Chapter 1

Introduction to basics of
bioinformatics

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Rajesh Kumar Pathak1 , Dev Bukhsh Singh2 and Rahul Singh3
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School of Agricultural Biotechnology, Punjab Agricultural University, Ludhiana, India, 2Department of
Biotechnology, Institute of Biosciences and Biotechnology, Chhatrapati Shahu Ji Maharaj University,
Kanpur, India, 3Department of Basic and Translational Sciences, School of Dental Medicine, University

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of Pennsylvania, Philadelphia, PA, United States
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1.1 Introduction
Researchers are now constantly making efforts to explore the function of the biological system. Efforts are only at a stage
of unprecedented development and growth, expressed in the amount of data produced from each experiment (Avashthi et
al., 2014; Kumar, Pathak, Gupta, Gaur, & Pandey, 2015; Mount, 2001). Via bioinformatics, these huge datasets from
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the experiments are turned into usable information (Mount, 2001; Wang, Zaki, Toivonen, & Shasha, 2005). Bioin-
formatics is recognized as the science of the 21st century and has tremendous potential for decoding complex biological
systems via analysis and integration of multiomics data. It uses information technology (IT) to allow various types of bio-
logical data to be analyzed, linked, and manipulated to understand new biological insights (Avashthi et al., 2020; Kumar
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et al., 2015; Pathak, Taj, Pandey, Arora, & Kumar, 2013).

In other words, bioinformatics is a data management and manipulation method for molecular biology, biochemistry,
the health sector, environmental biology, and agriculture, addressing the storage of data sets, data mining and processing,
structural and functional annotations of gene and protein, system modeling, and drugs’ discovery (Avashthi et al., 2018;
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Jayaram & Priyanka, 2010; Verma, Pathak, Kasana, & Kumar, 2017). It is used to predict the structure and function
of a newly examined protein and protein sequences to create a cluster of similar family sequences and construct phyloge-
netic trees for the study of evolutionary relationships (Jayaram & Priyanka, 2010; Mount, 2001; Wang et al., 2005).
Bioinformatics has a very important role to play in agriculture-dependent countries, where it can be used to boost nutri-
tional content, increase agricultural produce yields, and implant resistance to many biotic and abiotic stresses (Jayaram &
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Priyanka, 2010; Meidanis, 2003; Pathak, Giri, Taj, & Kumar, 2013).
For the agricultural science sector, plant and animal genome sequencing should have an enormous yield. In both the
integration and analysis of genomics, transcriptomics, and other high-throughput sequencing results, bioinformatics plays
a vital role, with great potential in redesigning to boost productivity. To understand the function and interaction of many
genes, there has been a paradigm change from the single-gene approach (i.e., gene-by-gene approach) (Kumar et al.,
2015). This change has resulted from the discovery that cross-talking of several biomolecules acting in an interdependent
manner and results in any biological answer. As a consequence, several high-throughput technologies have been developed
that offer insight into all the molecules involved in a process (Kumar et al., 2015). Study in the field of genomics has
accelerated the process. There is, however, a large difference in the expression of a trait between the genotype and the
phenotype (Kumar et al., 2015; Pathak & Singh, 2020b). Studies are performed at various levels to fill this gap: the
whole system, organism, biochemical, gene, and protein levels. All these fields have contributed to the collection of vast
amounts of biological knowledge due to unprecedented research efforts. Bioinformatics, which culminates in biology and
computational technology, aims to develop novel strategies for wide-scale analysis of biological system (Pathak & Singh,
2020a).
Bioinformatics. https://doi.org/10.1016/B978-0-323-89775-4.00006-7
Copyright © 2022. 1
2 Bioinformatics

Bioinformatics techniques, such as simulation, docking, protein–protein interaction, and analysis of next-generation se-
quencing (NGS) data, may be used to investigate or modify the sequence for better fitting of essential genes for a particular
function and to study the function of these genes or proteins at the system level. It was then possible to use this speci-
fied genetic, genomic, and proteomic information to grow resistant, nutritionally improved, and profitable crops and also
discover therapeutic drugs (Agnihotry, Pathak, Srivastav, Shukla, & Gautam, 2020; Singh & Pathak, 2020). Some
important tools and databases along with their application and link of availability are highlighted in Tables 1.1 and 1.2.

