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

 Package: OncoSimulR

 Type: Package

 Title: Forward Genetic Simulation of Cancer Progression with Epistasis 

-Version: 2.99.5

-Date: 2020-12-18

+Version: 2.99.6

+Date: 2020-12-13

 Authors@R: c(

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

  	   		     email = "rdiaz02@gmail.com"),

@@ -499,6 +499,8 @@ oncoSimulIndiv <- function(fp,

     if(inherits(fp, "fitnessEffects")) {

         s <- sh <- NULL ## force it soon!

     }

+    if(!inherits(fp, "fitnessEffects")) 

+        stop("v.1 functionality has been removed. Please use v.2")

     ## legacies from poor name choices

     typeFitness <- switch(model,

@@ -549,8 +551,8 @@ oncoSimulIndiv <- function(fp,

             stop("Unknown model")

     }

-    if( (length(mu) > 1) && !inherits(fp, "fitnessEffects"))

-        stop("Per-gene mutation rates cannot be used with the old poset format")

+    ## if( (length(mu) > 1) && !inherits(fp, "fitnessEffects"))

+    ##     stop("Per-gene mutation rates cannot be used with the old poset format")

     if(any(mu < 0)) {

         stop("(at least one) mutation rate (mu) is negative")

@@ -584,83 +586,83 @@ oncoSimulIndiv <- function(fp,

     if(is_null_na(sampleEvery)) stop("sampleEvery cannot be NULL or NA")

-    if(!inherits(fp, "fitnessEffects")) {

-        if(any(unlist(lapply(list(fp, 

-                                  numPassengers,

-                                  s, sh), is.null)))) {

-            m <- paste("You are using the old poset format.",

-                       "You must specify all of poset, numPassengers",

-                       "s, and sh.")

-            stop(m)

+    ## if(!inherits(fp, "fitnessEffects")) {

+        ## if(any(unlist(lapply(list(fp, 

+        ##                           numPassengers,

+        ##                           s, sh), is.null)))) {

+        ##     m <- paste("You are using the old poset format.",

+        ##                "You must specify all of poset, numPassengers",

+        ##                "s, and sh.")

+        ##     stop(m)

-        }

-        if(AND_DrvProbExit) {

-            stop("The AND_DrvProbExit = TRUE setting is invalid",

-                 " with the old poset format.")

-        }

-        if(!is.null(muEF))

-            stop("Mutator effects cannot be specified with the old poset format.")

-        if( length(initMutant) > 0)  

-            warning("With the old poset format you can no longer use initMutant.",

-                    " The initMutant you passed will be ignored.")

-        ## stop("With the old poset, initMutant can only take a single value.")

-        if(!is_null_na(fixation))

-            stop("'fixation' cannot be specified with the old poset format.")

-        ## Seeding C++ is now much better in new version

-        if(is.null(seed) || (seed == "auto")) {## passing a null creates a random seed

-            ## name is a legacy. This is really the seed for the C++ generator.

-            ## Nope, we cannot use 2^32, because as.integer will fail.

-            seed <- as.integer(round(runif(1, min = 0, max = 2^16)))

-        }

-        if(verbosity >= 2)

-            cat(paste("\n Using ", seed, " as seed for C++ generator\n"))

-

-        if(!is_null_na(detectionProb)) stop("detectionProb cannot be used in v.1 objects")

-        ## if(message.v1)

-        ##     message("You are using the old poset format. Consider using the new one.")

+        ## }

+        ## if(AND_DrvProbExit) {

+        ##     stop("The AND_DrvProbExit = TRUE setting is invalid",

+        ##          " with the old poset format.")

+        ## }

+        ## if(!is.null(muEF))

+        ##     stop("Mutator effects cannot be specified with the old poset format.")

+        ## if( length(initMutant) > 0)  

+        ##     warning("With the old poset format you can no longer use initMutant.",

+        ##             " The initMutant you passed will be ignored.")

+        ## ## stop("With the old poset, initMutant can only take a single value.")

+        ## if(!is_null_na(fixation))

+        ##     stop("'fixation' cannot be specified with the old poset format.")

+        ## ## Seeding C++ is now much better in new version

+        ## if(is.null(seed) || (seed == "auto")) {## passing a null creates a random seed

+        ##     ## name is a legacy. This is really the seed for the C++ generator.

+        ##     ## Nope, we cannot use 2^32, because as.integer will fail.

