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SIV 2001

Class 3
What is bioinformatics

Biology
• Science that deals with living organisms and life processes.
• Plant, animal and microbial life of an particular region or environment.
• Properties and vital phenomena exhibited by an organism or group of
organisms.
• Elements, processes and interactions in living beings

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Computer

• One or who or that which computes;

• specifically: a programmable electronic device that can store,
retrieve and process data, and can also store programs that
control its own action.

Information Science

• The collection, classification, storage, retrieval and

distribution of recorded knowledge
• Treated both as a pure and as an applied science

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Information Theory

• Theory that deals statistically with information.

• The measurement of its contents in terms of its
distinguishing characteristics.
• The efficiency of processes of communication of
information between humans and machines
(telecommunication and computing machines)

Knowledge
• Knowing something with familiarity gained through
experience or association
• Understanding of a science, art, or technique
• Being aware of something
• Apprehending fact through reasoning
• Being learned.

• The sum of what is known

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Summary
• Data are the facts.

• Information is the organisation of, associations between, and constraints

upon data that allow it to be used by a user or a machine.

• Knowledge is the interpretation of information and its use in a problem

solving context. Knowledge can lead to new insights, which in turn lead to
new innovations and ultimately to wealth creation and improvements in
the quality of life

Bioinformatics - definitions
• Bioinformatics (NIH):
“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, analyze, or visualize such data.”

• Bioinformatics involves the technology that uses computers or

information technologies for storage, retrieval, manipulation,
and distribution of information related to biological data

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What is bioinformatics?

What is Bioinformatics?
Biology
Molecular
Biology

Chemistry Medicine

Bioinformatics

Mathematics
Physics
Statistics

Computer
Science
Informatics

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Why Bioinformatics

• To better understand a living cell and how it functions at the

molecular level.

• Biologists were searching for methods and algorithms to

store, retrieve, analyze and interpret their huge amount of
empiric biological data.

Origin of bioinformatics and biological database

• The first protein sequence reported was that of bovine
insulin in 1956, consisting of 51 residues.

• Nearly a decade later, the first nucleic acid sequence was

reported, that of yeast tRNAalanine with 77 bases.

• In 1965, Dayhoff gathered all the available sequence data

to create the first bioinformatic database (Atlas of Protein
Sequence and Structure).

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Bioinformatics history
• Earliest bioinformatics exercise: Margaret Dayhoff (1965) first
protein sequence database Atlas of Protein Sequence and
Structure (now PIR).

• 1970s:
• Protein structure database (PDB) 1972 with a collection of
ten X-ray crystallographic protein structures.
• Protein Sequence Database (PSD) by Margaret Dayhoff
• Sequence alignment algorithm Needleman-Wunsch
• Sanger sequencing
• Routine sequence comparisons and database searching
• Protein structure prediction algorithm Chou and Fasman
1980s saw establishment of GenBank and FASTA and BLAST

Bioinformatics history
• 1980s:
• Human Genome Project started late 1980s
• The PCR reaction was described by Kary Mullis and co-
workers
• The Smith-Waterman algorithm for sequence alignment
• The SWISS-PROT database
• The FASTP algorithm was published by Lipman & Pearson
• The National Center for Biotechnology Information (NCBI)
was established
• 1990s:
• The BLAST program by Altschul, et. al.
• 2000 and beyond:
• A draft of the human genome (3,000 Mbp) was published

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The growth of biological data – nucleotide data

Scales of file size

As of 15 June 2019

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Top organisms in GenBank (Release 191)

Organism base pairs
Homo sapiens 1.6310774187×1010
Mus musculus 9.974977889×109
Rattus norvegicus 6.521253272×109
Bos taurus 5.386258455×109
Zea mays 5.062731057×109
Sus scrofa 4.88786186×109
Danio rerio 3.120857462×109
Strongylocentrotus purpuratus 1.435236534×109
Macaca mulatta 1.256203101×109
Oryza sativa Japonica Group 1.255686573×109
Nicotiana tabacum 1.197357811×109
Xenopus (Silurana) tropicalis 1.249938611×109
Drosophila melanogaster 1.11996522×109
Pan troglodytes 1.008323292×109
Arabidopsis thaliana 1.144226616×109
Canis lupus familiaris 951,238,343
Vitis vinifera 999,010,073
Gallus gallus 899,631,338
Glycine max 906,638,854
Triticum aestivum 898,689,329

