Introduction to Bioinformatics

Questions & Help

• Amir Mitchell – lecturer.

• Itay Mayros, Einat Hazkani-Covo, and Shira

Mintz – Teaching assistants

• Emails:
mitchel@post.tau.ac.il, itaymay@post.tau.ac.il,
einat@kimura.tau.ac.il, mintzshi@post.tau.ac.il

• Course site

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 Course Layout
• Eleven lessons – eleven weeks.
• Lecture, exercise, discussion.
• Presentations and exercises.
• Books and additional material.
• Missing lessons or exercises.
• Consultation hour.
• Personal gene/protein.
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 Final grade
• Final exam (80%):
– Multiple choice questions
– Open questions
– No online part

• Home assignment (20%)

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 Bioinformatics
• Buzzword …
Nanotechnology, Biotechnology …

Bioinformatics: Bioinformatics is the branch of computer science

that focuses on sub-domains of biology: research on genes and
proteins. Researchers in this field must use powerful computers and
special calculation methods to process the large body of complex data
generated by genetics. Using these tools, it was possible to sequence
the human genome .
Lexicon-encyclobio

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 Two separate approaches
• Computer science - inventing tools,
developing algorithms.

• Biology - Utilizing tools for biological

research.
1. Purely bioinformatics (comparing exon/intron
structure in human and mouse).
2. “Fairly” bioinformatics (Locating the active site of
an enzyme by identifying conserved residues in
the protein sequence).
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 Research outline
Databases (public, local)

Retrieve data

Analysis

Results

Lab (wet biology) Literature

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 Databases & Tools
• Free shared databases (on-line, bioinfo unit)

• Internet based tools (PC)

• GCG package tools (unix)

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 GCG
• Commercial DNA and protein sequence
analysis package.

• Written by Wisconsin Genetics Computing

Group.

• Includes more than 130 separate tools.

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 GCG
• GCG works in unix environment (OS)

• Same principles apply to all GCG programs

• On-line help

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 Divided work
PC1 Unix2 Web
- Databases Databases
(main ones only) (all)
Data storage Data storage -
Tools Tools Tools

1Access(unix and web)

2Advanced analysis, user databases, web site

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 Lesson 1 – Introduction,
Unix environment
1. Administration
2. Introduction to Bioinformatics.
3. NCBI
4. Working in Unix environment

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Lesson 2 – databases and text
based searching:
1. Databases: organization and entries.
2. Database problems.
3. Principles of database searching.
4. Unix and GCG.

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Lesson 3 – pairwise alignment

1. Comparing two sequences.

2. Scoring: good and bad alignments.
3. Comparison methods.
4. Comparison programs.
5. Unix.

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 Lesson 4 – Sequence based
searching
1. DNA or protein sequences as search queries.

2. Problems with sequence search.

3. Methods for searching (fasta, blast).

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Lesson 5 – Multiple sequence
alignment
1. Comparing multiple sequences.
2. Uses of multiple alignment.
3. Methods for multiple alignment, efficiency
and limitations.
4. Profiles and consensus sequences.

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 Lesson 6 – Phylogenies

1. Introduction to phylogeny.

2. Methods for constructing evolutionary trees.

3. Statistical analysis of constructed trees.

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Lesson 7 – Protein families,
secondary databases
1. Dividing proteins into families.
2. Patterns.
3. Different approaches: motifs, fingerprints.
4. Different databases.
5. Consurf.

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 Lesson 8 – DNA sequence
analysis
1. Gene structure.
2. Gene finding.
3. Predicting gene features.
4. Consurf.

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 Lesson 9 - genomes
• Genome features.
• Prokaryotic and Eukaryotic genomes.
• Genome viewers
• Model organisms

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 Lesson 10 - Various tools
• Making things easy, useful tools for lab
work.

Lesson 11 - Summary
• Overview, Q&A before the exam.

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 Last comments
• Introduction only.

• Finding sites: Links and google.

• Biology background.

• Unix accounts.

• Terminology

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 Milestones in bioinformatics
1965 Theory of molecular evolution (Zuckerkandl & Pauling)
1967 Atlas of protein sequences (Dayhoff)
1970 Global alignment algorithm (Needleman, Wunsch)
1981 Local alignment algorithm (Smith, Waterman)
1981 Sequence motif concept (Doolittle)
1982 GenBank made public
1982 Phage lambda genome fully sequenced
1983 Database search algorithm (Wilbur, Lipman)
1985 Fast sequence similarity searching
1990 Blast
1991 ESTs
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* 1953 Watson and Crick
 Milestones in bioinformatics
1995 First bacterial genome fully sequenced H. influenzae
1996 Yeast genome fully sequenced
1997 C. elegans genome fully sequenced
1999 Fruit fly genome fully sequenced
2000 Human genome fully sequenced (draft)

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 Today …
• Over 1500 fully sequenced genomes from
all domains of life.

• Numerous databases.

• Numerous tools.

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 Today …

Archea (16)

Eukarya (20)

Bacteria (139)

Viruses (1500)
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 Examples
• Human , mouse, rat, zebra fish, drosophila,
yeast, anopheles, tomato, rice, wheat.

• E. coli (4 strains), M. tuberculosis, M.

leprae.

• Mitochondria, chloroplast, plasmids.

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 Public interest:
Human Genome Project
• 2000 - Working draft of the Genome, work of 20
groups world wide.
(http://www.ncbi.nlm.nih.gov).
• 2003 - Obtain a complete, high-quality genomic
sequence.
• Determine the sequences of the 3 billion bases.
• Identify all the estimated 30,000 genes in human
DNA

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 Human Genome Project

Chromosome 21
9 May, 2000

Chromosome 22
2 Dec, 1999

Initial analysis
15 Feb, 2001

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 NCBI – at a glance
The biggest and most comprehensive site!
Includes numerous tools and databases!

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 NCBI - overview
PubMed OMIM

Books Exp’ profiles

Structure
NCBI Nucleotides

Domains Proteins

Taxonomy Genomes
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* Cross references between the databases
 NCBI
PubMed

• Citations, abstracts, full articles.

Books

• Online books, full text from books (Cell,

introduction to genetic analysis)

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 NCBI
OMIM

• Online Mendelian Inheritance in Man. A

comprehensive database of human genes
and genetic disorders.

• Entries include textual information and

,most importantly, references to literature
and sequences.
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 NCBI
GEO

• Gene Expression Omnibus

Results from a high throughput
experiments. mRNA, DNA, and protein
arrays.

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 NCBI
Genomes Nucleotides Proteins

• Sequence databases. Divided into sections

and sub-sections.

Domains

• Protein domains, both conserved sequence

domains and 3D domains.

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 NCBI
Structure

• 3D structure of proteins (~20,000 entries).

Taxonomy

• Taxonomy of all organisms found in NCBI

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 NCBI - Interconnectivity
PubMed OMIM

Books Exp’ profiles

Structure
NCBI Nucleotides

Domains Proteins

Taxonomy Genomes
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* Cross references between the databases