OncoSimulR: forward genetic simulation in asexual populations with arbitrary epistatic interactions and a focus on modeling tumor progression.2 months ago
Introduction | Key features of OncoSimulR | What kinds of questions is OncoSimulR suited for? | Examples of questions that can be addressed with OncoSimulR | Recovering restrictions in the order of accumulation of mutations | Sign epistasis and probability of crossing fitness valleys | Predictability of evolution in complex fitness landscapes | Mutator and antimutator genes | Epistatic interactions between drivers and passengers in cancer and the consequences of order effects | Epistatic interactions between drivers and passengers | Consequences of order effects for cancer initiation | Simulating evolution with frequency-dependent fitness | Trade-offs and what is OncoSimulR not well suited for | Random fitness landscapes, clonal competition, predictability, and the strong selection weak mutation (SSWM) regime | Steps for using OncoSimulR | Two quick examples of fitness specifications | Citing OncoSimulR and other documentation | HTML and PDF versions of the vignette | Testing, code coverage, and other examples | Versions | Running time and space consumption of OncoSimulR | Exp and McFL with "detectionProb" and pancreas example | Changing fitness: $s=0.1$ and $s=0.05$ | Several "common use cases" runs | Common use cases, set 1. | Common use cases, set 2. | Can we use a large number of genes? | Exponential model with 10,000 and 50,000 genes | Exponential, 10,000 genes, example 1 | Exponential, 10,000 genes, example 2 | Exponential, 50,000 genes, example 1 | Exponential, 50,000 genes, example 2 | Exponential, 50,000 genes, example 3 | Interlude: where is that 1 GB coming from? | McFarland model with 50,000 genes; the effect of keepEvery | McFarland, 50,000 genes, example 1 | McFarland, 50,000 genes, example 2 | McFarland, 50,000 genes, example 3 | McFarland, 50,000 genes, example 4 | McFarland, 50,000 genes, example 5 | McFarland, 50,000 genes, example 6 | Examples with $s = 0.05$ | The different consequences of keepEvery = NA in the Exp and McFL models | Are we keeping the complete history (genealogy) of the clones? | Population sizes $\geq 10^ | A summary of some determinants of running time and space consumption | Specifying fitness effects | Introduction to the specification of fitness effects | Explicit mapping of genotypes to fitness | How to specify fitness effects with the lego system | Numeric values of fitness effects | McFarland parameterization | Death rate under the McFarland model | No viability of clones and types of models | Genes without interactions | Using DAGs: Restrictions in the order of mutations as extended posets | AND, OR, XOR relationships | Fitness effects | Extended posets | DAGs: A first conjunction (AND) example | DAGs: A second conjunction example | DAGs: A semimonotone or "OR" example | An "XMPN" or "XOR" example | Posets: the three types of relationships | Modules | What does a module provide | Specifying modules | Modules and posets again: the three types of relationships and modules | Order effects | Order effects: three-gene orders | Order effects and modules with multiple genes | Order and modules with 325 genotypes | Order effects and genes without interactions | Epistasis | Epistasis: two alternative specifications | Epistasis with three genes and two alternative specifications | Why can we specify some effects with a "-"? | Epistasis: modules | I do not want epistasis, but I want modules! | Synthetic viability | A simple synthetic viability example | Synthetic viability, non-zero fitness, and modules | Synthetic mortality or synthetic lethality | Possible issues with Bozic model | Synthetic viability using Bozic model | Numerical issues with death rates of 0 in Bozic model | A longer example: Poset, epistasis, synthetic mortality and viability, order effects and genes without interactions, with some modules | Homozygosity, heterozygosity, oncogenes, tumor suppressors | Gene-specific mutation rates | Mutator genes | Plotting fitness landscapes | Specifying fitness effects: some examples from the literature | Bauer et al., 2014 | Using a DAG | Specifying fitness of genotypes directly | Misra et al., 2014 | Example 1.a | Example 1.b | Example 1.c | Ochs and Desai, 2015 | Weissman et al., 2009 | Figure 1.a | Figure 1.b | Gerstung et al., 2011, pancreatic cancer poset | Raphael and Vandin's 2014 modules | Running and plotting the simulations: starting, ending, and examples | Starting and ending | Can I start the simulation from a specific mutant? | Ending the simulations | Ending the simulations: conditions | Stochastic detection mechanism: "detectionProb" | Stochastic detection mechanism and minimum number of drivers | Fixation of genes/gene combinations | Fixation of genotypes | Fixation: tolerance, number of periods, minimal size | Mixing stopping on gene combinations and genotypes | Plotting genotype/driver abundance over time; plotting the simulated trajectories | Several examples of simulations and plotting simulation trajectories | Bauer's example again | McFarland model with 5000 passengers and 70 drivers | McFarland model with 50,000 passengers and 70 drivers: clonal competition | Simulation with a conjunction example | Simulation with order effects