+        ##     seed <- as.integer(round(runif(1, min = 0, max = 2^16)))

+        ## }

+        ## if(verbosity >= 2)

+        ##     cat(paste("\n Using ", seed, " as seed for C++ generator\n"))

+

+        ## if(!is_null_na(detectionProb)) stop("detectionProb cannot be used in v.1 objects")

+        ## ## if(message.v1)

+        ## ##     message("You are using the old poset format. Consider using the new one.")

-        ## A simulation stops if cancer or finalTime appear, the first

-        ## one. But if we set onlyCnacer = FALSE, we also accept simuls

-        ## without cancer (or without anything)

+        ## ## A simulation stops if cancer or finalTime appear, the first

+        ## ## one. But if we set onlyCnacer = FALSE, we also accept simuls

+        ## ## without cancer (or without anything)

-        op <- try(oncoSimul.internal(poset = fp, ## restrict.table = rt,

-                                     ## numGenes = numGenes,

-                                     numPassengers = numPassengers,

-                                     typeCBN = "CBN",

-                                     birth = birth,

-                                     s = s,

-                                     death = death,  

-                                     mu =  mu,  

-                                     initSize =  initSize, 

-                                     sampleEvery =  sampleEvery,  

-                                     detectionSize =  detectionSize, 

-                                     finalTime = finalTime, 

-                                     initSize_species = 2000, 

-                                     initSize_iter = 500, 

-                                     seed = seed, 

-                                     verbosity = verbosity, 

-                                     speciesFS = 10000,  

-                                     ratioForce = 2,

-                                     typeFitness = typeFitness,

-                                     max.memory = max.memory,

-                                     mutationPropGrowth = mutationPropGrowth,                                   

-                                     initMutant = -1, 

-                                     max.wall.time = max.wall.time,

-                                     max.num.tries = max.num.tries,

-                                     keepEvery = keepEvery,  

-                                     ## alpha = 0.0015,  

-                                     sh = sh,

-                                     K = K, 

-                                     minDetectDrvCloneSz = minDetectDrvCloneSz,

-                                     extraTime = extraTime,

-                                     detectionDrivers = detectionDrivers,

-                                     onlyCancer = onlyCancer,

-                                     errorHitWallTime = errorHitWallTime,

-                                     errorHitMaxTries = errorHitMaxTries),

-                  silent = !verbosity)

-        objClass <- "oncosimul"

-    } else {

+        ## op <- try(oncoSimul.internal(poset = fp, ## restrict.table = rt,

+        ##                              ## numGenes = numGenes,

+        ##                              numPassengers = numPassengers,

+        ##                              typeCBN = "CBN",

+        ##                              birth = birth,

+        ##                              s = s,

+        ##                              death = death,  

+        ##                              mu =  mu,  

+        ##                              initSize =  initSize, 

+        ##                              sampleEvery =  sampleEvery,  

+        ##                              detectionSize =  detectionSize, 

+        ##                              finalTime = finalTime, 

+        ##                              initSize_species = 2000, 

+        ##                              initSize_iter = 500, 

+        ##                              seed = seed, 

+        ##                              verbosity = verbosity, 

+        ##                              speciesFS = 10000,  

+        ##                              ratioForce = 2,

+        ##                              typeFitness = typeFitness,

+        ##                              max.memory = max.memory,

+        ##                              mutationPropGrowth = mutationPropGrowth,                                   

+        ##                              initMutant = -1, 

+        ##                              max.wall.time = max.wall.time,

+        ##                              max.num.tries = max.num.tries,

+        ##                              keepEvery = keepEvery,  

+        ##                              ## alpha = 0.0015,  

+        ##                              sh = sh,

+        ##                              K = K, 

+        ##                              minDetectDrvCloneSz = minDetectDrvCloneSz,

+        ##                              extraTime = extraTime,

+        ##                              detectionDrivers = detectionDrivers,

+        ##                              onlyCancer = onlyCancer,

+        ##                              errorHitWallTime = errorHitWallTime,

+        ##                              errorHitMaxTries = errorHitMaxTries),

+        ##           silent = !verbosity)

+        ## objClass <- "oncosimul"

+    ## } else {

         s <- sh <- NULL ## force it.

