BMS 2062: Introduction to Bioinformatics

• Convenor: A/Prof Martin Stone
• 6pts
• Monash Handbook

Subject Overview

This course provides an introduction to both the theoretical and practical aspects of bioinformatics, which can be used as the basis for studies in third year. Over the past few years our means of communication have changed rapidly, due primarily to the growth of the World Wide Web. The Web has provided biomedical scientists with immediate access to databases, literature and many other forms of information. In this course you will get a feel for how computers have enhanced biomolecular science, especially in the analysis of biological sequence data which are accumulating at an enormous rate. In order to exploit the information contained within these sequences a new science has arisen which combines biology with computer sciences and mathematics - BIOINFORMATICS. 

BMS2062 will emphasise the relevance and power of bioinformatics and communication to the biomolecular sciences. It will cover five major areas: 

1. the application of the internet to the molecular sciences
2. organisation and uses of scientific databases;
3. genome analysis
4. fundamentals of protein structure and molecular modelling
5. analysis and presentation of scientific data.

The basic theoretical principles and practical applications of these areas will be illustrated by examples taken from the bimolecular sciences. 

BMS2062 consists of 2 lectures per week, one 3 hour computer laboratory session per week and 1 hour of self-directed learning per week.

The student composition of practical classes will be made by ALLOCATE + program and finalised by the FIRST WEEK of semester. Students are to proceed to the Laboratory on the ground floor of Building 16 on their allocated day in the first week of semester. Allocation of prac class will depend on timetable clashes with other classes. Please finalise the day allocated to you for your practical classes during the first week of semester. Students will be divided up into groups per prac class, each containing 10-12 students. 

A/Prof Martin Stone	A/Prof Phil Bird	Prof Steve Bottomley	Dr George Kotsanas
Dr Tim Stinear	Prof James Whisstock	A/Prof Matthew Wilce

Assessment

• Practical: 45%
• Project Assignment: 15%
• Project talk: 5%
• End of semester examination: 35%

Resources

Enrolled students can access timetables, lecture notes and supplementary material on WebCT.

A. INTRODUCTION TO BMS2062

Introduction to Bioinformatics & course overview
Bioinformatics can be defined as "the creation, development, and operation of databases and other computing tools to collect, organise, and interpret biological data". This lecture introduces the important role of bioinformatics in today's science. It will also include an overview of the course

B. INFORMATION TECHNOLOGY AND ITS RELEVANCE TO BIOINFORMATICS

Practical uses of Internet Services
The power of the internet is hidden from many. It takes time, experience and a little exploration to discover the full potential of Internet services. This lecture looks at the number of services available on the internet, specifically looking at the Web. In addition, we will look at emerging technologies and what they can bring to the medical profession. Emphasis will be placed on finding, citing, validating and authenticating medically related Web information. This lecture provides an introduction to the first practical exercise.

Digitised images and image compression
"A picture says more that a thousand words". Does it? This lecture looks at digital images and how to obtain, manipulate, compress and use them.

The Internet and multimedia
Multimedia and the Web are both communication mediums, the convergence of the two opens many avenues for engagement and interactivity. This lecture looks at the world of multimedia on the web, what you need to consider when developing web content, and some of the constraints that need to be addressed.

C. BASIC PRINCIPLES OF MOLECULAR BIOLOGY

DNA structure, function and motifs
Over the last half-century, a picture of the biological information contained in DNA has been built up, allowing bioinformaticians to rapidly scan DNA sequences looking for patterns that reveal genes, protein binding sites, viral insertions and structural elements. In this lecture, we will review the structure, function and organization of DNA. Emphasis will be placed on sequence motifs that can be found in DNA, and how these contribute to our understanding of DNA function and information flow in the cell.

RNA structure, function and motifs
In this lecture we will review the structure and function of RNA. Information encoded in DNA flows to messenger RNA and eventually to proteins. Besides being an information carries, RNA plays a pivotal role in the machinery replicating and regulating genes, and driving protein synthesis. The latter functions of RNA largely depend on its ability to form complex secondary structures and bind proteins, and predicting these structures de novo remains a challenge for bioinformatics

Basic principles of protein structure
Amino acids and their contribution to protein structure. The 4 levels of protein structure. Primary structure. Secondary structure: a -helices, b -sheets and b -turns. Tertiary structure, major principles involved in determining structure of a protein. Quaternary structure, subunits, the advantages of quaternary structure

Introduction to protein motifs and domains
What does the primary structure of a protein tell us about it in terms of structure and function? How does this help us to make sense of the large amount information in the databases? Definition of motifs and domains. Examples of motifs. Examples of domains. Relationship of motifs and domains to the overall structure and function of proteins.

