BIO513: Lecture 1

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BIO513 Lecture 1
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Central dogma
The central dogma of molecular biology deals
with the detailed residue-by-residue transfer of
sequential information. It states that such
information cannot be transferred back from
protein to either protein or nucleic acid.
-Francis Crick
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The Alphabet of DNA

• DNA consists of a 4 letter alphabet, arranged in
  complementary pairs on a sugar/phosphate backbone
• A (adenine, a purine)
• C (cytosine, a pyrimidine)
• G (guanine, a purine)
• T (thymine, a pyrimidine)

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Bonds

• There are strict rules for the complementary
  strands (with nucleotides linked by a hydrogen
  bond).
• A T
• C G
• G C
• T A

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DNA double helix
http//academic.brooklyn.cuny.edu
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Gene and Genomics

• A gene is the basic unit of heredity in a living
  organism. All living things depend on genes.
  Genes hold the information to build and maintain
  their cells and pass genetic traits to offspring.
  
• The genome of an organism is its hereditary
  information encoded in DNA

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Species Genome size (Mb) Number of genes  
Mycoplasma genitalium 0.58 500
Streptococcus pneumoniae 2.2 2300
Escherichia coli 4.6 4400
Saccharomyces cerevisiae 12 5800
Arabidopsis thaliana 125 25,500
Caenorhabditis elegans 97 19,000
Sea urchin 814 23,300
Drosophila melanogaster 180 13,700
Mus musculus 2500 21,000
Homo sapiens 2900 20-25,000
Oryza sativa 466 45-55,000  

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RNA

• RNA is very similar to DNA
• RNA is usually single-stranded, while DNA is
  usually double-stranded
• RNA nucleotides contain ribose while DNA contains
  deoxyribose.
• and RNA has the base uracil rather than thymine
  that is present in DNA.

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RNA structure
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Transcription from DNA to RNA
RNA
DNA

• A
• C
• G
• T

• U
• G
• C
• A

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Steps of gene transcription
Pol II
TFIID
activator
TATA
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Steps of gene transcription
Pol II
TFIID
activator
TATA
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Steps of gene transcription
Pol II
TATA
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Transcription factors recognizes specific
sequences

• AGCTGGT gene 1
• AGCTGGT gene 2
• AGCTGGT gene 3
• CGCTGGT gene 4
• CGCTGGT gene 5
• CGCTGGT gene 6
• GGCTGGT gene 7
• GGCTGGT gene 8
• GGCTGGT gene 9
• TGCTGGT gene 10
• TGCTGGT gene 11
• TGCTGGT gene 12
• .... ...

Motif logo
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Protein

• Proteins are made of amino acids arranged in a
  linear chain and joined together by peptide
  bonds.
• Proteins are used to execute almost all cell
  functions (signaling, enzyme, structure,
  regulation, etc.)
• The biological functions of a protein is defined
  by its structure and ability to bind.

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Translation

• mRNA is used as the template for protein
  synthesis.
• Proteins are made in the cytoplasm (outside of
  the nucleus).
• Translation starts from the AUG (START) codon.

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U C A G
U Phe Ser Tyr Cys U
Phe Ser Tyr Cys C
Leu Ser STOP STOP A
Leu Ser STOP Trp G

C Leu Pro His Arg U
Leu Pro His Arg C
Leu Pro Gln Arg A
Leu Pro Gln Arg G

A Ile Thr Asn Ser U
Ile Thr Asn Ser C
Ile Thr Lys Arg A
Met Thr Lys Arg G

G Val Ala Asp Gly U
Val Ala Asp Gly C
Val Ala Glu Gly A
Val Ala Glu Gly G
Genetic Code Three nucleotides (CODON)
determine a amino acid. 64 possible codons
correspond to 20 amino acids. Example AAA, AAG
- Lysine
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Topics of reading

1. Genome sequencing technologies and their impact
   on public health approaches
2. Analysis of gene expression
3. Transcription factor regulation and motif finding
   
4. Epigenetics and its role in transcription
   regulation, development, and diseases.
5. Network structure analysis
6. Tools and paradigms for network analysis
7. Role of networks in offering systems level
   insights in interpretation of disease
8. Genetic variation within human population
9. Genome diversity in microbial pathogens 

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Genome sequencing technologies and their impact
on public health approaches

• What is next-generation sequencing?
• How do you search for a short DNA sequence
  fragment in a genome or large database?

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Genome sequencing technologies and their impact
on public health approaches

• What is next-generation sequencing?
• How do you search for a short DNA sequence
  fragment in a genome or large database?

Mardis 2008
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Genome sequencing technologies and their impact
on public health approaches

• What is next-generation sequencing?
• How do you search for a short DNA sequence
  fragment in a genome or large database?

Trapnell et al. 2009
Mardis 2008
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Analysis of gene expression

• Which genes are expressed in a given cell type
  under a specific environmental condition?
• What do these expressed genes do?
• What genes are expressed differently between
  disease and normal tissues?

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Analysis of gene expression

• Which genes are expressed in a given cell type
  under a specific environmental condition?
• What do these expressed genes do?
• What genes are expressed differently between
  disease and normal tissues?

Hughes et al. 2000
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Transcription factor regulation and motif finding

• How are gene expression levels regulated?
• To what extent is the gene expression pattern
  encoded in the genome?

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Transcription factor regulation and motif finding

• How are gene expression levels regulated?
• To what extent is the gene expression pattern
  encoded in the genome?

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Epigenetics and its role in transcription
regulation

• Why are different sets of genes expressed in
  different cell-types?
• How is tissue-specific regulatory information
  inherited?

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Epigenetics and its role in transcription
regulation

• Why are different sets of genes expressed in
  different cell-types?
• How is tissue-specific regulatory information
  inherited?

Mikkelsen 2007
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Tools and paradigms for network analysis

• How do the all the genes/proteins inside a cell
  interact with each other?
• How can we reconstruct a biological network from
  experimental data?

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Tools and paradigms for network analysis

• How do the all the genes/proteins inside a cell
  interact with each other?
• How can we reconstruct a biological network from
  experimental data?

Friedman 2004
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Network structure analysis

• Is a biological network made of modules?
• How does a biological network differ from a
  random network?
• Does biological networks change during
  development and evolution?

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Network structure analysis

• Is a biological network made of modules?
• How does a biological network differ from a
  random network?
• Does biological networks change during
  development and evolution?

Milo et al. 2002
Kim et al. 2008
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Network interpretation of diseases

• What does network analysis tell us about diseases?

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Network interpretation of diseases

• What does network analysis tell us about diseases?

Segal et al. 2004
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Genetic variation within human population

• How similar are the genome sequences of two
  random individuals?
• How much variation of gene expression can be
  linked to genetic differences?

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Genetic variation within human population

• How similar are the genome sequences of two
  random individuals?
• How much variation of gene expression can be
  linked to genetic differences?

Altschuler et al. 2008
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Genome diversity in microbial pathogens

• How many microorganisms are there living inside a
  human being?
• How do these microorganisms contribute to normal
  physiology and diseases?

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Genome diversity in microbial pathogens

• How many microorganisms are there living inside a
  human being?
• How do these microorganisms contribute to normal
  physiology and diseases?

Turnbaugh et al. 2007