         if(numPassengers != 0)

             warning(paste("Specifying numPassengers has no effect",

@@ -728,7 +730,7 @@ oncoSimulIndiv <- function(fp,

                                         fixation = fixation),

                   silent = !verbosity)

         objClass <- c("oncosimul", "oncosimul2")

-    }

+    ## }

     if(inherits(op, "try-error")) {

         ##         if(length(grep("BAIL OUT NOW", op)))

         stop(paste("Unrecoverable error:", op ))

@@ -1763,156 +1765,156 @@ get.mut.vector <- function(x, timeSample, typeSample,

-oncoSimul.internal <- function(poset, ## restrict.table,

-                               numPassengers, 

-                               ## numGenes,

-                               typeCBN,

-                               birth, 

-                               s,

-                               death,

-                               mu,

-                               initSize,

-                               sampleEvery,

-                               detectionSize,

-                               finalTime,

-                               initSize_species,

-                               initSize_iter,

-                               seed,

-                               verbosity,

-                               speciesFS,

-                               ratioForce,

-                               typeFitness,

-                               max.memory,

-                               mutationPropGrowth, ## make it explicit

-                               initMutant,

-                               max.wall.time,

-                               keepEvery,

-                               alpha,

-                               sh,                               

-                               K,

-                               ## endTimeEvery,

-                               detectionDrivers,

-                               onlyCancer,

-                               errorHitWallTime,

-                               max.num.tries,

-                               errorHitMaxTries,

-                               minDetectDrvCloneSz,

-                               extraTime) {

+## oncoSimul.internal <- function(poset, ## restrict.table,

+##                                numPassengers, 

+##                                ## numGenes,

+##                                typeCBN,

+##                                birth, 

+##                                s,

+##                                death,

+##                                mu,

+##                                initSize,

+##                                sampleEvery,

+##                                detectionSize,

+##                                finalTime,

+##                                initSize_species,

+##                                initSize_iter,

+##                                seed,

+##                                verbosity,

+##                                speciesFS,

+##                                ratioForce,

+##                                typeFitness,

+##                                max.memory,

+##                                mutationPropGrowth, ## make it explicit

+##                                initMutant,

+##                                max.wall.time,

+##                                keepEvery,

+##                                alpha,

+##                                sh,                               

+##                                K,

+##                                ## endTimeEvery,

+##                                detectionDrivers,

+##                                onlyCancer,

+##                                errorHitWallTime,

+##                                max.num.tries,

+##                                errorHitMaxTries,

+##                                minDetectDrvCloneSz,

+##                                extraTime) {

-    ## the value of 20000, in megabytes, for max.memory sets a limit of ~ 20 GB

+##     ## the value of 20000, in megabytes, for max.memory sets a limit of ~ 20 GB

-    ## if(keepEvery < sampleEvery)

-    ##     warning("setting keepEvery to sampleEvery")

-

-    ## a backdoor to allow passing restrictionTables directly

-    if(inherits(poset, "restrictionTable"))

-        restrict.table <- poset

-    else

-        restrict.table <- poset.to.restrictTable(poset)

-    numDrivers <- nrow(restrict.table)

-    numGenes <- (numDrivers + numPassengers)

-    if(numGenes < 2)

-        stop("There must be at least two genes (loci) in the fitness effects.",

-             "If you only care about a degenerate case with just one,",

-             "you can enter a second gene",

-             "with fitness effect of zero.")

-    if(numGenes > 64)

-        stop("Largest possible number of genes (loci) is 64 for version 1.",

-             "You are strongly encouraged to use the new specification",

-             "as in version 2.")

-

-    ## These can never be set by the user

-    ## if(initSize_species < 10) {

-    ##     warning("initSize_species too small?")

-    ## }

-    ## if(initSize_iter < 100) {

-    ##     warning("initSize_iter too small?")

-    ## }

+##     ## if(keepEvery < sampleEvery)

+##     ##     warning("setting keepEvery to sampleEvery")

+

+##     ## a backdoor to allow passing restrictionTables directly

+##     if(inherits(poset, "restrictionTable"))

+##         restrict.table <- poset

+##     else

+##         restrict.table <- poset.to.restrictTable(poset)

+##     numDrivers <- nrow(restrict.table)

+##     numGenes <- (numDrivers + numPassengers)

+##     if(numGenes < 2)

+##         stop("There must be at least two genes (loci) in the fitness effects.",

+##              "If you only care about a degenerate case with just one,",

+##              "you can enter a second gene",

+##              "with fitness effect of zero.")