1.1.1 Concept behind bioinformatics, in silico biology, and computational biology

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There are many definitions are available for bioinformatics in different books and the Internet. We can say that “Decoding
problems arising in the field of biological sciences via computation” is known as bioinformatics. It handles biological data

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obtained through several experimental techniques for their documentation in the form of databases for further availabil-
ity to the scientific community. This dataset is analyzed for dissecting the complexity of biological systems, and acquired
knowledge accelerates research activity and helps scientists to get fruitful results and novel insight. The term “in silico
biology” is concerned with bioinformatics. Generally, we can say that performing any work using a computer for biology
is known as in silico biology, for example, retrieval of biological sequences from databases.
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Computational biology is different from bioinformatics and in silico biology. Here, we are talking about the develop-
ment of algorithms and theoretical methods for solving biological problems. These developed algorithms and methods are
further utilized in the design and development of biological software or tools that help in analyzing biological data using
the computer to create knowledge, that is, bioinformatics. Therefore these disciplines are linked to each other and use sev-
eral disciplines of biology and natural sciences along with the computer, IT, mathematics, and statistics. That is why it is
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called interdisciplinary science.
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1.1.2 Scientific discipline and support systems for bioinformatics

Bioinformatics is a central discipline that is linked with several disciplines of science. These disciplines of science and
technology provide infrastructure and interdisciplinary nature to bioinformatics. In the sciences discipline, several tradi-
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tional and advanced subjects are associated with bioinformatics, such as plant sciences, animal sciences, molecular biol-
ogy, genetics, and evolutionary biology, pharmaceuticals, mathematical, and statistical sciences, and omics. Besides, in the
support system, bioinformatics is closely associated with computer science, IT, and computational resources because they
work as a backbone for bioinformatics. Therefore these scientific disciplines and support systems are combined to build
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a new discipline called bioinformatics for decoding intricate problems linked to biological systems via innovative manner
with fast processing due to the involvement of computer science and IT (Fig. 1.1).

1.1.3 Needs of bioinformatics

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Bioinformatics is a need of time because due to advances in several omics platforms have produced big data in biology re-
lated to genomes, transcriptomes, genotyping by sequencing, proteome, metabolome, etc. The management and analysis of
these high-throughput data need bioinformatics. In the era of omics and availability of organism and discipline/subject-spe-
cific data, that is, genomic data, proteomic data, etc., there is a need to develop specific databases for their documentation.
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This will further accelerate the research and help scientists to integrate these available data with novel discoveries. Besides,
these datasets will help in improving the accuracy of available tools and enable scientists to trained data for the develop-
ment of new tools via machine and deep learning approaches.
Thus in view of the above facts and contiguous process of experimental data generation needs bioinformatics profes-
sionals to manage and analyze these big data of biology to boosting research and development in a smart way for mining
useful information. This will deferentially help society.

1.2 Historical background of bioinformatics

The term “bioinformatics” was primarily used from the late 1980s onward to refer to computational analysis of genome
data and described more broadly as the “study of informatic processes in biotic systems” (Hogeweg, 2011). Paulien
Hogeweg and Ben Hesper first used the term “bioinformatics” at the beginning of the 1970s, and the term was published
by him in 1978 (Hogeweg, 1978, 2011; Hogeweg & Hesper, 1978).
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TABLE 1.1 List of important and popular database resources for bioinformatics.

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no. Database Application Availability References

1. National Centre for It offers access to biomedical and genomic information to https://www.ncbi. Benson, Boguski,
Biotechnology boost research activity. nlm.nih.gov/ Lipman, and
Information (NCBI) Ostell (1990)

2. GenBank It is a nucleotide database available at NCBI. It is used for the https://www.ncbi. Benson et al.

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retrieval of nucleotide sequences. nlm.nih.gov/genb (2012)
ank/

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3. European Nucleotide It is a nucleotide database available at EBI-EMBL. It provides https://www.ebi.a Leinonen,
Archive a detailed record of nucleotide sequencing data, covering raw c.uk/ena/browser/ Sugawara, and
sequencing data, information about sequence assembly, and home Shumway (2010)
functional annotation.

4. DDBJ It is a nucleotide database available at NIG, Japan. It is used https://www.ddbj. Tateno et al.

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for the retrieval of nucleotide sequences. nig.ac.jp/index-e.h (2002)
tml

5. Protein Information PIR is an integrated database to support research and scientific https://proteininfo Wu et al. (2003)
Resource (PIR) studies in genomics, proteomics, and systems biology. rmationresource.o
rg/
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6. UniProt UniProt aims to provide a complete, high-quality, and freely https://www.unipr Apweiler et al.
available protein sequence and functional information resource ot.org/ (2004)
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to the scientific community.

