Overview of Bioinformatics

A/P Shoba Ranganathan

Justin Choo

National University of Singapore

A Tutorial on Bioinformatics

What is Bioinformatics ?

Bioinformatics is “the study of the information content and information flow in biological systems and processes”.

- Michael Liebman in “Bioinformatics: An Editorial Perspective” (http://www.netsci.org/Science/Bioinform/feature01.html)

• Annotate -> store -> search/retrieve -> analyze -> visualize

• Nucleic acid sequence (genes and RNAs), protein sequence and structural information.

SARS & Its Implication ...

SARS - Bioinformatics In Action

Sequencing Of SARS …

Photo above shows the sequencing area of the lab. Taken from http://www.bcgsc.ca/bioinfo/SARS/

Partial Sequence of SARS …

>gi|30248028|gb|AY274119.3| SARS coronavirus TOR2, complete genome ATATTAGGTTTTTACCTACCCAGGAAAAGCCAACCAACCTCGATCTCTTGTAGATCTGTTCTCTAAACGA ACTTTAAAATCTGTGTAGCTGTCGCTCGGCTGCATGCCTAGTGCACCTACGCAGTATAAACAATAATAAA TTTTACTGTCGTTGACAAGAAACGAGTAACTCGTCCCTCTTCTGCAGACTGCTTACGGTTTCGTCCGTGT TGCAGTCGATCATCAGCATACCTAGGTTTCGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTTC TTGGTGTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTCCTTCAGGTTAGAGACGTGCTAGTGCG TGGCTTCGGGGACTCTGTGGAAGAGGCCCTATCGGAGGCACGTGAACACCTCAAAAATGGCACTTGTGGT CTAGTAGAGCTGGAAAAAGGCGTACTGCCCCAGCTTGAACAGCCCTATGTGTTCATTAAACGTTCTGATG CCTTAAGCACCAATCACGGCCACAAGGTCGTTGAGCTGGTTGCAGAAATGGACGGCATTCAGTACGGTCG TAGCGGTATAACACTGGGAGTACTCGTGCCACATGTGGGCGAAACCCCAATTGCATACCGCAATGTTCTT CTTCGTAAGAACGGTAATAAGGGAGCCGGTGGTCATAGCTATGGCATCGATCTAAAGTCTTATGACTTAG GTGACGAGCTTGGCACTGATCCCATTGAAGATTATGAACAAAACTGGAACACTAAGCATGGCAGTGGTGC ACTCCGTGAACTCACTCGTGAGCTCAATGGAGGTGCAGTCACTCGCTATGTCGACAACAATTTCTGTGGC CCAGATGGGTACCCTCTTGATTGCATCAAAGATTTTCTCGCACGCGCGGGCAAGTCAATGTGCACTCTTT CCGAACAACTTGATTACATCGAGTCGAAGAGAGGTGTCTACTGCTGCCGTGACCATGAGCATGAAATTGC CTGGTTCACTGAGCGCTCTGATAAGAGCTACGAGCACCAGACACCCTTCGAAATTAAGAGTGCCAAGAAA TTTGACACTTTCAAAGGGGAATGCCCAAAGTTTGTGTTTCCTCTTAACTCAAAAGTCAAAGTCATTCAAC CACGTGTTGAAAAGAAAAAGACTGAGGGTTTCATGGGGCGTATACGCTCTGTGTACCCTGTTGCATCTCC ACAGGAGTGTAACAATATGCACTTGTCTACCTTGATGAAATGTAATCATTGCGATGAAGTTTCATGGCAG ACGTGCGACTTTCTGAAAGCCACTTGTGAACATTGTGGCACTGAAAATTTAGTTATTGAAGGACCTACTA

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The complete genome of SARS, obtained from http://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?30248028:NCBI:4812069

Bioinformatics -Timeline1980

2005

2000

1990

1985

1995

Single Structures• Modeling & Geometry• Forces & Simulation• Docking

Sequences, Sequence-Structure Relationships• Alignment• Structure Prediction• Fold recognition

Genomics• Dealing with many sequences• Gene finding & Genome Annotation • Databases

Integrative Analysis• Expression & Proteomics Data• Data mining• Simulation again…(whole cells?).

Biological Databases

• Collect, organise and classify data

• Query the dataset

• Retrieve entries based on keyword search

GenbankPDBEMBL

Sequence Analysis Software

• What is the information contained in a biological sequence?

• How can we analyse it to gain knowledge?

• Does it contain any functional clues?

Sequence Comparison

• How can we compare a given sequence to the millions in the database?

• Which ones are truly related by evolution?

• What can the study of related sequences tell us?

Sequence Alignment

• After collecting a set of related sequences, how can we compare them as a set?

• How should we line up the sequences so that the most similar portions are together?

• What do we do with sequences of different lengths?

Protein Structure

• The function of a protein is a consequence of its folded state: Anfinsen, 1961

• The 3D fold of a protein is called its structure

• In 3D, the business end of the protein has contributions from different regions of its sequence Picture taken from http://www.strgen.org/

Visualization

• Using graphic tools to view structures

• Simple commands to analyse structures and active sites

• Different graphic representations and colouring schemes

Picture taken from http://www.nature.com/

Careers in Bioinformatics

Genomics:• Genome sequencing of

– Bacteria, viruses

– Animals

– Plants• Comparative genomics• Annotation and

Mapping• Gene Discovery

Careers in Bioinformatics

Functional Genomics (Gene Expression and Regulation):• Control Regions

– Switches– Circuits– Bypass– Feedback loops

• Environmental Effects• Diseased States• Chemical Consequences

Careers in Bioinformatics

Pharmacogenomics:• SNPs

– Regional, ethnic variations

– Inheritance patterns

– Radiological/ecological modifications• Therapeutic target recognition• Correlation of drug and expression effects• Pathway Effects

Careers in Bioinformatics

Proteomics:• Protein Profiling

– Alternate splice variants

– Orphan genes

– Cryptic introns• Gene Therapy

Careers in Bioinformatics

Structural Genomics:• Experimental Protein structures

– Apo state

– Holo state

– Structural modifications• Membrane Proteins• Homology Modelling• Comparative Modelling

Careers in Bioinformatics

Drug and Vaccine Design:• Screening Natural Products

– Plants

– Fungi

– Bacteria• Chemicals • In silico modifications of ligands• Vaccine design and delivery

Job Sectors

Academia

Research Institutes

Biotechnology

Bioinformatics

Pharmaceutical

Agriculture

Biodiversity

The End