Genomic Arrays: Tools for cancer gene discovery

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Genomic Arrays Tools for cancer gene discovery

• Ian Roberts
• MRC Cancer Cell Unit
• Hutchison MRC Research Centre
• ir210_at_cam.ac.uk

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Whats a genomic array?

• A platform of regularly spaced genomic sequences
• All known genes or a subset of genes of interest
• A tool for querying the genome about damage
• Genomic gains (oncogenes)
• Genomic losses (tumour suppressor genes)
• Applications
• Research ? disease gene discovery
• Clinical ? diagnostic tests

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Comparative genomic hybridisation
Available probe

Tumour DNA (Test)
Normal DNA (Reference)
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New generation arrays produce large amounts of
data
Agilent 244K array
Raw data is foreground and background signal
intensities in two channels Median ratio of
foreground is important.
243,504 defined spots
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aCGH data analysis ...

• ... using camgrid

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Genomic array analysis strategy using R

• array data is processed by snapCGH R package
• Correct array data for background noise and mean
  distribution
• Order data by genomic location
• Apply an aCGH segmentation algorithm
• Draw some plots
• Determine significant findings (in house R
  functions)
• Common and minimum genomic regions of gain and
  loss
• Summarise output

R ? www.cran.r-project.org snapCGH ?
www.bioconductor.org parrot R on camgrid ?
http//www.bio.cam.ac.uk/local/condor-parrot.html
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Old vs. New genomic array plots
Chromosome 7
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Significant region detection is computationally
intensive
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Distributed aCGH analysis
Consolidate output
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Condor job scripting in BASH R

• BASH function
• Responsible for producing required condor files
  for discrete jobs
• Default_submit has 2 positional parameters
• R script name ? 1
• Data files ? 2
• Initiates aCGH analysis on grid.
• Condor dagman R function set
• R-scripter
• Writes the appropriate R script for the current
  job
• R-condor-submitter
• Writes the condor job submission file
• R-condor-executer
• Writes the condor job executable file
• R-job-descriptor
• Writes the condor dagman description file

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End user abstraction start_aCGH.sh

• aCGH analysis undertaken by a single shell
  command
• Manages array data input
• Collects user specified parameters
• Chromosome range
• Segmentation algorithms
• Significance thresholds
• Links condor R job scripting

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start_aCGH.sh session on mole
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. continued
1 hr 6 hr later!
aCGH region information and plots
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Summary findings (38 arrays)

• Rapid identification of regions of interest
• Easy comparison of aCGH analysis via different
  algorithms

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Real life application
Retrospective analysis confirms initial
findings! (summary of 38 samples)
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Future development

• Tailor output for specific user requirements
• Produce overall summary plot
• Apply approach to expression arrays

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www.bio.cam.ac.uk/ir210

• Grace Ng
• Steph Carter
• Konstantina Karagavriliidou
• Jenny Barna
• Mark Calleja
• Nick Coleman