+##     if(numGenes > 64)

+##         stop("Largest possible number of genes (loci) is 64 for version 1.",

+##              "You are strongly encouraged to use the new specification",

+##              "as in version 2.")

+

+##     ## These can never be set by the user

+##     ## if(initSize_species < 10) {

+##     ##     warning("initSize_species too small?")

+##     ## }

+##     ## if(initSize_iter < 100) {

+##     ##     warning("initSize_iter too small?")

+##     ## }

-    ## numDrivers <- nrow(restrict.table)

-    if(length(unique(restrict.table[, 1])) != numDrivers)

-        stop("BAIL OUT NOW: length(unique(restrict.table[, 1])) != numDrivers)")

-    ddr <- restrict.table[, 1]

-    if(any(diff(ddr) != 1))

-        stop("BAIL OUT NOW:  any(diff(ddr) != 1")

-    ## sanity checks

-    if(max(restrict.table[, 1]) != numDrivers)

-        stop("BAIL OUT NOW: max(restrict.table[, 1]) != numDrivers")

-    if(numDrivers > numGenes)

-        stop("BAIL OUT NOW: numDrivers > numGenes")

+##     ## numDrivers <- nrow(restrict.table)

+##     if(length(unique(restrict.table[, 1])) != numDrivers)

+##         stop("BAIL OUT NOW: length(unique(restrict.table[, 1])) != numDrivers)")

+##     ddr <- restrict.table[, 1]

+##     if(any(diff(ddr) != 1))

+##         stop("BAIL OUT NOW:  any(diff(ddr) != 1")

+##     ## sanity checks

+##     if(max(restrict.table[, 1]) != numDrivers)

+##         stop("BAIL OUT NOW: max(restrict.table[, 1]) != numDrivers")

+##     if(numDrivers > numGenes)

+##         stop("BAIL OUT NOW: numDrivers > numGenes")

-    non.dep.drivers <- restrict.table[which(restrict.table[, 2] == 0), 1]

+##     non.dep.drivers <- restrict.table[which(restrict.table[, 2] == 0), 1]

-    ## if( (is.null(endTimeEvery) || (endTimeEvery > 0)) &&

-    ##    (typeFitness %in% c("bozic1", "exp") )) {

-    ##     warning(paste("endTimeEvery will take a positive value. ",

-    ##                   "This will make simulations not stop until the next ",

-    ##                   "endTimeEvery has been reached. Thus, in simulations ",

-    ##                   "with very fast growth, simulations can take a long ",

-    ##                   "time to finish, or can hit the wall time limit. "))

-    ## }

-    ## if(is.null(endTimeEvery))

-    ##     endTimeEvery <- keepEvery

-    ## if( (endTimeEvery > 0) && (endTimeEvery %% keepEvery) )

-    ##     warning("!(endTimeEvery %% keepEvery)")

-    ## a sanity check in restricTable, so no neg. indices for the positive deps

-    neg.deps <- function(x) {

-        ## checks a row of restrict.table

-        numdeps <- x[2]

-        if(numdeps) {

-            deps <- x[3:(3+numdeps - 1)]

-            return(any(deps < 0))

-        } else FALSE

-    }

-    if(any(apply(restrict.table, 1, neg.deps)))

-        stop("BAIL OUT NOW: Negative dependencies in restriction table")

+##     ## if( (is.null(endTimeEvery) || (endTimeEvery > 0)) &&

+##     ##    (typeFitness %in% c("bozic1", "exp") )) {

+##     ##     warning(paste("endTimeEvery will take a positive value. ",

+##     ##                   "This will make simulations not stop until the next ",

+##     ##                   "endTimeEvery has been reached. Thus, in simulations ",

+##     ##                   "with very fast growth, simulations can take a long ",

+##     ##                   "time to finish, or can hit the wall time limit. "))

+##     ## }

+##     ## if(is.null(endTimeEvery))

+##     ##     endTimeEvery <- keepEvery

+##     ## if( (endTimeEvery > 0) && (endTimeEvery %% keepEvery) )

+##     ##     warning("!(endTimeEvery %% keepEvery)")

+##     ## a sanity check in restricTable, so no neg. indices for the positive deps

+##     neg.deps <- function(x) {

+##         ## checks a row of restrict.table

+##         numdeps <- x[2]