7. Pfam It is a broad set of protein families database used for domain https://pfam.xfam. Bateman et al.
analysis. org/ (2002)

8. CATH (Class, The CATH database offers information on the evolutionary https://www.cathd Orengo et al.
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Architecture, Topology, relationships of protein domains as a free, publicly accessible b.info/ (1997)
and Homology) online database resource.

9. SCOP The purpose of the SCOP database is to provide a detailed and http://scop.mrc-lm Murzin, Brenner,
systematic explanation of the structural and evolutionary b.cam.ac.uk/ Hubbard, and
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relationships between proteins deposited in the RCSB Protein Chothia (1995)

Data Bank.

10. Protein Data Bank (PDB) It is a structural database that contains the 3D structure of https://www.rcsb. Berman et al.
macromolecules. It is crucial for research in the area of org/ (2000)
structural bioinformatics, drug discovery and protein structure
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prediction, etc.

11. PubChem It is the largest database of chemical information. Here, we https://pubchem.n Bolton, Wang,
search chemical molecules and retrieve their structure for cbi.nlm.nih.gov/ Thiessen, and
molecular docking/virtual screening. Bryant (2008)
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12. ZINC It is a database that contains commercially available molecules https://zinc.dockin Sterling and Irwin
for computational screening. We can search and retrieve g.org/ (2015)
analogs for any molecule based on similarity. It plays a key
role in the discovery of lead molecules for drug development.

13. GEO GEO is a database for functional genomics. It contains gene https://www.ncbi. Edgar,
expression/microarray data. Here, we can download gene nlm.nih.gov/geo/ Domrachev, and
expression profiles submitted by the scientific community Lash (2002)
throughout the world for further investigation as per need.
4 Bioinformatics

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no. Database Application Availability References

14. Sequence Read Archive It is the largest publicly available repository of high- https://www.ncbi. Leinonen et al.
throughput sequencing data. Here, we can download NGS data nlm.nih.gov/sra (2010)
submitted by the scientific community throughout the world
for further investigation as per need.

15. The Arabidopsis It is a database of the model plant Arabidopsis thaliana https://www.arabi Rhee et al. (2003)
Information Resource provides genetic and genomic information to the scientific dopsis.org/

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community.

16. Rice Genome Annotation It provides sequence and annotation data for the rice genome. http://rice.plantbio Kawahara et al.

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Project logy.msu.edu/ (2013)

17. Gramene It is a curated, open-source, integrated database platform for https://www.gram Ware et al. (2002)
research in the area of comparative functional genomics of ene.org/
crop plant species.

18. Kyoto Encyclopedia of

Genes and Genomes
(KEGG)
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Database of gene/genome sequencing information for the
understanding function of biological system
https://www.geno
me.jp/kegg/
Kanehisa and
Goto (2000)

19. Search Tool for the It is a database resource for known and predicted https://string-db.or Szklarczyk et al.
Retrieval of Interacting protein–protein interactions derived from experimental, g/ (2019)
Genes/Proteins computational methods, and text mining.
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(STRING)

20. BioModel It is a repository of mathematical models. It provides a wide https://www.ebi.a Le Novere et al.
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variety of current physiologically and pharmaceutically c.uk/biomodels/ (2006)

