classical"
bioinformatics: "The mathematical, statistical and computing methods that aim to solve biological
problems using DNA and amino acid sequences and related information.” The National Center for
Biotechnology Information (NCBI 2001) defines bioinformatics as: "Bioinformatics is the field of
science in which biology, computer science, and information technology merge into a single
discipline. There are three important subdisciplines within bioinformatics: the development of new
algorithms and statistics with which to assess relationships among members of large data sets; the
analysis and interpretation of various types of data including nucleotide and amino acid sequences,
protein domains, and protein structures; and the development and implementation of tools that
enable efficient access and management of different types of information 3 Even though the three
terms: bioinformatics, computational biology and bioinformation infrastructure are often times used
interchangeably, broadly, the three may be defined as follows: 1. bioinformatics refers to database-
like activities, involving persistent sets of data that are maintained in a consistent state over
essentially indefinite periods of time; 2. computational biology encompasses the use of algorithmic
tools to facilitate biological analyses; while 3. bioinformation infrastructure comprises the entire
collective of information management systems, analysis tools and communication networks
supporting biology. Thus, the latter may be viewed as a computational scaffold of the former two.
There are three important sub-disciplines within bioinformatics: • the development of new
algorithms and statistics with which to assess relationships among members of large data sets; • the
analysis and interpretation of various types of data including nucleotide and amino acid sequences,
protein domains, and protein structures; • and the development and implementation of tools that
enable efficient access and management of different types of information Bioinformatics definition -
other sources • Bioinformatics or computational biology is the use of mathematical and
informational techniques, including statistics, to solve biological problems, usually by creating or
using computer programs, mathematical models or both. One of the main areas of bioinformatics is
the data mining and analysis of the data gathered by the various genome projects. Other areas are
sequence alignment, protein structure prediction, systems biology, protein-protein interactions and
virtual evolution. (source: www.answers.com) • Bioinformatics is the science of developing
computer databases and algorithms for the purpose of speeding up and enhancing biological
research. (source: www.whatis.com) • "Biologists using computers, or the other way around.
Bioinformatics is more of a tool 4 than a discipline.(source: An Understandable Definition of
Bioinformatics , The O'Reilly Bioinformatics Technology Conference, 2003) (4) • The application of
computer technology to the management of biological information. Specifically, it is the science of
developing computer databases and algorithms to facilitate and expedite biological research.
(source: Webopedia) • Bioinformatics: a combination of Computer Science, Information Technology
and Genetics to determine and analyze genetic information. (Definition from BitsJournal.com) •
Bioinformatics is the application of computer technology to the management and analysis of
biological data. The result is that computers are being used to gather, store, analyse and merge
biological data.(EBI - 2can resource) • Bioinformatics is concerned with the creation and
development of advanced information and computational technologies to solve problems in biology.
• Bioinformatics uses techniques from informatics, statistics, molecular biology and high-
performance computing to obtain information about genomic or protein sequence data.
Bioinformaticist versus a Bioinformatician A bioinformaticist is an expert who not only knows how to
use bioinformatics tools, but also knows how to write interfaces for effective use of the tools. A
bioinformatician , on the other hand, is a trained individual who only knows to use bioinformatics
tools without a deeper understanding. Aims of Bioinformatics In general, the aims of bioinformatics
are three-fold. 1. The first aim of bioinformatics is to store the biological data organized in form of a
database. This allows the researchers an easy access to existing information and submit new entries.
These data must be annoted to give a suitable meaning or to assign its functional characteristics. The
databases must also be able to correlate between different hierarchies of information. For example:
GenBank for nucleotide and protein sequence information, Protein Data Bank for 3D
macromolecular structures, etc. 5 2. The second aim is to develop tools and resources that aid in the
analysis of data. For example: BLAST to find out similar nucleotide/amino-acid sequences, ClustalW
to align two or more nucleotide/amino-acid sequences, Primer3 to design primers probes for PCR
techniques, etc. 3. The third and the most important aim of bioinformatics is to exploit these
computational tools to analyze the biological data interpret the results in a biologically meaningful
manner. Goals The goals of bioinformatics thus is to provide scientists with a means to explain 1.