+##         if(numdeps) {

+##             deps <- x[3:(3+numdeps - 1)]

+##             return(any(deps < 0))

+##         } else FALSE

+##     }

+##     if(any(apply(restrict.table, 1, neg.deps)))

+##         stop("BAIL OUT NOW: Negative dependencies in restriction table")

-    ## transpose the table

-    rtC <- convertRestrictTable(restrict.table)

+##     ## transpose the table

+##     rtC <- convertRestrictTable(restrict.table)

-    return(c(

-        BNB_Algo5(restrictTable = rtC,

-        numDrivers = numDrivers,

-        numGenes = numGenes,

-        typeCBN_= typeCBN,

-        s = s, 

-        death = death,

-        mu = mu,

-        initSize = initSize,

-        sampleEvery = sampleEvery,

-        detectionSize = detectionSize,

-        finalTime = finalTime,

-        initSp = initSize_species,

-        initIt = initSize_iter,

-        seed = seed,

-        verbosity = verbosity,

-        speciesFS = speciesFS,

-        ratioForce = ratioForce,

-        typeFitness_ = typeFitness,

-        maxram = max.memory,

-        mutationPropGrowth = as.integer(mutationPropGrowth),

-        initMutant = initMutant,

-        maxWallTime = max.wall.time,

-        keepEvery = keepEvery,

-        sh = sh,

-        K = K,

-        detectionDrivers = detectionDrivers,

-        onlyCancer = onlyCancer,

-        errorHitWallTime = errorHitWallTime,

-        maxNumTries = max.num.tries,

-        errorHitMaxTries = errorHitMaxTries,

-        minDetectDrvCloneSz = minDetectDrvCloneSz,

-        extraTime = extraTime

-    ),

-    NumDrivers = numDrivers

-             ))

+##     return(c(

+##         BNB_Algo5(restrictTable = rtC,

+##         numDrivers = numDrivers,

+##         numGenes = numGenes,

+##         typeCBN_= typeCBN,

+##         s = s, 

+##         death = death,

+##         mu = mu,

+##         initSize = initSize,

+##         sampleEvery = sampleEvery,

+##         detectionSize = detectionSize,

+##         finalTime = finalTime,

+##         initSp = initSize_species,

+##         initIt = initSize_iter,

+##         seed = seed,

+##         verbosity = verbosity,

+##         speciesFS = speciesFS,

+##         ratioForce = ratioForce,

+##         typeFitness_ = typeFitness,

+##         maxram = max.memory,

+##         mutationPropGrowth = as.integer(mutationPropGrowth),

+##         initMutant = initMutant,

+##         maxWallTime = max.wall.time,

+##         keepEvery = keepEvery,

+##         sh = sh,

+##         K = K,

+##         detectionDrivers = detectionDrivers,

+##         onlyCancer = onlyCancer,

+##         errorHitWallTime = errorHitWallTime,

+##         maxNumTries = max.num.tries,

+##         errorHitMaxTries = errorHitMaxTries,

+##         minDetectDrvCloneSz = minDetectDrvCloneSz,

+##         extraTime = extraTime

+##     ),

+##     NumDrivers = numDrivers

+##              ))

-}

+## }

 OncoSimulWide2Long <- function(x) {

     ## Put data in long format, for ggplot et al

@@ -5,10 +5,6 @@ nr_BNB_Algo5 <- function(rFE, mu_, death, initSize_, sampleEvery, detectionSize,

     .Call('OncoSimulR_nr_BNB_Algo5', PACKAGE = 'OncoSimulR', rFE, mu_, death, initSize_, sampleEvery, detectionSize, finalTime, initSp, initIt, seed, verbosity, speciesFS, ratioForce, typeFitness_, maxram, mutationPropGrowth, initMutant_, maxWallTime, keepEvery, K, detectionDrivers, onlyCancer, errorHitWallTime, maxNumTries, errorHitMaxTries, minDetectDrvCloneSz, extraTime, keepPhylog, MMUEF, full2mutator_, n2, p2, PDBaseline, cPDetect_i, checkSizePEvery, AND_DrvProbExit, fixation_list)