Bioinformatics approaches
1. Data acquisition

2. Data management/storage

3. Data retrieval

4. Data analysis/interpretation

5. Data compilation

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Biological information

Molecular Sequences 3D Structure Biological Functions

Biological information
Molecular Sequences
• Nucleic acid
• Amino acid
• Sequencing Technology
• Sanger sequencing
Gene prediction Genome viewer/browser
• NGS
• 3rd generation sequencing
• Molecular Sequence Analysis
• Sequence alignments  conservation pattern
• Variant (SNPs) analysis
• Comparative genomics Comparative genomics
• Genome Annotation
• Open reading frame
• Functional sites
• Genome Viewer
• ...

Genome annotation (bacteria) Multiple sequence alignment

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Biological information

3D structure
• Double helix DNA
• RNA structure
• Protein x-ray crystallography
• 3D structure prediction
double helix DNA

RNA structure Protein x-ray crystallography

Biological information

Biological functions
• Pathway analysis
• Network analysis
• Gene Ontology
• Protein-protein interaction
• Proteomics
Pathway analysis Network analysis
• Metabolomics
• Molecular modeling
• Molecular dynamics
• Phylogenetics
• Evolutional relationship
• Drug design
• Vaccine design
• ...

Molecular dynamics Phylogenetics

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Bioinformatics approaches
1. Data acquisition

2. Data management/storage

3. Data retrieval

4. Data analysis/interpretation

5. Data compilation

Where do we use bioinformatics

• Basic genomic and molecular biology research.

• Biotechnology.
• Biomedical sciences.
• Forensic DNA analysis.
• Agriculture biotechnology
• Pharmacology
• Anthropology

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What do bioinformatics do?

Input:
Biological information
(data)

BIOINFORMATICS

Output:
New Biological information
( New data and Knowledge)

What do bioinformatics do?

1. Development of computational tools and databases
• Software for sequence analysis
• Sequence alignment, sequence database searching, motif and pattern
discovery, gene and promoter finding, reconstruction of evolutionary
relationships, genome assembly and comparison
• Software for structural analysis
• Protein and nucleic acid structural analysis, comparison, classification and
prediction
• Software for functional analysis
• Gene expression profiling, protein-protein interaction prediction, protein
sub-cellular location prediction, metabolic pathway reconstruction
• Construction and curation of biological databases

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What do bioinformatics do?

2. Generate biological knowledge to better understand living systems
• Analyse and interpret the various types of biological data.
• Often identify new problems that require new software to analyze.
• Bioinformatics is essential for basic genomic and molecular biology research
• Sequence assembly
• Genome annotation
• Molecular evolution
• Analysis of gene expression
• Analysis of gene regulation
• Major impact in biotechnology and biomedical sciences
• Structural bioinformatics and Knowledge-based drug design
• Protein structure analysis
• Protein structure prediction
• 3D structure allows design of ligands that fit
• Reduces time and cost to develop drugs

What do bioinformatics do?

2. Generate biological knowledge to better understand living systems (cont.)
• Forensic DNA analysis
• Bayesian statistics and likelihood-based methods
• Personalised healthcare
• Agricultural biotechnology
• Plant genome databases
• Gene expression profiles
• New crop varieties

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Main players

Organization Database

NCBI (NIH) GenBank

EMBL Nucleotide Reorganized into

EMBL 
Sequence Database ENA

NIG, Shizuoka, Japan DDBJ

International Nucleotide Sequence Database Collaboration:

• GenBank
• ENA
• DDBJ

https://www.nih.gov/

Institutes at NIH

National Library of Medicine (NLM)

National Center for

Biotechnology Information (NCBI)

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https://www.ncbi.nlm.nih.gov/

