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

 Package: OncoSimulR

 Type: Package

 Title: Forward Genetic Simulation of Cancer Progression with Epistasis 

-Version: 3.99.11

-Date: 2022-10-13

+Version: 3.99.12

+Date: 2022-10-19

 Authors@R: c(

 	      person("Ramon", "Diaz-Uriarte", role = c("aut", "cre"),	

  	   		     email = "rdiaz02@gmail.com"),

@@ -1,3 +1,23 @@

+Changes in version 4.0 (for BioC 3.16):

+	- MAJOR change: users can simulate interventions and adaptive therapy,

+	  as well as define, track, and use in fitness-dependent specifications

+	  user-defined variables.

+	- MAJOR change: users can specify birth and death rates as they want,

+	  including making both or just one frequency-dependent.

+	- onlyCancer = FALSE by default in all calls to oncoSimul*.

+	  This is a possible BRAEKING CHANGE.

+	- Plot fails with a meaningful error if simulations

+	  had unrecoverable exception or hit max wall time

+	  or max num tries.	  

+	- Improvements in vignette speed.

+	- Improvements in compilation speed.

+

+Changes in version 3.99.12 (2022-10-19):

+	- Try to allow vignette to build successfully in the ARM64 Mac build:

+	  use a try(plot) in chunk fdfmutex2.

+	- Use apa style citation and a few fixes to bib.

+	- Minor additions to vignette.

+

 Changes in version 3.99.11 (2022-10-13):

 	- Increase max.wall.time of two tests, as in very slow Windoze machines

 	  they can hit max wall time.

@@ -96,12 +96,12 @@ test_that("2. Drastically reducing a high-fitness genotype population (Exp) | Tr

     set.seed(1)

     df3x <- data.frame(Genotype = c("WT", "B", "R"),

                        Fitness = c("1 + (n_ * 0)",

-                                    "1.5",

-                                    "1.003 + 0.002 * (n_B > 120)"))

+                                   "1.5",

+                                   "1.003 + 0.002 * (n_B > 120)"))

     afd3 <- allFitnessEffects(genotFitness = df3x,

-                          frequencyDependentFitness = TRUE,

-                          frequencyType = "abs")

+                              frequencyDependentFitness = TRUE,

+                              frequencyType = "abs")

     interventions <- list(

         list(

@@ -142,33 +142,31 @@ test_that("2. Drastically reducing a high-fitness genotype population (Exp) | Tr

     ## }`: argument is of length zero

     ## So only run if not on a Mac

     ## FIXME: this is because the above fails hitting wall time

-##    if (Sys.info()["sysname"] != "Darwin") {

-        flag <- FALSE

-        i <- 20002

-        while(i <= 70001){

-            if(ep2$pops.by.time[i, 3:3] >= 210){

-                flag <- TRUE

-            }

-            i <- i + 1

+    ##    if (Sys.info()["sysname"] != "Darwin") {

+    flag <- FALSE

+    i <- 20002

+    while(i <= 70001) {

+        if(ep2$pops.by.time[i, 3:3] >= 210) {

+            flag <- TRUE

         }

-        testthat::expect_equal(flag, FALSE)

-

-

-        ## then, between the time intervals, T >= 80 and T<=85

-        ## we control that the B population

-        flag <- FALSE

-        i <- 80002

-        while(i <= 85000){

-            if(ep2$pops.by.time[i, 3:3] > 40){

-                flag <- TRUE

-            }

-            i <- i + 1

+        i <- i + 1

+    }

+    testthat::expect_equal(flag, FALSE)

+

+

+    ## then, between the time intervals, T >= 80 and T<=85

+    ## we control that the B population

+    flag <- FALSE

+    i <- 80002

+    while(i <= 85000) {

+        if(ep2$pops.by.time[i, 3:3] > 40){

+            flag <- TRUE

         }

+        i <- i + 1

+    }

-        testthat::expect_equal(flag, FALSE)

-        ## we plot the simulation when no interventions are specified.

