Lecture 1A

1
Lecture 1A

• Introduction to BioInformatics

2
Outline

• Define Bioinformatics
• What questions can be answered?
• History
• Human genome project
• Different application of BioInformatics
• Omics Revolution

3
What is BioInformatics?

• Application of tools of computation and analysis
  to the capture and interpretation of biological
  data
• Interdisciplinary field
• Essential for the management of data in modern
  biology and medicine

4
BioInformatics vs Computational Biology

• Used Interchangeably
• Really different terms
• Distinction made by National Institutes of Health
• Bioinformatics
• Refers to the creation and advancement of
  algorithms
• algorithm is a sequence of finite instructions,
  often used for calculation and data processing
• Computational and statistical techniques to solve
  problems arising from management and analysis of
  biological data
• Computational Biology
• Refers to hypothesis-driven investigation of a
  specific problem using computers, using
  experimental or simulated data to advance
  scientific knowledge

5
Disciplines that have contributed
Physics
Biology
Medicine
Bioinformatics
Mathematics
Computer Science
Chemistry/Biochemistry
Statistics
6
Why BioInformatics?

• Solve biological problems usually on the
  molecular level
• Problems too great fro human discernment

7
What areas of biology use bioinformatics?

• Molecular Biology
• Genetic material
• Information in nucleic acids analyzed using
  bioinformatics
• Evolutionary Biology
• Developmental history of species
• Common ancestor phylogeny and how evolution
  works
• Structural Biology
• Physical forms of molecules
• Position of atoms within molecules
• Genetics
• Model molecular changes (over time)
• Mutations- gene changes and protein products

8
Tools of Bioinformatics

• Computer software programs
• Internet
• Sequence analysis of DNA and protein using
  various programs and databases available
• Evolving discipline
• Bioinformaticians
• Pharmaceutical companies
• Biomedical laboratories

9
BioInformatics

• Used to answer fundamental questions in the life
  sciences
• What are the evolutionary origins of this
  protein?
• What gene does this DNA sequence code for?
• What does this gene do?
• How does this enzyme/ribozyme work and what does
  it look like?
• When is this gene expressed?
• What genes are expressed before the onset of
  cancer?
• What drugs can be used to treat this disease?
• What mutations are responsible for this genetic
  disorder?

10
Applications

• No Single comprehensive database exists for
  accessing all the information needed to manage
  data
• Construction of phylogeny trees
• Predict gene location and products
• ORF finder
• Blast or FastA
• Predict protein structure
• Protein Explorer
• Literature Searches
• PubMed and Galileo
• Sequencing of genomes
• Sequence alignments
• Microarray analysis

11
Human Significance

• Locate mutations responsible for genetic
  diseases.
• Aids in the treatment and diagnosis of those
  diseases
• Pharmacogenomics
• Designer drugs and therapies
• Biotechnology
• Discover and exploit new enzymes
• Environmental clean-up
• Antibiotics and other chemotherapeutic agents
• Useful products

12
Major Events in Molecular Biology History

• 1869 DNA discovered
• Johann Friedrich Mieschers nuclein
• 1941 Central Dogma revealed
• Beadle and Tatum
• 1950 Complementary Bases discovered
• Edwin Chargaff
• 1953 DNA is a double helix
• Watson, Crick and Franklin
• 1956Role of ribosomes
• George Emil Palade

13
Major Events in the History of Molecular Biology

• 1950s
• The first protein sequenced
• Frederick Sanger
• Edman degradation
• Simplified Sangers method
• 1960s
• Ion exchange columns, chromatography and
  electrophoresis
• Sped up the process
• Pehr Edman
• Sequenatorautomated sequencing
• 1975 (Sanger)
• Dideoxy termination sequencing for DNA

14
Other Important Dates

• http//www.geocities.com/bioinformaticsweb/his.htm
  l
• 1955
• 1973
• 1977
• 1980
• 1985
• 1988
• 1990
• 1995 -2000
• 2001 - 2003

