Single-Cell mutation Identification via finite-sites Phylogenetic Inference (SCIPhIN) is a new approach to mutation detection in individual tumor cells by leveraging the evolutionary relationship among cells. SCIPhIN is based on SCIPhI, which jointly calls mutations in each individual cell and estimates the tumor phylogeny on these cells. In contrast to SCIPhI, SCIPhIN allows for mutation loss and parallele mutations, relaxing the infinite sites assumption. Employing a Markov Chain Monte Carlo scheme we robustly account for the various sources of noise in single-cell sequencing data. Our approach enables us to reliably call mutations in each single cell even in experiments with high dropout rates and missing data
SCIPhIN is freely available under a GNU General Public License v3.0 at https://github/cbg-ETHZ/SCIPhIN
SCIPhIN has the following dependencies which need to be installed:
Boost >= 1.6.x,DLIB >= 19.9
Clone SCIPhIN with submodules from the soucre code:
git clone --recurse-submodules https://github.com/cbg-ethz/SCIPhIN.git
In order to install SCIPhIN issue the following commands in the github directory:
autoreconf -vif
./configure --with-boost=BOOST_PATH SEQAN_INCLUDEDIR=SEQAN_PATH DLIB_INCLUDEDIR=DLIB_PATH
make
An alternative is to use CMake (tested with version >= 3.11.1). Simply issue the commands:
mkdir build
cd build
cmake ..
cmake --build . --config Release
Afterwards you will find SCIPhIN in the build directory.
SCIPhIN expects the sequencing information to be passed in form of the well known mpileup format (http://www.htslib.org/doc/samtools.html). In order to generate such a file you need to align your fastq files to a reference and post process the result (e.g., following the instuctions here: https://gatk.broadinstitute.org/hc/en-us/articles/360035535912-Data-pre-processing-for-variant-discovery).
In order to see all available options type
sciphin -h
Executing
sciphin -o result --in cellNames.txt --seed 42 --im example.mpileup
will run SCIPhIN using the cell names provided in cellNames.txt (same order as in the mpileup file). Note that cellNames.txt is a tab delimited file with the cell name in the first column and a cell type identifier in the second column. The cell type can be either CT (tumor cell), CN (control normal cell), or BN (control bulk normal). Note that SCIPhIN assumes a pileup against a reference and ignores positions with 'N' as reference.