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Algorithms in Computational Biology (236522) Spring 2006 

Lecturer: Golan Yona Office hours: Wednesday or Thursday 2-3pm (Taub 632, Tel 4356)

TA: Itai Sharon Office hours: Tuesday 2:30-3:20 (Taub 621, Tel 4946)

Lecture: Monday 12:30-2:20, Taub 4

Tutorial: Tuesday 1:30-2:20, Taub 7

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Computational BiologyComputational biology is the application of computational tools and techniques to (primarily) molecular biology.  It enables new ways of study in life sciences, allowing analytic and predictive methodologies that support and enhance laboratory work. It is a multidisciplinary area of study that combines Biology, Computer Science, and Statistics.

Computational biology is also called Bioinformatics, although many practitioners define Bioinformatics somewhat narrower by restricting the field to molecular Biology only.

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Examples of Areas of Interest• Understanding the structure of genomes (detecting

genes, regulatory elements, variations)• Deciphering structure and function of proteins• Discovery of cellular “procedures” (pathways)• Indentifying disease-causing genes• Building the tree of life• More ..

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Exponential growth of biological information: growth of sequences, structures, and literature.

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Course’s goals

The focus of this course is the set of algorithms, tools and models used today to analyse molecular biological data, recover and discover hidden information.

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Course PrerequisitesComputer Science and Probability Background

• Data structure 1 (cs234218)• Algorithms 1 (cs234247)• Probability (any course)

Or permission from instructor

Biology background• Formally: none (to allow CS studnets to take this course)• Recommended: Molecular Biology 1 (especially for those in

the Bioinformatics track), or a similar Biology course, and/or a serious desire to complement your knowledge in Biology by reading the appropriate material (see the course home).

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Requirements & Grades• 40% homework, in five or six assignments. Homework is

obligatory.

• 60% test. Must pass 55 for the homework’s grade to count

• Exam date: 17.7.06

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Syllabus

• Introduction, biological background (0.5 weeks)

• Gene detection and function prediction– Pairwise alignment (2 weeks)

– Multiple sequence alignment (2 weeks)

– Profile and Hidden Markov Models (2 weeks)

• Motif detection (1 week)

• Phylogenetic trees (2 weeks)

• Expression data analysis, pathways (2.5 weeks)

• Protein structure analysis (2 weeks)

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Bibliography• Biological Sequence Analysis, R.Durbin et al. , Cambridge

University Press, 1998

• Introduction to Molecular Biology, J. Setubal, J. Meidanis, PWS publishing Company, 1997 

• Misc papers

• Some slides adopted from courses taught by Nir Friedman (Hebrew U), Dan Geiger and Shlomo Moran

• Course home: webcourse.cs.technion.ac.il/~cs236522

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Biological Background

First home work assignment: Read the first chapter (pages 1-30) of Setubal et al., 1997. (copies are available in the Taub building library, and in the central library). Answer the questions of the first assignment in the course site.

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Course starts..

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Human GenomeMost human cells contain

46 chromosomes:

• 2 sex chromosomes (X,Y):

XY – in males.

XX – in females.

• 22 pairs of chromosomes named autosomes.

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DNA OrganizationS

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The Double HelixS

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DNA ComponentsFour nucleotide types:

• Adenine• Guanine• Cytosine• Thymine

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Base pairsHydrogen bonds (electrostatic connection):

• A-T• C-G

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Genome Sizes• E.Coli (bacteria) 4.6 x 106 bases• Yeast (simple fungi) 15 x 106 bases• Smallest human chromosome 50 x 106 bases• Entire human genome 3 x 109 bases

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Genetic Information

• Genome – the collection of genetic information.

• Chromosomes – storage units of genes.

• Gene – basic unit of genetic information. They determine the inherited characters.

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GenesThe DNA strings include:• Coding regions (“genes”)

– E. coli has ~4,000 genes – Yeast has ~6,000 genes– C. Elegans has ~13,000 genes– Humans have ~32,000 genes

• Control regions – These typically are adjacent to the genes– They determine when a gene should be “expressed”

• “Junk” DNA (unknown function - ~90% of the DNA in human’s chromosomes)

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The cell

All cells of an organism contain the same DNA content (and the same genes) yet there is a variety of cell types.

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Example: Tissues in Stomach

How is this variety encoded and expressed ?

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Central Dogma

Transcription

mRNA

Translation

ProteinGene

cells express different subset of the genesIn different tissues and under different conditions

שעתוק תרגום

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Central dogma

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Transcription• Coding sequences can be transcribed to

RNA

• RNA – Similar to DNA, slightly different nucleotides:

different backbone– Uracil (U) instead of Thymine (T)

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Transcription: Junk DNA, RNA Editing, Alternative Splicing

Exons hold information, they are more stable during evolution.This process takes place in the nucleus. The mRNA molecules diffuse through the nucleus membrane to the outer cell plasma.

1. Transcribe to RNA2. Eliminate introns3. Splice (connect) exons* Alternative splicing exists

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RNA roles• Messenger RNA (mRNA)

– Encodes protein sequences. Each three nucleotide acids translate to an amino acid (the protein building block).

• Transfer RNA (tRNA)– Decodes the mRNA molecules to amino-acids. It connects

to the mRNA with one side and holds the appropriate amino acid on its other side.

• Ribosomal RNA (rRNA) – Part of the ribosome, a machine for translating mRNA to

proteins. It catalyzes (like enzymes) the reaction that attaches the hanging amino acid from the tRNA to the amino acid chain being created.

• ...

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Central dogma

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ProteinsMade of 20

Amino acids

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Translation

• Translation is mediated by the ribosome• Ribosome is a complex of protein & rRNA

molecules• The ribosome attaches to the mRNA at a

translation initiation site• Then ribosome moves along the mRNA

sequence and in the process constructs a sequence of amino acids (polypeptide) which is released and folds into a protein.

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Helper molecules: tRNA

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The Genetic Code

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Protein Structure

• Proteins are poly-peptides of 70-3000 amino-acids

• This structure is (mostly) determined by the sequence of amino-acids that make up the protein

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Various structures with different functions

• Structural framework (keratin, collagen)• Transport and storage of small molecules

(hemoglobin)• Transmit information (hormones, receptors)• Antibodies• Blood clotting factors• Enzymes

Protein structures

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Protein-Protein interactions

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Pathways

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Evolution

• Related organisms have similar DNA– Similarity in sequences of proteins– Similarity in organization of genes along the

chromosomes

• Evolution plays a major role in biology– Many mechanisms are shared across a wide

range of organisms– During the course of evolution existing

components are adapted for new functions

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Evolution

Evolution of new organisms is driven by

• Diversity– Different individuals carry different variants of

the same basic blue print

• Mutations– The DNA sequence can be changed due to

single base changes, deletion/insertion of DNA segments, etc.

• Selection bias

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The Tree of Life

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