SCHISM (SubClonal Hierarchy Inference from Somatic Mutations)

is a computational framework that reconstructs tumor subcolonal phylogenies using somatic mutation cellularities in patient's tumor sample(s).

SCHISM combines information about somatic mutation cellularity (aka mutation cancer cell fraction) across all tumor sample(s) available from a patient in a hypothesis testing framework to identify the statistical support for the lineage relationship between each pair of mutations or mutation clusters. The results of the hypothesis test are represented as Cluster Order Precedence Violation (CPOV) matrix which informs the subsequent step in SCHISM and ensures compliance of candidate tree topologies with lineage precedence rule.

Finally, an implementation of genetic algorithm (GA) based on a fitness function that incorporates considerations for both lineage precedence (CPOV) rule and lineage divergence rule explores the space of tree topologies and returns a prioritized list of candidate subclonal phylogenetic trees, most compatible with observed cellularity data.

SCHISM is free for non-commercial use. For more details please refer to our Software License. Commercial users should contact the Johns Hopkins Technology Transfer office.

Current stable release is SCHISM.1.1.2, last updated on 05/11/2016.

Source Code Releases

SCHISM-1.1.2.tar.gz    05/11/2016    Better color handling in cellularity plots. Dockerfile added.

SCHISM-1.1.1.tar.gz    02/19/2016    POV and cellularity visualization added.

SCHISM-1.1.0.tar.gz    01/26/2016    Mutation clustering module added.

SCHISM-1.0.1.tar.gz    01/01/2016    Initial release with the manuscript, with minor visualization update

SCHISM-1.0.1.tar.gz    03/15/2015    Initial release with the manuscript

Docker Image Releases

SCHISM-1.1.1.docker-Image.tar.gz    01/26/2016    Docker Image of the package after addition of POV and cellularity visualization modules SCHISM-1.1.0.docker-Image.tar.gz    01/26/2016    Docker Image of the package after addition of mutation clustering module SCHISM-1.0.1.docker-Image.tar.gz    01/01/2016    Docker Image of initial package release with the manuscript, with minor visualization update

Documentation for the user

Please consult the project wiki page for installation and usage details.

Example workflow

Materials corresponding to two SCHISM usage examples described on project wiki are available for download here (E1, E2). Please follow the wiki page for a step-by-step walk-through.

Gallery

Sample performance of SCHISM on a subclonal phylogeny with 15 nodes, with 7 simulated biopsy samples

Platform

Basic functionality of SCHISM scripts developed in python should be available across all platforms. The plotting functionality of SCHISM relies on matplotlib, igraph c core and python-igraph. Matplotlib should run across all platforms. igraph dependencies (c core, and python-igraph), however, have been verified to work on Fedora Core (FC19) and Ubuntu (1.14) linux distributions. An installation guide for igraph dependencies is available on the project wiki page.

Primary citation

If you use our software for a publication, please cite the following:

Niknafs N, Beleva-Guthrie V, Naiman DQ, Karchin R (2015) SubClonal Hierarchy Inference from Somatic Mutations: automatic reconstruction of cancer evolutionary trees from multi-region next generation sequencing. PLoS Computational Biology 11(10):e1004416 Abstract

Software primary contact/developer

Noushin Niknafs:  niknafs at jhu dot edu