applicable mechanistic models based on literature in standard
file formats.
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More than 50 years ago, bioinformatics took place when desktop computers and deoxyribonucleic acid (DNA) sequenc-
ing were a dream. Not much was known about deoxyribonucleic acid (DNA) in the early 1950s. At that moment, its role
as the carrier molecule of genetic information was still controversial (Gauthier, Vincent, Charette, & Derome, 2019).
Avery, Colin, and McCarty (1944) demonstrated that the absorption of pure DNA from a virulent bacterial strain could
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give a nonvirulent strain virulence, but their findings were not immediately recognized by the scientific community. Many
assumed that proteins were worked as genetic information carriers. Hershey and Chase confirmed the role of DNA as a
genetic information encoding molecule in 1952 when they proved beyond a reasonable doubt that it was DNA, not protein,
which was absorbed and transmitted by bacterial cells infected by a bacteriophage (Gauthier et al., 2019; Hershey &
Chase, 1952). So, the information about the function of DNA is known but its structure was not determined. In 1953 Wat-
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son, Crick, and Franklin finally resolved the double-helix structure of DNA. Despite this major discovery, it would take
13 more years before the genetic code was deciphered and 25 more years before the first methods for DNA sequencing
were available. Consequently, in DNA analysis, the use of bioinformatics lagged almost two decades behind the analysis
of proteins whose chemical nature was already better understood than that of DNA (Maxam & Gilbert, 1977; Nirenberg
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& Leder, 1964; Sanger, Nicklen, & Coulson, 1977; Tamm, Shapiro, & Lipshitz, 1953; Watson & Crick, 1953).
Therefore the analysis of protein was the starting point in bioinformatics (Gauthier et al., 2019).
The major progress in solving protein structure through crystallography during the late 1950s, the first sequence of a
protein, insulin, was published. Furthermore, many advancements in the determination of protein sequence and their struc-
ture were reported. Margaret Dayhoff (1925–1983), the first bioinformatician, was an American physical chemist, known
for her significant contribution and application of computational methods in the field of biochemistry and protein sciences.
Therefore she is known as the mother and father of bioinformatics (Jaskolski, Dauter, & Wlodawer, 2014; Moody,
2004; Sanger & Thompson, 1953).
The first dynamic programming algorithm for pairwise alignments of protein sequence was developed by Needleman
and Wunsch in 1978 and the first multiple sequence alignment (MSA) algorithms emerged in the 1980s. The software
CLUSTAL was introduced in 1988 for MSA. Then, the concept of a mathematical framework for amino acid substitutions
was introduced with the development of a point accepted mutation matrix by Dayhoff. In 1970–80 the paradigm has been
shifted from protein to DNA analysis. Between 1980 and 1990 the parallel advances in biology and computer science oc-
curred. In the establishment of the National Centre for Biotechnology Information (NCBI) database in 1988 and at NIH
 Introduction to basics of bioinformatics Chapter | 1 5

TABLE 1.2 A list of commonly used bioinformatics software.

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no. Software/tool Application Availability References

1. Basic Local It is a very common tool in bioinformatics used for https://blast.ncbi.nlm. Altschul, Gish,
Alignment Search similarity searching and identification of homologs and nih.gov/Blast.cgi Miller, Myers, and
Tool (BLAST) paralogous sequences. Lipman (1990)

2. CLUSTAL It is a widely used program for multiple sequence http://www.clustal.or Chenna et al. (2003)

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alignment. Many versions of the Clustal program are g/omega/ and Sievers et al.
available for sequence analysis. (2011)

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3. Molecular It is a software program for performing statistical analysis https://www.megasof Kumar, Tamura, and
Evolutionary of molecular evolution and for building phylogenetic trees. tware.net/ Nei (1994)
Genetics Analysis
(MEGA)

4. Modeller It is a well-known program for modeling protein 3D https://salilab.org/mo Eswar et al. (2006)

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structure based on sequence information. deller/

5. PyMOL PyMOL is a comprehensive software package for the https://pymol.org/2/ DeLano (2002)
visualization and animation of 3D structures.

6. Swiss PDB Viewer Swiss PDB Viewer is a bioinformatics program that offers a https://spdbv.vital-it. Guex and Peitsch
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user-friendly interface for the simultaneous study of many ch/ (1997)
proteins. It is used for structural alignments and
comparison, calculation of H-bonds, angles, and distances
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between atoms.

7. Chimera It is an interactive visualization and analysis software for https://www.cgl.ucsf. Pettersen et al.
molecular structures and related data, including maps of edu/chimera/ (2004)
density, trajectories, and alignments of sequences. It is
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possible to create high-quality images and animations.

8. MarvinSketch It is used to draw, edit, import, and export chemical https://chemaxon.co Bunin, Siesel,
structures, and also for the conversion of structural file m/products/marvin Morales, and
formats. Bajorath (2007)
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9. AutoDock It is a computer program used for the identification of lead http://autodock.scripp Goodsell, Morris,
compounds through molecular docking. s.edu/ and Olson (1996)

10. Gromacs It is a molecular dynamics package developed specifically http://www.gromacs. Van Der Spoel et al.
for protein, lipid, and nucleic acid simulations. org/ (2005)
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11. Velvet It is a de novo based genome assembly program developed https://www.ebi.ac.u Zerbino and Birney
especially for short-read sequencing data. k/~zerbino/velvet/ (2008)

12. Trinity It is a transcriptome/RNA-seq data assembly program https://github.com/tri Grabherr et al.

generated by the Illumina NGS platform based on the de nityrnaseq/trinityrnas (2011)
novo algorithm. eq/wiki
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13. FastQC It provides a quick way to check the quality control of raw https://www.bioinfor Andrews (2010)
sequencing data generated from NGS platforms. matics.babraham.ac.u
k/projects/fastqc/

14. Trimmomatic It is a widely used flexible read trimming tool for NGS data http://www.usadella Bolger, Lohse, and
coming from Illumina. b.org/cms/?page=tri Usadel (2014)
mmomatic

15. Cutadapt It detects and removes adapter sequences, poly-A tails, https://cutadapt.readt Martin (2011)
primer sequences, and other regions from sequencing reads. hedocs.io/en/stable/
6 Bioinformatics

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no. Software/tool Application Availability References

16. DIAMOND It is a sequence aligner for protein or translated DNA http://www.diamonds Buchfink, Xie, and
searches, developed for big sequence data analysis. It is earch.org/index.php Huson (2015)
very fast as compare to BLAST.

