├── bin └── demon ├── .github ├── ISSUE_TEMPLATE │ ├── bug_report.md │ └── feature_request.md ├── PULL_REQUEST_TEMPLATE │ └── pull_request_template.md └── workflows │ └── ci.yml ├── resources └── configfile-example.dat ├── .gitignore ├── README.md ├── CODE_OF_CONDUCT.md ├── src └── demon.h └── LICENSE /bin/demon: -------------------------------------------------------------------------------- https://raw.githubusercontent.com/robjohnnoble/demon_model/HEAD/bin/demon -------------------------------------------------------------------------------- /.github/ISSUE_TEMPLATE/bug_report.md: -------------------------------------------------------------------------------- 1 | --- 2 | name: Bug report 3 | about: Create a report to help us improve the codebase 4 | title: '' 5 | labels: '' 6 | assignees: '' 7 | 8 | --- 9 | 10 | **Describe the bug** 11 | A clear and concise description of what the bug is. 12 | 13 | **To Reproduce** 14 | Steps to reproduce the behavior (including all commands). 15 | 16 | **Expected behavior** 17 | A clear and concise description of what you expected to happen. 18 | 19 | **Screenshots** 20 | If applicable, add screenshots to help explain your problem. 21 | 22 | **Additional context** 23 | Add any other context about the problem here. 24 | -------------------------------------------------------------------------------- /.github/ISSUE_TEMPLATE/feature_request.md: -------------------------------------------------------------------------------- 1 | --- 2 | name: Feature request 3 | about: Suggest an idea for this project 4 | title: '' 5 | labels: '' 6 | assignees: '' 7 | 8 | --- 9 | 10 | **Is your feature request related to a problem? Please describe.** 11 | A clear and concise description of what the problem is. Ex. I'm always frustrated when [...] 12 | 13 | **Describe the solution you'd like** 14 | A clear and concise description of what you want to happen. 15 | 16 | **Describe alternatives you've considered** 17 | A clear and concise description of any alternative solutions or features you've considered. 18 | 19 | **Additional context** 20 | Add any other context or screenshots about the feature request here. 21 | -------------------------------------------------------------------------------- /.github/PULL_REQUEST_TEMPLATE/pull_request_template.md: -------------------------------------------------------------------------------- 1 | ## Description 2 | 3 | Please include a summary of the change and which issue is fixed. 4 | Please also include relevant motivation and context. 5 | 6 | Fixes # (issue) 7 | 8 | ## Type of change 9 | 10 | Please delete options that are not relevant. 11 | 12 | - [ ] Bug fix (non-breaking change which fixes an issue) 13 | - [ ] New feature (non-breaking change which adds functionality) 14 | - [ ] Breaking change (fix or feature that would cause existing functionality to not work as expected) 15 | - [ ] Documentation updated 16 | - [ ] Testing updated 17 | - [ ] Codebase refactoring 18 | 19 | ## Checklist: 20 | 21 | - [ ] My code follows the style guidelines of this project 22 | - [ ] I have performed a self-review of my own code 23 | - [ ] I have commented my code, particularly in hard-to-understand areas 24 | - [ ] My changes generate no new warnings 25 | - [ ] I have added tests that prove my fix is effective or that my feature works 26 | -------------------------------------------------------------------------------- /.github/workflows/ci.yml: -------------------------------------------------------------------------------- 1 | ############################################################################### 2 | # 3 | # AUTHOR: Maciej_Bak 4 | # CONTACT: wsciekly.maciek@gmail.com 5 | # CREATED: 15-08-2022 6 | # LICENSE: Apache_2.0 7 | # 8 | ############################################################################### 9 | --- 10 | name: ci 11 | 12 | on: push 13 | 14 | jobs: 15 | 16 | testrun: 17 | runs-on: ubuntu-20.04 18 | 19 | steps: 20 | 21 | - name: Checkout Repository 22 | uses: actions/checkout@v2 23 | 24 | - name: Install Boost lib. 25 | run: sudo apt-get install libboost-all-dev 26 | 27 | - name: Print compiler path 28 | run: which g++ 29 | 30 | - name: Prepare testrun directory 31 | run: | 32 | mkdir testrun 33 | cp resources/configfile-example.dat testrun/config.dat 34 | 35 | - name: Compile demon 36 | run: g++ -o testrun/demon src/demon.cpp -I/usr/local/include/boost/ -lm 37 | 38 | - name: Testrun 39 | run: ./testrun/demon testrun config.dat 40 | 41 | ... 42 | -------------------------------------------------------------------------------- /resources/configfile-example.dat: -------------------------------------------------------------------------------- 1 | parameters 2 | { 3 | spatial_structure 4 | { 5 | log2_deme_carrying_capacity 7 6 | } 7 | dispersal 8 | { 9 | migration_type 0 10 | init_migration_rate 2e-03 11 | migration_edge_only 1 12 | migration_rate_scales_with_K 1 13 | } 14 | mutation_rates 15 | { 16 | mu_driver_birth 1e-05 17 | mu_passenger 0.01 18 | mu_driver_migration 0.01 19 | passenger_pop_threshold -1 20 | } 21 | fitness_effects 22 | { 23 | normal_birth_rate 0.9 24 | baseline_death_rate 0 25 | s_driver_birth 0.1 26 | s_passenger 0 27 | s_driver_migration 0 28 | max_relative_birth_rate 10 29 | max_relative_migration_rate 10 30 | } 31 | non_biological_parameters 32 | { 33 | init_pop 1 34 | matrix_max -1 35 | max_pop 1000000 36 | max_time 86400 37 | max_generations 2000 38 | seed 10 39 | write_grid 0 40 | write_clones_file 0 41 | write_demes_file 0 42 | record_matrix 0 43 | write_phylo 0 44 | calculate_total_diversity 0 45 | biopsy_size_per_sample 100 46 | } 47 | } 48 | -------------------------------------------------------------------------------- /.gitignore: -------------------------------------------------------------------------------- 1 | # Created by https://www.toptal.com/developers/gitignore/api/c++,macos 2 | # Edit at https://www.toptal.com/developers/gitignore?templates=c++,macos 3 | 4 | ### C++ ### 5 | # Prerequisites 6 | *.d 7 | 8 | # Compiled Object files 9 | *.slo 10 | *.lo 11 | *.o 12 | *.obj 13 | 14 | # Precompiled Headers 15 | *.gch 16 | *.pch 17 | 18 | # Compiled Dynamic libraries 19 | *.so 20 | *.dylib 21 | *.dll 22 | 23 | # Fortran module files 24 | *.mod 25 | *.smod 26 | 27 | # Compiled Static libraries 