Normal biological processes 2. Malfunctions in these processes which lead to diseases 3. Approaches
to improving drug discovery To study how normal cellular activities are altered in different disease
states, the biological data must be combined to form a comprehensive picture of these activities.
Therefore, the field of bioinformatics has evolved such that the most pressing task now involves the
analysis and interpretation of various types of data. This includes nucleotide and amino acid
sequences, protein domains, and protein structures. The actual process of analyzing and interpreting
data is referred to as computational biology. Important sub-disciplines within bioinformatics and
computational biology include: • Development and implementation of computer programs that
enable efficient access to, use and management of, various types of information • Development of
new algorithms (mathematical formulas) and statistical measures that assess relationships among
members of large data sets. For example, there are methods to locate a gene within a sequence, to
predict protein structure and/or function, and to cluster protein sequences into families of related
sequences. The primary goal of bioinformatics is to increase the understanding of biological
processes. What sets it apart from other approaches, however, is its focus on developing and
applying 6 computationally intensive techniques to achieve this goal. Examples include: pattern
recognition, data mining, machine learning algorithms, and visualization. Major research efforts in
the field include sequence alignment, gene finding, genome assembly, drug design, drug discovery,
protein structure alignment, protein structure prediction, prediction of gene expression and
protein–protein interactions, genome-wide association studies, the modeling of evolution and cell
division/mitosis. Bioinformatics now entails the creation and advancement of databases, algorithms,
computational and statistical techniques, and theory to solve formal and practical problems arising
from the management and analysis of biological data. Tools: Used in three areas • Molecular
Sequence Analysis • Molecular Structural Analysis • Molecular Functional Analysis Over the past few
decades, rapid developments in genomic and other molecular research technologies and
developments in information technologies have combined to produce a tremendous amount of
information related to molecular biology. Bioinformatics is the name given to these mathematical
and computing approaches used to glean understanding of biological processes. Common activities
in bioinformatics include mapping and analyzing DNA and protein sequences, aligning DNA and
protein sequences to compare them, and creating and viewing 3- D models of protein structures.
Bioinformatics encompasses the use of tools and techniques from three separate disciplines;
molecular biology (the source of the data to be analyzed), computer science (supplies the hardware
for running analysis and the networks to communicate the results), and the data analysis algorithms
which strictly define bioinformatics. For this reason, the editors have decided to incorporate events
from these areas into a brief history of the field. A SHORT HISTORY OF BIOINFORMATICS 1933 A new
technique, electrophoresis, is introduced by Tiselius for separating proteins in solution. 7 1951
Pauling and Corey propose the structure for the alpha-helix and beta-sheet (Proc. Natl. Acad. Sci.
USA, 27: 205-211, 1951; Proc. Natl. Acad. Sci. USA, 37: 729- 740, 1951). 1953 Watson and Crick
propose the double helix model for DNA based on x-ray data obtained by Franklin and Wilkins
(Nature, 171: 737-738, 1953). 1954 Perutz's group develop heavy atom methods to solve the phase
problem in protein crystallography. 1955 The sequence of the first protein to be analyzed, bovine
insulin, is announced by F. Sanger. 1969 The ARPANET is created by linking computers at Stanford
and UCLA. 1970 The details of the Needleman-Wunsch algorithm for sequence comparison are
published. 1972 The first recombinant DNA molecule is created by Paul Berg and his group. 1973 The
Brookhaven Protein Data Bank is announced (Acta. Cryst. B, 1973, 29: 1746). Robert Metcalfe
receives his Ph.D. from Harvard University. His thesis describes Ethernet. 1974 Vint Cerf and Robert
Kahn develop the concept of connecting networks of computers into an "internet" and develop the
Transmission Control Protocol (TCP). 1975 Microsoft Corporation is founded by Bill Gates and Paul
Allen. Two-dimensional electrophoresis, where separation of proteins on SDS polyacrylamide gel is
combined with separation according to isoelectric points, is announced by P. H. O'Farrell (J. Biol.
