Transcript Bioinformatics: A New Frontier for Computer - People

Bioinformatics:
A New Frontier for
Computer Scientists
Ruth G. Alscher
Lenwood S. Heath
The Language of the New
Biology
A new language has been created. Words in the
language that are useful for today’s talk.
Genomics
Functional Genomics
Proteomics
cDNA microarrays
Global Gene Expression Patterns
Human Genome Project
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How many individuals?
Which races?
Statistics about sequencing
Etc. (Ruth)
New Computational Tools
Needed for Biology
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Sequencing
Analyzing experimental data
Representing vast quantities of information
Searching
Pattern matching
Data mining
Gene discovery
Function discovery
Molecular Biology
• Cell function
• Nucleic acids, DNA, RNA, chromosomes,
genes
• Amino acids, proteins
DNA Strand
A= adenine complements T= thymine
C = cytosine complements G=guanine
Complementary DNA Strands
Double-Stranded DNA
RNA Strand
U=uracil replaces T= thymine
Proteins
Unlike DNA, proteins have three-dimensional structure
Protein folds to a three-dimensional shape that
minimizes energy
Amino Acids
• Protein is a large molecule that is a chain of
amino acids (100 to 5000).
• There are 20 common amino acids
(Alanine, Cysteine, …, Tyrosine)
• Three bases --- a codon --- suffice to encode
an amino acid.
• There are also START and STOP codons.
Chromosomes
• Long molecules of DNA: 10^4 to 10^8 base
pairs
• 26 matched pairs in humans
• A gene is a subsequence of a chromosome
that encodes a protein.
• Proteins associated with regulation.
• Only a fraction of the genes are in use at
any time.
• Every gene is present in every cell.
Cell’s Fetch-Execute Cycle
• Stored Program: DNA, chromosomes, genes
• Fetch/Decode: RNA, ribosomes
• Execute Functions: Proteins --- oxygen
transport, cell structures, enzymes
• Inputs: Nutrients, environmental signals,
external proteins
• Outputs: Waste, response proteins, enzymes
Evolution
• Genotype: Genetic makeup of individuals
or species
• Mutations are basis for evolution of species
• Phenotype: Perceived traits of organism
(eye color, number of limbs, etc.);
controlled by interaction of many genes
Genetics
• An individual organism has some set of
genes, stored in DNA of each cell.
• Gene set determines biological functions
and individual characteristics.
• Genetic makeup of a particular species
defines that species.
Protein-Coding Genes
Genomics
Genomics: Discovery of genetic sequences and
the ordering of those sequences into individual
genes, into gene families, and into chromosomes.
Identification of sequences that code for gene
products/proteins and sequences that act as
regulatory elements.
Functional Genomics
Functional Genomics: The biological role of
individual genes, mechanisms underlying the
regulation of their expression, and regulatory
interactions among them.
Biologists Need Computer
Scientists
•Assembling DNA fragments
•Physical mapping
•Identifying genes and gene families
•Protein folding
•Determining protein function
•Data analysis (microarrays)
•Data visualization
•Searching
•Sequence alignment
•Data mining
Microarray Data Analysis
How to use microarrays to learn more about the
influence of drought stress on gene expression?
Where the biologists need the computer scientists.
A. Confounding factors in the raw data
1. Limitations in accuracy (technique)
2. Biological variation (individuals)
B. How to apply corrections for these
confounding factors to maximize the
predictive power of the data.
C. Modeling regulatory networks.
Effects of drought stress on loblolly pine- a pilot
experiment. 1999-
Effects of Drought Stress
Virginia Tech:
Plant Biologists: Ruth Alscher, Boris Chevone.
CS: Lenny Heath and colleagues.
Statistics: Ina Hoeschele, Shun-Hwa Li.
NC State (Forest Biotechnology):
Ying-Hsuan Sun, Ron Sederoff, Ross Whetten
Relative Abundance
Relative
Abundance
Detection
Detection
Detection
Treatment
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Control
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Mix
Spots: 1
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(Sequences affixed to slide)
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Hybridization
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Biological Variation as Reflected in A Comparison
of Expression in Two Trees of the Same Clone. A
Subquadrant
Biological Variation
Iterative strategy for detection of genetic
interactions
microarrays
Iterativeusing
Strategy
Detection of gene
expression effects
on microarrays
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Genetic
Regulatory
Networks
Test mutant
phenotypes
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Identify mutants
Characterize
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gene function
Glycolysis, Citric Acid Cycle, and
Related Metabolic Processes
Gene Expression:
Control Points
Responses to Environmental
Signals
Intracellular
Decision Making
Drosophila Genome
Drosophila Genome
Expressed Sequence Tags
A publicly accessible collection of cDNAs
representing mRNAs present in specific tissues.
The cDNAs have been partially sequenced and
identified, where possible, as homologs to publicly
accessible genes of known function.
Microarray Quotes
• “ A fresh, comprehensive and open-mined look at
every problem in biology” Brown and Botstein,
page 33. WOW!
•“… the construction of a Biological Periodic Table…”
Lander, page 3.
•“… as model-independent as possible…” Brown and
Botstein, page 33.
From The Chipping Forecast
ROS arise throughout the cell.
ROS arise throughout the cell
Wounding ,
Chilling
Pathogens
Ozone
Cell Wall
Pathogens
Wounding ,
Chilling
Ozone
Cell Wall
Mitochondrion
Mitochondrion
Pos t-tra nscriptiona l
Effe ctsPos t-tra nscriptiona l
Drought ,
Salinity
(ROS
su bce llul ar
si tes
un clear)
Effe cts
Drought ,
Salinity
Cytosol
Cytosol
Antioxidant
genes
Antioxidant
genes
Nucleus
(ROS
su bce llul ar
si tes
un cle ar)
Nucleus
Gene
Ex pression
Gene
Ex pression
Chloroplast
Chloroplast
Pos t-tra nscriptiona l
Effe cts
Pos t-tra nscriptiona l
Paraquat ,
Effe cts
High Light + Chilling
Sulfur Dioxide
Paraquat ,
High Light + Chilling
Sulfur Dioxide
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Free Radicals
Bioinformatics Institute
• Research institute based at Virginia Tech
• Begins July 1 with $3 million
• Will occupy 2 building and have 100+ employees in 4 years
Getting Into Bioinformatics
• Get a minor in biology
• Get involved with bioinformatics research
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Dr. Alscher
Dr. Heath
Dr. Keller
Dr. Ramakrishnan
Dr. Watson