 }

-BNB_Algo5 <- function(restrictTable, numDrivers, numGenes, typeCBN_, s, death, mu, initSize, sampleEvery, detectionSize, finalTime, initSp, initIt, seed, verbosity, speciesFS, ratioForce, typeFitness_, maxram, mutationPropGrowth, initMutant, maxWallTime, keepEvery, sh, K, detectionDrivers, onlyCancer, errorHitWallTime, maxNumTries, errorHitMaxTries, minDetectDrvCloneSz, extraTime) {

-    .Call('OncoSimulR_BNB_Algo5', PACKAGE = 'OncoSimulR', restrictTable, numDrivers, numGenes, typeCBN_, s, death, mu, initSize, sampleEvery, detectionSize, finalTime, initSp, initIt, seed, verbosity, speciesFS, ratioForce, typeFitness_, maxram, mutationPropGrowth, initMutant, maxWallTime, keepEvery, sh, K, detectionDrivers, onlyCancer, errorHitWallTime, maxNumTries, errorHitMaxTries, minDetectDrvCloneSz, extraTime)

-}

-

 evalRGenotype <- function(rG, rFE, spPop, verbose, prodNeg, calledBy_, currentTime) {

     .Call('OncoSimulR_evalRGenotype', PACKAGE = 'OncoSimulR', rG, rFE, spPop, verbose, prodNeg, calledBy_, currentTime)

 }

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

+Changes in version 2.99.6 (2020-12-13):

+	- No longer v.1 functionality.

+

 Changes in version 2.99.5 (2020-12-18):

 	- Random timeouts when building in tokay2 (Windows, BioC); fixing

 	seed in vignette.

@@ -8,7 +8,7 @@

 }

 \description{

-  Conver the \code{pops.by.time} component from its "wide" format (with

+  Convert the \code{pops.by.time} component from its "wide" format (with

   one column for time, and as many columns as clones/genotypes) into

   "long" format, so that it can be used with other functions, for

   instance for plots.

@@ -43,16 +43,8 @@ OncoSimulWide2Long(x)

 }

 \examples{

-data(examplePosets)

-## An object of class oncosimul

-p705 <- examplePosets[["p705"]]

-p1 <- oncoSimulIndiv(p705)

-class(p1)

-lp1 <- OncoSimulWide2Long(p1)

-head(lp1)

-summary(lp1)

-

-## An object of class oncosimul2

+

+

 data(examplesFitnessEffects)

 sm <-  oncoSimulIndiv(examplesFitnessEffects$cbn1,

@@ -867,74 +867,13 @@ of the individual done, and the number of attempts and time used.}

 \seealso{

-  \code{\link{plot.oncosimul}}, \code{\link{examplePosets}},

+  \code{\link{plot.oncosimul}}, 

   \code{\link{samplePop}}, \code{\link{allFitnessEffects}}

 }

 \examples{

-#################################

-#####

-##### Examples using v.1

-#####

-#################################

-

-

-## use poset p701

-data(examplePosets)

-p701 <- examplePosets[["p701"]]

-

-## Exp Model

-

-b1 <- oncoSimulIndiv(p701)

-summary(b1)

-

-plot(b1, addtot = TRUE)

-

-## McFarland; use a small sampleEvery, but also a reasonable

-##   keepEvery.

-## We also modify mutation rate to values similar to those in the

-##   original paper.

-## Note that detectionSize will play no role

-## finalTime is large, since this is a slower process

-## initSize is set to 4000 so the default K is larger and we are likely

-## to reach cancer. Alternatively, set K = 2000.

-

-m1 <- oncoSimulIndiv(p701,

-                     model = "McFL",

-                     mu = 5e-7,

-                     initSize = 4000,

-                     sampleEvery = 0.025,

-                     finalTime = 15000,

-                     keepEvery = 10,

-                     onlyCancer = FALSE)

-plot(m1, addtot = TRUE, log = "")

-

-

-

-

-## Simulating 4 individual trajectories

-## (I set mc.cores = 2 to comply with --as-cran checks, but you

-##  should either use a reasonable number for your hardware or

-##  leave it at its default value).

-

-

-p1 <- oncoSimulPop(4, p701,

-                   keepEvery = 10,

-                   mc.cores = 2)

-summary(p1)

-samplePop(p1)

-

-p2 <- oncoSimulSample(4, p701)

-

-

-#########################################

-######

-###### Examples using v.2:

-######

-#########################################

-

 #### A model similar to the one in McFarland. We use 270 genes.

@@ -1001,7 +940,7 @@ object.size(oiP1)

-######## Using a poset for pancreatic cancer from Gerstung et al.