Chem., 250: 4007-4021, 1975). E. M. Southern published the experimental details for the Southern
Blot technique of specific sequences of DNA (J. Mol. Biol., 98: 503-517, 1975). 1977 The full
description of the Brookhaven PDB (http://www.pdb.bnl.gov) is published (Bernstein, F.C.; Koetzle,
T.F.; Williams, G.J.B.; Meyer, E.F.; Brice, M.D.; Rodgers, J.R.; Kennard, O.; Shimanouchi, T.; Tasumi,
M.J.; J. Mol. Biol., 1977, 112:, 535). Allan Maxam and Walter Gilbert (Harvard) and Frederick Sanger
(U.K. Medical Research Council), report methods for sequencing DNA. 1980 The first complete gene
sequence for an organism (FX174) is published. The gene consists of 5,386 base pairs which code
nine proteins. 8 Wuthrich et. al. publish paper detailing the use of multi-dimensional NMR for
protein structure determination (Kumar, A.; Ernst, R.R.; Wuthrich, K.; Biochem. Biophys. Res. Comm.,
1980, 95:, 1). IntelliGenetics, Inc. founded in California. Their primary product is the IntelliGenetics
Suite of programs for DNA and protein sequence analysis. 1981 The Smith-Waterman algorithm for
sequence alignment is published. IBM introduces its Personal Computer to the market. 1982
Genetics Computer Group (GCG) created as a part of the University of Wisconsin of Wisconsin
Biotechnology Center. The company's primary product is The Wisconsin Suite of molecular biology
tools. 1983 The Compact Disk (CD) is launched. 1984 Jon Postel's Domain Name System (DNS) is
placed on-line. The Macintosh is announced by Apple Computer. 1985 The FASTP algorithm is
published. The PCR reaction is described by Kary Mullis and co-workers. 1986 The term "Genomics"
appeared for the first time to describe the scientific discipline of mapping, sequencing, and analyzing
genes. The term was coined by Thomas Roderick as a name for the new journal. Amoco Technology
Corporation acquires IntelliGenetics. NSFnet debuts. The SWISS-PROT database is created by the
Department of Medical Biochemistry of the University of Geneva and the European Molecular
Biology Laboratory (EMBL). 1987 The use of yeast artifical chromosomes (YAC) is described (David T.
Burke, et. al., Science, 236: 806-812). The physical map of E. coli is published (Y. Kohara, et. al., Cell
51: 319-337). 1988 The National Center for Biotechnology Information (NCBI) is established at the
National Cancer Institute. The Human Genome Initiative is started (Commission on Life Sciences,
National Research Council. Mapping and Sequencing the Human Genome, National Academy Press:
Washington, D.C.), 1988. The FASTA algorithm for sequence comparison is published by Pearson and
Lupman. A new program, an Internet computer virus designed by a student, infects 6,000 military
computers in the US. 9 1989 The Genetics Computer Group (GCG) becomes a private company.
