Bioinformatics and Graphical Models: Computation, approximation, and their value

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Bioinformatics and Graphical ModelsComputation,
approximation, and their value

• MSR
• Nebojsa Jojic, Vladimir Jojic, Chris Meek, David
  Heckerman

UW Jim Mullins, Mark Jensen, Jerry Learn
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Overview

• Computational cost of usual algorithms
• State of the art
• Phylogeny alignment
• Phylogeny sequence modeling
• Approximations and their pitfalls
• Recombination
• Analogy to other ML domains
• Graphical model
• Experiments and computational cost
• Value of the computation
• Potential applications
• Drug discovery cycle
• Value of time and clinical success
• Market size and growth
• Discussion

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Rational vaccine design(Jim Mullins et al)

• Rational design
• Analysis of sequences to form a model of virus
  evolution (phylogenies, etc.)
• Develop vaccines that target as much variability
  as possible
• Traditional design
• Trial and error
• Educated guesses

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State of the art sequence analysis programs

• Example
• Rational AIDS vaccine design
• Analysis of the envelope gene from a single
  patient in one visit
• 200 sequences with 600 base pairs each
• Overnight to align
• 1-2 hours to 2-3 days to build a tree, depending
  on how much search you are willing to do
• This does not include modeling the inter-sequence
  dependencies, coupling alignment and tree search,
  and it ignores recombination
• The total length of the HIV genome is 10000 and
  the number of samples is practically only limited
  by cost

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Computational cost of a slightly more detailed
analysis

• Metropolis search over all trees on 400 sequences
  of the full genome (10k) would last around 2
  years on one machine
• Exact search intractable!

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Approximation

• Free energy as a bound on negative log-likelihood
• Computation and approximation of the free energy
• Iterative conditional modes
• Mean-field method
• Structured variational techniques
• (Loopy) belief propagation
• Sampling techniques
• How tight is the bound?
• What does the looseness translate to?

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An example of the approximation issues
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An example of the approximation issues
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An example of the approximation issuesTightness
of the bounds
Variational technique
Exact EM algorithm
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Recombination

• In HIV, the rate of recombination has recently
  been estimated to be ¼ of the rate of mutation!
• Combinatorial explosion in inference

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Similar situations in other domains where
graphical models work well

• Occlusion in video
• Source interaction in audio
• Composition of images

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Occlusion in audio
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Speaker1
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Retrieved Speaker1
Retrieved Speaker2
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Epitome of an image
A set of image patches
Input image
Epitome
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Layers from a single photograph
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em
S1
s2
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x
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Modeling alignment and recombination by learning
a library of gene patterns
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Experimental results
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Value of computation(from Tufts Center)
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Growth

• Human viruses
• West Nile
• SARS
• Hepatitis C
• Polio
• Animal viruses
• FIV
• Pig, chicken and cow viruses
• Most bacterial diseases
• Parasitic diseases
• The first sign of success of rational design
  might trigger great increase in the number of
  diseases tackled

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How can MS/MSR be involved?

• MS Architecture, platform, tools
• Storage, transmission, computation
• E.g., parallelizable computation on a single
  machine pear-to-pear networks for parallel
  computation on multiple machines
• MSR
• Helping to speed up the scientific progress
  leading to the new opportunities for growth
• Advising MS on the research direction in the
  community and the future requirements for the
  platform