Practical Bioinformatics Mark Voorhies 5/26/2015 Mark Voorhies - - PowerPoint PPT Presentation

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Practical Bioinformatics Mark Voorhies 5/26/2015 Mark Voorhies - - PowerPoint PPT Presentation

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Practical Bioinformatics Mark Voorhies 5/26/2015 Mark Voorhies Practical Bioinformatics Habits are things you get for free, without requiring any special work. Cory Doctorow Advice to Writers, 4/5/2012 Mark Voorhies Practical

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Practical Bioinformatics

Mark Voorhies 5/26/2015

Mark Voorhies Practical Bioinformatics

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Habits are things you get for free, without requiring any special work. –Cory Doctorow Advice to Writers, 4/5/2012

Mark Voorhies Practical Bioinformatics

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Why compare sequences?

Mark Voorhies Practical Bioinformatics

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EM: Training an HMM

Mark Voorhies Practical Bioinformatics

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EM: Estimating transcript abundances

L

  • m

i =m i–1

(i −1)c ic −1 ) ∝ λL · ρ · ωp|−,L ·φ − |

−,L

P (

L

m

i P (−) P p (−) P(−)

∝ α ∝ λ Online EM algorithm Update parameters Constrain estimated counts Output

Relative abundances Estimated counts

Augmented alignment file

Effective counts

Get next read pair Update masses Input Capture target sequences Fragment and sequence Align to target references Calculate assignment probabilities

Error probabilities

A A C G T C G T +

Bias Targets

p,

Roberts and Pachter, Nature Methods 10:71

Mark Voorhies Practical Bioinformatics

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Evolution implies a self-consistent model

Distances (Pairwise relationships) Topology (Evolutionary history)

Mark Voorhies Practical Bioinformatics

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Measure all pairwise distances by dynamic programming

Mark Voorhies Practical Bioinformatics

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Measure all pairwise distances by dynamic programming

Mark Voorhies Practical Bioinformatics

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Generate a guide tree by UPGMA

Mark Voorhies Practical Bioinformatics

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Generate a guide tree by UPGMA

Mark Voorhies Practical Bioinformatics

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Generate a guide tree by UPGMA

Mark Voorhies Practical Bioinformatics

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Generate a guide tree by UPGMA

Mark Voorhies Practical Bioinformatics

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Generate a guide tree by UPGMA

Mark Voorhies Practical Bioinformatics

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Progressive alignment following the guide tree

Mark Voorhies Practical Bioinformatics

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Progressive alignment following the guide tree

Mark Voorhies Practical Bioinformatics

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Progressive alignment following the guide tree

Mark Voorhies Practical Bioinformatics

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Measure distances directly from the alignment

Mark Voorhies Practical Bioinformatics

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Generate neighbor-joining tree from new distances

Mark Voorhies Practical Bioinformatics

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Generate neighbor-joining tree from new distances

Mark Voorhies Practical Bioinformatics

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Generate neighbor-joining tree from new distances

Mark Voorhies Practical Bioinformatics

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Generate bootstrap values from subsets of the alignment

Mark Voorhies Practical Bioinformatics

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Generating a multiple alignment in CLUSTALX

Mark Voorhies Practical Bioinformatics

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Generating a multiple alignment in CLUSTALX

Mark Voorhies Practical Bioinformatics

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Generating a neighbor joining tree in CLUSTALX

Mark Voorhies Practical Bioinformatics

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Viewing the alignment and tree in JALVIEW

Mark Voorhies Practical Bioinformatics

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Related tools

Protein Multiple Alignment

MUSCLE Clustal Omega Probcons hmmalign (HMMer3)

Tree Building

MrBayes (Bayesian MCMC) PhyML (maximum likelihood) RaxML (fast maximum likelihood) FastTree2 (very large heuristic trees)

Mark Voorhies Practical Bioinformatics

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Homework

Finish your dynamic programming implementation.

Mark Voorhies Practical Bioinformatics