17. Blast2GO Used for gene ontology, and annotation of genomic data. https://www.blast2g Conesa et al. (2005)
o.com/

18. EffectorP It is a tool used for the prediction of fungal effector proteins. http://effectorp.csiro. Sperschneider et al.

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It is trained in plant-pathogenic fungi to differentiate au/ (2016)
secreted proteins from secreted effectors.

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19. CellDesigner It is a computational systems biology program used for http://celldesigner.or Funahashi,
pathway modeling and simulation analysis. g/ Morohashi, Kitano,
and Tanimura (2003)

20. Cytoscape It is a widely used and well-known software platform in the https://cytoscape.org/ Shannon et al. (2003)

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field of complex network science and network biology for
visualization and analysis. Different types of Cytoscape
Apps are available for different types of analysis.
NGS, Next-generation sequencing.
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FIGURE 1.1 Scientific disciplines associated with bioinformatics and their support systems.

and launched of Human Genome Project in 1990, bioinformatics gains huge importance due to its application in bioin-
formatics for the management and analysis of biological data, which lead to the development of genomics and structural
bioinformatics between 1990 and 2000. In 2000–10 the concepts of high-throughput bioinformatics were introduced and
gain a lot of attention by the scientific community in this field and their importance in biology (Dayhoff, Schwartz, &
Orcutt, 1978; Gauthier et al., 2019; Murata, Richardson, & Sussman, 1985; Needleman & Wunsch, 1970; Sievers
& Higgins, 2014).
 Introduction to basics of bioinformatics Chapter | 1 7

Yoshizumi Ishino first defined the signature repeat spacer architecture of CRISPR arrays in 1987 (Ishino, Shina-
gawa, Makino, Amemura, & Nakata, 1987). Francisco Mojica later revealed, backed by bioinformatics analyses, that
CRISPR arrays were present not only in Escherichia coli but also in most archaeal and several bacterial genomes (Mojica,
Díez‐Villaseñor, Soria, & Juez, 2000). Subsequent studies of bioinformatics showed bacteriophageal spacer matches,
leading to the right conclusion that CRISPR-Cas systems function as an acquired immune system. Furthermore, another
bioinformatics analysis on spacer matches fruitfully investigated that CRISPR-Cas systems will mostly target DNA rather
than RNA (Mojica, García-Martínez, & Soria, 2005). It was an excellent breakthrough in the area of genome editing
(Alkhnbashi, Meier, Mitrofanov, Backofen, & Voß, 2020). Bioinformatics has a very big history from 1950 to yet,
where many tools and databases were introduced, they have tremendous potential for solving complex biological problems

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and data management. Therefore it is not possible to cover the complete history of bioinformatics in a single chapter.
Nowadays, due to advances in high-throughput technology, in terms of data mining and management, the advent of

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“Big Data” has raised new problems, calling for more computer science skills in the area. Biological Big Data has (and
continues to have) significant consequences for the predictive capacity and reproducibility of bioinformatics outcomes cou-
pled with an ever-growing number of bioinformatics tools. Many universities have included bioinformatics in their course
curriculum to address this issue. The ever-increasing complementarities between computer science and biology have led to
recent subdisciplines, such as synthetic biology, systems biology, and whole-cell modeling (Gauthier et al., 2019).

1.3 Aim of bioinformatics PR

As we know that bioinformatics is a need of time in the era of omics, you do not think about research without bioinformat-
ics or it is necessary for finding new information. The aim of bioinformatics-related projects is generally
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• Documentation of useful information about medicinal plants available in literature/public domains in the form of a
database.
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• Documentation of available information about plants and animal genetic resources.