-        ## plot(ep2, show = "genotypes", type = "line")

-##    }

+    testthat::expect_equal(flag, FALSE)

+    ##    }

 })

 cat(paste("\n Ending interventions tests", date(), "\n"))

@@ -23,7 +23,8 @@ classoption: a4paper

 geometry: margin=3cm

 fontsize: 12pt

 bibliography: OncoSimulR.bib

-biblio-style: "apalike"

+biblio-style: apa

+csl: apa.csl

 link-citations: true

 vignette: >

   %\VignetteIndexEntry{OncoSimulR: forward genetic simulation in asexual populations with arbitrary epistatic interactions and a focus on modeling tumor progression.}

@@ -1365,7 +1366,11 @@ starting from BioConductor 3.2 (and, of course, available too from

 development versions of BioC).  So, if you are using the current stable or

 development version of BioConductor, or you grab the sources from GitHub

 (<https://github.com/rdiaz02/OncoSimul>) you are using what we call

-version 2. **The functionality of version has been removed.**

+version 2. **The functionality of version 1 has been removed.**

+

+Version 3 (for BioConductor 3.13) made frequency dependent fitness available in the stable version. 

+

+Version 4 (BioConductor 3.16) introduces interventions and the possibility to specify, separately, birth and death (including frequency dependence).

@@ -3484,7 +3489,7 @@ Exp and Bozic models, or depends on the population size). This is

 also shown in Table \@ref(tab:osrfeatures), in the rows for "Fitness

 components", under "Evolutionary Features".

-In the case of frequency-dependent fitness simulations (\@ref(fdf)), the

+In the case of frequency-dependent fitness simulations (see section \@ref(fdf)), the

 fitness effects must be reevaluated frequently so that birth rate, death

 rate, or both, depending the model used, are updated. To do this it is

 necessary to use a short step to reevaluate fitness; this is done using a

@@ -3565,7 +3570,7 @@ as possible. Thus, there are two main ways of specifying fitness effects:

 * Explicitly passing to OncoSimulR a mapping of genotypes to

   fitness. Here you specify the fitness of each genotype. We will refer to

-  this as the **explicit mapping of genotypes to fitness**.

+  this as the **explicit mapping of genotypes to fitness**. This includes frequency-dependent fitness (section \@ref(fdf)).

@@ -9856,7 +9861,13 @@ s2fd <- oncoSimulIndiv(afe4,

                      seed = NULL, 

                      errorHitMaxTries = FALSE, 

                      errorHitWallTime = FALSE)

-plot(s2fd, show = "genotypes")

+

+## In the Mac ARM64 architecture, the above

+## run leads to an exception, which is really odd.

+## While that is debugged, use try to prevent

+## failure of the plot to abort vignette building.

+

+try(plot(s2fd, show = "genotypes"))

 ```

 ```{r echo=FALSE}

@@ -243,7 +243,7 @@ year = {1962}

 }

 @article{Ortmann2015,

-  author =        {Ortmann, Christina a. and Kent, David G. and

+  author =        {Ortmann, Christina A. and Kent, David G. and

                    Nangalia, Jyoti and Silber, Yvonne and

                    Wedge, David C. and Grinfeld, Jacob and

                    Baxter, E. Joanna and Massie, Charles E. and

@@ -314,13 +314,13 @@ year = {1962}

 @article{McFarland2014,

+  author = {McFarland, Christopher D and Mirny, Leonid and Korolev, Kirill S},

   title = {A Tug-of-War between Driver and Passenger Mutations in Cancer and Other Adaptive Processes},

   volume = {111},

   issn = {10916490},

   doi = {10.1101/003053},

   number = {42},

   journal = {Proc Natl Acad Sci U S A},

-  author = {McFarland, Christopher and Mirny, Leonid and Korolev, Kirill S.},

   year = {2014},

   pages = {15138--15143},

 }

@@ -424,7 +424,7 @@ year = {1962}

 }

 @phdthesis{McFarland2014-phd,

-  author =        {McFarland, CD},

+  author =        {McFarland, Christopher D},

   school =        {Harvard University},

   title =         {{The role of deleterious passengers in cancer}},

   year =          {2014},

@@ -663,18 +663,18 @@ year = {2007}

 }

 @article{tomlinson_mutation_1996,

+  author = {Tomlinson, I P and Novelli, M R and Bodmer, W F},

   title = {The mutation rate and cancer},

   volume = {93},

   issn = {0027-8424},

   language = {eng},

   number = {25},

   journal = {Proceedings of the National Academy of Sciences of the United States of America},

