gitsvnid: file:///home/git/hedgehog.fhcrc.org/bioconductor/trunk/madman/Rpacks/OncoSimulR@125222 bc3139a867e503109ffcced21a209358
Ramon DiazUriarte authored on 15/12/2016 18:43:47...  ... 
@@ 1,8 +1,8 @@ 
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Package: OncoSimulR 
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Type: Package 
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Title: Forward Genetic Simulation of Cancer Progression with Epistasis 
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Version: 2.5.6 

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Date: 20161214 

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+Version: 2.5.7 

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+Date: 20161215 

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Authors@R: c(person("Ramon", "DiazUriarte", role = c("aut", "cre"), 
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email = "rdiaz02@gmail.com"), 
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person("Mark", "Taylor", role = "ctb", email = "ningkiling@gmail.com")) 
...  ... 
@@ 3688,15 +3688,56 @@ For the Bozic model [@Bozic2010], however, the birth rate is set to 
3688  3688 
In the original model of @McFarland2013, the effects of drivers 
3689  3689 
contribute to the numerator of the birth rate, and those of the 
3690  3690 
(deleterious) passengers to the denominator as: $\frac{(1 + 
3691 
s)^d}{(1  s_p)^p}$, where $d$ and $p$ are, respectively, the total 

3691 
+s)^d}{(1 + s_p)^p}$, where $d$ and $p$ are, respectively, the total 

3692  3692 
number of drivers and passengers in a genotype, and here the fitness 
3693  3693 
effects of all drivers is the same ($s$) and that of all passengers 
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the same too ($s_p$). However, we can map from this ratio to the 

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usual product of terms by using a different value of $s_p$, that we 

3696 
will call $s_{pp} = s_p/(1 + s_p)$ (see @McFarland2014phd, his 

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eq. 2.1 in p.9). This reparameterization applies to v.2. In v.1 we 

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use the same parameterization as in the original one in 

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@McFarland2013. 

3694 
+the same too ($s_p$). Note that, as written above, and as explicitly 

3695 
+said in @McFarland2013 (see p. 2911) and @McFarland2014phd (see 

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+p. 9), "(...) $s_p$ is the fitness disadvantage conferred by a 

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+passenger". In other words, the larger the $s_p$ the more 

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+deleterious the passenger. 

3699 
+ 

3700 
+This is obvious, but I make it explicit because in our 

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+parameterization a positive $s$ means fitness advantage, whereas 

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+fitness disadvantages are associated with negative $s$. Of course, 

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+if you rewrite the above expression as $\frac{(1 + s)^d}{(1  

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+s_p)^p}$ then we are back to the "positive means fitness advantage 

3705 
+and negative means fitness disadvantage". 

3706 
+ 

3707 
+ 

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+As @McFarland2014phd explains (see p.\ 9, bottom), we can rewrite 

3709 
+the above expression so that there are no terms in the 

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+denominator. McFarland writes it as (I copy verbatim from the fourth 

3711 
+and fifth lines from the bottom on his p.\ 9) 

3712 
+$(1 + s_d)^{n_d} (1  s_p^{'})^{n_p}$ where $s_p^{'} = s_p/(1 + s_p)$. 

3713 
+ 

3714 
+ 

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+However, if we want to express everything as products (no ratios) 

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+and use the "positive s means advantage and negative s means 

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+disadvantage" rule, we want to write the above expression as 

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+$(1 + s_d)^{n_d} (1 + s_{pp})^{n_p}$ where $s_{pp} = s_p/(1 + s_p)$. And 

3719 
+this is actually what we do in v.2. There is an example, for 

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+instance, in section \@ref(mcf5070) where you will see: 

3721 
+ 

3722 
+```{r mcflparam} 

3723 
+sp < 1e3 

3724 
+spp < sp/(1 + sp) 

3725 
+``` 

3726 
+ 

3727 
+so we are going from the "(...) $s_p$ is the fitness disadvantage 

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+conferred by a passenger" in @McFarland2013 (p. 2911) and 

3729 
+@McFarland2014phd (p. 9) to the expression where we have a product 

3730 
+$\prod (1 + s_i)$, with the "positive s means advantage and negative 

3731 
+s means disadvantage" rule. This reparameterization applies to 

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+v.2. In v.1 we use the same parameterization as in the original one 

3733 
+in @McFarland2013, but with the "positive s means advantage and negative 

3734 
+s means disadvantage" rule (so we are using expression 

3735 
+$\frac{(1 + s)^d}{(1  s_p)^p}$). 

3736 
+ 

3737 
+ 

3738 
+<! However, we can map from this ratio to the usual product of terms by > 

3739 
+<! using a different value of $s_p$, that we will call $s_{pp} = > 

3740 
+<! s_p/(1 + s_p)$ (see @McFarland2014phd, his eq. 2.1 in p.9). > 

3700  3741 

3701  3742 
For death rate, we use the expression that @McFarland2013 (see their 
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p. 2911) use "(...) for large cancers (grown to $10^6$ cells)": $D(N) = 
...  ... 
@@ 1,15 +1,15 @@ 
1  1 
\usepackage[% 
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+ shash={4dc6adf}, 

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+ lhash={4dc6adf0f20920ff51825aa8ac8563837d4f1239}, 

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authname={Ramon DiazUriarte (at Coleonyx)}, 
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authemail={rdiaz02@gmail.com}, 
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 authsdate={20161213}, 

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 authidate={20161213 20:38:33 +0100}, 

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 authudate={1481657913}, 

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+ authsdate={20161215}, 

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+ authidate={20161215 17:47:46 +0100}, 

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+ authudate={1481820466}, 

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commname={Ramon DiazUriarte (at Coleonyx)}, 
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commemail={rdiaz02@gmail.com}, 
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 commsdate={20161213}, 

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 commidate={20161213 20:38:33 +0100}, 

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 commudate={1481657913}, 

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+ commsdate={20161215}, 

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+ commidate={20161215 17:47:46 +0100}, 

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+ commudate={1481820466}, 

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refnames={ (HEAD, origin/master, origin/HEAD)} 
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]{gitsetinfo} 
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\ No newline at end of file 