Population Genomics Course: Difference between revisions

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imported>Weigang
imported>Weigang
 
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*In-class exercise: 2-3
*In-class exercise: 2-3
*Data set: three pairs of sister-group cp26 plasmids
*Data set: three pairs of sister-group cp26 plasmids
#MUGSY visualization
*LDhat: [http://ldhat.sourceforge.net/instructions.shtml Instructions]; [http://ldhat.sourceforge.net/manual.pdf PDF Manual]; Based on the "Four-Gamete Test" by [http://www.genetics.org/content/111/1/147.full.pdf+html Hudson & Kaplan, 1985]
*LDhat: [http://ldhat.sourceforge.net/instructions.shtml Instructions]; [http://ldhat.sourceforge.net/manual.pdf PDF Manual]; Based on the "Four-Gamete Test" by [http://www.genetics.org/content/111/1/147.full.pdf+html Hudson & Kaplan, 1985]
#Download and Install: <pre pre style="white-space: pre-wrap;">svn checkout https://ldhat.svn.sourceforge.net/svnroot/ldhat; make; make clean</pre>
#Download and Install: <pre style="white-space: pre-wrap;">svn checkout https://ldhat.svn.sourceforge.net/svnroot/ldhat; make; make clean</pre>
#Data: cp26.ss.fas
#Data: cp26.ss.fas
#Convert to LDhat file format: <pre pre style="white-space: pre-wrap;">../ldhat/convert -seq cp26.ss.fas -2only -prefix cp26</pre>
#Convert to LDhat file format: <pre style="white-space: pre-wrap;">../ldhat/convert -seq cp26.ss.fas -2only -prefix cp26</pre>
#Generate likelihood lookup table: <pre pre style="white-space: pre-wrap;">../ldhat/lkgen -lk lk_n100_t0.01 -nseq 14; mv new_lk.txt lk_n14_t0.01</pre>
#Generate likelihood lookup table: <pre style="white-space: pre-wrap;">../ldhat/lkgen -lk lk_n100_t0.01 -nseq 14; mv new_lk.txt lk_n14_t0.01</pre>
#In RStudio: <pre pre style="white-space: pre-wrap;">source("http://ldhat.sourceforge.net/R/coalescent.r")</pre>
#Estimate recombination rates: <pre style="white-space:pre-wrap;">../ldhat/pairwise -lk lk_n14_t0.01 -seq cp26sites.txt -loc cp26locs.txt</pre>
 
#Identify hotspots: <pre style="white-space:pre-wrap;">../ldhat/interval -lk lk_n14_t0.01 -seq cp26sites.txt -loc cp26locs.txt</pre>
*Own script for sister-group counts? (D statistics)
#Summarize results:<pre style="white-space:pre-wrap;">../ldhat/stat -input bounds.txt -burn 500 -loc cp26locs.txt</pre>
#Visualize in RStudio
##<pre pre style="white-space: pre-wrap;">source("http://ldhat.sourceforge.net/R/coalescent.r")</pre>
##Plot "outfile.txt"
##Plot "fit.txt"
##Plot "res.txt"


===Part 4. Simulation of natural selection & Summary===
===Part 4. Simulation of natural selection & Summary===

Latest revision as of 04:54, 24 June 2013

Learning Goals

  • Identification of lineage-specific genomic changes of pathogens
  • Estimate recombination, mutation, and selection in natural pathogen populations

Learning outcomes

  • Be able to construct genome trees using genome-wide SNPs
  • Use genome trees to identify orthologs and paralogs, and gene gains and losses
  • Detecting recombination among bacterial genomes
  • Use of coalescence tree to describe process of microbial genome evolution

Syllabus

Part 1. Introduction & Overview

  • Lecture: 8:30-9:30
  • Population processes
    • Recombination: Muller's Rachet; Hill-Roberson effect
    • Recombination and natural selection: Background selection & selective sweeps
  • Applications
    • GWAS
    • Population history: phylogeny, structuring, gene flow, and selective sweeps (e.g., Neandertal genomes; Borrelia burgdorferi in Northeast US)
    • Genomic surveillance of infectious diseases
  • Bioinformatics pipeline/protocol
  • In-Class Exercise: Software setup & data download

Part 2. Building genome phylogeny/Geographic structuring/Population growth?

  • In-class exercise: 10:00-11:30
  • Data set: cp26 plasmids from 23 B. burgdorferi sensu lato genomes
  • Genome alignment: MUGSY & Alignment viewer: Gmaj
  • Genome tree: FastTree
  • Tree re-rooting: R package APE see syllabus
  • Interactive tree viewer: trexonline

Part 3. Estimation of recombination rate

  • In-class exercise: 2-3
  • Data set: three pairs of sister-group cp26 plasmids
  1. MUGSY visualization
  1. Download and Install:
    svn checkout https://ldhat.svn.sourceforge.net/svnroot/ldhat; make; make clean
  2. Data: cp26.ss.fas
  3. Convert to LDhat file format:
    ../ldhat/convert -seq cp26.ss.fas -2only -prefix cp26
  4. Generate likelihood lookup table:
    ../ldhat/lkgen -lk lk_n100_t0.01 -nseq 14; mv new_lk.txt lk_n14_t0.01
  5. Estimate recombination rates:
    ../ldhat/pairwise -lk lk_n14_t0.01 -seq cp26sites.txt -loc cp26locs.txt
  6. Identify hotspots:
    ../ldhat/interval -lk lk_n14_t0.01 -seq cp26sites.txt -loc cp26locs.txt
  7. Summarize results:
    ../ldhat/stat -input bounds.txt -burn 500 -loc cp26locs.txt
  8. Visualize in RStudio
    1. source("http://ldhat.sourceforge.net/R/coalescent.r")
    2. Plot "outfile.txt"
    3. Plot "fit.txt"
    4. Plot "res.txt"

Part 4. Simulation of natural selection & Summary

  • In-class exercise: 3:30-5
  • ms, seq-gen; Genomes
  • BacSim

Assignment & Assessment