D. SEQUENCING, DATABASES AND DATABASE SEARCHING

Sequencing and annotating genomes
Why sequence a genome? Stages and problems in assembling a genomic sequence.
Identification of segments encoding protein. Use of nucleotide sequence to identify: tRNA and rRNA genes, mobile genetic elements, repetitive DNA sequences. Use of predicted amino acid sequence to assign possible functions. Annotation errors and their propagation: the need for experimentation. Sequential versus parallel analyses.

Recommended Reading: Frangeul, L., K.E. Nelson, C. Buchrieser, A. Danchin, P. Glaser and F. Hurst. 1999. Cloning and assembly strategies in microbial genome projects. Microbiology 145: 2625-2634.

Comparative genomics
Evolution of cells. Evolution of genome size. Extent of horizontal gene transfer. Concept of the minimal cell. What makes some bacteria pathogenic? Development of new vaccines and therapeutics.

Recommended Reading:
Knowles. New strategies for antibacterial drug design. Trends in Microbiology 5:379-383 (1998).
Strauss and Falkow. Microbial pathogenesis: genomics and beyond. Science 276:707-712 (1997).

Blasting and mining
A basic introduction to searching protein sequence databases: (1) the concepts behind BLAST. (2) When is a hit real or not? (3) Using database mining tools. (4) Why mine the archives?

E. THE IMPACT OF BIOINFORMATICS ON BIOMOLECULAR SCIENCE

Proteomics
The relationship between the genome and the proteome. Techniques used in proteomic studies. Characterization of pathways. The concept of molecular systems engineering.

Phylogeny: evolution and its relationship to conserved residues, conservative and non-conservative substitutions
Introduction to the concepts and application of phylogenetic analysis - techniques which methodically demonstrate a family relationship between species. In this lecture we will examine how phylogenetic trees can be reconstructed, and how the evolutionary relationship can be deduced. Specific examples will also be used to illustrate how phylogeny can provide insight into the evolution and/or persistence of protein structure and function.

Protein folding and structure prediction
Prediction of protein structure and the protein folding problem. Secondary structure prediction. Molecular dynamics simulations.

Protein structure determination
Proteins are the molecular machines of our bodies. The three-dimensional (3-D) structures of proteins are essential for their function and activity. Knowledge of the 3-D structure of a protein provides an understanding, at the atomic level, of how a protein functions, or as in the diseased state, how a protein malfunctions. This two lecture series will review the principles of protein structure, and give an overview of the methods involved in protein structure determination and analysis.

Protein structure modelling
An overview of the techniques that can be used for modelling proteins in the absence of experimental data. This will include de novo calculation, threading and homology modelling.

The Human Genome Project – past and future
2003 marked the 50th anniversary of the description of the structure of DNA by Crick and Watson. By the end of 2003 it is envisaged that sequencing of the human genome will be essentially complete. Bioinformatics has played a key part in the Human Genome Project (HGP), and will be central to exploiting the vast amount of data it has generated. Here we look at the achievements of the HGP and the implications for future biomedical research, using single nucleotide polymorphisms (SNPs) as an example.

From Sequence to Structure
"Similar polypeptide sequences adopt similar 3-dimensional structures" – this is the underlying tenet of protein modelling and functional genomics. This lecture will explore how to infer the function of a novel predicted protein sequence.

DNA micro-arrays and expression profiling
Recent technological advances in molecular biology and in microprinting have drastically changed our ability to examine gene expression. Micro-array technology enables up to 40,000 genes to be spotted onto a single chip and the relative expression of all genes can be analysed in a single sample. The importance of this technology will be discussed and its future applications to human disease detection and genetics.

Drug design
Traditional drug discovery relies on either serendipity or screening vast libraries of compounds for the identification of lead molecules. Recent advances in computational biology have allowed the development of rational drug design. Some of the basic principles of structure-based drug design will be described.

The Victorian Bioinformatics Consortium
A description of bioinformatics in action at Monash.