and McFL model | Interactive graphics | Multiple initial mutants: starting the simulation from arbitrary configurations | Multispecies simulations | Sampling multiple simulations | Whole-tumor and single-cell sampling, and do we always want to sample? | Differences between "samplePop" and "oncoSimulSample" | Showing the genealogical relationships of clones | Parent-child relationships from multiple runs | Generating random fitness landscapes | Random fitness landscapes from a Rough Mount Fuji model | Random fitness landscapes from Kauffman's NK model | Random fitness landscapes from an additive model | Random fitness landscapes from Eggbox model | Random fitness landscapes from Ising model | Random fitness landscapes from Full models | Epistasis and fitness landscape statistics | Frequency-dependent fitness | A first example with frequency-dependent fitness | Hurlbut et al., 2018: a four-cell example with angiogenesis and cytotoxicity | An example with absolute numbers and population collapse | Predator-prey, commensalism, and consumer-resource models | Competition | Competition | Predator-prey, first example | Predator-prey, second example | Commensalism | Frequency-dependent fitness: can I mix relative and absolute frequencies? | Frequency-dependent fitness: can I use genes with mutator effects? | Can we use the BNB algorithm to model frequency-dependent fitness? | Additional examples of frequency-dependent fitness | Rock-paper-scissors model in bacterial community | Introduction | Case 1 | Case 2 | Case 3 | Hawk and Dove example | Game Theory with social dilemmas of tumour acidity and vasculature | Fully glycolytic tumours: | Fully angiogenic tumours: | Heterogeneous tumours: | Prostate cancer tumour–stroma interactions | Simulations | First scenario | Second scenario | Third scenario | Fourth scenario | Evolutionary Dynamics of Tumor-Stroma Interactions in Multiple Myeloma | Scenario 1 | Scenario 2 | An example of modellization in Parkinson disease related cell community | Evolutionary Game between Commensal and Pathogenic Microbes in Intestinal Microbiota | Antibiotic absence situation | Antibiotic presence situation | Modeling of breast cancer through evolutionary game theory. | Cancer kept under control | Development of a non-metastatic cancer | Development of a metastatic cancer | Improving the previous example. Modeling of breast cancer with the presence chemotherapy and resistance. | Absence of chemotherapy | Chemotherapy with low R mutation rate | Chemotherapy with considerable R mutation rate | Death and Birth specification | Changes in nomenclature | Explicit mapping of genotypes to death rates | Simulating with constant total population size | Simulating therapeutic interventions and adaptive therapy, and using user-defined variables | Interventions | A first example with interventions | Intervening over the total population | Differences between intervening on the total population or over specific genotypes: when do each occur? | Intervening in Rock-Paper-Scissors model in bacterial comunity | User variables | Basic example with user variables | User Variables Example 2 | Adaptive therapy. Interventions using user variables | Another example of adaptive therapy | Adaptive therapy: a canonical example | Interventions: how to specify WT | Simulating therapeutic interventions that depend on time | Adaptive control of competitive release and chemotherapeutic resistance | Scenario without chemotherapy | Scenario with continuous chemotherapy: fixed dose | Scenario with switching doses of chemotherapy | Growth factors as chemotherapy target | Scenario without chemotherapy | Scenario with GF as target for chemotherapy | Examples using time dependent frequency definition | Increasing fitness at a certain timepoint | Intervention at a certain point to stop subpopulation growth | Intervention to slow down collapsing populations | Measures of evolutionary predictability and genotype diversity | Generating random DAGs for restrictions | FAQ, odds and ends | What we mean by "clone"; and "I want clones disregarding passengers" | Does OncoSimulR keep track of individuals or of clones? And how can it keep track of such large populations? | sampleEvery, keepPhylog, and pruning | Dealing with errors in "oncoSimulPop" | Whole tumor sampling, genotypes, and allele counts: what gives? And what about order? | Doesn't the BNB algorithm require small mutation rates for it to be advantageous? | Can we use the BNB algorithm with state-dependent birth or death rates? | Sometimes I get exceptions when running with mutator genes | What are good values of sampleEvery? | mutationPropGrowth and is mutation associated to division? | Messages about 'Using old version of fitnessEffects' and 'v2 functionality detected. Adapting to v3 functionality.' | Session info and packages used | Time it takes to build the vignette and most time consuming chunks | Funding | References
OncoSimulR 4.15.0Ramon Diaz-Uriarte, Sergio Sanchez-Carrillo, Juan Antonio Miguel-Gonzalez, Javier López Cano, Alberto González Klein, Javier Muñoz Haro Department of Biochemistry, School of Medicine, Universidad Autónoma de Madrid, and Instituto de Investigaciones Biomédicas Sols-Morreale (IIBM), CSIC-UAM, Madrid, Spain.\ [email protected], [email protected], https://ligarto.org/rdiazOncoSimulR.Rmd