Saturday, May 30, 2015

What is Bioinformatics?

  • Emerging interdisciplinary area of Science & Technology
  • Encompasses systematic development and application of IT solutions
    • Handle biological information
    • Addresses biological data collections and warehousing
    • Data mining
    • Database searches
    • Analyses and interpretation
    • Modeling and product design

What is Bioinformatics?

  • Involves DISCOVERY, DEVELOPMENT, and IMPLEMENTATION of computational algorithms and SW tools to facilitate understanding of biological processes with applications to the sectors of Agruculture and Healthcare.

Bioinformatics Applications

  • Agriculture
    • Increase nutritional content
    • Increase production volume
    • Implant disease resistance
  • Healthcare
    • Reduce time and cost involved in drug discovery processes
      • i.e. for third world diseases
    • Custom design of drugs
    • Develop personalized medicine

The Tree of Life

  • Assuming
    • Life originated from a common ancestor
    • All higher organisms evolved from a common unicellular prokaryotic organism
  • There is a division of different forms of life from this
    • This made DIVERSITY in:
      • Morphological and genetic characters

The Tree of Life

  • Common to all
    • Cell
      • Unicellular organism
      • Complex multicellular organism
        • Human adults approx. 30 trillion cells
    • Cell composed of
      • Nucleus that carries the genetic material
        • Polymetric chains of DNA (deoxyribonucleic acid)
        • Holds hereditary information
        • Controls functioning
    • Challenge to decipher how DNA (the genetic material) leads to the formation of organisms

The Tree of Life

The Tree of Life

The Cell

  • Comparing plant and animal cells The Cell

Levels of Organization

  • The entire content of DNA of a cell is called genome
  • The entire content in a cell is called the proteome
  • The complement of molecules is called cellome
  • Tissues consist of collections of cells
  • Tissue collections make organs
  • Organism is a collection of several organ systems

Levels of Organization

Levels of Organization

Molecules

Molecules

Organisms

  • Organisms self replicate
    • Using genetic material of DNA
      • Polynucleotide consisted of four bases
        • Adenine (A)
        • Thymine (T)
        • Guanine (G)
        • Cytosine (C)
  • The entire DNA content of the cell is known as the GENOME
  • The segment of genome that is transcribed into RNA is called GENE
  • Hereditary information is transferred in the form of **GENES* containing the four bases

Organisms

  • We do research to understand these genes
    • 5% of the entire DNA is in form of genes
    • What about the other 95%?
    • When does genes are expressed?
    • Where?
    • When?
    • How gene expression is regulated?

Codons

Codons

Codons

Codons

Research Topics

  • Genome Analysis study segments of a genome that
    • Code for messenger ribonucleic acids (mRNAs)
    • Transfer ribonucleic acids (tRNAs)
    • Are called genes or ribosomal ribonucleic acids (rRNAs)
  • Process in procaryotics, simple
    • mRNAs determine the sequence of amino acids in proteins
    • All genes are converted into the corresponding mRNA (messenger ribonucleic acid) and then into proteins

Research Topics

  • Process in eucaryotic cells, more complex
    • Some parts of genes called exons are expressed in the form of mRNA interrupted at places by random DNA sequences called introns
    • Some parts are expressed as proteins while others are not!
    • Which exons are combided and, under what conditions, to make proteins necessary for the organism?

Analyzing Genomes

  • Human Genome Project initiated in 1990, US government
  • Why are genomes sizes so different?
    • Wheat vs. rice
    • Compared to that of humans
  • Mice & humans
    • About the same number of genes
    • About 28K protein coding regions
    • About 90% of human genome is in large blocks of homology with mouse
    • Chimpanzee and human genomes vary by average of just 5%

Genomes Sizes

Genome Sizes

Genetic Disorders

  • Caused due to mutations in the genes or a set of genes inherited from one generation to another
    • Huntington's disease
    • Parkinson's disease
    • Sickle cell anemia
  • Need to understand the genetic origins of these disorders
    • How to prevent them?

Genetic Disorders

Genome Disorders

Drug Target Identification

  • Understand the genome organization to progress in drug-target identification
  • Genome level comparisons
    • Individuals with some disorder vs. healthy ones
      • Identify drug targets
    • Genome of humans vs. a pathogen
      • Identify a virus causing harm
      • Use comparitive genomics to predict possible drug-targets
      • Eliminate the invader without causing side effects to humans

Single Nucleotide Polymorphism

  • SNP's (Single Nucleotide Polymorphism)
    • Common DNA sequence variations
    • Occur when a single nucleotide in the genome sequence changes
    • SNPs occur every 100 to 300 bases along the human genome
    • Promise significant advance to understand and treat human diseases
    • The dbSNP database

Single Nucleotide Polymorphism

  • SNP's
    • Small-scale multi-base deletions or insertions
    • Microsatellite repeat variations
      • Short tandem repeats or SRTs

Comparative Genomics

  • Find relation between 2 genes from different organisms
    • Generates intergenomic maps
    • Identify evolutionary process responsible for divergence of two genomes / species

Functional Genomics

  • Identify gene function
    • DNA micro array data analysis
      • Quantify levels of gene expression in various tissues or at different stages in the development of diseases

Genetic Modifications

  • Plant breeders to develop new varieties of crops
    • Cereals, soya, maize (at faster rate)
    • Transfer genes from one species to another transgenic varieties
    • Engineering characteristics to make better species
    • Genetically Modified (GM) crops to produce therapeutic plants
  • Improve crop characteristics
    • Size, height, seed, flower color —- phenotypes

Sustainability of Rural Agriculture

  • Identify medicinal substances based on indigenous knowledge
  • Evaluate using controlled functional genomics experiments and bioinformatics
  • Evaluate effectiveness of traditional therapeutics on inflammatory and parasitic processes in livestock (cows and goats)
  • Plants used in traditional medicine
    • Neem, wormwood, garlic
    • Anti-helmintic, anti-inflammatory properties

Sustainability of Rural Agriculture

Medicinal

Comparative Genomics of Plant Genomes

  • Helped understand that organization of genes has been conserved during evolution
  • Complete genoms of crop plants (Oryza, sativa, wheat)
    • Provide information about genes
    • Used to improve food crops
  • Genes from Bacillus thuringiensis – used to control pests
    • Transferred to crops
      • Cotton, maize, potatoes
    • Plants become insect resistant
    • Use of insecticides is reduced
    • Improve overall economics

Finding Genes

  • Given the whole genome, FIND THE GENES
    • Challenging task
    • Sophisticated mathematical methods
    • Database driven approaches based on existing experimental information
    • Make use of correlation between bases along the genome
      • Markov models
    • Others based on long range / global correlations
      • Fourier transform techniques

Gene Prediction Software

Gene Prediction