28 | *.lai 29 | *.la 30 | *.a 31 | *.lib 32 | 33 | # Executables 34 | *.exe 35 | *.out 36 | *.app 37 | 38 | ### macOS ### 39 | # General 40 | .DS_Store 41 | .AppleDouble 42 | .LSOverride 43 | 44 | # Icon must end with two \r 45 | Icon 46 | 47 | 48 | # Thumbnails 49 | ._* 50 | 51 | # Files that might appear in the root of a volume 52 | .DocumentRevisions-V100 53 | .fseventsd 54 | .Spotlight-V100 55 | .TemporaryItems 56 | .Trashes 57 | .VolumeIcon.icns 58 | .com.apple.timemachine.donotpresent 59 | 60 | # Directories potentially created on remote AFP share 61 | .AppleDB 62 | .AppleDesktop 63 | Network Trash Folder 64 | Temporary Items 65 | .apdisk 66 | 67 | ### macOS Patch ### 68 | # iCloud generated files 69 | *.icloud 70 | 71 | # End of https://www.toptal.com/developers/gitignore/api/c++,macos -------------------------------------------------------------------------------- /README.md: -------------------------------------------------------------------------------- 1 | # demon 2 | Demon (deme-based oncology model) is a flexible framework for modelling intra-tumour population genetics with varied spatial structures and modes of cell dispersal. 3 | 4 | ## Prerequisites 5 | 6 | The program is written in C++ (mostly plain C); it requires gnuplot and the Boost Property Tree C++ library. 7 | 8 | ## Running a simulation 9 | 10 | Copy the following three files into a new folder: 11 | 12 | * `src/demon.cpp` (model code); 13 | * `src/demon.h` (header file); 14 | * `resources/configfile-example.dat` (configuration file); 15 | 16 | In a terminal window, navigate to your folder and type the following commands: 17 | ``` 18 | # 1) Compilation 19 | g++ -o demon demon.cpp -I/usr/local/include/boost/ -lm 20 | 21 | # 2) Execution 22 | ./demon ./ configfile-example.dat 23 | ``` 24 | 25 | ## Configuration file 26 | 27 | The configuration file sets the following model parameters: 28 | 29 | Spatial structure 30 | * `int log2_deme_carrying_capacity`: log2 of deme carrying capacity 31 | 32 | Dispersal 33 | * `float migration_type`: type of cell dispersal (0 = invasion; 2 = deme fission) 34 | * `float init_migration_rate`: initial invasion rate or deme fission rate (-1 = set automatically) 35 | * `int migration_edge_only`: whether dispersal is limited to the tumour boundary (0 = no; 1 = yes) 36 | * `int migration_rate_scales_with_K`: whether to divide dispersal rates by the square root of the deme carrying capacity (0 = no; 1= yes) 37 | 38 | Mutation rates 39 | * `float mu_driver_birth`: driver mutation rate per cell division (for drivers affecting division rate) 40 | * `float mu_passenger`: passenger mutation rate per cell division 41 | * `float mu_driver_migration`: driver mutation rate per cell division (for drivers affecting dispersal rate) 42 | * `int passenger_pop_threshold`: population size at which passenger mutations stop occurring (-1 = no threshold) 43 | 44 | Fitness effects 45 | * `float normal_birth_rate`: normal cell division rate, relative to tumour cell division rate (-1 = no normal cells) 46 | * `float baseline_death_rate`: baseline death rate, independent of deme population size 47 | * `float s_passenger`: deleterious effect on division rate per passenger mutation 48 | * `float s_driver_birth`: beneficial effect on division rate per driver mutation (for drivers affecting division rate) 49 | * `float s_driver_migration`: beneficial effect on dispersal rate per driver mutation (for drivers affecting dispersal rate) 50 | * `float max_relative_birth_rate`: maximum division rate, relative to initial division rate 51 | * `float max_relative_migration_rate`: maximum dispersal rate, relative to initial dispersal rate 52 | 53 | Non-biological parameters 54 | * `int seed`: seed for pseudo-random number generator 55 | * `int init_pop`: initial tumour cell population 56 | * `int max_time`: max elapsed time before program halts, in seconds 57 | * `int max_pop`: max tumour cell population before program halts 58 | * `int max_generations`: max cell generations before program halts 59 | * `int matrix_max`: max number of genotypes before program halts (larger value => more allocated memory) 60 | * `int write_grid`: whether to generate plots of grid states during execution (can significantly increase running time) 61 | * `int write_clones_file`: whether to write contents of all clones (can be a very large file; typically unnecessary) 62 | * `int write_demes_file`: whether to write contents of all demes (can be a very large file; typically unnecessary) 63 | * `int record_matrix`: whether to record genetic distance matrix for all genotypes (can be a very large file; typically unnecessary) 64 | * `int write_phylo`: whether to write phylogeny for all genotypes (can be a very large file; typically unnecessary) 65 | * `int calculate_total_diversity`: whether to calculate diversity across all genotypes (can be computationally expensive) 66 | * `int biopsy_size_per_sample`: max number of cells per biopsy sample (reserved for future applications) 67 | 68 | -------------------------------------------------------------------------------- /CODE_OF_CONDUCT.md: -------------------------------------------------------------------------------- 1 | 2 | # Contributor Covenant Code of Conduct 3 | 4 | ## Our Pledge 5 | 6 | We as members, contributors, and leaders pledge to make participation in our 7 | community a harassment-free experience for everyone, regardless of age, body 8 | size, visible or invisible disability, ethnicity, sex characteristics, gender 9 | identity and expression, level of experience, education, socio-economic status, 10 | nationality, personal appearance, race, caste, color, religion, or sexual 11 | identity and orientation. 12 | 13 | We pledge to act and interact in ways that contribute to an open, welcoming, 14 | diverse, inclusive, and healthy community. 