Computer Application in Pharmacy Unit-4

UNIT-IV

Bioinformatics: Introduction, Objective of Bioinformatics, Bioinformatics Databases, Concept of

Bioinformatics, Impact of Bioinformatics in Vaccine Discovery
Introduction and concept of Bioinformatics
Paulien Hogeweg and Ben Hesper coined it in 1970 to refer to the study of information
processes in biotic systems.
Bioinformatics is a combination of computer science and biology concerned with the
attainment, storage, analysis, and dissemination of biological data.
or
Bioinformatics is defined as the analysis, collection, classification, manipulation, recovery,
storage and visualization of all biological information using computation technology.
Biological data: information on DNA, RNA, proteins, and genes.

The father and mother of Bioinformatics, Dr. Margaret Belle Dayhoff (March 11, 1925 –
February 5, 1983) was an American biophysicist and a pioneer in the field of bioinformatics.
She dedicated her career to applying computational methods in the creation of protein and
nucleic acid databases and tools to retrieve information from these databases.

Dr. Margaret Belle Dayhoff

Molecular Bioinformatics involves the use of computational tools to discover new information
in complex data sets (from the information of DNA through the information of RNA and the
information of proteins, to the information of evolving living systems).
Cell - Nucleus
Nucleus - Storehouse of molecule known as DNA
DNA- Packed in chromosomes
DNA and chromosomes- Genome
Genes- genes are specific region of the genomes (about 1%)

The dogma is a framework for understanding the transfer of sequence information between
information carrying biopolymers, in the most common or general case, in living organisms.
There are 3 major classes of such biopolymers: DNA and RNA (both nucleic acids),
and protein.

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Protein data presentation in the form of amino acids.

Data presentation of DNA, RNA

The components of bioinformatics

1. Database formation: This involves the organizing, storage and management the
biological data sets. The databases are accessible to researchers to know the existing
information and submit new entries, e.g. protein sequence data bank for molecular
structure.
2. The development of software tools and algorithms: This involves the development of
tools and resources to determine the relationship among the members of large data
sets e.g. comparison of protein sequence data with the already existing protein
sequences.

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3. The analysis and interpretation of biological data by using a variety of software

tools and particular algorithms: The appropriate use of components 1 and 2 (given
above) to analyse the data and interpret the results in a biologically meaningful manner.
This includes DNA, RNA and protein sequences, protein structure, gene expression
profiles and biochemical pathways.
Example of biological data is information contained in DNA. RNA, protein

Major areas of bioinformatics are:

1. Functional Genomics: Identification of genes and their respective functions.
2. Structural Genomics: Predictions related to functions of proteins.
3. Comparative Genomics: For understanding the genomes of different species of
organisms.
4. DNA Microarrays: These are designed to measure the levels of gene expression in
different tissues, various stages of development and in different diseases.
5. Medical Informatics: This involves the management of biomedical data with special
referee to biomolecules, in vitro assays and clinical trials.

The objective of bioinformatics are:

1. Understand Biology-
• Cataloguing biomolecules
• Understand their function
• Understand mechanism of that function
2. Cure disease-
• Drug target approach – Classical
• Integrated approach – Futuristic
Multiple drugs
Address the source of disease

Application of Bioinformatics
1. Molecular medicine:
• Every disease has a genetic component and inherited to body's response to an
environmental stress which causes alterations in the genome (e.g. cancers, heart
disease, and diabetes.
• The genes directly associated with different diseases can be identified.
• 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.

2. Gene therapy: Gene therapy is the approach used to treat, cure or even prevent disease by
changing the expression of a person’s gene.
Strategies of Gene Therapy are following:
- Gene addition
- Removal of harmful gene
- Control of gene expression
-
3. Drug Discovery: Computational biology, an essential element of bioinformatics help
scientists to analyse the disease mechanism process and validate new and cost-effective drugs.
If we consider the COVID 19 outbreak, bioinformatics can be effectively used to produce an
effective drug at a low cost.

