August 19, 2002 Slide 1

Bioinformatics at Virginia Tech

David Bevan (BCHM)Lenwood S. Heath (CS)

Ruth Grene (PPWS)Layne Watson (CS)

Chris North (CS)Naren Ramakrishnan (CS)

August 19, 2002

August 19, 2002 Slide 2

• Some relevant biology

• New language of biology

• Bioinformatics research at Virginia Tech

• Getting into bioinformatics at Virginia Tech

Overview

August 19, 2002 Slide 3

Some Molecular Biology

•The encoded instruction set for an organism is kept in DNA molecules.

• Each DNA molecule contains 100s or 1000s of genes.

•A gene is transcribed to an mRNA molecule.

• An mRNA molecule is translated to a protein (molecule).

August 19, 2002 Slide 4

Transcription and Translation

DNA mRNA ProteinTranscription Translation

August 19, 2002 Slide 5

DNA Strand

A= adenine complements T= thymine

C = cytosine complements G=guanine

August 19, 2002 Slide 6

RNA Strand

U=uracil replaces T= thymine

August 19, 2002 Slide 7

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, according to the genetic code.

• There are also START and STOP codons.

August 19, 2002 Slide 8

Translation to a Protein

Unlike DNA, proteins have three-dimensional structure

Protein folds to a three-dimensional shape thatminimizes energy

August 19, 2002 Slide 9

A new language has been created. Words in the language that are useful today.

Genomics

Functional Genomics

Proteomics

Global Gene Expression Patterns

Networks and Pathways

The Language of the New Biology

August 19, 2002 Slide 10

• Genome sequencing projects: Drosophila, yeast, human, mouse, Arabidopsis, microbes, …

• Identification of genetic sequences:• Sequences that code for proteins; • Sequences that act as regulatory elements.

Genomics

August 19, 2002 Slide 11

• The biological role of individual genes;

• Mechanisms underlying the regulation of their expression;

• Regulatory interactions among them.

Functional Genomics

August 19, 2002 Slide 12

• When a gene is transcribed (copied to mRNA), it is said to be expressed.

• The mRNA in a cell can be isolated and examined using microarrays. Its contents give a snapshot of the genes currently being expressed.

• Correlating gene expression with conditions gives hints into the dynamic functioning of the cell.

Gene Expression

August 19, 2002 Slide 13

Gene Expression Varies

August 19, 2002 Slide 14

Networks and Pathways:Glycolysis, Citric Acid Cycle, and Related

Metabolic Processes

August 19, 2002 Slide 15

Computer Science interacts with the life sciences.

Bioinformatics at Virginia Tech

• Joint research with: plant biologists, microbial biologists, biochemists, cell-cycle biologists, animal scientists, crop scientists, statisticians.• Projects: Expresso; NutriPotato; MURI; Multimodal Networks; Barista; Fusion;

Arabidopsis Genome; Cell-Cycle Modeling• Graduate option in bioinformatics

August 19, 2002 Slide 16

• Integration of design, experimentation, and analysis

• Data mining; inductive logic programming (ILP)

• Closing the loop

• Drought stress experiments with pine trees and Arabidopsis

Expresso: A Problem Solving Environment (PSE) for Microarray Experiment Design and Analysis

August 19, 2002 Slide 17

NutriPotato

Microarray technology used to investigate genes responsible for stress resistance and for the production of nutrients in Andean potato varieties.

August 19, 2002 Slide 18

MURI• Some microorganisms have the ability to

survive drying out or intense radiation.

• Using microarrays and proteomics, we are attempting to correlate computationally the genes in the genomes with the special traits of the microorganisms.

August 19, 2002 Slide 19

Other Projects

• Multimodal Networks: represent, manipulate, and identify biological networks

• Barista: serves software for Expresso, et al.

• Fusion: visualization via redescription

• Arabidopsis Genome Project: mine the Arabidopsis genome for regulatory sequences

August 19, 2002 Slide 20

Getting Into Bioinformatics at VT

• Learn some biology: genetics, molecular biology, cell biology, biochemistry (2 courses)

• Study computational biology: CS 5984• Get involved with bioinformatics research

in interdisciplinary teams• Work with biologists to solve their

problems

August 19, 2002 Slide 21

CS 5984: Algorithms in Bioinformatics

• Genetic and physical mapping• Sequence comparison• Sequence alignment• Sequence alignment• Probabilistic models for molecular biology• Fragment assembly• Genome rearrangements• Evolutionary tree (re-)construction