15
History of Bioinformatics

• Margaret Dayhoff (Bioinformatics Founder)
• Established the Atlas of Protein Sequence and
  Structure
• Annual Publication to catalogue all know amino
  acid sequences
• Protein Information Resource (PIR) database in
  1983
• Algorithms to study protein sequences
• Tools to design and utilize sequence databases

16
Dayhoffs Contributions
Dayhoff wrote FORTRAN programs to solve a
puzzle sequence assembly from weeks to minutes!
AVTALWGKVNVDEVG
VHLTPEEKS
AVTALWGKVNV
LVVYPWTQRF
GEALGRLLVVYP
PEEKSAVTA
KVNVDEVGGEALGR
These represent short segments of amino acid
sequences that make up hemoglobin.
17
Dayhoffs Contributions
Dayhoff wrote FORTRAN programs to solve a
puzzle sequence assembly from weeks to minutes!
AVTALWGKVNVDEVG
VHLTPEEKS
LVVYPWTQRF
PEEKSAVTA
AVTALWGKVNV
GEALGRLLVVYP
KVNVDEVGGEALGR
18
Dayhoffs Contributions
Dayhoff wrote FORTRAN programs to solve a
puzzle sequence assembly from weeks to minutes!
VHLTPEEKS
PEEKSAVTA
AVTALWGKVNV
AVTALWGKVNVDEVG
KVNVDEVGGEALGR
GEALGRLLVVYP
LVVYPWTQRF
19
Dayhoffs Contributions
Dayhoff wrote FORTRAN programs to solve a
puzzle sequence assembly from weeks to minutes!
VHLTPEEKSAVTALWGKVNVDEVGGEALGRLLVVYPWTQRF

• Her programs were later added to automated
  sequencers.
• She also established the Atlas of Protein
  Sequence (65) and Structure (a book), which later
  became the PIR (80)
• The PIR allowed sequence comparison, which lead
  to molecular evolutionary biology (molecular
  phylogeny)

20
Human Genome Project

• Began 1990
• Estimated cost 13 billion
• Landmark achievement for bioinformatics
• Random sequencing

21
Human Genome Project

• http//www.ornl.gov/sci/techresources/Human_Genome
  /project/journals/journals.shtml
• Click on Feb. 16th
• Human genome
• Read abstract

22
Functional Genomics

• Since the sequence of human genome
• Emphasis is changing from genes themselves to
  gene products
• Functional genomics
• Assigns functional relevance to genomic
  information
• Study of gene, their resulting proteins,and roles
  played by the proteins
• Proteomics analysis of the proteins expressed
  by the cell

23
Comparative Genomics

• Comparison of the sequencing of genomes from a
  number of model organisms
• Study gene structure and function
• Human
• Plants- Arabidopsis thaliana
• Yeast- Saccharomyces cerevisia
• Fruit fly- Drosophila melanogaster
• Nematode worm- Caenorhabditis elegans
• Mouse- Mus musculus

24
Clinical Applications

• New drugs
• Targeted drugs
• Gene therapy for single genes
• Diagnosis and treatment plans
• Information on genetic disorders
• Potential adverse reactions
• Pharmacogenomics

25
Human Genome Project and Omics Revolution

• Genomics
• DNA Sequence
• Homology locations of genes and functional
  sites phylogeny mapping
• Infer function
• Transcriptomics
• mRNA sequence and structure
• Determine expression mechanisms via identifying
  alternative splicing regions
• Proteomics
• Amino acid Sequence and protein structure
• Predict structure
• Solve structure
• Infer function from structure

26
Omics

• Metabolomics
• Studying proteins and enzymatic pathways involved
  in cell metabolism
• Glycomics
• Studying the carbohydrates of a cell
• Interactomics
• Studying the complex interactions of protein
  networks in a cell
• Nutrigenomics
• Interations between diet and genes