@@ -1,8 +1,8 @@

 Package: OncoSimulR

 Type: Package

 Title: Forward Genetic Simulation of Cancer Progression with Epistasis 

-Version: 2.5.6

-Date: 2016-12-14

+Version: 2.5.7

+Date: 2016-12-15

 Authors@R: c(person("Ramon", "Diaz-Uriarte", role = c("aut", "cre"),

 		     email = "rdiaz02@gmail.com"),

 	      person("Mark", "Taylor", role = "ctb", email = "ningkiling@gmail.com"))

@@ -1,3 +1,6 @@

+Changes in version 2.5.7 (2016-12-15):

+	- Clarified McFarland parameterization.

+

 Changes in version 2.5.6 (2016-12-14):

 	- Fixed a few typos in help files.

@@ -3688,15 +3688,56 @@ For the Bozic model [@Bozic2010], however, the birth rate is set to

 In the original model of @McFarland2013, the effects of drivers

 contribute to the numerator of the birth rate, and those of the

 (deleterious) passengers to the denominator as: $\frac{(1 +

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

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

 number of drivers and passengers in a genotype, and here the fitness

 effects of all drivers is the same ($s$) and that of all passengers

-the same too ($s_p$). However, we can map from this ratio to the

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

-will call $s_{pp} = -s_p/(1 + s_p)$ (see @McFarland2014-phd, his

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

-use the same parameterization as in the original one in

-@McFarland2013.

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

+said in @McFarland2013 (see p. 2911) and @McFarland2014-phd (see

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

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

+deleterious the passenger.

+

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

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

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

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

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

+and negative means fitness disadvantage".

+

+

+As @McFarland2014-phd explains (see p.\ 9, bottom), we can rewrite

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

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

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

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

+

+

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

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

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

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

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

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

+

+```{r mcflparam}

+sp <- 1e-3 

+spp <- -sp/(1 + sp)

+```

+

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

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

+@McFarland2014-phd (p. 9) to the expression where we have a product

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

+s means disadvantage" rule. This reparameterization applies to

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

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

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

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

+

+

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

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

+<!-- -s_p/(1 + s_p)$ (see @McFarland2014-phd, his eq. 2.1 in p.9).  -->

 For death rate, we use the expression that @McFarland2013 (see their

 p. 2911) use "(...) for large cancers (grown to $10^6$ cells)": $D(N) =

@@ -1,15 +1,15 @@

 \usepackage[%

-		shash={1031e69},

-		lhash={1031e697f4a920ae6120c78b3c1f3e818ffcad53},

+		shash={4dc6adf},

+		lhash={4dc6adf0f20920ff51825aa8ac8563837d4f1239},

 		authname={Ramon Diaz-Uriarte (at Coleonyx)},

 		authemail={rdiaz02@gmail.com},

-		authsdate={2016-12-13},

-		authidate={2016-12-13 20:38:33 +0100},

-		authudate={1481657913},

+		authsdate={2016-12-15},

+		authidate={2016-12-15 17:47:46 +0100},

+		authudate={1481820466},

 		commname={Ramon Diaz-Uriarte (at Coleonyx)},

 		commemail={rdiaz02@gmail.com},

-		commsdate={2016-12-13},

-		commidate={2016-12-13 20:38:33 +0100},

-		commudate={1481657913},

+		commsdate={2016-12-15},

+		commidate={2016-12-15 17:47:46 +0100},

+		commudate={1481820466},

 		refnames={ (HEAD, origin/master, origin/HEAD)}

 	]{gitsetinfo}

\ No newline at end of file