• Development of useful organism/species-based databases for the documentation of omics data.
• Improvement of the contents and usefulness of already developed/available databases.
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• Development of better and fast graphical user interface (GUI)-based tools for data integration and analysis.
• Improvement of available tool/software for biologist/wet lab scientists/noncomputer background scientists for their ef-
fortless use.
• Development of platform-independent software’s for the computational analysis of biological data.
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1.4 The recent development in the field of bioinformatics

To understand the code of life that is DNA, bioinformatics has developed and contributed to the growth of research projects
associated with high-throughput DNA sequencing and other fields of biology. Its ultimate aim is to visualize the wealth of
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biological knowledge hidden in sequences, structures, literature, and other big data of biology. In the era of omics, the use
of computational tools becomes necessary for the investigation of useful information from large sets of biological data. The
analysis of these data required good bioinformatics skills and most biologists are not familiar with command-line tools,
bioinformatics analysis, and interpretation. Therefore much collaboration has been established among experimental biolo-
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gists and bioinformatics groups to make their data meaningful. Now in recent years, several GUI-based software platforms
have been developed that can easily understandable for biologists to integrate and analyze high-throughput omics data.
Bioinformatics has evolved into a full stream of multiple opportunities for researchers from different areas, such as
medicine, biotechnology, plant breeding, chemistry, statistics, mathematics, computer sciences, and IT. The main motto of
this field is to turn data into knowledge through computation. With the advancement of many other significant research
areas, such as systems biology, synthetic biology, nanotechnology, and pharmacogenomics, it is still growing. Due to ad-
vances in technology and data accumulation at an unprecedented rate, bioinformaticians are expected to be in constant de-
mand to decode the complexity of data for addressing the biological problem (Moussa, Vannier, Yennamalli, & Singh,
2016; Pathak, Baunthiyal, Pandey, & Kumar, 2020).
8 Bioinformatics

1.5 Challenges in bioinformatics

Different disciplines of science and technology are associated with bioinformatics. This association is also a challenge to
understand the subject due to its interdisciplinary nature for the peoples in different backgrounds, for example, people with
biology background generally facing problem with computer and people from computer science background facing some
problem with the concept of biology. Therefore bioinformatics gained importance in recent years as compulsory courses
for many postgraduate programs run by universities in different disciplines of science and technology to trained students
in this area. The major challenges in the area of bioinformatics faced by scientists from biology background are:
• Design of small drug-like molecule,

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• Development of a quantitative model for signal transduction pathway,

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• Accurate prediction of protein secondary and tertiary structure using amino acid sequence,
• Understanding the evolution of protein,
• Understanding the speciation event,
• Understanding gene ontology,
Besides, there are many challenges faced by computer scientists working in the area of bioinformatics, such as:
•
•
•
Management of big data in biology,
Information management,
Improve the accuracy of software, and
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• Programmability.
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Therefore it is an urgent need to develop manpower in this emerging field, they know about biology and computer along
with associated disciplines/subjects for solving complex problems in biology (Meidanis, 2003; Moussa et al., 2016).
This will ultimately accelerate the outcome of the research projects but developing interest in computer science/program-
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ming to the biology students and in biology to the computer science/mathematics students is also a common challenge right
now. Due to dependency on the computer for every work, it may be solved by the near future.
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1.6 Application of bioinformatics

Bioinformatics has great potential to solve complex problems in biology and associated disciplines. With the start of the
human genome project, it becomes an essential tool for scientists and playing a key role in the area of life sciences, chem-
ical sciences, physical sciences, agricultural sciences, and medical sciences (Fig. 1.2). Some important applications of
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bioinformatics are discussed in the following sections.

1.6.1 Sequence analysis

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Sequence analysis is one of the major applications of bioinformatics with the development of the Basic Local Alignment
Search Tool (BLAST) program in 1990 and has become popular. The area of sequence analysis is very broad; here, we
analyze the nucleotide or protein sequence of any organism for several purposes. Here, we can analyze single or multi-
ple sequences to find out similarity and identity among them via several sequence alignment tools, such as BLAST and
FASTA Clustal. It is also used in the annotation of newly discovered sequences, find out conserved regions, and other reg-
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ulatory regions among them. Besides, the prediction of the physicochemical properties of sequences also comes under the
sequence analysis (Chinchole, Pathak, Singh, & Kumar, 2017; Sidhu, Bhangu, Pathak, Yadav, & Chhuneja, 2020).

