Bioinformatics Overview

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Bioinformatics Overview

• VIBE Education Edition (VIBE-Ed) Initiative

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Outline

• Bio-technology Then and Now
• Bioinformatics Golden Age?
• Challenges in Bioinformatics
• VIBE

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Origins of Biotechnology

• Early Speculation
• 6000 BC Yeast was used to make beer by Sumerians
  and Babylonians.
• 400 BC Hippocrates - male contribution to a
  child's heredity is carried in the semen
• 320 BC Aristotle - all inheritance comes from
  the father. Female babies are caused by
  interference from the mother's blood.
• 100 AD Romans speculated that mares can be
  fertilized by the wind.
• 1673 AD Anton van Leeuwenhoek describes protozoa
  and bacteria confirms existence of sperm cells.
• Thing are getting smaller
• 1859 Charles Darwin - "On the Origin of
  Species
• 1865 Gregor Mendel - laws of heredity, internal
  units of information later become known as genes
• Converging on DNA
• 1900 The science of genetics is born.
• 1953 Watson and Crick propose the
  double-stranded, helical, complementary,
  anti-parallel model for DNA.

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Origins of Biotechnology, contdThe Dawn of
Modern Biotech

• 1977 Genentech reports the production of
  somatostatin.
• 1980 USSC rules in that genetically altered life
  forms can be patented.
• 1981 Scientists at Ohio University produce a
  transgenic mouse.
• 1985 Genetic fingerprinting enters the court
  room.
• 1989 Creation of NCHGR
• 1990
• Launch of Human Genome Project (Projected
  duration 15 years, projected cost 13 billion)
• First gene therapy ethics concerns
• Publication of Jurassic Park
• 1994
• Flavr Savr gains FDA approval
• The first crude but thorough linkage map of the
  human genome appears.
• 1995
• DUMC researchers transplant hearts from
  genetically altered pigs into baboons
• H. infuenzae sequence completed
• 1998
• C. elegans is sequenced
• A rough draft of the human genome map is produced
• Celera is founded Venter proposes new method to
  sequence the genome

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Biotechnology NowGolden Age ?

• Human genome sequence completed
• Tens of model organism sequenced
• Hundreds of new biotechnology companies
• Integral component of pharmaceutical and
  agricultural research
• Pharmaceutical benefits
• Agricultural research benefits
• Key source of economic growth and employment

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Biotechnology Nowor Hype ?

• Billions of dollars spent on research that didnt
  go anywhere
• Unfulfilled promises, conflicting egos, lack of
  standards and interoperability, IP conflicts
• The VC bubble, dozens of companies floundered
• Genomics doesnt yield all the answers
• How many genes are there, finally?

So which is it?
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• Well get there, but its going to take a while
  and itll be a lot more difficult than most
  people thought.
• Significant challenges

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DNA 101
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Genome Sizes and Number of Genes

• HIV Virus 9,750 bp 1,000 genes
• E. coli 4,600,000 bp 5,400 genes
• Yeast 12,000,000 bp 8,000 genes
• Fruitfly 180,000,000 bp 13,400 genes
• Chicken 1,200,000,000 bp 15-20,000 genes
• Human 3,400,000,000 bp 25-35,000 genes
• Gorilla 3,500,000,000 bp same as human
• Maize 5,000,000,000 bp ?
• Amoeba 670,000,000,000 bp ?

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Challenge 1 Data Explosion
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Challenge 2 Data Heterogeneity
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DNA Fingerprinting

• Gel electrophoresis
• separation by charge/mass ratio through
  electrophoresis
• unique identity of each clone based on its DNA
  sequence restriction pattern

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DNA Sequencing
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DNA Macroarrays

• association of two complementary
  nucleic acid strands
• strand acting as the probe is radiolabeled
• hybridization event (hit) occurs when the probe
  hybridizes to a clone containing the
  complementary sequence
• hits can be scored and a matrix of hits vs.
  probes can be created

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DNA Microarrays

• Array sequences
• corresponding to
• genes onto glass
• slides
• Study expression
• patterns of those
• genes

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Protein/Antibody Microarrays
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Mass Spectrometry
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Challenge 3 Knowledge Discovery
Agent Planner Coordinator
Focused Text-Mining
Normalized Experiments
Knowledge Assembly
Semantically-Indexed Databases
Goal-directed Analyses
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GenomicDNA
mRNA
Protein Products
Functional Protein
Biological System
activity profiling
data integration
emerging
Post-translational modification
system simulation
expression profiling
subcellular localization
qualitative protein profiling
structural determination
prototype
protein linkage maps (catalog)
protein linkage maps (dynamic)
sequencing
mature
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Integrative Biology/Science

• Requires the melding of traditionally divergent
  disciplines, such as
• Molecular biology
• Clinical research
• Physics
• Computer Science
• Statistics,
• Etc.

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Enter Bioinformatics

• a scientific discipline that encompasses all
  aspects of biological information acquisition,
  processing, storage, distribution, analysis and
  interpretation that combines the tools and
  techniques of mathematical and computer science
  and biology with the aim of understanding the
  biological significance of a variety of data
• NIH publication No.90 - 1590
• April 1990

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Roles of Bioinformatics

• Provide infrastructure to conduct projects
• Analysis and presentation of data
• Research and development of new analysis tools

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What is VIBE?

• Visual Integrated Bioinformatics Environment
• Bioinformatics Workflow Management
• Drag-and-drop pipeline creation
• Analysis parameterization
• Bioinformatics Exploration Platform (Workbench)
• Step-by-step process creation, filtering and
  visualization
• Archives and templates
• Technical Highlights
• visual programming applied to bioinformatics
• distributable, grid-compatible, scalable,
  extensible
• Simple interface for centralized access to tools
  and data sources
• Built-in reproducibility and tracking (archives,
  templates, execution monitoring, etc.)

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The VIBE Interface
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Tool Information

• In-depth details on each tool and its parameters
• Easy-to-use table of parameters
• Notes page for user-annotation of an analysis

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Results Visualization

• Interactive, graphical views of results
• Active links to external resources (e.g., Genbank)

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System Layout

• 100 Java
• OS-Independent
• Web-protocol (HTTP, SOAP, etc)
• Multi-server, multi-client, multi-resource
• Mix internal and external resources

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VIBE SDK

• Software Development Kit
• Allows integration of in-house or 3rd party tools
  into the VIBE client or server
• Integration API (iAPI) and guides
• External XML configuration

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VIBE as a Bioinformatics Teaching Platform

• Build on existing ease-of-use and extensive help
  features
• Allows students to explore many tools in
  biologically relevant contexts
• Concentrate on usage of tools and correct
  application
• Incorporate more sophisticated tracking
  capabilities, multi-media tutorial, etc.
• Feedback critical for success and subsequent
  stages