15 | 16 | ## Our Standards 17 | 18 | Examples of behavior that contributes to a positive environment for our 19 | community include: 20 | 21 | * Demonstrating empathy and kindness toward other people 22 | * Being respectful of differing opinions, viewpoints, and experiences 23 | * Giving and gracefully accepting constructive feedback 24 | * Accepting responsibility and apologizing to those affected by our mistakes, 25 | and learning from the experience 26 | * Focusing on what is best not just for us as individuals, but for the overall 27 | community 28 | 29 | Examples of unacceptable behavior include: 30 | 31 | * The use of sexualized language or imagery, and sexual attention or advances of 32 | any kind 33 | * Trolling, insulting or derogatory comments, and personal or political attacks 34 | * Public or private harassment 35 | * Publishing others' private information, such as a physical or email address, 36 | without their explicit permission 37 | * Other conduct which could reasonably be considered inappropriate in a 38 | professional setting 39 | 40 | ## Enforcement Responsibilities 41 | 42 | Community leaders are responsible for clarifying and enforcing our standards of 43 | acceptable behavior and will take appropriate and fair corrective action in 44 | response to any behavior that they deem inappropriate, threatening, offensive, 45 | or harmful. 46 | 47 | Community leaders have the right and responsibility to remove, edit, or reject 48 | comments, commits, code, wiki edits, issues, and other contributions that are 49 | not aligned to this Code of Conduct, and will communicate reasons for moderation 50 | decisions when appropriate. 51 | 52 | ## Scope 53 | 54 | This Code of Conduct applies within all community spaces, and also applies when 55 | an individual is officially representing the community in public spaces. 56 | Examples of representing our community include using an official e-mail address, 57 | posting via an official social media account, or acting as an appointed 58 | representative at an online or offline event. 59 | 60 | ## Enforcement 61 | 62 | Instances of abusive, harassing, or otherwise unacceptable behavior may be 63 | reported to the community leaders responsible for enforcement at 64 | robert.noble@city.ac.uk. 65 | All complaints will be reviewed and investigated promptly and fairly. 66 | 67 | All community leaders are obligated to respect the privacy and security of the 68 | reporter of any incident. 69 | 70 | ## Enforcement Guidelines 71 | 72 | Community leaders will follow these Community Impact Guidelines in determining 73 | the consequences for any action they deem in violation of this Code of Conduct: 74 | 75 | ### 1. Correction 76 | 77 | **Community Impact**: Use of inappropriate language or other behavior deemed 78 | unprofessional or unwelcome in the community. 79 | 80 | **Consequence**: A private, written warning from community leaders, providing 81 | clarity around the nature of the violation and an explanation of why the 82 | behavior was inappropriate. A public apology may be requested. 83 | 84 | ### 2. Warning 85 | 86 | **Community Impact**: A violation through a single incident or series of 87 | actions. 88 | 89 | **Consequence**: A warning with consequences for continued behavior. No 90 | interaction with the people involved, including unsolicited interaction with 91 | those enforcing the Code of Conduct, for a specified period of time. This 92 | includes avoiding interactions in community spaces as well as external channels 93 | like social media. Violating these terms may lead to a temporary or permanent 94 | ban. 95 | 96 | ### 3. Temporary Ban 97 | 98 | **Community Impact**: A serious violation of community standards, including 99 | sustained inappropriate behavior. 100 | 101 | **Consequence**: A temporary ban from any sort of interaction or public 102 | communication with the community for a specified period of time. No public or 103 | private interaction with the people involved, including unsolicited interaction 104 | with those enforcing the Code of Conduct, is allowed during this period. 105 | Violating these terms may lead to a permanent ban. 106 | 107 | ### 4. Permanent Ban 108 | 109 | **Community Impact**: Demonstrating a pattern of violation of community 110 | standards, including sustained inappropriate behavior, harassment of an 111 | individual, or aggression toward or disparagement of classes of individuals. 112 | 113 | **Consequence**: A permanent ban from any sort of public interaction within the 114 | community. 115 | 116 | ## Attribution 117 | 118 | This Code of Conduct is adapted from the [Contributor Covenant][homepage], 119 | version 2.1, available at 120 | [https://www.contributor-covenant.org/version/2/1/code_of_conduct.html][v2.1]. 121 | 122 | Community Impact Guidelines were inspired by 123 | [Mozilla's code of conduct enforcement ladder][Mozilla CoC]. 124 | 125 | For answers to common questions about this code of conduct, see the FAQ at 126 | [https://www.contributor-covenant.org/faq][FAQ]. Translations are available at 127 | [https://www.contributor-covenant.org/translations][translations]. 128 | 129 | [homepage]: https://www.contributor-covenant.org 130 | [v2.1]: https://www.contributor-covenant.org/version/2/1/code_of_conduct.html 131 | [Mozilla CoC]: https://github.com/mozilla/diversity 132 | [FAQ]: https://www.contributor-covenant.org/faq 133 | [translations]: https://www.contributor-covenant.org/translations 134 | -------------------------------------------------------------------------------- /src/demon.h: -------------------------------------------------------------------------------- 1 | #include 2 | #include 3 | #include 4 | #include 5 | #include 6 | #include 7 | #include 8 | #include 9 | #include 10 | #include 11 | #include 12 | 13 | ///// mathematical constants: 14 | #define INVROOT2 0.70710678118 15 | #define ROOT2 1.41421356237 16 | #define PI 3.14159265359 17 | #define TRUE 1 18 | #define FALSE 0 19 | 20 | // macros: 21 | #define MIN(X, Y) (((X) < (Y)) ? (X) : (Y)) 22 | #define MAX(X, Y) (((X) > (Y)) ? (X) : (Y)) 23 | #define SIGN(X) (0 < X) - (X < 0) // returns -1 if X<0, 0 if X=0, 1 if X>0 24 | #define ROUNDIT(X) floor(X + 0.5) 25 | 26 | ///// maximum grid width for gnuplot: 27 | #define max_grid_for_output 523 28 | 29 | ///// options for main_calculations_and_output function: 30 | #define PHYLO_AND_POPS 1 31 | #define DIVERSITIES 2 32 | #define GENOPROPS 4 33 | 34 | ///// event types (for event_type variable and event_counter array): 35 | #define BIRTH_EVENT 0 36 | #define DEATH_EVENT 1 37 | #define MIGRATION_EVENT 2 38 | #define MUTATION_EVENT 3 39 | #define FISSION_EVENT 4 40 | #define NORMALBIRTH_EVENT 5 41 | #define NORMALDEATH_EVENT 6 42 | 43 | ///// model-specific