steepness, hill - different parameters

  • problem/goal/basics
    • steepness
      • log(size_99th) - log(size_95th)
        • the percentiles are parameters, these are the defaults, they were used in the article
    • steepness and hill is highly correlated
    • why isn't lkb1 the best?
      • steepness will be high if there is a high probability of a big tumor
        • we saw on the CDFs that lkb1 has a "bump" (dúsulás)
        • so we expect lkb1 to have a high steepness value
      • => is it because of the parameters?
    • is there correlation between the fitting error and the steepness? (default and new parameters)
      • we expect correlation (with "good" parameters) because we saw that all the badly fitting ones have that "bump"
  •  original size cdf:
    • (red is lkb1, green is pten)
    • pten's high steepness:
      • 99th percentile size is the highest
      • 95th percentile is not that different from the others
      • => log(size_99th) - log(size_95th) will be big
    • lkb1's "low" steepness
      • 99th percentile size is high
      • 95th percentile is the highest by a big margin!
      • => log(size_99th) - log(size_95th) won't be big!
    • lkb1 is "steep" as well, but we don't get a high value, because the steepness ("the linear part") starts lower
  • new parameters (hand-picked, to get a higher score for the lkb1)
    • lower percentile: where the size is still close to the other ones => 90th percentile
    • higher percentile: where the size is the highest => anywhere between 93-98 => 95th
  • changes in steepness with new parameters
    • lkb1 is now the highest
  • correlation between fitting error
    • single mutants:
    • every genotype (dualguide)
  • similar results with hill
    • instead of the default 95th percentile, use the 90th percentile, because we think that lkb1's steep part starts there
    • new idea
      • for every mutant calculate the hill estimate for several percentiles (1-99)
      • we normalize to the inert in every percentile
      • plot these (x - percentile, y - normalized hill estimate, every line is a genotype)
      • we calculate these values for every genotype and then get the percentile corresponding to the maximum hill estimate, then we plot the percentile and the fitting error:
      • the outlier with an error of 0.021 is p53;rb1
      • the other 3 outliers: 'Keap1', 'Rasa1', 'Apc_Rnf43'
        • if we plot the percentile-hill estimate for these, we can see that it has a maximum at ~0.8, but the line is mostly flat
        • p53;rb1 is red, others are grey

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