+######## Using an extended poset for pancreatic cancer from Gerstung et al.

 ###      (s and sh are made up for the example; only the structure

 ###       and names come from Gerstung et al.)

@@ -1042,7 +981,7 @@ femuv <- allFitnessEffects(noIntGenes = ni)

 oncoSimulIndiv(femuv, mu = muv)

 }

-#########Frequency dependent fitness examples

+######### Frequency dependent fitness examples

 ## An example with cooperation. Presence of WT favours all clones

 ## and all clones have a positive effect on themselves

@@ -324,34 +324,6 @@

   \code{\link{oncoSimulIndiv}}

 }

 \examples{

-\dontrun{

-data(examplePosets)

-p701 <- examplePosets[["p701"]]

-

-## Simulate and plot a single individual, including showing

-## Shannon's diversity index

-b1 <- oncoSimulIndiv(p701)

-plot(b1, addtot = TRUE, plotDiversity = TRUE)

-

-## A stacked area plot

-plot(b1, type = "stacked", plotDiversity = TRUE)

-

-## And what if I show a stream plot?

-plot(b1, type = "stream", plotDiversity = TRUE)

-

-## Simulate and plot 2 individuals

-## (I set mc.cores = 2 to comply with --as-cran checks, but you

-##  should either use a reasonable number for your hardware or

-##  leave it at its default value).

-

-p1 <- oncoSimulPop(2, p701, mc.cores = 2)

-

-par(mfrow = c(1, 2))

-plot(p1, ask = FALSE)

-

-## Stacked; we cannot log here, and harder to see patterns

-plot(p1, ask = FALSE, type = "stacked")

-}

 ## Show individual genotypes and drivers for an

 ## epistasis case with at most eight genotypes

@@ -41,6 +41,10 @@

   This specification of restrictions is for version 1. See

   \code{\link{allFitnessEffects}} for a much more flexible one for

   version 2. Both can be used with  \code{\link{oncoSimulIndiv}}.

+

+

+  Note that simulating using posets directly is no longer

+  supported. This function is left here only for historical purposes.

 }

 \references{

@@ -168,14 +168,26 @@ sampledGenotypes(y, genes = NULL)

 }

 \examples{

-data(examplePosets)

-p705 <- examplePosets[["p705"]]

+######## Using an extended poset for pancreatic cancer from Gerstung et al.

+###      (s and sh are made up for the example; only the structure

+###       and names come from Gerstung et al.)

+

+

+pancr <- allFitnessEffects(data.frame(parent = c("Root", rep("KRAS", 4), "SMAD4", "CDNK2A",

+                                          "TP53", "TP53", "MLL3"),

+                                      child = c("KRAS","SMAD4", "CDNK2A",

+                                          "TP53", "MLL3",

+                                          rep("PXDN", 3), rep("TGFBR2", 2)),

+                                      s = 0.15,

+                                      sh = -0.3,

+                                      typeDep = "MN"))

+

 ## (I set mc.cores = 2 to comply with --as-cran checks, but you

 ##  should either use a reasonable number for your hardware or

 ##  leave it at its default value).

-p1 <- oncoSimulPop(4, p705, mc.cores = 2)

+p1 <- oncoSimulPop(4, pancr, mc.cores = 2)

 (sp1 <- samplePop(p1))

 sampledGenotypes(sp1)

@@ -190,7 +202,7 @@ sampledGenotypes(sp2)

 ## Now single cell sampling

-r1 <- oncoSimulIndiv(p705)

+r1 <- oncoSimulIndiv(pancr)

 samplePop(r1, typeSample = "single")

 sampledGenotypes(samplePop(r1, typeSample = "single"))

deleted file mode 100644

@@ -1,2314 +0,0 @@

-//     Copyright 2013-2021 Ramon Diaz-Uriarte

-

-//     This program is free software: you can redistribute it and/or modify

-//     it under the terms of the GNU General Public License as published by

-//     the Free Software Foundation, either version 3 of the License, or

-//     (at your option) any later version.

-

-//     This program is distributed in the hope that it will be useful,

-//     but WITHOUT ANY WARRANTY; without even the implied warranty of

-//     MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE.  See the

-//     GNU General Public License for more details.

-

-//     You should have received a copy of the GNU General Public License

-//     along with this program.  If not, see <http://www.gnu.org/licenses/>.