NCBI resources
• Databases:
• PubMed
• Bookshelf
• Sequence Read Archive (SRA)
• Online Mendelian Inheritance in Man (OMIM)
• ClinVar
• BioSystems
• Nucleotide Database
• GenBank  BLAST tools
• Reference Sequence (RefSeq)
• Database of Short Genetic Variations (dbSNP)
• Tools
• 1000 Genomes Browser
• Basic Local Alignment Search Tool (BLAST)
• Genome Data Viewer (GDV)

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https://www.embl.org/
• EMBL Heidelberg, Germany - Main
laboratory
• EMBL Hamburg, Germany - Structural
biology
• EMBL Barcelona, Spain - Tissue biology
and disease modelling
• EMBL-EBI Hinxton, United kingdom -
European Bioinformatics Institute
• EMBL Grenoble, France -Structural
biology
• EMBL Rome, Italy - Epigenetics and
neurobiology

Resources and tools in EMBL

• ArrayExpress – archive of gene expression experiments
• BioModels – a database of computational models relevant to the life sciences
• BioStudies – a database that serves as a generic data archive at EMBL-EBI for
biomolecular datasets
• European Nucleotide Archive (ENA) – resource of nucleotide sequencing
information
• Ensembl project – genome databases for vertebrates and other eukaryotic species
(joint with Wellcome Trust Sanger Institute)
• Expression Atlas – database of summary information on which genes are
expressed under which conditions
• Gene ontology – ontology of gene functions and processes
• InterPro – database of protein functional domains and families
• MetaboLights – repository of metabolomics data
• Protein Data Bank in Europe – European resource for the collection, organisation
and dissemination of data on biological macromolecular structures
• UniProt – database of protein sequence and functional information (joint with
Swiss Institute of Bioinformatics and Protein Information Resource)

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https://www.nig.ac.jp/nig/

NIG resources
Mouse Microorganisms NBRP – National BioResource
– Mouse Genetic Resources – E. Coli: Strain/Vector/Antibody Project
– Mouse Genome Database – E. Coli: Genome Database SHIGEN – Shared Information of
– Mouse Phenotype Database – E. Coli: TEC Database Genetic Resources
– Japan Mouse/Rat Strain – S. Japonicus (JapoNet) RRC – Research Resource Circulation
– Microsatellite Data Base of Japan – Bacillus subtilis DDBJ - DNA Data Bank of Japan
– RefEx for Mouse or Rat Fish
Human – Zebrafish: zTRAP
– dbHERV-REs – Zebrafish: Knock Out Fish Project
– RefEx for human – Coelacanth
Drosophila Aquatic organisms
– Drosophila Strains (NIG-FLY) – Hydra
– Segmentation Antibodies – Xenopus laevis
C. Elegans – Sea urchin (Hemicentrotus pulcherrimus)
– Gene Expression Database (NEXTDB) Plants
– cDNA library – Rice (Oryzabase)
– Liverwort (Marchantia polymorph

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International Nucleotide Sequence

Database Collaboration
• GenBank
• ENA
• DDBJ

Impact of bioinformatics
• Personal Genomics
• Increased vigilance and taking action to prevent disease
• Improving health care  provide individual/specific medical care
• Understanding the link between genomics and environment
• Novel Drug Development
• Identifying novel drug targets
• Validating drug targets
• Predicting toxicity and adverse reactions
• Improving clinical trials and testing
• Gene therapy
• Replacing the gene rather than the gene product
• Stem cells therapies
• Replacing the entire cell type or tissue to cure a disease

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Impact of Bioinformatics

• Pharmacogenomics
• Personalized medicine  Adjusting drug, amounts and delivery to suit
patients
• Maximize efficacy and minimize side effects
• Identify genetics of adverse reactions
• Identify patients who respond optimally

Impact of Bioinformatics

• Ethical, Legal and Social Issues Personal Privacy

• Insurability
• Employability
• Discrimination
• Genetic selection versus eugenics
• Cosmetic genetics
• Patentability of genes, proteins and other natural products

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Limitations

• Realize the limitation and avoid over-reliance on and

over-expectation of bioinformatics output.
• Accuracy.
• Quality.

Bioinformatics is expanding…

• More reliable tools for sequence, structural analysis and

functional analysis.
• Development of tools to understand the functions and
interactions of all gene products in a cell: system biology.

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