Oxford Molecular Group, Ltd. (OMG) founded in Oxford, UK by Anthony Marchington, David Ricketts,
James Hiddleston, Anthony Rees, and W. Graham Richards. Primary products: Anaconda, Asp,
Cameleon and others (molecular modeling, drug design, protein design). 1990 The BLAST program
(Altschul, et. al.) is implemented. Molecular Applications Group is founded in California by Michael
Levitt and Chris Lee. Their primary products are Look and SegMod which are used for molecular
modeling and protein design. InforMax is founded in Bethesda, MD. The company's products
address sequence analysis, database and data management, searching, publication graphics, clone
construction, mapping and primer design. 1991 The research institute in Geneva (CERN) announces
the creation of the protocols which make-up the World Wide Web. The creation and use of
expressed sequence tags (ESTs) is described (J. Craig Venter, et. al., Science, 252: 1651-1656). Incyte
Pharmaceuticals, a genomics company headquartered in Palo Alto California, is formed. Myriad
Genetics, Inc. is founded in Utah. The company's goal is to lead in the discovery of major common
human disease genes and their related pathways. The Company has discovered and sequenced, with
its academic collaborators, the following major genes: BRCA1, BRCA2, CHD1, MMAC1, MMSC1,
MMSC2, CtIP, p16, p19, and MTS2. 1992 Human Genome Systems, Gaithersburg Maryland, is
formed by William Haseltine. The Institute for Genomic Research (TIGR) is established by Craig
Venter. Genome Therapeutics announces its incorporation. Mel Simon and coworkers announce the
use of BACs for cloning. 1993 CuraGen Corporation is formed in New Haven, CT. Affymetrix begins
independent operations in Santa Clara, California 1994 Netscape Comminications Corporation
founded and releases Navigator, the commercial version of NCSA's Mozilla. Gene Logic is formed in
Maryland. 10 The PRINTS database of protein motifs is published by Attwood and Beck. Oxford
Molecular Group acquires IntelliGenetics. 1995 The Haemophilus influenzea genome (1.8 Mb) is
sequenced. The Mycoplasma genitalium genome is sequenced. 1996 Oxford Molecular Group
acquires the MacVector product from Eastman Kodak. The genome for Saccharomyces cerevisiae
(baker's yeast, 12.1 Mb) is sequenced. The Prosite database is reported by Bairoch, et.al. Affymetrix
produces the first commercial DNA chips. 1997 The genome for E. coli (4.7 Mbp) is published. Oxford
Molecular Group acquires the Genetics Computer Group. LION bioscience AG founded as an
integrated genomics company with strong focus on bioinformatics. The company is built from IP out
of the European Molecular Biology Laboratory (EMBL), the European Bioinformatics Institute (EBI),
the German Cancer Research Center (DKFZ), and the University of Heidelberg. Paradigm Genetics
Inc., a company focussed on the application of genomic technologies to enhance worldwide food
and fiber production, is founded in Research Triangle Park, NC. deCode genetics publishes a paper
that described the location of the FET1 gene, which is responsible for familial essential tremor, on
chromosome 13 (Nature Genetics). 1998 The genomes for Caenorhabditis elegans and baker's yeast
are published. The Swiss Institute of Bioinformatics is established as a non-profit foundation. Craig
Venter forms Celera in Rockville, Maryland. PE Informatics was formed as a Center of Excellence
within PE Biosystems. This center brings together and leverages the complementary expertise of PE
Nelson and Molecular Informatics, to further complement the genetic instrumentation expertise of
Applied Biosystems. Inpharmatica, a new Genomics and Bioinformatics company, is established by
University College London, the Wolfson Institute for Biomedical Research, five leading scientists
from major British academic centers and Unibio Limited. GeneFormatics, a company dedicated to
the analysis and prediction of protein structure and function, is formed in San Diego. 11 Molecular
Simulations Inc. is acquired by Pharmacopeia 1999 deCode genetics maps the gene linked to pre-
eclampsia as a locus on chromosome 2p13. 2000 The genome for Pseudomonas aeruginosa (6.3
Mbp) is published. The A. thaliana genome (100 Mb) is secquenced. The D. melanogaster genome
(180Mb) is sequenced. Pharmacopeia acquires Oxford Molecular Group. 2001 The human genome
(3,000 Mbp) is published. 2002 Chang Gung Genomic Research Center established. -Bioinformatics
Center, -Proteomics Center, -Microarray Center Figure 1 Applications Bioinformatics joins
mathematics, statistics, and computer science and information technology to solve complex
biological problems. These problems are usually at the molecular level which cannot be solved by
other means. This interesting field of science has many applications and research areas where it can
be applied. 1950 1960 1970 1980 1990 2000 2010 2020 Key milestones 12 All the applications of
bioinformatics are carried out in the user level. Here is the biologist including the students at various
level can use certain applications and use the output in their research or in study. Various
