1. Topics The topics: basic concepts of molecular biology more on Perl
overview of the field
biological databases and database searching
sequence alignments
phylogenetic trees
protein structure prediction
microarray data analysis

2. The Human Genome Project
The human genome sequence is complete - almost - approximately 3 billion base pairs.
23 chromosomes, starting from 1990
Some of these slides are adapted from Lecture Notes of Stuart M. Brown at NYU

3. Whole genome sequencing has now become routine

4. How does the human genome stack up?
Organism
Genome Size (Bases)
Estimated Genes
Human (Homo sapiens)
3.2 billion
25,000
Laboratory mouse (M. musculus)
2.6 billion
Mustard weed (A. thaliana)
100 million
Roundworm (C. elegans)
97 million
19,000
Fruit fly (D. melanogaster)
137 million
13,000
Yeast (S. cerevisiae)
12.1 million
6,000
Bacterium (E. coli)
4.6 million
3,200
Human immunodeficiency virus (HIV)
9700 9
U.S. Department of Energy Genome Programs, Genomics and Its Impact on Science and Society, 2003

5. The Path Forward How does DNA impact health? What do all the genes do?
Identify and understand the difference in DNA sequence (A,T,C,G) among human populations
What do all the genes do?
Discover the functions of human genes by experimentation and by finding genes with similar funcs in the model organisms
What are the functions of nongene areas?
Identify important elements in the nongene regions of DNA
How does info in the genome enable life?
Explore life at the ultimate level of the whole organism instead of single genes/proteins.
U.S. Department of Energy, 2005

6. Diverse applications Medicine – customized treatments, …
Microbes for energy and the environment – generate clean energy source, clean up toxic wastes,…
Bioanthropology – human lineage
Agriculture, livestock breeding, Bioprocessing – crops&animals more resistant to diseases, efficient industrial processes,…
DNA identification – implicate people accused of crimes, identify contaminants in air, water, …
U.S. Department of Energy, 2005

7. Genomics: Journey to the Center of Biology
Without doubt, the greatest achievement in biology over the past millennium has been the elucidation of the mechanism of heredity. The instructions for assembling every organism on the planet are all specified in DNA sequences that can be translated into digital information and stored in a computer for analysis. As a consequence of this revolution, biology in the 21st century is rapidly becoming an information science. Powerful new types of bioinformatics will clearly be required to assimilate and interpret the data that will issue from various types of genomics research.
Eric Lander & Robert Weinberg, Science, 2000

8. Nucleic Acid Sequence Databases
the principal nucleic acid sequence databases are GeneBank, EMBL and DDBJ, which each collect a portion of the total sequence data reported world-wide, and exchange new and updated entries on a daily basis
Nucleic acid sequence Databases
EMBL (European Molecular Biology Laboratory)
GenBank (USA)
DDBJ (DNA Data Bank of Japan)
ENSEMBL (project between EMBL - EBI and the Sanger Institute, to produce and maintain automatic annotation on selected eukaryotic genomes )
dbEST (division of GenBank)
GSDB (Genome Sequence DataBase, division of GenBank)

9. GenBank
Once upon a time, GenBank sent out sequence updates on CD-ROM disks a few times per year. .

12. Specialised Genomic Resources
In addition to the comprehensive DNA sequence DBs, there is a variety of more specialised genomic resources.
These so called boutique DBs bring focus to species-specific genomics and to particular sequencing techniques.
Specialised Genomic Resources
SGD – Saccharomyces Genome Database
UniGene - gene-oriented clusters from GenBank
TIGR - Databases of The Institute for Genomic Research
ACeDB – A C.elegans DataBase

13. Protein Information Resources
The primary structure of a protein is its amino acid sequence
The second structure of a protein corresponds to regions of local regularity (e.g., α-helices and β-strands).
The tertiary structure of a protein arises from the packing of its secondary structure elements, which may form discrete domains within a fold.
Levels of protein sequence and structural organisation:
primary
tertiary
secondary

14. Primary Protein Databases
The primary structure of a protein is its amino acid sequence. These are stored in primary databases as linear alphabets that denote the constituent residues.
Protein sequence Databases
SWISS-PROT - Protein knowledgebase
TrEMBL - Computer-annotated supplement to Swiss-Prot
PIR – Protein Information Resource
MIPS – Munich Information Centre for Protein Sequences
NRL-3D - produced by PIR

15. Structure Classification DBs
Contain 3D structures available from crystallographic and spectroscopic studies
Structure Classification Databases
PDB – Protein Data Bank
CATH – Class, Architecture, Topology, Homology
SCOP – Structural Classification of Proteins

16. PDB: Growth (2006)

17. Databases concerning Mutations
dbSNP
HGBASE (Human Genome Variation Database)
The SNP Consortium (TSC)

18. Literature Databases PubMed http://www.ncbi.nlm.nih.gov/entrez/query
Bioinformatics Online
Nature
Science

19. Systems Biology Integrate different levels of
information to understand
how biological systems function
Use computational and mathematical models to analyze, model and simulate cellular networks, interactions and pathways.

20. Microarray
DNA microarray is a new technology to measure the level of the mRNA gene products of a living cell.

21. Affymetrix GeneChip® Probe Arrays
Hybridized Probe Cell * *
GeneChip Probe Array * * * *
Single stranded, fluorescently
labeled cRNA target
Oligonucleotide probe
24~50µm
1.28cm
Each probe cell or feature contains
millions of copies of a specific
oligonucleotide probe
Image of Hybridized Probe Array
BGT108_DukeUniv

22. Bioinformatics Tools Database & searching Computational algorithms
Alignment
Similarity
Clustering
Pattern Searching
Structure predictions
Statistical methods
Data visualization

23. Bioinformatics
Bioinformatics is the research, development, or application of computational tools and approaches for expanding the use of biological, medical, behavioral or health data, including those to acquire, store, organize, archive, analyze, or visualize such data;
Computational biology is the development and application of data-analytical and theoretical methods, mathematical modeling and computational simulation techniques to the study of biological, behavioral, and social systems.