Class 1: Introduction

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Class 1 Introduction
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The Tree of Life
Source Alberts et al
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The Cell
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Example Tissues in Stomach
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DNA Components

• Four nucleotide types
• Adenine
• Guanine
• Cytosine
• Thymine
• Hydrogen bonds
• A-T
• C-G

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The Double Helix
Source Alberts et al
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DNA Duplication
Source Mathews van Holde
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DNA Organization
Source Alberts et al
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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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Genes

• The 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)

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Transcription

• Coding sequences can be transcribed to RNA
• RNA nucleotides
• Similar to DNA, slightly different backbone
• Uracil (U) instead of Thymine (T)

Source Mathews van Holde
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RNA Editing
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RNA Editing
Source Mathews van Holde
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RNA roles

• Messenger RNA (mRNA)
• Encodes protein sequences
• Transfer RNA (tRNA)
• Adaptor between mRNA molecules and amino-acids
  (protein building blocks)
• Ribosomal RNA (rRNA)
• Part of the ribosome, a machine for translating
  mRNA to proteins
• ...

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Transfer RNA

• Anticodon
• matches a codon (triplet of mRNA nucleotides)
• Attachment site
• matches a specific amino-acid

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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 poly-peptide
• When the ribosome encounters a stop signal, it
  releases the mRNA. The construct poly-peptide is
  released, and folds into a protein.

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Translation
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Translation
Source Alberts et al
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Translation
Source Alberts et al
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Translation
Source Alberts et al
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Translation
Source Alberts et al
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Translation
Source Alberts et al
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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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Protein Structure
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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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Course Goals

• Computational tools in molecular biology
• We will cover computational tasks that are posed
  by modern molecular biology
• We will discuss the biological motivation and
  setup for these tasks
• We will understand the the kinds of solutions
  exist and what principles justify them

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Four Aspects

• Biological
• What is the task?
• Algorithmic
• How to perform the task at hand efficiently?
• Learning
• How to adapt parameters of the task form examples
• Statistics
• How to differentiate true phenomena from artifacts

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Example Sequence Comparison

• Biological
• Evolution preserves sequences, thus similar genes
  might have similar function
• Algorithmic
• Consider all ways to align one sequence against
  another
• Learning
• How do we define similar sequences? Use
  examples to define similarity
• Statistics
• When we compare to 106 sequences, what is a
  random match and what is true one

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Topics I

• Dealing with DNA/Protein sequences
• Genome projects and how sequences are found
• Finding similar sequences
• Models of sequences Hidden Markov Models
• Transcription regulation
• Protein Families
• Gene finding

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Topics II

• Gene Expression
• Genome-wide expression patterns
• Data organization clustering
• Reconstructing transcription regulation
• Recognizing and classifying cancers

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Topics III

• Models of genetic change
• Long term evolutionary changes among species
• Reconstructing evolutionary trees from current
  day sequences
• Short term genetic variations in a population
• Finding genes by linkage and association

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Topics IV

• Protein World
• How proteins fold - secondary tertiary
  structure
• How to predict protein folds from sequences data
  alone
• How to analyze proteins changes from raw
  experimental measurements (MassSpec)
• 2D gels

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Class Structure

• 2 weekly meeting
• Class Mondays 16-18
• Targil Tuesday 18-20
• Grade
• 60 in five question sets
• Each contains theoretical problems practical
  computer questions
• 40 test
• 5 bonus for active participation

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Exercises Handouts

• Check regularly
• http//www.cs.huji.ac.il/cbio