bioinformatics application can be categorized under following groups: Sequence Analysis Function
Analysis Structure Analysis Figure 2 Sequence Analysis: All the applications that analyzes various
types of sequence information and can compare between similar types of information is grouped
under Sequence Analysis. Function Analysis: These applications analyze the function engraved within
the sequences and helps predict the functional interaction between various proteins or genes. Also
expressional analysis of various genes is a prime topic for research these days. Structure Analysis:
When it comes to the realm of RNA and Proteins, its structure plays a vital role in the interaction
with any other thing. This gave birth to a whole new branch termed 13 Structural Bioinformatics
with is devoted to predict the structure and possible roles of these structures of Proteins or RNA
Sequence Analysis: The application of sequence analysis determines those genes which encode
regulatory sequences or peptides by using the information of sequencing. For sequence analysis,
there are many powerful tools and computers which perform the duty of analyzing the genome of
various organisms. These computers and tools also see the DNA mutations in an organism and also
detect and identify those sequences which are related. Shotgun sequence techniques are also used
for sequence analysis of numerous fragments of DNA. Special software is used to see the
overlapping of fragments and their assembly. Prediction of Protein Structure:- It is easy to determine
the primary structure of proteins in the form of amino acids which are present on the DNA molecule
but it is difficult to determine the secondary, tertiary or quaternary structures of proteins. For this
purpose either the method of crystallography is used or tools of bioinformatics can also be used to
determine the complex protein structures. Genome Annotation:- In genome annotation, genomes
are marked to know the regulatory sequences and protein coding. It is a very important part of the
human genome project as it determines the regulatory sequences. Comparative Genomics:-
Comparative genomics is the branch of bioinformatics which determines the genomic structure and
function relation between different biological species. For this purpose, intergenomic maps are
constructed which enable the scientists to trace the processes of evolution that occur in genomes of
different species. These maps contain the information about the point mutations as well as the
information about the duplication of large chromosomal segments. Health and Drug discovery: The
tools of bioinformatics are also helpful in drug discovery, diagnosis and disease 14 management.
Complete sequencing of human genes has enabled the scientists to make medicines and drugs which
can target more than 500 genes. Different computational tools and drug targets has made the drug
delivery easy and specific because now only those cells can be targeted which are diseased or
mutated. It is also easy to know the molecular basis of a disease. Application of Bioinformatics in
various Fields Molecular medicine The human genome will have profound effects on the fields of
biomedical research and clinical medicine. Every disease has a genetic component. This may be
inherited (as is the case with an estimated 3000-4000 hereditary disease including Cystic Fibrosis and
Huntingtons disease) or a result of the body's response to an environmental stress which causes
alterations in the genome (eg. cancers, heart disease, diabetes.). The completion of the human
genome means that we can search for the genes directly associated with different diseases and
begin to understand the molecular basis of these diseases more clearly. This new knowledge of the
molecular mechanisms of disease will enable better treatments, cures and even preventative tests to
be developed. Personalised medicine Clinical medicine will become more personalised with the
development of the field of pharmacogenomics. This is the study of how an individual's genetic
inheritence affects the body's response to drugs. At present, some drugs fail to make it to the
market because a small percentage of the clinical patient population show adverse affects to a drug
due to sequence variants in their DNA. As a result, potentially life saving drugs never make it to the
marketplace. Today, doctors have to use trial and error to find the best drug to treat a particular
patient as those with the same clinical symptoms can show a wide range of responses to the same
treatment. In the future, doctors will be able to analyse a patient's genetic profile and prescribe the
best available drug therapy and dosage from the beginning. Preventative medicine With the specific
details of the genetic mechanisms of diseases being unravelled, the development of diagnostic tests
to measure a persons susceptibility to different diseases may become a distinct reality. Preventative
actions such as change of lifestyle or having treatment 15 at the earliest possible stages when they
are more likely to be successful, could result in huge advances in our struggle to conquer disease.