-

-

-#include "debug_common.h"

-#include "common_classes.h"

-#include "bnb_common.h"

-#include <cfloat> 

-#include <limits>

-#include <iostream>

-#include <random>

-#include <bitset>

-#include <set>

-#include <iterator>

-#include <map>

-#include <sstream>

-#include <string>

-#include <ctime>

-#include <sys/time.h> 

-

-#include <stdexcept>

-

-using namespace Rcpp;

-using std::vector;

-

-

-// To track if mutation is really much smaller than birth/death

-#define MIN_RATIO_MUTS

-#ifdef MIN_RATIO_MUTS

-// There is really no need for these to be globals?

-// Unless I wanted to use them inside some function. So leave as globals.

-double g_min_birth_mut_ratio = DBL_MAX;

-double g_min_death_mut_ratio = DBL_MAX;

-double g_tmp1 = DBL_MAX;

-#endif

-

-

-typedef std::bitset<64> Genotype64;

-

-

-// Format of restrictTable

-// - mutations in columns

-// - first row, the number

-// - second row, the number of dependencies

-//   - rest of rows, the id of the dependency

-//   - past number of dependencies: a -9

-// In fact, the first row is redundant. Leave it, just in case.

-

-

-// Genotypes: the first (or column 0) genotype is the all ceros.

-// would not be needed, but makes Algo5 a lot simpler.

-

-// But mutatedPos start at 0. 

-// Will need to add 1 when plotting and analyzing with R.

-

-// Ojo: typeCBN is going to be an int.

-// But from R we pass a string, and that determined the integer.

-

-

-static void fitness(spParamsP& tmpP,

-		    const spParamsP& parentP,

-		    const int& mutatedPos, 

-		    Rcpp::IntegerMatrix restrictTable,

-		    const std::string& typeCBN,

-		    const Genotype64& newGenotype,

-		    // const double& birthRate, 

-		    const double& s,

-		    // const double& death,

-		    const int& numDrivers,

-		    const std::string& typeFitness,

-		    // const double& genTime,

-		    // const double& adjust_fitness_B,

-		    const double& sh){

-  //const double& adjust_fitness_MF) {

-

-  using namespace Rcpp;

-  // Two pieces: split into two functions??

-  //    - checking restrictions

-  //    - returning actual fitness according

-

-

-  int numDependencies;

-  int sumDriversMet = 0;

-  int sumDriversNoMet = 0;

-  int sumDependenciesMet = 0;

-

-  // set appropriate defaults. Change only needed stuff.

-  tmpP.birth = parentP.birth;

-  tmpP.death = parentP.death;

-  tmpP.absfitness = parentP.absfitness;

-

-

-

-

-

-  //      **** Are driver constraints met? ***

-

-

-  // Two cases: same s, sh, sp or different ones. If same, return three

-  // integers: sumDriversMet, sumDriversNoMet, sumPassengers.  If

-  // different, return three vectors, filled with the non-zero

-  // entries. These vectors then are combined as dictated by the fintness

-  // functions.

-

-  // If same single s, sh, sp: function takes three integers. O.w. it

-  // takes three integer vectors.

-

-  

-

-  if(mutatedPos >= numDrivers) { //the new mutation is a passenger

-    return;

-  } else {

-    for(int m = 0; m < numDrivers; ++m) {

-      if( newGenotype[m] ) { // this m is mutated

-	const Rcpp::IntegerMatrix::Column thisRestrict = 

-	  restrictTable(_, m);

-	numDependencies = thisRestrict[1];

-	if(!numDependencies) { // this driver has no dependencies

-	  sumDriversMet++;

-#ifdef DEBUGZ

-	  Rcpp::Rcout << "\n No dependencies:  ";

-	  DP2(sumDriversMet);

-#endif

-

-	}

-	else {

-	  sumDependenciesMet = 0;

-	  for(int i = 2; i < (2 + numDependencies); i++) {

-	    sumDependenciesMet += newGenotype[ thisRestrict[i] ];

-	  }

-	  if( ( (typeCBN == "Multiple") && (sumDependenciesMet) ) ||

-	      ( (typeCBN == "CBN") && (sumDependenciesMet == numDependencies) )) {

-	    sumDriversMet++;   

-	  } else {

-	    sumDriversNoMet++;

-	  }

-	}

-      }