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Project team: Vitalina Komashko, Justin Guinney, Jonathan Derry

Table of contents:

1. Project proposal

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Aim1: Characterize CIMP phenotype in colon cancer using the 450k arrays

–Identify patient groups in relation to characteristic DNA methylation signature (CIMP)

–Where does it occur? CpG islands/shores/shelves

–Any correlation with overall survival/presence of (no information available) metastasis, tumor stage, lymphocyte invasion

–Methods: comethylation networks and clustering

Aim2:  Characterize CIMP phenotype in relation to the gene mutations 

- All genes with the focus on the known players such as KRAS and BRAF

-Focus on epigenes (EZH2, DNMT, etc)

-Casual relationship between mutations and CIMP (what comes first)

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2. Literature
   
   1. MINT markers
   2. Shen, 2007 CIMP CpGs on 450k platform
   3. Laird (2006, 2011) markers
   4. Hinoue 2012: re-analysis
3. Platforms
   
   1. IlluminaHumanMethylation450k.db Bioconductor package
   2. 27k platform: how I removed probes that overlap with SNPs and repetitive regions
4. Clinical information
   
   1. Correlation with technical variables (processing batch/slide): 450k platform
   2. Correlation with the batch with clinical variables in CRC dataset (148 patients): 27k
   3. Correlation of processing batch with clinical variables in colon cancer: 27k
   4. Clinical variables of interest
5. DNA methylation
   
   1. 27k array platform
      
      1. Normalization
      2. Shen, 2007: attempt to reproduce results
      3. Laird 2006, 2011 markers: attempt to reproduce results
      4. Forcing CIMP clusters (using K means) and correlation with mutational status
         
         1. Colon cancer: Shen and Laird markers
         2. Colorectal cancer: Shen and Laird markers
      5. De novo discovery of clusters (based on Hinoue 2012 methodology) in TCGA CRC and correlation with mutational status
   2. 450k array platform
      
      1. Reading raw data files (.idat)
      2. Relationship between various types of batches in the data
      3. Normalization
      4. Shen, 2007: attempt to reproduce the results using TCGA data
6. more