Introduction to Bioinformatics

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Introduction to Bioinformatics

• Alexandra M Schnoes
• Univ. California San Francisco
• Alexandra.Schnoes_at_ucsf.edu

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What is Bioinformatics?

• Intersection of Biology and Computers
• Broad field
• Often means different things to different people
• Personal Definition
• The utilization of computation for biological
  investigation and discoverythe process by which
  you unlock the biological world through the use
  of computers.

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What does one do in Bioinformatics? (a small
sample)

• Our Lab Understanding Protein (Enzyme) Function

• dsafd

• dsafd

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What does one do in Bioinformatics? (a small
sample)

• Discover new drug targetscomputational docking

Atreya, C. E. et al. J. Biol. Chem.
200327814092-14100 Shoichet, B. K. Nature.
2004432862-865
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What does one do in Bioinformatics? (a small
sample)

• Systems Biology

sbw.kgi.edu/ www.sbi.uni-rostock.de/
research.html
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This lab Nucleotide Protein Informatics

• Sequence analysis
• Finding similar sequences
• Multiple sequence alignment
• Phylogenetic analysis

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Sequence?Structure?Function
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Process of Evolution

• Sequences change due to
• Mutation
• Insertion
• Deletion

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Use Evolutionary Principles to Analyze Sequences

• If sequence A and sequence B are similar
• A and B evolutionarily related
• If sequence A, B and C are all similar but A and
  B are more similar than A and C and B and C.
• A and B are more closely evolutionarily related
  to each other than to C

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Extremely Powerful Idea

1. Start with unknown sequence
2. Find what the unknown is similar to
3. Use information about the known to make
   predictions about the unknown

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How do you know when sequences are similar?

• Align two sequences together and score their
  similarity

TASSWSYIVE TATSFSYLVG

• Use substitution matrices to score the alignment

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Substitution Matrices Give a Score for Each
Mutation
Blosum 62 Scoring matrix

• Many different matrices available
• Blosum matrices standard in the field

http//www.carverlab.org/images/
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Scoring Add up the positional Scores
TASSWSYIVE TATSFSYLVG
TASSWSYIVE TATSFSYLVG

• Score of 1

• Score of 30

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Additional issues

• Gaps (insertions/deletions)
• Have scoring penalties for opening and continuing
  a gap

TASSWSYIVE TASSWSYIVE TATSFLVG
TATSF--LVG
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How do we find similar sequences?

• Start at the National Center for Biotechnology
  Information
• http//www.ncbi.nlm.nih.gov/

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How do we find similar sequences?

• Nucleotide Sequence Databases

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How do we find similar sequences?

• Protein Sequence Databases

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How do we find similar sequences?

• Similarity Search BLAST
• Basic Local Alignment Search Tool

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BLAST is very quick but

• Only local alignments
• Alignments arent great
• Only pair-wise alignments

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Want better alignments

• Multiple alignment
• Multiple sequences
• Better signal to noise
• More Sequences Better alignment
• More accurate reflection of evolution

• ClustalW
• Commonly used
• Easy to use

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Visualize the Multiple Alignment
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Use the Alignment to Calculate Evolutionary
Distances

• See how close sequences are to each other
• Best way to tell what is most similar
• Can calculate simple tree from clustalW

Taubenberger et al., Nature 437, 889-893, 2005
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Caveats!

• In reality
• Sequences (even parts of sequences) can evolve at
  different rates
• Dont have a good understanding of sequence and
  function
• High sequence identity does not always mean the
  same function
• Getting good alignments and good trees can be
  very hard

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Bioinformatics Sequence Analysis

1. Start with unknown sequence
2. Find similar sequences
3. Create alignment
4. Create phylogenetic tree
5. Use information about knowns to make predictions
   about unknown

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Mini Virus Intro

• Often considered not alive
• Extremely small (much smaller than a cell)
• Cellular parasites
• Has a genome but can only reproduce inside a host
  cell

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Different Viruses

• RNA DNA viruses
• Both single and double-stranded

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Different Viruses

• RNA DNA viruses
• Both single and double-stranded

• Influenza Virus

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Influenza Virus (flu)

• Small genome8 RNA molecules
• Evolves quickly genetic drift, antigenic shift

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Influenza Virus (flu)

• Sequencing

Reverse Transcriptase
Sequencing
Genomic Nucleotide Sequence
DNA
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Influenza Pandemics

• 1918 Flu
• Killed from 50-100 Mil. people worldwide
• Considered to be one of the most deadly pandemics
• Killed many of the young and healthy
• Influenza A, Type H1N1
• Thought to have derived from Avian Influenza
• Recently reconstituted from recovered human
  samples
• Considerable ethical debate

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Avian Influenza

• Current fear of pandemic
• High mortality rate (including young and healthy)
• Current concern is Influenza A, Type H5N1
• Still only transmitted by contact with birds
• Is now in Asia and Eastern and Western Europe

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This lab Nucleotide Protein Informatics

• Sequence analysis
• Finding similar sequences
• Multiple sequence alignment
• Phylogenetic analysis

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