• ctdna 0.1.0 2020-05-06: Initial release of package.
• ctdna 0.1.1 2020-08-18: Added various examples and unittests. Added methods to calculate detection probabilities.

1. Easiest is to install Mini anaconda and create a new python environment in a terminal window with conda create --name py36 python=3.6 and activate it with conda activate py36
2. Clone the repository from GitHub with git clone https://github.com/reiterlab/ctdna.git
3. If you want to have system-wide access, create distribution packages by going into the main folder with cd <CTDNA_DIRECTORY>, run python setup.py clean sdist bdist_wheel and install ctdna to your python environment by executing pip install -e <CTDNA_DIRECTORY>
4. Test installation with python -c 'import ctdna' and pytest <CTDNA_DIRECTORY>/tests/
5. To uninstall the package use pip uninstall ctdna or conda remove ctdna

ctdna can be run in the following modes:

1. dynamics: simulates the evolutionary dynamics of a tumor and its biomarkers over time
2. distribution: simulates the biomarker distribution at a given tumor size or tumor age
3. detection: simulates the detection size of a growing tumor for repeated testing at a desired annual false positive rate or a specified p-value threshold
4. roc: computes the ROC (receiver operating characteristic)

See <CTDNA_DIRECTORY>/ctdna/settings.py for default parameter values.

• -b <> or --birth_rate <>: birth rate of cancer cells

• -d <> or --death_rate <>: death rate of cancer cells

• --q_d <>: ctDNA shedding probability per cell death

• --q_b <>: ctDNA shedding probability per cell birth

• --lambda1 <>: ctDNA shedding probability per cell per day

• --t12_mins <>: cfDNA half-life time in minutes

• --tube_size <>: size of blood sample tube (liters; default 0.015 l)

• --panel_size <>: sequencing panel size

• --seq_err <>: sequencing error rate per base-pair (default: 1e-5)

• --seq_eff <>: sequencing efficiency, ie. fraction of the sampled molecules that are actually successfully sequenced (default: 0.5)

• --n_muts <>: number of clonal mutations in the cancer that are covered by the sequencing panel

• -M <> or --det_size <>: tumor detection size where biomarker level is evaluated or size where dynamics simulations are stopped

• -T <> or --sim_time <>: simulations end when cancer reaches the given time

• --exact_th <>: approximate growth of tumor after this given threshold is reached

• -o <> or --output_dir <>: output directory for files (default is defined in <CTDNA_DIRECTORY>/ctdna/settings.py)

• --biomarker_wt_freq_ml <> Optional argument to fix the wildtype haploid genome equivalents (hGE) per plasma ml to the given number instead of sampling the plasma DNA concentration from a Gamma distribution with parameters specified in <CTDNA_DIRECTORY>/ctdna/settings.py