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4. Preventative medicine:
• Preventative medicine is a critical aspect of healthcare that involves early detection and
treatment of diseases before they manifest.
• Genetic testing involves analyzing DNA samples to detect specific genetic mutations
associated with inherited conditions.
• Through genetic screening and counseling, healthcare providers can develop targeted
prevention and treatment plans to reduce disease burden and improve outcomes.
• Eg of disease such as cardiac diseases, diabetes, cancer.

Bioinformatics Tools
Bioinformatic tools have helped in drug discoveries, veterinary sciences, crop improvement,
forensics are many more fields. Bioinformatics applications include sequence analysis,
molecular modeling, molecular dynamics, etc. Here is the list of names of bioinformatics tools
for different applications:
• BLAST
• BioPerl
• InterMine
• Biojava Bioinformatics Tool for Linux
• IGV Genomic Sequencing Tool
• GROMACS
• Taverna Workbench
• Clustal Omega

Bioinformatics Databases
Basic definitions
Database: A structured collection of data held in computer storage or any large collection of
information.
Database management: The organization and manipulation of data in a database.
database management system (DBMS): A software package that provides all the functions
required for database management.
Database system: A database together with a database management system.

Biological databases
1. Exponentiel growth in biological data (More than 1000 databases are available).
2. Data (genomic sequences, 3D structures, 2D gel analysis, MS analysis etc) are no longer
published in a conventional manner, but directly submitted to databases.
3. Variable size: <100Kb to >20Gb, DNA: > 20 Gb, Protein: 1 Gb, 3D structure: 5 Gb
4. Update frequency: daily to annually to seldom to forget about it. Usually accessible
through the web (some free, some not)

Classification of databases
1. Model organism databases: Species wise organism information
2. Nucleic acid databases: DNA information
3. Proteins: Protein information
4. Bibliographic Databases: Literature
5. Taxonomic Databases: Classsification

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S.No Database Definition Example

Name
1. Model It provide in-depth biological Eg: Pombase database for fission yeast,
organism data for studied model FlyBase database for fruitfly
databases organisms. Model organism
databases generate, source
and collate species-specific
information.
2 Nucleic acid a) DNA databases: It is Example:
databases a database of DNA profiles • DNA Data Bank of Japan (National
which can be used in the Institute of Genetics)
analysis of genetic diseases, • EMBL (European Bioinformatics
genetic fingerprinting for Institute)
criminology, or genetic • GenBank (National Center for
genealogy. Biotechnology Information)
b) Phenotype databases: Eg: PHI-base: Pathogen-host interaction
The term "phenotype" database.
refers to the observable
physical properties of an
organism. these include
the organism's
appearance, development,
and behavior. An
organism's phenotype is
determined by its
genotype.
c) RNA databases: data Eg: miRBase: the microRNA database,
related to RNA structure- Rfam: a database of RNA family.
function, sequence etc
d) Genomic Database: Eg: The RGD, TAIR, Gramene
These databases
collect genome sequences
and analyze them, and
provide public access.
These databases may hold
many species genomes, or a
single model
organism genome.
e) Gene expression • Ensembl: provides automatic annotation
databases: It contains databases for human, mouse,
gene expression-related other vertebrate and eukaryote genomes.
information • Gene Disease Database:The Rat
Genome Database (RGD).
3. Protein a) Protein • DisProt: database of experimental
databases sequence database: evidences of disorder in proteins (Indiana
determining the amino University School of Medicine, Temple
acid sequence and support University, University of Padua)
and manage protein related
information