1.6.2 Phylogenetic analysis

Phylogenetic analysis is another important research area in bioinformatics. Here, we can visualize the evolutionary event
and construct a relationship among organisms or sequences. It is extensively used in evolutionary biology for the objective
of determining the evolutionary event via multiple sequence alignment followed by tree construction. It also supports the
identification of key regions within sequences and plays an important role in vaccine and drug designing programs etc.
(Allaby & Woodwark, 2004; Chinchole et al., 2017; Gupta et al., 2018; Mount, 2001).
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FIGURE 1.2 Application of bioinformatics in different areas of biological, agricultural, and medical sciences.
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1.6.3 Prediction of protein secondary structure

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Right now, three computational methods, that is, Chau Fasman, GOR, and PHD, are available for protein secondary struc-
ture prediction. As it is a key area of the structure in the field of structural bioinformatics, various computational algorithms
have been developed and used. Artificial Neural Network and Hidden Markov Model are the commonly used methods for
the different available software. The secondary structure prediction methods are generally used to determine the number of
amino acid residues involved in the formation of different types of secondary structures, that is, which or how many amino
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acid residues are involved in the formation of the helix, strand, coil, and turn. It provides support in the building of the 3D
structure of a protein based on secondary structure information when a suitable structural homolog is not available in the
protein data bank (Pathak, Singh, Sagar, Baunthiyal, & Kumar, 2020; Sidhu et al., 2020).
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1.6.4 Protein 3D structure prediction

Prediction of protein 3D structure from sequence information is a challenging task in bioinformatics for the quality of
the model. Right now three computational approaches are used, that is, homology or comparative modeling, threading or
fold-recognition, and ab initio. It plays a crucial role when the experimentally determined structure of the target protein
is not available in the PDB database. It is used to determine the structure of newly discovered proteins or other proteins
their structures are not solved by NMR or X-ray crystallography for ligand small molecule screening for identification of
lead molecules for drugs/agrochemicals development. Besides, modeled structures are utilized for predicting protein–pro-
tein interactions, structural comparison, alignment, etc., for new insight via computation (Gupta, Gaur, Pathak, Gupta,
& Kumar, 2014; Gupta et al., 2018; Singh & Pathak, 2020).
10 Bioinformatics

1.6.5 Evaluation and validation of predicted protein model

Various computational methods are developed by bioinformatics scientists for the quality analysis and validation of the
predicted protein 3D model. The most popular program used for evaluation and model validation is Swiss PDB viewer,
structural analysis and verification server (SAVES), Rampage, and PROCHECK. We can evaluate and refined our pre-
dicted model with the help of the above tools for further investigation (Mamgain, Sharma, Pathak, & Baunthiyal, 2015;
Sidhu et al., 2020).

1.6.6 Discovery and designing of small molecules leading to drugs/agrochemical development

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Bioinformatics plays a vital role in the discovery of lead molecules. Techniques, such as molecular docking, virtual screen-

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ing, and molecular dynamics simulation, are widely used for this purpose (Sagar et al., 2014). With the help of molecular
docking and virtual screening, we can identify novel molecules for the treatment and prevention of diseases in humans, an-
imals, and plants (Pathak et al., 2016). Furthermore, it can be validated in terms of conformational behavior and stability
during target–ligand interaction with respect to time using a molecular dynamics simulation study (Rana, Pathak, Shukla,
& Baunthiyal, 2020). This study helps in the identification of lead compound quickly with the help of computational
PR
tools and reduced the time and experimental cost, the fast drug discovery process for downstream validation (Mamgain,
Dhiman, Pathak, & Baunthiyal, 2018; Pathak & Sagar, 2012; Pathak, Baunthiyal, Taj, & Kumar, 2014; Pathak,
Baunthiyal, Shukla, et al., 2017; Rai, Pathak, Singh, Bhatt, & Baunthiyal, 2021; Singh, Gupta, & Pathak, 2020).

1.6.7 Next-generation sequencing data analysis

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Due to progress and recent development in several omics platforms and various sequencing technologies, a big amount
of data has been generated every day that need bioinformatics for their analysis and management. In recent years a bunch
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of tools and databases has been developed for the management, integration, and analysis of such big data. These tools are
useful in the identification of differentially expressed genes via analysis of microarray and RNAseq/transcriptome data,
assembly and annotation of genome and transcriptome, SNP discovery, genome-wide association study, identification and
characterization of gene families, the discovery of new genes, etc. The obtained information from big data analysis will
EC

help in different research programs associated with plant and animal breeding, marker development, drug target identifica-
tion, and drug discovery (Magi et al., 2010; Pathak, Baunthiyal, et al., 2020; Pereira, Oliveira, & Sousa, 2020).

1.6.8 SNP and SSR identification

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Progress in NGS and bioinformatics has enabled the large-scale discovery of SNP and SSR markers. It has revolution-
ized research related to genomics and assists in the molecular breeding program, and it will also help in analyzing genetic
diversity and population structure, designing genetic maps of high density, and providing genotypes for genome-wide as-
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sociation research.

