November 16, 2001Slide 1 Opportunities in Bioinformatics for Computer Science Lenwood S. Heath Virginia Tech Blacksburg, VA University of Iowa November 16, 2001
Slide 2 The New Biology Existing bioinformatics tools Bioinformatics challenges Bioinformatics at Virginia Tech Overview
November 16, 2001Slide 3 Some Molecular Biology The instruction set for a cell is contained in its chromosomes. Each chromosome is a long molecule called DNA. Each DNA molecule contains 100s or 1000s of genes. Each gene encodes a protein. A gene is transcribed to mRNA in the nucleus. An mRNA is translated to a protein in a ribosome.
November 16, 2001Slide 4 Transcription and Translation DNAmRNAProtein TranscriptionTranslation
November 16, 2001Slide 5 Elaborating Cellular Function DNAmRNAProtein TranscriptionTranslation Reverse Transcription Degradation Regulation Functions: Structure Catalyze chemical reactions Respond to environment (Genetic Code)
November 16, 2001Slide 6 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 cell function, structure, and regulation. Only a fraction of the genes are in use at any time. Every gene is present in every cell.
November 16, 2001Slide 7 DNA Strand A= adenine complements T= thymine C = cytosine complements G=guanine
November 16, 2001Slide 8 Complementary DNA Strands Double-Stranded DNA
November 16, 2001Slide 9 RNA Strand U=uracil replaces T= thymine
November 16, 2001Slide 10 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.
November 16, 2001Slide 11 Genetic Code
November 16, 2001Slide 12 Translation to a Protein Unlike DNA, proteins have three-dimensional structure Protein folds to a three-dimensional shape that minimizes energy
November 16, 2001Slide 13 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
November 16, 2001Slide 14 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 The Language of the New Biology
November 16, 2001Slide 15 Discovery of genetic sequences and the ordering of those sequences into individual genes; gene families; chromosomes. Identification of sequences that code for gene products/proteins; sequences that act as regulatory elements. Genomics
November 16, 2001Slide 16 Genome Sequencing Projects Drosophila Yeast Mouse Rat Arabidopsis Human Microbes …
November 16, 2001Slide 17 Drosophila Genome
November 16, 2001Slide 18 The biological role of individual genes; mechanisms underlying the regulation of their expression; regulatory interactions among them. Functional Genomics
November 16, 2001Slide 19 Glycolysis, Citric Acid Cycle, and Related Metabolic Processes
November 16, 2001Slide 20 Only certain genes are “turned on” at any particular time. When a gene is transcribed (copied to mRNA), it is said to be expressed. The mRNA in a cell can be isolated. Its contents give a snapshot of the genes currently being expressed. Correlating gene expressions with conditions gives hints into the dynamic functioning of the cell. Gene Expression
November 16, 2001Slide 21 Gene Expression: Control Points
November 16, 2001Slide 22 Free Radicals
November 16, 2001Slide 23 Responses to Environmental Signals
November 16, 2001Slide 24 Virginia Tech: Plant Biologists: Ruth Alscher, Boris Chevone. CS: Lenny Heath, Naren Ramakrishnan, and colleagues. Statistics: Ina Hoeschele, Shun-Hwa Li. NC State (Forest Biotechnology): Ying-Hsuan Sun, Ron Sederoff, Ross Whetten Effects of Drought Stress
November 16, 2001Slide 25 Intracellular Decision Making
November 16, 2001Slide 26 Spots: (Sequences affixed to slide) TreatmentControl Mix 123 Excitation Emission Detection Relative Abundance Detection Hybridization
November 16, 2001Slide 27 Gene Expression Varies
November 16, 2001Slide 28 Existing Computational Tools in Bioinformatics Sequence similarity Multiple sequence alignments Database searching Evolutionary (phylogenetic) tree construction Sequence assemblers Gene finders
November 16, 2001Slide 29 Challenges for Bioinformatics Analyzing and synthesizing complex experimental data Representing and accessing vast quantities of information Pattern matching Data mining Gene discovery Function discovery Modeling the dynamics of cell function
November 16, 2001Slide 30 Computer science interacts with the life sciences. Bioinformatics at Virginia Tech Computer Science in Bioinformatics: Joint research with: plant biologists, microbial biologists, biochemists, cell-cycle biologists, animal scientists, crop scientists, statisticians. Projects: Expresso; Nupotato; MURI; Arabidopsis Genome; Barista; Cell-Cycle Modeling Graduate option in bioinformatics Virginia Bioinformatics Institute (VBI)
November 16, 2001Slide 31 Integration of design and procedures Integration of image analysis tools and statistical analysis Data mining using inductive logic programming (ILP) Closing the loop Integrating models Expresso: A Problem Solving Environment (PSE) for Microarray Experiment Design and Analysis
November 16, 2001Slide 32 Flow of a Microarray Experiment Hypotheses Select cDNAs PCR Test of Hypotheses Extract RNA Replication and Randomization Reverse Transcription and Fluorescent Labeling Robotic Printing HybridizationIdentify SpotsIntensitiesStatisticsClusteringData Mining, ILP
November 16, 2001Slide 33 Expresso: A Microarray Experiment Management System
November 16, 2001Slide 34 Nupotato Potatoes originated in the Andes, where there are many varieties. Many varieties survive at high altitude in cold, dry conditions. Microarray technology can be used to investigate genes that are responsible for stress resistance and that are responsible for the production of nutrients.
November 16, 2001Slide 35 MURI Some microorganisms have the ability to survive drying out or intense radiation. Their genomes are just being sequenced. Using microarrays and proteomics, we will try to correlate computationally the genes in the genomes with the special traits of the microorganisms. We are currently using multiple genome analysis.
November 16, 2001Slide 36 Arabidopsis Genome Project Arabidopsis is a model higher plant. It is the first higher plant whose genome has been fully sequenced. Gene finder software has been used to identify putative genes. We are computationally mining the regulatory regions of these genes for promoter patterns.
November 16, 2001Slide 37 Barista Barista serves Expresso! Software development team across projects to minimize duplication of effort. Work with Linux, Perl, C, Python, cvs, Apache, PHP, …
November 16, 2001Slide 38 Virginia Bioinformatics Institute (VBI) Research institute based at Virginia Tech Established July 1, 2000, with $3 million Will occupy 2 building and have 100+ employees in 4 years
November 16, 2001Slide 39 Getting Into Bioinformatics Learn some biology --- genetics, cell biology Study computational (molecular) biology Get involved with bioinformatics research in interdisciplinary teams Work with biologists to solve their problems