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• InterPro: classifies proteins into families

and predicts the presence of domains and
sites
b) Protein • Protein Data Bank (PDB),
structure databases: to • Protein DataBank in Europe (PDBe)
determine 3D structure of • ProteinDatabank in Japan (PDBj)
protein. It can be done by X- • Research Collaboratory for Structural
Ray crystallgraphy and Bioinformatics (RCSB)
NMR techniques.
c) Protein-protein and BioGRID: general repository for
other molecular interaction datasets (Samuel Lunenfeld
interactions: How protein Research Institute)
interact with another RNA-binding protein database
protein or another
molecule
d)Protein Example: Human Protein Atlas
expression databases:: It
contains data related to
mapping all the human
proteins in cells, tissues
and organs
4. Bibliographic A bibliographic database is Example:
database a database that contains • MEDLINE (Medical Literature Analysis
descriptive records of books, and Retrieval System Online, or
periodical articles, conference MEDLARS Online) is a
proceedings, and audio-visual bibliographic database of life sciences
collections. and biomedical information.
• BIOSIS: for biology
5. Taxonomic A taxonomic database is Example:
database a database created to hold Avibase - the World Bird Database
information related to
biological taxa - for example
groups of organisms
organized by species name or
other taxonomic identifier -
for efficient data
management and information
retrieval as required.

Bioinformatics in vaccine development

Bioinformatics can help us in designing vaccines. In generally vaccine design require a time
period of 5 to 15 years but with the help of bioinformatics tool we can shorter the timeline down
to 1 to 2 years.
Vaccine
• A vaccine is a biological preparation that provides active acquired immunity to a
particular infectious disease.

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• The vaccine stimulates the body's immune system to recognize the agent as a threat,
destroy it, and to further recognize and destroy any of the microorganisms associated
with that agent that it may encounter in the future.
• Scientists identify natural or synthetic antigens that might help prevent or treat a
disease. These antigens could include virus-like particles, weakened viruses or
bacteria, weakened bacterial toxins, or other substances derived from pathogens.

Steps of vaccine discovery (Bioinformatics in vaccine discovery)

1. Gene sequence determination: The first step in any mining operation (data mining) is
to identify the genomic sequence of causative agent (the complete DNA sequence of an
organism's genome at a single time). Example of tool is BLAST.
2. ORF identification: Identify the genes or open reading frames (ORFs) contained within
the genomic sequence. An open reading frame (ORF) is the part of a reading frame that
has the ability to be translated.
Sample sequence showing three different possible reading frames. Start codons are
highlighted in purple, and stop codons are highlighted in red.

Eg of tool: GeneMark, GLIMMER

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3. DNA annotation or genome annotation is the process of identifying the locations

of genes and all of the coding regions in a genome and determining what those genes
do. Example: BLAST is gene annotation tool.
4. ORF Target: ORF Predictor is a web server designed for identifying protein-coding
regions. The identification of the pathogenic genome and complete screening of open
reading frames (ORFs) is performed to select the specific sequence of the peptides
responsible for an immunogenic response. Example: NERVE program
5. A wet lab is a type of laboratory in which a wide range of experiments are performed,
for example, characterizing of enzymes in biology, formulation development, titration
in chemistry, diffraction of light in physics, etc. - all of which may sometimes involve
dealing with hazardous substances. It also involves immunization study in animals
such as mice and rats.
6. A Clinical trial: Phase I, II, III, IV. All documentation part will be done with the help of
computer. Data management and retrieval.
• Phase I: small groups of people receive the trial vaccine.
• Phase II: the clinical study is expanded and vaccine is given to people who have
characteristics (such as age and physical health) similar to those for whom the
new vaccine is intended.
• Phase III: the vaccine is given to thousands of people and tested for efficacy and
safety.
• Phase IV: Phase IV trial are optional studies that drug companies may conduct
after a vaccine is released. The manufacturer may continue to test the vaccine for
safety, efficacy, and other potential uses.
Bioinformatics in COVID Vaccine
• A nucleic acid sequence of SAR-CoV-2 Virus was determined using bioinformatics tool.
• The protein sequence can be determined from the gene sequence using computational
methods.
• The structure of the SARS-CoV-2 virus could be predicted through AlphaFold
• The RNA sequence and knowledge of the SARS virus structure, or a 3D reconstruction
from imaging techniques, like Cryo-EM, using the software RELION