ReDeNovo

Hybrid detection of known and novel mutational signatures with ReDeNovo

Installation

Clone the GitHub repository and move into the project directory:

git clone https://github.com/ncbi/ReDeNovo.git
cd redenovo

conda env create -f environment.yml
conda activate redenovo

pip install -e ./
redenovo -h

Examples

Sample run:

redenovo -M src/redenovo/data/M.txt -O src/redenovo/output

• specify cosmic version, genome, and WGS/WES

redenovo -M src/redenovo/data/M.txt -O src/redenovo/output -g 38 -w WGS --cosmic-version 3.4

• specify manual reference signature database

redenovo -M src/redenovo/data/M.txt -O src/redenovo/output --manual-cosmic --manual-cosmic-file src/redenovo/data/COSMIC.txt

• run with a given set of signatures (no novel signature inference)

redenovo -M src/redenovo/data/M.txt -O src/redenovo/output -N 0 -P SBS1 SBS2 SBS3 SBS5 SBS8 SBS13 SBS17b SBS18 

• run with a given set of signatures (with given number of novel signature inference, here 2)

redenovo -M src/redenovo/data/M.txt -O src/redenovo/output -N 2 -P SBS1 SBS2 SBS3 SBS5 SBS8 SBS13 SBS17b SBS18 

• include the inferred signature and rerun the tool

redenovo -M src/redenovo/data/M.txt -O src/redenovo/output --novel-signatures-file src/redenovo/output/Cluster_signature_profiles_one_k1.txt --add-novel-signatures

• include the inferred signature and rerun the tool with given set of signatures included

redenovo -M src/redenovo/data/M.txt -O src/redenovo/output -P SBS1 SBS2 SBS3 SBS5 SBS8 SBS13 SBS17b SBS18  --novel-signatures-file src/redenovo/output/Cluster_signature_profiles_one_k1.txt --add-novel-signatures

• exclude signature/s from the given reference database

redenovo -M src/redenovo/data/M.txt -O src/redenovo/output -E SBS2  

• if input mutation count matrix file has row and column names

redenovo -M src/redenovo/data/redenovo_M.txt -O src/redenovo/output --has-header-and-index True

• update number of run and iteration (for example: 20 runs and 10 iterations)

redenovo -M src/redenovo/data/redenovo_M.txt -O src/redenovo/output --has-header-and-index True -n 20 -i 10

• be more selective to add a signature waiting for it to be selected repeatedly at least two times

redenovo -M src/redenovo/data/redenovo_M.txt -O src/redenovo/output --has-header-and-index True --consno 2

Hyperparameters and Definitions

User-defined Parameters

Parameter	Description	Default
--consno	Minimum number of times a signature must be selected to be included in the inferred signature set	1
-i, --numiters	Maximum number of iterations allowed while attempting to add a new fixed signature (patience for novel signature detection)	10
-n, --numruns	Number of runs to repeat the analysis	10
--thr1	Minimum fraction of patients with exposure ≥ thr1 required for a signature to be considered present	0.1
--thr2	Minimum cosine similarity required to match a signature with a known COSMIC signature and include it in the inferred set	0.70
--thr3	Minimum exposure weight required for a signature to contribute to the final exposure profile (For example, a signature is accepted as inferred if it is present in ≥7 runs out of 10 when --thr3 = 0.70 and --numruns = 10)	0.70
--thr4	Minimum cosine similarity to consider a signature as known and exclude it from novel candidate detection	0.80
--thr5	Minimum fraction of the cohort with nonzero exposure required for a signature to be considered present	0.1
--exposure-thr1	Minimum patient-wise normalized exposure required for a signature to be considered present	0.05
--exposure-thr2	Minimum raw exposure required for a signature to be considered present	1
-E, --exclude	List of SBS signatures to exclude from COSMIC (e.g., ["SBS1", "SBS5"])	[]

Database of Catalogue Signatures

Parameter	Description	Default
-g, --genome	Genome version to use (37 or 38)	38
-w, --whole	Sequencing platform for the data and COSMIC catalogue (WGS or WES)	WGS
--cosmic-version	COSMIC version to use (3.4, 3.3, 3.2, 3.1, 3, 2, or 1)	3.4
--manual-cosmic	Whether to use a user-provided COSMIC reference file (True or False)	False
--manual-cosmic-file	Path to the file containing reference signatures (used only if --manual-cosmic is enabled)	None

Input File–Related Parameters

Parameter	Description	Default
-d, --delimiter	Delimiter used to separate columns in input matrices; also used for output files	\t
--has-header-and-index	Whether the input file contains row names and column headers (True or False)	False
--add-novel-signatures	Whether to evaluate using novel signatures provided in an external file (True or False)	False
--check-novel	Whether to check novel signatures (True or False)	False
--novel-signatures-file	Path to the file containing novel signatures (used only if --add-novel-signatures is enabled)	None

Output Options

Parameter	Description	Default
-O, --out	Path to the output directory. The folder will be created if it does not exist. Existing files will be overwritten.	Current directory