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” ( 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

Partial Sequence of SARS … >gi| |gb|AY | SARS coronavirus TOR2, complete genome ATATTAGGTTTTTACCTACCCAGGAAAAGCCAACCAACCTCGATCTCTTGTAGATCTGTTCTCTAAACGA ACTTTAAAATCTGTGTAGCTGTCGCTCGGCTGCATGCCTAGTGCACCTACGCAGTATAAACAATAATAAA TTTTACTGTCGTTGACAAGAAACGAGTAACTCGTCCCTCTTCTGCAGACTGCTTACGGTTTCGTCCGTGT TGCAGTCGATCATCAGCATACCTAGGTTTCGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTTC TTGGTGTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTCCTTCAGGTTAGAGACGTGCTAGTGCG TGGCTTCGGGGACTCTGTGGAAGAGGCCCTATCGGAGGCACGTGAACACCTCAAAAATGGCACTTGTGGT CTAGTAGAGCTGGAAAAAGGCGTACTGCCCCAGCTTGAACAGCCCTATGTGTTCATTAAACGTTCTGATG CCTTAAGCACCAATCACGGCCACAAGGTCGTTGAGCTGGTTGCAGAAATGGACGGCATTCAGTACGGTCG TAGCGGTATAACACTGGGAGTACTCGTGCCACATGTGGGCGAAACCCCAATTGCATACCGCAATGTTCTT CTTCGTAAGAACGGTAATAAGGGAGCCGGTGGTCATAGCTATGGCATCGATCTAAAGTCTTATGACTTAG GTGACGAGCTTGGCACTGATCCCATTGAAGATTATGAACAAAACTGGAACACTAAGCATGGCAGTGGTGC ACTCCGTGAACTCACTCGTGAGCTCAATGGAGGTGCAGTCACTCGCTATGTCGACAACAATTTCTGTGGC CCAGATGGGTACCCTCTTGATTGCATCAAAGATTTTCTCGCACGCGCGGGCAAGTCAATGTGCACTCTTT CCGAACAACTTGATTACATCGAGTCGAAGAGAGGTGTCTACTGCTGCCGTGACCATGAGCATGAAATTGC CTGGTTCACTGAGCGCTCTGATAAGAGCTACGAGCACCAGACACCCTTCGAAATTAAGAGTGCCAAGAAA TTTGACACTTTCAAAGGGGAATGCCCAAAGTTTGTGTTTCCTCTTAACTCAAAAGTCAAAGTCATTCAAC CACGTGTTGAAAAGAAAAAGACTGAGGGTTTCATGGGGCGTATACGCTCTGTGTACCCTGTTGCATCTCC ACAGGAGTGTAACAATATGCACTTGTCTACCTTGATGAAATGTAATCATTGCGATGAAGTTTCATGGCAG ACGTGCGACTTTCTGAAAGCCACTTGTGAACATTGTGGCACTGAAAATTTAGTTATTGAAGGACCTACTA The complete genome of SARS, obtained from

Bioinformatics -Timeline 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 Genbank PDB EMBL

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

Visualization Using graphic tools to view structures Simple commands to analyse structures and active sites Different graphic representations and colouring schemes Picture taken from

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

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