Introduction to Bioinformatics

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Introduction to Bioinformatics
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What is Bioinformatics

• Easy Answer
• Using computers to solve molecular biology
  problems Intersection of molecular biology and
  computer science
• Hard Answer
• Computational techniques (e.g. algorithms,
  artificial intelligence, databases) for
  management and analysis of biological data and
  knowledge

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Bioinformatics

• Bioinformatics Biology Information
• Biology is becoming an information science
• Computation methods are necessary to analyze the
  massive amount of information that coming out of
  the genome projects

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Bioinformatics is Another Revolution in Biology
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Three concepts, which remain central to
Bioinformatics

• Data representation

A complex, dynamic, three-dimensional molecule
a simple string of characters
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Three concepts, which remain central to
Bioinformatics

• The concept of similarity
• Evolution has operated on every sequence
• In biomolecular sequences (DNA, RNA or amino acid
  sequences). High sequence similarity usually
  implies significant functional or structural
  similarity.
• The opposite is not true
• Algorithms for comparing sequences and finding
  similar regions are at the heart of bioinformatics

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Three concepts, which remain central to
Bioinformatics

• Bioinformatics is not a theoretical science it
  is driven by the data, which in turn is driven by
  the needs of biology.
• Sequences
• Microarray technologies

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GenBank Growth
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Moores Law
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What do you need to know?

• It all depends on your background
• Are you a ?
• Biologist with some computer knowledge, or
• Computer scientist with some biology background
• Few do both well

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Background

• Biology for Computer Scientists
• Computer Science for Biologists

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Biological Information Flow
Genome
Introns/Exons
Gene Sequence
Protein Sequence
Bioinformatics attempts to model this pathway
Protein Structure
Protein Functions
Cellular Pathways
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Living Things

• Entropy (the tendency to disorder) always
  increase
• Living organisms have low entropy compared with
  things like soil
• They are relatively orderly
• The most critical task is to maintain the
  distinction between inside and outside

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Living Things

• In order to maintain low entropy, living
  organisms must expend energy to keep things
  orderly.
• They figured out how to do this 4 billion years
  ago
• The functions of life, therefore, are meant to
  facilitate the acquisition and orderly
  expenditure of energy

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Living Things

• The compartments with low entropy are separated
  from the world.
• Cells are the smallest unit of such compartments.
• Bacteria are single-cell organisms
• Humans are multi-cell organisms

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The living things have the following tasks

• Gather energy from environment
• Use energy to maintain inside/outside distinction
• Use extra energy to reproduce
• Develop strategies for being successful and
  efficient at the above tasks
• Develop ways to move around
• Develop signal transduction capabilities (e.g.
  vision)
• Develop methods for efficient energy capture
  (e.g. digestion)
• Develop ways to reproduce effectively

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How to accomplish?

• Living compartments on earth have developed three
  basic technologies
• Ability to separate inside from outside (lipids)
• Ability to build three-dimensional molecules that
  assist in the critical functions of life
  (Protein, RNA)
• Ability to compress the information about how
  (and when) to build these molecules in linear
  code (DNA)

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Bioinformatics Schematic of a Cell
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Lipids

• Made of hydrophilic (water loving) molecular
  fragment connected to hydrophobic fragments
• Spontaneously form sheets (lipid membranes) in
  which all the hydrophilic ends align on the
  outside, and hydrophobic ends align on the inside
• Creates a very stable separation, not easy to
  pass through except for water and a few other
  small atoms/molecules

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What is Nucleotide?

• Pentose, base, phosphate group

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Pentose RNA and DNA
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Base

• Adenine (A), Cytosine (C), Guanine (G), Thymine
  (T),
• Uracil (U).

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Nucleic Acid Chain

• Condensation reaction
• Orientation
• From 5 to 3
• In DNA or RNA, a nucleic acid chain is called
  Strand
• DNA double-stranded
• RNA a single strand
• The number of bases
• Base pair (bp) in DNA

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DNA Structure
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DNA Structure
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DNA Structure
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RNA Structure and Function

• The major role of RNA is to participate in
  protein synthesis
• Messenger RNA (mRNA)
• Transfer RNA (tRNA)
• Ribosomal RNA (rRNA)

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mRNA
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The Genetic Code
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What is gene?

• A gene includes the entire nucleic acid sequence
  necessary for the expression of its product.
• Such sequence may be divided into
• Regulatory region
• Transcriptional region exons and introns
• Exons encode a peptide or functional RNA
• Introns will be removed after transcription

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Gene
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Genome

• The total genetic information of an organism.
• For most organisms, it is the complete DNA
  sequence
• For RNA viruses, the genome is the complete RNA
  sequence

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Genes and Control

• Human genome has 3,000,000,000 bps divided into
  23 liner segments (chromosome)
• A gene has an average 1340 DNA bps, thus
  specifying a protein of about ? (how many) amino
  acids
• Humans have about 35,000 genes 40,000,000 DNA
  bps 3 of total DNA in genome
• Human have another 2,960,000,000 bps for control
  information. (e.g. when, where, how long, etc)

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Gene Expression

• An organism may contain many types of cells, each
  with distinct shape and function
• However, they all have the same genome
• The genes in a genome do not have any effect on
  cellular functions until they are expressed
• Different types of cells express different sets
  of genes, thereby exhibiting various shapes and
  functions

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Gene Expression

• The production of a protein or a functional RNA
  from its gene
• Several steps are required
• Transcription
• RNA processing
• Nuclear transport
• Protein synthesis

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Gene Expression
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Central Dogma
DNA
RNA
Protein
Next Protein Structure and Function
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An Amino Acid

• An amino acid is defined as the molecule
  containing an amino group (NH2), a carboxyl group
  (COOH) and an R group.
• R-CH(NH2)-COOH
• The R group differs among various amino acids.
• In a protein, the R group is also call a
  sidechain.

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An Amino Acid
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The Twenty Amino Acids of Proteins
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The Twenty Amino Acids of Proteins
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Protein

• Peptide ? a chain of amino acids linked together
  by peptide bonds.
• Polypeptides ? long peptides
• Oligopeptides ? short peptides (lt 10 amino acids)
• Protein are made up of one or more polypeptides
  with more than 50 amino acids

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Protein Structure

• Primary Structure
• Refers to its amino acid sequence

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Secondary structure

• Regular, repeated patterns of folding of the
  protein backbone.
• Two most common folding patterns
• Alpha helix
• Beta sheet

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Tertiary Structure

• The overall folding of the entire polypeptide
  chain into a specific 3D shape

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Quaternary Structure

• Many proteins are formed more than one
  polypeptide chain
• Describe the way in which the different subunits
  are packed together to form the overall structure
  of the protein
• Hemoglobin molecule

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Quaternary Structure
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Evolution

• Mutation ? rare events, sometimes single base
  changes, sometimes larger events
• Recombination ? how your genome was constructed
  as a mixture of your two parents
• Through Natural Selection
• Homology (similarity) different species are
  assumed to have common ancestors
• The genetic variation between different people is
  (surprisingly ..)

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References

• http//www.biology.arizona.edu/biochemistry/proble
  m_sets/large_molecules/
• http//helix-web.stanford.edu/bmi214/index2004.htm
  l
• http//www.web-books.com/MoBio/
• http//www.cs.sunysb.edu/skiena/549/