-  author = {Tomlinson, I. P. and Novelli, M. R. and Bodmer, W. F.},

   month = dec,

   year = {1996},

   pages = {14800--14803},

   pmid = {8962135},

-  pmcid = {PMC26216}

+  pmcid = {PMC26216},

 }

@@ -797,6 +797,7 @@ year = {2007}

 @article{tomlinson1997a,

+  author = {Tomlinson, I P },

   title = {Game-Theory Models of Interactions between Tumour Cells},

   volume = {33},

   issn = {09598049},

@@ -804,10 +805,9 @@ year = {2007}

   journal = {European Journal of Cancer},

   doi = {10.1016/S0959-8049(97)00170-6},

   url = {https://linkinghub.elsevier.com/retrieve/pii/S0959804997001706},

-  author = {Tomlinson, I.P.M.},

   month = aug,

   year = {1997},

-  pages = {1495-1500}

+  pages = {1495-1500},

 }

new file mode 100644

@@ -0,0 +1,1917 @@

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+    <updated>2022-10-02T20:08:41+00:00</updated>

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+              <names variable="author">

+                <name and="symbol" delimiter=", " initialize-with=". "/>

+                <substitute>

+                  <text macro="title-intext"/>

+                </substitute>

+              </names>

+              <!-- Replace with term="personal-communication" if that becomes available -->

+              <text term="letter"/>

+            </group>

+          </if>

+          <else>

+            <names variable="author" delimiter=", ">

+              <name form="short" and="symbol" delimiter=", " initialize-with=". "/>

+              <substitute>

+                <text macro="title-intext"/>

+              </substitute>

+            </names>

+          </else>

+        </choose>

+      </else-if>

+      <else>

+        <names variable="composer" delimiter=", ">

+          <name form="short" and="symbol" delimiter=", " initialize-with=". "/>

+          <substitute>

+            <names variable="author"/>

+            <names variable="illustrator"/>

+            <names variable="director"/>

+            <choose>

+              <if variable="container-title">

+                <choose>

+                  <if type="book entry entry-dictionary entry-encyclopedia" match="any">

+                    <text macro="title-intext"/>

+                  </if>

+                </choose>

+              </if>

+            </choose>

+            <names variable="editor"/>

+            <names variable="editorial-director"/>

+            <text macro="title-intext"/>

+          </substitute>

+        </names>

+      </else>

+    </choose>

+  </macro>

+  <macro name="date-bib">

+    <group delimiter=" " prefix="(" suffix=")">

+      <choose>

+        <if is-uncertain-date="issued">

+          <text term="circa" form="short"/>

+        </if>

+      </choose>

+      <group>

+        <choose>

+          <if variable="issued">

+            <date variable="issued">

+              <date-part name="year"/>

+            </date>

+            <text variable="year-suffix"/>

+            <choose>

+              <if type="article-magazine article-newspaper broadcast interview motion_picture pamphlet personal_communication post post-weblog song speech webpage" match="any">

+                <!-- Many video and audio examples in manual give full dates. Err on the side of too much information. -->

+                <date variable="issued">

+                  <date-part prefix=", " name="month"/>

+                  <date-part prefix=" " name="day"/>

+                </date>

+              </if>

+              <else-if type="paper-conference">

+                <!-- Capture 'speech' stored as 'paper-conference' -->

+                <choose>

+                  <if variable="collection-editor editor editorial-director issue page volume" match="none">

+                    <date variable="issued">

+                      <date-part prefix=", " name="month"/>

+                      <date-part prefix=" " name="day"/>

+                    </date>

+                  </if>

+                </choose>

+              </else-if>

+              <!-- Only year: article article-journal book chapter entry entry-dictionary entry-encyclopedia dataset figure graphic

+                   manuscript map musical_score paper-conference[published] patent report review review-book thesis -->

+            </choose>

+          </if>

+          <else-if variable="status">

+            <group>

+              <text variable="status" text-case="lowercase"/>

+              <text variable="year-suffix" prefix="-"/>

+            </group>

+          </else-if>

+          <else>

+            <text term="no date" form="short"/>

+            <text variable="year-suffix" prefix="-"/>

+          </else>

+        </choose>

+      </group>

+    </group>

+  </macro>

+  <macro name="date-sort-group">

+    <!-- APA sorts 1. no-date items, 2. items with dates, 3. in-press (status) items -->

