The Role of Bioinformatics in Infectious Diseases

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The Role of Bioinformatics in Infectious Diseases

• Prof Jamuna Vadivelu
• Dept of Medical Microbiology
• Faculty of Medicine
• University Of Malaya

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A Few Basic Concepts of Molecular Biology

• Genetic material - DNA RNA.
• DNA as a sequence of bases (A,C,T,G).
• Watson-Crick complementation.
• Proteins.
• The central dogma of molecular biology.

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Central Dogma
Cells express different subset of the genes in
different tissues and under different conditions
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Centarl Paradigm of Molecular Biology
DNA RNA Protein
Symptomes (Phenotype)
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Central Paradigm of Bioinformatics
Genetic information
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Central Paradigm of Bioinformatics
Molecular Structure
Genetic Information
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Central Paradigm of Bioinformatics
Molecular Structure
Biochemical Function
Genetic Information
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Central Paradigm of Bioinformatics
Molecular Structure
Genetic Information
Biochemical Function
Symptoms
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What is BIOINFORMATICS ?
A field of science in which Biology, Computer
Science and Information Technology merge into a
single discipline. Goal To enable the
discovery of new biological insights and create
a global perspective for biologists.
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• Disciplines
• Development of new algorithms and statistics
  to
• assess relationships among members of large
  data
• sets.
• Analysis and interpretation of various types
  of
• data.
• Development and implementation of tools to
• efficiently access and manage different types
  of
• information.

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Why use BIOINFORMATICS ?

• An explosive growth in the amount of
  biological information necessitates the use of
  computers for cataloging and retrieval.
• A more global perspective in experimental
  design
• (from one scientist one gene/protein/disease
  paradigm to whole organism consideration).
• Data mining - functional/structural
  information is
• important for studying the molecular basis of
  diseases (and evolutionary patterns).

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Genome Sequencing

• On June 26, 2000, "working draft" of the human
  genome.
• Project goals were to
• identify all the approximately 20,000-25,000
  genes in human DNA,
• determine the sequences of the 3 billion chemical
  base pairs that make up human DNA,
• store this information in databases,
• improve tools for data analysis,
• transfer related technologies to the private
  sector, and
• address the ethical, legal, and social issues
  (ELSI) that may arise from the project.

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Scientists Spell Out Recipe for Human Beings 

• With new techniques and powerful computers,
  scientists have finally pieced together the
  entire human genome.
• all three billion biochemical rungs of our spiral
  ladder-shaped DNA molecule have been strung
  together in the correct order.
• What we now have is the entire book of life for
  making a human being.

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Why microbes?

• microbes make up most of the earths biomass,
• evolved for some 3.8 billion years.
• found in virtually every environment, surviving
  and thriving in extremes of heat, cold,
  radiation, pressure, salt, acidity, and darkness
• microbes are in the air we breathe, the ground we
  walk on, the food we eatthey're even inside us!

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What are microbes?

• Microbe is a term for tiny creatures that
  individually are too small to be seen with the
  unaided eye.
• Microbes include
• bacteria
• fungi
• viruses

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Bacterium
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Virus
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Fungus
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Why Microbes?

• broad and far-reaching implications for
  environmental, energy, health, and industrial
  applications.
• cleanup of toxic-waste
• production of novel therapeutic agents
• energy generation (e.g., methane and hydrogen).
• production of chemical catalysts, reagents, and
  enzymes for industrial processes.

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Why Microbes?

• management of environmental carbon dioxide, which
  is related to climate change.
• detection of disease-causing organisms and
  monitoring of the safety of food and water
  supplies.
• use of genetically altered bacteria as living
  sensors (biosensors)
• understanding of specialized systems used by
  microbial cells to live in natural environments
  with other cells.

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Teen's Research Points to Possible Danger in
Water Supplies

• could a kid do scientific research that even real
  scientists would take note of?
• 17-year-old Ashley Mulroy did.
• she set out to test drinking water for traces of
  antibiotic drugs.
• two issues
• water safety, and
• the growing threat of antibiotic resistance.

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Challenges in Tropical Diseases

• avian influenza emerged in east Asia and
  continues today.
• the probability that this virulent virus will
  acquire genetic traits for increased
  person-to-person transmissibility,
• potential to set the stage for the next global
  influenza pandemic

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Challenges in Tropical Diseases

• antimicrobial resistance is common, has developed
  against every class of antimicrobial drug,
• developing effective and safe vaccines is
  urgently needed to prevent infection by severe
  acute respiratory syndrome (SARS)
• dengue fever continues to plague South East Asia

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Microbial Genome Project

• In 1995, the first microbe sequencing project,
  Haemophilus influenzae (a bacterium causing upper
  respiratory infection) was completed
• continue to sequence other medically important
  organisms
• bacteria that cause tuberculosis, gonorrhea,
  chlamydia and cholera, and
• organisms that are considered agents of
  bioterrorism.
• protozoan pathogens such as the organism causing
  malaria

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Benefits of Genome Sequencing

• the availability of microbial and human DNA
  sequence and advances in
• molecular biology,
• immunology,
• human and pathogen genetics,
• plus the computational sciences (bioinformatics)
• suggest rapid progress in the search for new
  chemotherapeutic agents and new vaccines to treat
  and prevent infection

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How can bioinformatics help?

• Current research in bioinformatics can be
  classified into
• genomics sequencing and comparative study of
  genomes to identify gene and genome
  functionality,
• proteomics identification and characterization of
  protein related properties and reconstruction of
  metabolic and regulatory pathways,
• cell visualization and simulation to study and
  model cell behavior, and
• application to the development of drugs and
  anti-microbial agents.

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How can Bioinformatics Help?

• Bioinformatics research can be classified under
  three major approaches
• analysis based upon the available experimental
  wet-lab data,
• the use of mathematical modeling to derive new
  information, and
• an integrated approach that integrates search
  techniques with mathematical modeling

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How can Bioinformatics Help?

• The major impact of bioinformatics research is to
• automate the genome sequencing, and development
  of integrated genomics and proteomics databases,
• automate genome comparisons to identify the
  genome function,
• automate derivation of metabolic pathways, and
• gene expression analysis to derive regulatory
  pathways,
• develop statistical techniques, clustering
  techniques and data mining techniques to derive
  protein-protein and protein-DNA interactions

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How can Bioinformatics Help?

• model 3D structure of proteins and 3D docking
  between proteins and biochemicals for rational
  drug design,
• differential analysis between pathogenic and
  non-pathogenic strains to identify candidate
  genes for vaccines and anti-microbial agents, and
  
• the whole genome comparison to understand the
  microbial evolution

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Limitations and Future Challenges for
Bioinformaticians

• current analysis is limited by
• the lack of available gene-functionality from the
  wet-lab data,
• the lack of computer algorithms to explore vast
  amount of data with unknown functionality,
• limited availability of protein-protein and
  protein-DNA interactions, and
• the lack of knowledge of temporal and transient
  behavior of genes and pathways.

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THANK YOU