constants: 44 | #define EMPTY -9 // value of grid[][] when the site has not yet been occupied by a cancer cell 45 | #define SET_SIZE 3 // max number of elements per bintree (in layer 0, each bintree element contains <=3 demes; in subsequent layers, each bintree element contains <=3 elements from the previous layer) 46 | #define MAX_DRIVERS_TO_COUNT 10 // max value of n when counting number of cells with n drivers 47 | #define MAX_TRIALS 200 // number of times to restart simulation in case of entinction, before giving up; 48 | // Note: probability of success in a single trial, starting from a single cell, is p_fix = (1-r)/(1-r^K) > 1-r, where r = 1/normal_birth_rate; probability of failure in MAX_TRIALS is 1-(1-p_fix)^MAX_TRIALS 49 | // For example, if normal_birth_rate = 0.95 and MAX_TRIALS = 200 then the chance of a successful trial is more than 99.996% 50 | 51 | ///// clone: 52 | #define POPULATION 0 // number of cancer cells 53 | #define DEME 1 // index of the deme in which the clone is located 54 | #define GENOTYPE 2 // index of the genotype of the clone 55 | #define DRIVER_GENOTYPE 3 // index of the driver genotype of the clone 56 | #define INDEX_IN_DEME 4 // index of the clone within its deme 57 | 58 | #define NUM_CLONE_INT_PROPS 5 59 | 60 | ///// genotype and driver genotype: 61 | //POPULATION already defined as 0 62 | #define PARENT 1 // parent's unique ID 63 | #define IDENTITY 2 // unique ID 64 | #define DRIVER_IDENTITY 3 // unique ID of corresponding driver genotype 65 | #define NUM_DRIVER_MUTATIONS 4 // number of driver mutations 66 | #define NUM_MIGRATION_MUTATIONS 5 // number of migration rate mutations 67 | #define IMMORTAL 6 // whether genotype record can be overwritten 68 | #define NUM_PASSENGER_MUTATIONS 7 // number of passenger mutations 69 | 70 | #define NUM_GENOTYPE_INT_PROPS 8 71 | // 72 | #define BIRTH_RATE 0 // birth rate conferred by the genotype 73 | #define MIGRATION_RATE 1 // migration rate conferred by the genotype 74 | #define ORIGIN_TIME 2 // generation at which genotype originated 75 | 76 | #define NUM_GENOTYPE_FLOAT_PROPS 3 77 | 78 | ///// genotype relatives: 79 | #define PARENT_INDEX 0 80 | #define FIRST_DAUGHTER 1 81 | #define LAST_DAUGHTER 2 82 | #define NEXT_SISTER 3 83 | 84 | ///// deme: 85 | //POPULATION already defined as 0 86 | #define XCOORD 1 // x coordinate of the deme 87 | #define YCOORD 2 // y coordinate of the deme 88 | #define NORMAL_CELLS 3 // number of normal cells in the deme 89 | #define NUM_CLONES_IN_DEME 4 // number of clones in the deme 90 | 91 | #define NUM_DEME_INT_PROPS 5 92 | // 93 | #define DEATH_RATE 0 // death rate of the deme 94 | #define MIGRATION_MODIFIER 1 // factor by which migration rate is multiplied (depends on what cells are in the deme) 95 | 96 | #define NUM_DEME_FLOAT_PROPS 2 97 | // 98 | #define SUM_BIRTH_RATES 0 // sum of birth rates of cancer cells in the deme 99 | #define SUM_MIGRATION_RATES 1 // sum of migration rates of cancer cells in the deme 100 | #define SUM_RATES 2 // sum of all rates of cancer cells and normal cells in the deme 101 | 102 | #define NUM_DEME_DOUBLE_PROPS 3 103 | 104 | ///// parameters of random number generator: 105 | #define IA 16807 106 | #define IM 2147483647 107 | #define AM (1.0/IM) 108 | #define IQ 127773 109 | #define IR 2836 110 | #define NTAB 32 111 | #define NDIV (1+(IM-1)/NTAB) 112 | #define EPS 1.2e-7 113 | #define RNMX (1.0-EPS) 114 | 115 | ////////////// 116 | 117 | // set up: 118 | char* get_input_path(int argc, char *argv[]); 119 | void read_parameters(boost::property_tree::ptree pt); 120 | float set_init_migration_rate(int K, float init_migration_rate, float A, float B, float C); 121 | void initialise(int *num_cells, int *num_clones, int *num_demes, int *num_matrix_cols, int *num_empty_cols, int init_driver_birth_mutations, 122 | int init_driver_mig_mutations, int init_passengers, int *num_empty_driver_cols, int *num_driver_matrix_cols, int *next_driver_genotype_id, 123 | int *next_genotype_id, long *idum, int *num_extinct_genotypes, int *num_empty_demes, int *num_extinct_driver_genotypes); 124 | 125 | // run the simulation: 126 | void run_sim(char *input_and_output_path, char *config_file_with_path); 127 | 128 | // choose update type: 129 | int choose_bintree_doubles(double *bintree, int max_layer_needed, int max_array_index, int array_size, long *idum); 130 | int choose_bintree_ints(int *bintree, int max_layer_needed, int max_array_index, int array_size, long *idum); 131 | int choose_clone_without_bintree(int chosen_deme, float *buff_array, float deme_sum_cancer, long *idum); 132 | int choose_clone_with_bintree_by_population(int bintree_index, int chosen_deme, int num_clones_in_deme, long *idum); 133 | int choose_clone_with_bintree_by_rates(int bintree_index, int chosen_deme, int num_clones_in_deme, long *idum); 134 | int choose_event_for_clone(bool include_death, int chosen_deme, int chosen_clone, float *buff_array, long *idum); 135 | int choose_event_for_deme(int chosen_deme, float *buff_array, long *idum); 136 | 137 | // cell events (top level): 138 | void cell_division(int *event_counter, int *num_cells, int parent_deme_num, int *new_passengers, int *new_mig_mutations, int *new_birth_mutations, 139 | int *new_mutations, long *idum, int chosen_clone, int parent_geno_num, int *daughter_clone_nums, int *num_empty_cols, int *num_matrix_cols, 140 | int *empty_cols, int *num_clones, int parent_driver_geno_num, int *num_empty_driver_cols, int *num_driver_matrix_cols, int *empty_driver_cols, 141 | int *next_driver_genotype_id, int num_demes, int *next_genotype_id, int *num_extinct_genotypes, int *num_empty_demes, 142 | int *num_extinct_driver_genotypes, float gens_elapsed); 143 | void cell_death(int *event_counter, int *num_cells, int parent_deme_num, int parent_geno_num, int *empty_cols, int *num_empty_cols, 144 | int chosen_clone, int *num_clones, int parent_driver_geno_num, int *num_empty_driver_cols, int *empty_driver_cols, int num_demes, 145 | int *num_extinct_genotypes, int *num_empty_demes, int *num_extinct_driver_genotypes); 146 | void cell_migration(int *event_counter, int parent_deme_num, long *idum, int *num_demes, int *num_clones, int parent_clone, int *num_cells, 147 | int daughter_geno_num, int daughter_driver_geno_num, int *num_empty_demes, int *empty_cols, int *num_empty_cols, int *num_empty_driver_cols, int *empty_driver_cols, 148 | int *num_extinct_genotypes, int *num_extinct_driver_genotypes); 149 | void deme_fission(int *event_counter, int origin_deme_num, long *idum, int *num_demes, int *num_clones, int *num_cells, int *num_empty_demes, int *num_empty_cols, int *num_empty_driver_cols, 150 | int *empty_cols, int *empty_driver_cols, int *num_extinct_genotypes, int *num_extinct_driver_genotypes, int num_matrix_cols); 151 | 152 | // genotype and driver genotype events (lower level): 153 | void choose_number_mutations(int *new_passengers, int *new_mig_mutations, int *new_birth_mutations, int *new_mutations, long *idum); 154 | int select_genotype_index(int *num_empty_cols, int *num_matrix_cols, int *empty_cols); 155 | void create_genotype(int **geno_or_driver_ints, float **geno_or_driver_floats, int *num_matrix_cols, int daughter_geno_num, int parent_geno_num, int *next_genotype_id, int daughter_driver_id, 156 | float new_birth_rate, float new_migration_rate, int new_passengers, int new_birth_mutations, int new_mig_mutations, float gens_elapsed); 157 | void increment_or_decrement_genotype(int **geno_or_driver_ints, int parent_geno_num, int *empty_cols, int *num_empty_cols, int change, int *num_extinct_genotypes); 158 | void create_column(int **either_matrix, int num_matrix_cols, int parent_geno_num, int daughter_geno_num, int num_mutations); 159 | 160 | // clone events (lower level): 161 | int select_clone_in_deme(int deme_index, int genotype_index); 162 | void create_clone(int daughter_geno_num, int *num_clones, int daughter_deme_num, int daughter_driver_geno_num, int num_demes, int initial_clone_pop); 163 | void increment_or_decrement_clone(int chosen_clone, int deme_index, int *num_clones, int change, int num_demes); 164 | void remove_clone(int chosen_clone, int deme_index, int *num_clones, int num_clones_in_deme); 165 | 166 | // deme events (lower level): 167 | void move_cells(long *idum, int origin_deme_num, int dividing_beyond_the_edge, int new_deme_index, int *num_cells, int *num_demes, int *num_empty_demes, int *num_clones, 168 | int *num_empty_cols, int *num_empty_driver_cols, int *num_extinct_genotypes, int *num_extinct_driver_genotypes, int *event_counter); 169 | void budge_demes(int old_x, int old_y, int *x_to_fill, int *y_to_fill); 170 | void get_deme_coordinates(int *x_to_fill, int *y_to_fill, int old_x, int old_y, long *idum); 171 | void choose_grid_square(int old_deme_index, long *idum, int *new_x, int *new_y); 172 | void create_deme(int new_x, int new_y, int *num_demes, int num_cells); 173 | void remove_deme(int deme_index, int *num_cells, int *num_clones, int *num_demes, int *num_empty_demes, int *empty_cols, int *num_empty_cols, int *num_empty_driver_cols, int *empty_driver_cols, 174 | int *num_extinct_genotypes, int *num_extinct_driver_genotypes); 175 | void increment_or_decrement_deme(int change, int deme_index, int num_cells, int num_demes, int *num_empty_demes); 176 | void add_or_remove_normal_cell(int change, int deme_index, int num_cells, int *event_counter, int num_demes); 177 | 178 | // memory handling: 179 | void assign_memory(); 180 | void free_memory(); 181 | 182 | // file handling (top level): 183 | void open_files(char *input_and_output_path); 184 | void initiate_files(int *num_samples_list); 185 | void main_calculations_and_output(long *idum, int num_demes, int num_matrix_cols, int num_driver_matrix_cols, float gens_elapsed, int *driver_counts, int num_cells, int num_clones, 186 | int record_phylogenies, int *num_samples_list, int next_genotype_id, int next_driver_genotype_id, int *event_counter, int num_empty_cols, int num_empty_driver_cols, int num_extinct_genotypes, 187 | int num_extinct_driver_genotypes, int num_empty_demes, long t1, int print_output, int which_parts); 188 | void grids_output(char *preamble_text, char *preamble_drivers_text, char *preamble_passengers_text, float gens_elapsed, int num_clones, int num_demes, char *input_and_output_path, 189 | char *buffer_text_short, char *buffer_text_long, bool to_file); 190 | void end_of_loop_output(int num_cells, float gens_elapsed, long t1); 191 | void final_output(int trial_num, int num_cells, long t1); 192 | void close_files(); 193 | 194 | // write system state to screen or file (lower level): 195 | void print_to_screen(float gens_elapsed, int num_cells, long t1, int num_demes, int num_matrix_cols, int num_clones, float mean_num_passengers, float mean_num_drivers, float diversity, float driver_diversity, 196 | double sum_birth_rates, double sum_death_rates, double sum_migration_rates, int num_empty_cols, float alpha_diversity, float alpha_driver_diversity, int *event_counter, int num_driver_matrix_cols, 197 | double sum_normal_death_rates, double sum_normal_birth_rates, float edge_diversity, int num_empty_driver_cols, int num_empty_demes, int num_extinct_genotypes, int num_extinct_driver_genotypes, int next_genotype_id); 198 | void write_output_pops(FILE *output_pops, int num_cells, int *event_counter, float mean_num_passengers, float mean_num_drivers, double sum_birth_rates, double sum_migration_rates, 199 | float var_num_passengers, float var_num_drivers, float variance_birth_rate, float variance_mig_rate, int num_matrix_cols, int num_empty_cols, int num_driver_matrix_cols, int num_empty_driver_cols, 200 | int num_extinct_genotypes, int num_extinct_driver_genotypes, int num_demes, int num_empty_demes, float gens_elapsed, int num_clones, int *driver_counts, int next_genotype_id); 201 | void write_diversities(FILE *output_diversities, float diversity, float alpha_diversity, float edge_diversity, float driver_diversity, float alpha_driver_diversity, float edge_driver_diversity, 202 | float **depth_diversity, float **depth_diversity_bigsample, float gens_elapsed, int num_cells); 203 | void write_other_files(FILE *output_demes, FILE *output_clones, FILE *output_genotype_counts, FILE *output_driver_genotype_counts, FILE *output_phylo, float gens_elapsed, 204 | int num_demes, int num_matrix_cols, int num_driver_matrix_cols, int num_clones, float *within_deme_diversity, float *within_deme_driver_diversity, int num_cells); 205 | void write_output_phylo(FILE* output, int num_cols, float gens_elapsed, int *populations, int **genotype_or_driver_ints, float **genotype_or_driver_floats, 206 | int samples, int biopsy_size_per_sample, int depth, int num_cells); 207 | void write_frequency_table(FILE *output_allele_counts, int **freq_table, int num_cells, float gens_elapsed, int num_freqs); 208 | void write_genotypes(FILE *output_genotype_properties, int num_matrix_cols, int *allele_count, int **genotype_or_driver_ints, float **genotype_or_driver_floats); 209 | void write_matrix_to_file(FILE *output_matrix, int **either_matrix, int num_matrix_cols); 210 | void write_pops_grid_to_file(FILE *output_popgrid); 211 | void write_passengers_grid_to_file(FILE *output_passengersgrid, int num_clones, int num_demes); 212 | void write_normalcells_grid_to_file(FILE *output_normalcellsgrid); 213 | void write_deathrates_grid_to_file(FILE *output_deathrates_grid); 214 | void write_rates_grid_to_file(FILE *output, double *deme_rates, int *deme_pops); 215 | void write_drivers_grid_to_file(FILE *output); 216 | void plot_birth_rate_grid(FILE *gp, char *preamble_text, float gens_elapsed, int num_clones, char *input_and_output_path, char *buffer_text_short, char *buffer_text_long); 217 | void plot_drivers_grid(FILE *gp, char *preamble_drivers_text, float gens_elapsed, char *input_and_output_path, char *buffer_text_short, char *buffer_text_long); 218 | void plot_pops_grid(FILE *gp, char *preamble_text, float gens_elapsed, char *input_and_output_path, char *buffer_text_short, char * buffer_text_long); 219 | void plot_passengers_grid(FILE *gp, char *preamble_text, float gens_elapsed, int num_clones, int num_demes, char *input_and_output_path, char *buffer_text_short, char *buffer_text_long); 220 | void plot_migration_grid(FILE *gp, char *preamble_text, float gens_elapsed, int num_clones, char *input_and_output_path, char *buffer_text_short, char *buffer_text_long); 221 | 222 | // set rates: 223 | float set_birth_rate(int new_birth_mutations, int new_passengers, float parent_birth_rate, long *idum); 224 | float set_death_rate(int deme_index, int num_cells); 225 | float set_migration_rate(int new_mig_mutations, float parent_mig_rate, long *idum); 226 | float set_migration_modifier(int normal_cells, int population); 227 | 228 | // calculate or reset sums of rates: 229 | void update_deme_bintree_environmental_rates(int change_pop, int change_normal_cells, int num_demes, int deme_index, int num_cells); 230 | void update_deme_bintree_phenotype_rates(int chosen_clone, int deme_index, int change, int num_demes); 231 | void set_clone_in_deme(int deme_num, int geno_num, int index_in_deme, int clone_pop); 232 | void reset_deme_and_bintree_sums(int num_demes, int num_clones, int print_always); 233 | void reset_clone_bintree_sums(int num_demes, int num_clones); 234 | void calculate_sums_of_rates(double *sum_death_rates, double *sum_birth_rates, double *sum_migration_rates, double *sum_normal_birth_rates, double *sum_normal_death_rates, int num_demes, 235 | int num_matrix_cols, float gens_elapsed); 236 | float sum_of_all_rates(int num_demes); 237 | 238 | // checks: 239 | void check_clone_bintree_sums(bool full); 240 | void check_deme_sums(int chosen_deme, float deme_sum_cancer); 241 | void check_rates_sum(float b0, float b1, int chosen_deme, int cell_type); 242 | void check_geno_populations(int chosen_clone, int event_type); 243 | void check_matrix_cols1(int num_matrix_cols, int num_driver_matrix_cols, int num_cells); 244 | void check_matrix_cols2(int num_matrix_cols, int num_driver_matrix_cols, int num_empty_cols, int num_empty_driver_cols, int num_extinct_genotypes, int num_extinct_driver_genotypes); 245 | void check_clones_in_deme1(int origin_deme_num, int clone_num); 246 | void check_clones_in_deme2(int num_clones_in_deme); 247 | void check_chosen_clone(int chosen_clone, int num_clones_in_deme); 248 | void check_clone_populations(int chosen_clone, int event_type, int parent_deme_num); 249 | void check_normal_pops(int chosen_deme); 250 | void check_genotype_counts(int num_matrix_cols, int num_empty_cols, int num_extinct_genotypes, int num_driver_matrix_cols, int num_empty_driver_cols, int num_extinct_driver_genotypes, 251 | int cell_type, int event_type, int chosen_deme); 252 | 253 | // generic bintree functions: 254 | void set_bintree_sums_layer0(double *bintree, double *array, int num_array_elements); 255 | void set_bintree_sums_layer0_int(int *bintree, int *array, int num_array_elements); 256 | void set_bintree_sums_subsequent_layers(double *bintree, int num_demes, int max_layer_needed, int array_length); 257 | void set_bintree_sums_subsequent_layers_int(int *bintree, int num_demes, int max_layer_needed, int array_length); 258 | void update_bintree_layers(double summand, double *bintree, int array_index, int max_layer_needed, int array_length); 259 | void update_bintree_layers_int(int summand, int *bintree, int array_index, int max_layer_needed, int array_length); 260 | void extend_bintree(double *bintree, int array_index, int max_layer_needed, int array_length); 261 | void extend_bintree_int(int *bintree, int array_index, int max_layer_needed, int array_length); 262 | int get_bintree_index(int layer, int array_index, int array_size); 263 | int get_deme_bintree_index(int layer, int array_index); 264 | int get_clone_bintree_index(int layer, int array_index); 265 | int get_max_layer_needed(int n); 266 | 267 | // calculate diversity metrics (top level): 268 | void get_diversity_metrics(int rao, float *diversity, float *edge_diversity, float *alpha_diversity, float *within_deme_diversity, int num_demes, int num_cells, int num_matrix_cols, int num_clones, 269 | int *clone_genotype, int **either_matrix, int dmax, int *populations, long *idum, float gens_elapsed, int* position_in_edge_list, int* demes_at_edge, int* sides_at_edge, int* genotype_edge_pop, int is_drivers_only); 270 | void get_biopsy_data(int rao, float *depth_array, int samples, int biopsy_size_per_sample, int num_demes, int num_cells, int num_matrix_cols, int num_clones, int *clone_genotype, int **either_matrix, 271 | int dmax, long *idum, FILE *sample_size_log, float gens_elapsed, FILE *output_phylo_of_sample, int calculate_sample_diversities, int record_phylogenies, float centre_X, float centre_Y, 272 | int **genotype_or_driver_ints, float **genotype_or_driver_floats, int *at_edge); 273 | void calculate_mutation_metrics(float *mean_num_passengers, float *mean_num_drivers, float *var_num_passengers, float *var_num_drivers, int *driver_counts, int num_matrix_cols, int num_cells); 274 | float calculate_variance_of_rate(int num_matrix_cols, int num_cells, double sum_of_rates, float *list_of_rates); 275 | void get_relatives(int num_matrix_cols, int next_genotype_id, int **geno_or_driver_ints); 276 | void get_allele_frequencies(int num_matrix_cols, int *allele_count, int **geno_or_driver_ints); 277 | void get_frequency_table(int input_length, int *count, int **freq_table, int *output_length); 278 | 279 | // calculate diversity metrics (lower level): 280 | float centre_of_gravity(int direction, int num_cells); 281 | float calculate_diversity(int num_matrix_cols, int N, int *populations, int **either_matrix, int dmax, int rao); 282 | float calculate_edge_diversity(int num_matrix_cols, int num_cells, int **either_matrix, int dmax, int num_demes, int num_clones, int *clone_genotype, long *idum, int rao, int* position_in_edge_list, 283 | int* demes_at_edge, int* sides_at_edge, int* genotype_edge_pop); 284 | float calculate_within_deme_diversity(int deme_index, int num_matrix_cols, int num_clones, int *clone_genotype, int **either_matrix, int dmax, int rao, int is_drivers_only, int* genotype_edge_pop); 285 | void find_sample_genotype_pops(int *genotype_populations_in_sample, int *sampled_cells, int num_matrix_cols, int num_cells, int **either_matrix, int dmax, int num_demes, int num_clones, 286 | int depth, float centre_X, float centre_Y, int *clone_genotype, int num_directions, int biopsy_size_per_sample, long *idum, FILE *sample_size_log, float gens_elapsed, int rao, int *at_edge); 287 | int move_down(int start_index); 288 | int move_right(int start_index); 289 | int move_up(int start_index); 290 | 291 | // generate preamble gnuplot code for images: 292 | char *preamble(char *text, char *buffer_text_long); 293 | char *preamble_drivers(char *text, char *buffer_text_long); 294 | 295 | // generic functions: 296 | int weighted_random_floats(float *rates, long *idum, int start_index, int num_elements); 297 | int weighted_random_doubles(double *rates, long *idum, int start_index, int num_elements); 298 | int weighted_random_ints(int *rates, long *idum, int start_index, int num_elements); 299 | int weighted_random_known_sums_floats(float *cumulative_rates, long *idum, int num_elements); 300 | int weighted_random_known_sums_doubles(double *cumulative_rates, long *idum, int num_elements); 301 | int weighted_random_known_sums_ints(int *cumulative_rates, long *idum, int num_elements); 302 | char *zeroes(int, int, char *buffer_text_short, char *buffer_text_long); 303 | char *concat(char *, char *, char *buffer_text_long); 304 | double ran1(long *); 305 | int which_quadrant(int x, int y, float theta, float tan_theta, int l); 306 | float expdev(long *); 307 | unsigned int hypergeometric(long *, unsigned int, unsigned int, unsigned int); 308 | unsigned int poisson(long *idum, double mu); 309 | unsigned int binomial(long *idum, double p, unsigned int n); 310 | double gamma(long *idum, const unsigned int a); 311 | double power(double x, unsigned int n); 312 | int component(int sum, int part); 313 | int stochastic_round(float, long *); 314 | void mallocArray_int(int ***a, int m1, int m2); 315 | void mallocArray_float(float ***a, int m1, int m2); 316 | void mallocArray_double(double ***a, int m1, int m2); 317 | void freeArray_int(int **a, int m); 318 | void freeArray_float(float **a, int m); 319 | void freeArray_double(double **a, int m); -------------------------------------------------------------------------------- /LICENSE: -------------------------------------------------------------------------------- 1 | GNU GENERAL PUBLIC LICENSE 2 | Version 3, 29 June 2007 3 | 4 | Copyright (C) 2007 Free Software Foundation, Inc. 5 | Everyone is permitted to copy and distribute verbatim copies 6 | of this license document, but changing it is not allowed. 7 | 8 | Preamble 9 | 10 | The GNU General Public License is a free, copyleft license for 11 | software and other kinds of works. 12 | 13 | The licenses for most software and other practical works are designed 14 | to take away your freedom to share and change the works. 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You may not convey a covered 525 | work if you are a party to an arrangement with a third party that is 526 | in the business of distributing software, under which you make payment 527 | to the third party based on the extent of your activity of conveying 528 | the work, and under which the third party grants, to any of the 529 | parties who would receive the covered work from you, a discriminatory 530 | patent license (a) in connection with copies of the covered work 531 | conveyed by you (or copies made from those copies), or (b) primarily 532 | for and in connection with specific products or compilations that 533 | contain the covered work, unless you entered into that arrangement, 534 | or that patent license was granted, prior to 28 March 2007. 535 | 536 | Nothing in this License shall be construed as excluding or limiting 537 | any implied license or other defenses to infringement that may 538 | otherwise be available to you under applicable patent law. 539 | 540 | 12. No Surrender of Others' Freedom. 541 | 542 | If conditions are imposed on you (whether by court order, agreement or 543 | otherwise) that contradict the conditions of this License, they do not 544 | excuse you from the conditions of this License. If you cannot convey a 545 | covered work so as to satisfy simultaneously your obligations under this 546 | License and any other pertinent obligations, then as a consequence you may 547 | not convey it at all. For example, if you agree to terms that obligate you 548 | to collect a royalty for further conveying from those to whom you convey 549 | the Program, the only way you could satisfy both those terms and this 550 | License would be to refrain entirely from conveying the Program. 551 | 552 | 13. Use with the GNU Affero General Public License. 