1.6.9 Pharmacogenomics
In the postgenomic era, pharmacogenomics is recognized as one of the keys and highly demanded research areas to study
UN

the response of a drug based on genetic variants for the development of personalized medicine. As we know that some
drugs are working on a particular population and or group of peoples but no desired response of these drugs was reported
in other populations or countries due to minute change in genomic regions. So that the concept of pharmacogenomics has
been introduced for the development of a person or population or area-specific medicine to reduce the risk of side effect
and increase their potency. Therefore bioinformatics tools are rapidly utilized for the analysis of high-throughput genomics
data for the detection of how genes alter the response of a drug; this investigation will lead to the development of per-
sonalized medicine (Aneesh, Sekhar, Jose, Chandran, & Zachariah, 2009; Takahashi, Luzum, Nicol, & Jacobson,
2020).
 Introduction to basics of bioinformatics Chapter | 1 11

1.6.10 Metabolomics and metabolic flux analysis

A quantitative and qualitative understanding of metabolic rates or fluxes over a metabolic network and in particular cellu-
lar compartments offers insights into metabolic regulation and helps to understand the contribution of metabolic changes
to pathology. Bioinformatics facilitates researchers to analyze metabolomics data and develop a metabolic model for flux
balance analysis. This will help in the metabolic engineering program for various purposes.

1.6.11 Systems biology and omics data integration

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Nowadays systems biology is one of the essential areas in bioinformatics and has outstanding contributions in decoding the
complexity of biological systems via modeling, simulation, and network analysis. It helps us to integrate different omics

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data, that is, genomics, proteomics, metabolomics, transcriptomics, and other omics, for the development of a model that
will describe the behavior of biological systems in different conditions holistically with respect to time (Pathak, Baun-
thiyal, Pandey, Pandey, & Kumar, 2017).
In past years scientists were working on a single gene or protein, but in recent years the paradigm has been a shift
from a reductionist approach to a holistic approach due to the augmentation of omics technology and systems biology. So,

PR
with the help of systems biology, we can predict the behavior of whole systems and identify key components involved
in different biological processes through network modeling and analysis. The systems-based approaches are highly useful
in investigations of key genes/proteins, drug targets, modeling of pharmacokinetic and pharmacodynamic activity of drug
molecules at particular concentration/amount with respect to time computationally before going to the experimental stud-
ies for evaluating the drug-likeness of molecules. Besides, it is useful in the modeling and simulation of host–pathogen
D
interaction to identify key components involved in disease progression as well as resistance for the development of suitable
disease resistance strategy and their implementation (Kokane, Pathak, Singh, & Kumar, 2018; Kumar et al., 2018;
Pathak, Baunthiyal, Pandey, Kumar, 2018; Pathak, Gupta, Shukla, Baunthiyal, 2018).
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1.7 Future perspective

Bioinformatics got a lot of attention from the time of the human genome project and has become an essential tool for re-
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search and development right now. Without the use of bioinformatics, we cannot think about the novel discovery in the
21st century. In the current era of omics, many leading research groups around the world imagine that bioinformatics is
the future of next-generation science and technology because everywhere most of the work has been conducted by com-
puter software for speed and accuracy. Therefore in the future, it becomes an essential part of every research lab. Near
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the future, lots of bioinformaticians are required for handling big data in biology for their management and mining of key
information for further research, which will directly decrease experimental work and cost. As we know that the world pop-
ulation is increasing rapidly, more and more food is required to meet the need of peoples.In the future, the development of
high-yielding crop varieties with nutritional value and disease-resistant crop varieties is needed, and it is possible by the
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use of bioinformatics to dissect the complexity of crop plants systems for better productivity. However, it will play a major
role in the fundamental and advance research in the area of health, biomedical, and veterinary sciences for the discovery of
medicines, therapeutics, and management of diseases for a better future for mankind.

1.8 Conclusion
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In recent years bioinformatics has become an essential subject and hot research topic that is associated with several dis-
cipline and methodology. The present chapter highlights the power of bioinformatics and its approaches for solving a
complex biological problem, which leads to research and development. Besides, it presents several important database re-
sources and tools along with their uses and availability. In the future, rapid advancement in the generation of big data
through omics and other advancements in different areas are expected in which bioinformatics provide a broad range of
applications for their management, analysis, and novel discovery. Furthermore, this chapter provides career opportunities
to students and researchers in the area of computational and integrated science, that is, bioinformatics.

Conflict of interest
The authors declare that they have no conflict of interest.
12 Bioinformatics

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