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Encode (Future aims: (where to stop? (rate of discoveries falls below a…

- - - - in theory w/ number of cell lines and TF to explore project could fo on forever
      - Imputation? prediction? once we have enough date?
        
        scientists could eventually accumulate enough data to predict the function of unexplored sequences. This process, called imputation, has long been a goal for genome annotation. “I think there’s going to be a phase transition where sometimes imputation is going to be more powerful and more accurate than actually doing the experiments,” Kellis says.
- - - - DNase1
      - CAGE
        
        ?
      - ChIP
      - 5c method
      - Faire-Ses
- - - - DNase1 has little effect on DNA that hugs histones but chops up DNA this is bound to other regulatory proteins such as transcription factors
        
        sequence the chopped DNA = where proteins bind in different cell types
        
        FINDINGS 2.9 million sites altogether, 3,700 shared in all cell types and others vary
      - Putting the Data together = experiments looking at patterns of histone borders of the DNase1 sensitive sites
        
        then scientists can add data showing exactly where transcription factors bind
        
        every cell type uses different combinations and permutations of these features to generate its unique biology
        
        Shows how relatively few protein coding genes convect such diversity in the cells
- - - - enhancers or other functional sequences included
        
        Systemic lupus erythematosus, a disease where immune system attacks its own body
        
        the variants identified in GWAS tended to be in regulatory regions that were active in an immune cell line
        
        HAPLOREG (C) a web portal to screen variants identified in GWAS against encode data in a systemic way now thanks to encode able to attack much more complex diseases
- - - - develop antibodies
        
        for these DNA binding proteins (one by one)
        
        use to pull protein nd any attached DNA out of cell extracts
        
        sequence
        
        +ve is that this is bound protein (clear end point) as only about 2,00 proteins to explore
        
        how many cell lines to look at?
- - - - (enhancer s cAN REGULAT E genes 100s of 1000s of bp away )
      - mapping these interactions (dekker)
        
        use chemicals to fuse DNA binding proteins togetehr
        
        cut out loops and sequence bound DNA
        
        this reveals the distant relationships between regulatory elements, scaling up to explore interactions across the genome
        
        is this the next phase ( beyond scope of annotation)