+    <choose>

+      <if variable="issued">

+        <text value="1"/>

+      </if>

+      <else-if variable="status">

+        <text value="2"/>

+      </else-if>

+      <else>

+        <text value="0"/>

+      </else>

+    </choose>

+  </macro>

+  <macro name="date-sort-date">

+    <date variable="issued" form="numeric"/>

+  </macro>

+  <macro name="date-intext">

+    <choose>

+      <if variable="issued">

+        <group delimiter="/">

+          <group delimiter=" ">

+            <choose>

+              <if is-uncertain-date="original-date">

+                <text term="circa" form="short"/>

+              </if>

+            </choose>

+            <date variable="original-date">

+              <date-part name="year"/>

+            </date>

+          </group>

+          <group delimiter=" ">

+            <choose>

+              <if is-uncertain-date="issued">

+                <text term="circa" form="short"/>

+              </if>

+            </choose>

+            <group>

+              <choose>

+                <if type="interview personal_communication" match="any">

+                  <choose>

+                    <if variable="archive container-title DOI publisher URL" match="none">

+                      <!-- These variables indicate that the communication is retrievable by the reader.

+                           If not, then use the in-text-only personal communication format -->

+                      <date variable="issued" form="text"/>

+                    </if>

+                    <else>

+                      <date variable="issued">

+                        <date-part name="year"/>

+                      </date>

+                    </else>

+                  </choose>

+                </if>

+                <else>

+                  <date variable="issued">

+                    <date-part name="year"/>

+                  </date>

+                </else>

+              </choose>

+              <text variable="year-suffix"/>

+            </group>

+          </group>

+        </group>

+      </if>

+      <else-if variable="status">

+        <text variable="status" text-case="lowercase"/>

+        <text variable="year-suffix" prefix="-"/>

+      </else-if>

+      <else>

+        <text term="no date" form="short"/>

+        <text variable="year-suffix" prefix="-"/>

+      </else>

+    </choose>

+  </macro>

+  <!-- APA has two description elements following the title:

+       title (parenthetical) [bracketed]  -->

+  <macro name="title-and-descriptions">

+    <choose>

+      <if variable="title">

+        <group delimiter=" ">

+          <text macro="title"/>

+          <text macro="parenthetical"/>

+          <text macro="bracketed"/>

+        </group>

+      </if>

+      <else>

+        <group delimiter=" ">

+          <text macro="bracketed"/>

+          <text macro="parenthetical"/>

+        </group>

+      </else>

+    </choose>

+  </macro>

+  <macro name="title">

+    <choose>

+      <if type="post webpage" match="any">

+        <!-- Webpages are always italicized -->

+        <text variable="title" font-style="italic"/>

+      </if>

+      <else-if variable="container-title" match="any">

+        <!-- Other types are italicized based on presence of container-title.

+             Assume that review and review-book are published in periodicals/blogs,

+             not just on a web page (ex. 69) -->

+        <text variable="title"/>

+      </else-if>

+      <else>

+        <choose>

+          <if type="article-journal article-magazine article-newspaper post-weblog review review-book" match="any">

+            <text variable="title" font-style="italic"/>

+          </if>

+          <else-if type="paper-conference">

+            <choose>

+              <if variable="collection-editor editor editorial-director" match="any">

+                <group delimiter=": " font-style="italic">

+                  <text variable="title"/>

+                  <!-- Replace with volume-title as that becomes available -->

+                  <choose>

+                    <if is-numeric="volume" match="none">

+                      <group delimiter=" ">

+                        <label variable="volume" form="short" text-case="capitalize-first"/>

+                        <text variable="volume"/>

+                      </group>

+                    </if>

+                  </choose>

+                </group>

+              </if>

+              <else>

+                <text variable="title" font-style="italic"/>

+              </else>

+            </choose>

+          </else-if>

+          <else>

+            <group delimiter=": " font-style="italic">

+              <text variable="title"/>

+              <!-- Replace with volume-title as that becomes available -->

+              <choose>

+                <if is-numeric="volume" match="none">

+                  <group delimiter=" ">

+                    <label variable="volume" form="short" text-case="capitalize-first"/>

+                    <text variable="volume"/>

+                  </group>

+                </if>

+              </choose>

+            </group>

+          </else>

+        </choose>

+      </else>

+    </choose>

+  </macro>

+  <macro name="title-intext">

+    <choose>