Gene therapy In the not too distant future, the potential for using genes themselves to treat disease
may become a reality. Gene therapy is the approach used to treat, cure or even prevent disease by
changing the expression of a persons genes. Currently, this field is in its infantile stage with clinical
trials for many different types of cancer and other diseases ongoing. Drug development At present
all drugs on the market target only about 500 proteins. With an improved understanding of disease
mechanisms and using computational tools to identify and validate new drug targets, more specific
medicines that act on the cause, not merely the symptoms, of the disease can be developed. These
highly specific drugs promise to have fewer side effects than many of today's medicines. Microbial
genome applications Microorganisms are ubiquitous, that is they are found everywhere. They have
been found surviving and thriving in extremes of heat, cold, radiation, salt, acidity and pressure.
They are present in the environment, our bodies, the air, food and water. Traditionally, use has been
made of a variety of microbial properties in the baking, brewing and food industries. The arrival of
the complete genome sequences and their potential to provide a greater insight into the microbial
world and its capacities could have broad and far reaching implications for environment, health,
energy and industrial applications. For these reasons, in 1994, the US Department of Energy (DOE)
initiated the MGP (Microbial Genome Project) to sequence genomes of bacteria useful in energy
production, environmental cleanup, industrial processing and toxic waste reduction. By studying the
genetic material of these organisms, scientists can begin to understand these microbes at a very
fundamental level and isolate the genes that give them their unique abilities to survive under
extreme conditions. Waste cleanup Deinococcus radiodurans is known as the world's toughest
bacteria and it is the most radiation resistant organism known. Scientists are interested in this
organism because of its potential 16 usefulness in cleaning up waste sites that contain radiation and
toxic chemicals. Climate change Studies Increasing levels of carbon dioxide emission, mainly through
the expanding use of fossil fuels for energy, are thought to contribute to global climate change.
Recently, the DOE (Department of Energy, USA) launched a program to decrease atmospheric
carbon dioxide levels. One method of doing so is to study the genomes of microbes that use carbon
dioxide as their sole carbon source. Alternative energy sources Scientists are studying the genome of
the microbe Chlorobium tepidum which has an unusual capacity for generating energy from light
Biotechnology The archaeon Archaeoglobus fulgidus and the bacterium Thermotoga maritima have
potential for practical applications in industry and government-funded environmental remediation.
These microorganisms thrive in water temperatures above the boiling point and therefore may
provide the DOE, the Department of Defence, and private companies with heat-stable enzymes
suitable for use in industrial processes Other industrially useful microbes include, Corynebacterium
glutamicum which is of high industrial interest as a research object because it is used by the
chemical industry for the biotechnological production of the amino acid lysine. The substance is
employed as a source of protein in animal nutrition. Lysine is one of the essential amino acids in
animal nutrition. Biotechnologically produced lysine is added to feed concentrates as a source of
protein, and is an alternative to soybeans or meat and bonemeal. Xanthomonas campestris pv. is
grown commercially to produce the exopolysaccharide xanthan gum, which is used as a viscosifying
and stabilising agent in many industries. Lactococcus lactis is one of the most important micro-
organisms involved in the dairy industry, it is a nonpathogenic rod-shaped bacterium that is critical
for manufacturing dairy products like buttermilk, yogurt and cheese. This bacterium, Lactococcus
lactis ssp., is also used to prepare pickled vegetables, beer, wine, some breads and sausages and
other fermented foods. Researchers anticipate that understanding the physiology and genetic make-
up of this bacterium will prove invaluable for food manufacturers as well as the pharmaceutical
industry, 17 which is exploring the capacity of L. lactis to serve as a vehicle for delivering drugs