User:Matthew Whiteside/Notebook/Malaria Microarray/2009/09/11

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Mouse Malaria Microarray Datasets to Use in Meta-Analysis

  • Next step in the meta-analysis - is selection of the studies to use.
  • Selection will depend on the question being addressed (see task page).

Contrasts of Interest

To address the research question, i will look at two contrasts in gene expression:

  1. Late-stage CM infected mice vs. Late stage non-CM infected mice.
  2. Late-stage CM infected mice vs. uninfected baseline

Brain gene expression will be compared. Here late-stage is onset of CM symptoms around day 6

The following acronyms will be used:

  • CM - CM infected mice
  • NCM - Non-CM infected mice
  • B - healthy baseline

Studies

Outlined below are the arrays that will be used to compute the contrasts (arrays classified as either CM, NCM or B) - UPDATE m2 and m3 were not carried forward, see Ref for explanation.

Contrast ID GEO ID Authors PMID Arrays Platform Contrast
m1.2 GSE7814 Lovegrove et al. (Hughes Lab) 17991715 PbA + CB57BL/6 (susceptible) vs. CB57BL/6 GPL8321 Affy Mouse Genome 430A 2.0 CM vs B
m1.3 GSE7814 Lovegrove et al. (Hughes Lab) 17991715 PbA + BALB/C (resistant) vs BALB/C GPL8321 Affy Mouse Genome 430A 2.0 NCM vs B
m1.1 GSE7814 Lovegrove et al. (Hughes Lab) 17991715 PbA + CB57BL/6 (susceptible) vs PbA + BALB/C (resistant) GPL8321 Affy Mouse Genome 430A 2.0 CM vs NCM
m2.1 GSE9808 Miu et al. 18299338 PbA (CM-strain) + C57BL/6 vs C57BL/6 PGL1261 Affy Mouse Genome Array 430 2.0 (1st rep) PGL1832 Mouse Compugen 22k array (subsequent reps) CM vs B
m2.2 GSE9808 Miu et al. 18299338 PbK (Non-CM strain) + C57BL/6 vs C57BL/6 PGL1261 Affy Mouse Genome Array 430 2.0 (1st rep) PGL1832 Mouse Compugen 22k array (subsequent reps) NCM vs B
m2.3 GSE9808 Miu et al. 18299338 PbA (CM-strain) + C57BL/6 vs PbK (Non-CM strain) PGL1261 Affy Mouse Genome Array 430 2.0 (1st rep) PGL1832 Mouse Compugen 22k array (subsequent reps) CM vs NCM
m3.1 GSE6019 Randall et al. 18474652 PbA + C57BL/6 (susceptible) vs C57BL/6 PGL1261 Affy Mouse Genome Array 430 2.0 CM vs B
m3.2 GSE6019 Randall et al. 18474652 PbA + CBA/CaH (susceptible) vs CBA/CaH PGL1261 Affy Mouse Genome Array 430 2.0 CM vs B
m3.3 GSE6019 Randall et al. 18474652 PbA + C57BL/6 (susceptible) vs PbA + CBA/CaH PGL1261 Affy Mouse Genome Array 430 2.0 CM vs CM (what is the same?)

I have avoided custom cDNA arrays to keep things simple (its easier to annotate affy arrays). However in the future it may be necessary to include these too, in which case i would use the GEO array annotations.

Analysis Plans

With the two contrasts, i am planning to peform two different analyses

  1. CM vs NCM
    • Compute a PLD matrix for each study. Compute OR pathways for each study. Compare pathways.
    • I believe this approach is necessary because of the differences in NCM arrays - one study uses different malaria strains the other uses different mouse strains.
  2. CM vs B
    • Compute PLD matrix for each study. Combine PLD matrices into z-scores using meta-analysis.
    • This will provide a more statistical sound result and is possible because of the similar malaria infection models used in the three studies.
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