553 | 554 | Notwithstanding any other provision of this License, you have 555 | permission to link or combine any covered work with a work licensed 556 | under version 3 of the GNU Affero General Public License into a single 557 | combined work, and to convey the resulting work. The terms of this 558 | License will continue to apply to the part which is the covered work, 559 | but the special requirements of the GNU Affero General Public License, 560 | section 13, concerning interaction through a network will apply to the 561 | combination as such. 562 | 563 | 14. Revised Versions of this License. 564 | 565 | The Free Software Foundation may publish revised and/or new versions of 566 | the GNU General Public License from time to time. Such new versions will 567 | be similar in spirit to the present version, but may differ in detail to 568 | address new problems or concerns. 569 | 570 | Each version is given a distinguishing version number. If the 571 | Program specifies that a certain numbered version of the GNU General 572 | Public License "or any later version" applies to it, you have the 573 | option of following the terms and conditions either of that numbered 574 | version or of any later version published by the Free Software 575 | Foundation. If the Program does not specify a version number of the 576 | GNU General Public License, you may choose any version ever published 577 | by the Free Software Foundation. 578 | 579 | If the Program specifies that a proxy can decide which future 580 | versions of the GNU General Public License can be used, that proxy's 581 | public statement of acceptance of a version permanently authorizes you 582 | to choose that version for the Program. 583 | 584 | Later license versions may give you additional or different 585 | permissions. However, no additional obligations are imposed on any 586 | author or copyright holder as a result of your choosing to follow a 587 | later version. 588 | 589 | 15. Disclaimer of Warranty. 590 | 591 | THERE IS NO WARRANTY FOR THE PROGRAM, TO THE EXTENT PERMITTED BY 592 | APPLICABLE LAW. EXCEPT WHEN OTHERWISE STATED IN WRITING THE COPYRIGHT 593 | HOLDERS AND/OR OTHER PARTIES PROVIDE THE PROGRAM "AS IS" WITHOUT WARRANTY 594 | OF ANY KIND, EITHER EXPRESSED OR IMPLIED, INCLUDING, BUT NOT LIMITED TO, 595 | THE IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR 596 | PURPOSE. THE ENTIRE RISK AS TO THE QUALITY AND PERFORMANCE OF THE PROGRAM 597 | IS WITH YOU. SHOULD THE PROGRAM PROVE DEFECTIVE, YOU ASSUME THE COST OF 598 | ALL NECESSARY SERVICING, REPAIR OR CORRECTION. 599 | 600 | 16. Limitation of Liability. 601 | 602 | IN NO EVENT UNLESS REQUIRED BY APPLICABLE LAW OR AGREED TO IN WRITING 603 | WILL ANY COPYRIGHT HOLDER, OR ANY OTHER PARTY WHO MODIFIES AND/OR CONVEYS 604 | THE PROGRAM AS PERMITTED ABOVE, BE LIABLE TO YOU FOR DAMAGES, INCLUDING ANY 605 | GENERAL, SPECIAL, INCIDENTAL OR CONSEQUENTIAL DAMAGES ARISING OUT OF THE 606 | USE OR INABILITY TO USE THE PROGRAM (INCLUDING BUT NOT LIMITED TO LOSS OF 607 | DATA OR DATA BEING RENDERED INACCURATE OR LOSSES SUSTAINED BY YOU OR THIRD 608 | PARTIES OR A FAILURE OF THE PROGRAM TO OPERATE WITH ANY OTHER PROGRAMS), 609 | EVEN IF SUCH HOLDER OR OTHER PARTY HAS BEEN ADVISED OF THE POSSIBILITY OF 610 | SUCH DAMAGES. 611 | 612 | 17. Interpretation of Sections 15 and 16. 613 | 614 | If the disclaimer of warranty and limitation of liability provided 615 | above cannot be given local legal effect according to their terms, 616 | reviewing courts shall apply local law that most closely approximates 617 | an absolute waiver of all civil liability in connection with the 618 | Program, unless a warranty or assumption of liability accompanies a 619 | copy of the Program in return for a fee. 620 | 621 | END OF TERMS AND CONDITIONS 622 | 623 | How to Apply These Terms to Your New Programs 624 | 625 | If you develop a new program, and you want it to be of the greatest 626 | possible use to the public, the best way to achieve this is to make it 627 | free software which everyone can redistribute and change under these terms. 628 | 629 | To do so, attach the following notices to the program. It is safest 630 | to attach them to the start of each source file to most effectively 631 | state the exclusion of warranty; and each file should have at least 632 | the "copyright" line and a pointer to where the full notice is found. 633 | 634 | 635 | Copyright (C) 636 | 637 | This program is free software: you can redistribute it and/or modify 638 | it under the terms of the GNU General Public License as published by 639 | the Free Software Foundation, either version 3 of the License, or 640 | (at your option) any later version. 641 | 642 | This program is distributed in the hope that it will be useful, 643 | but WITHOUT ANY WARRANTY; without even the implied warranty of 644 | MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. See the 645 | GNU General Public License for more details. 646 | 647 | You should have received a copy of the GNU General Public License 648 | along with this program. If not, see . 649 | 650 | Also add information on how to contact you by electronic and paper mail. 651 | 652 | If the program does terminal interaction, make it output a short 653 | notice like this when it starts in an interactive mode: 654 | 655 | Copyright (C) 656 | This program comes with ABSOLUTELY NO WARRANTY; for details type `show w'. 657 | This is free software, and you are welcome to redistribute it 658 | under certain conditions; type `show c' for details. 659 | 660 | The hypothetical commands `show w' and `show c' should show the appropriate 661 | parts of the General Public License. Of course, your program's commands 662 | might be different; for a GUI interface, you would use an "about box". 663 | 664 | You should also get your employer (if you work as a programmer) or school, 665 | if any, to sign a "copyright disclaimer" for the program, if necessary. 666 | For more information on this, and how to apply and follow the GNU GPL, see 667 | . 668 | 669 | The GNU General Public License does not permit incorporating your program 670 | into proprietary programs. If your program is a subroutine library, you 671 | may consider it more useful to permit linking proprietary applications with 672 | the library. If this is what you want to do, use the GNU Lesser General 673 | Public License instead of this License. But first, please read 674 | . 675 | --------------------------------------------------------------------------------