MM2S: personalized diagnosis of medulloblastoma patients and model systems.

Abstract

Background: Medulloblastoma (MB) is a highly malignant and heterogeneous brain tumour that is the most common cause of cancer-related deaths in children. Increasing availability of genomic data over the last decade had resulted in improvement of human subtype classification methods, and the parallel development of MB mouse models towards identification of subtype-specific disease origins and signaling pathways. Despite these advances, MB classification schemes remained inadequate for personalized prediction of MB subtypes for individual patient samples and across model systems. To address this issue, we developed the Medullo-Model to Subtypes ( MM2S ) classifier, a new method enabling classification of individual gene expression profiles from MB samples (patient samples, mouse models, and cell lines) against well-established molecular subtypes [Genomics 106:96-106, 2015]. We demonstrated the accuracy and flexibility of MM2S in the largest meta-analysis of human patients and mouse models to date. Here, we present a new functional package that provides an easy-to-use and fully documented implementation of the MM2S method, with additional functionalities that allow users to obtain graphical and tabular summaries of MB subtype predictions for single samples and across sample replicates. The flexibility of the MM2S package promotes incorporation of MB predictions into large Medulloblastoma-driven analysis pipelines, making this tool suitable for use by researchers.

Results: The MM2S package is applied in two case studies involving human primary patient samples, as well as sample replicates of the GTML mouse model. We highlight functions that are of use for species-specific MB classification, across individual samples and sample replicates. We emphasize on the range of functions that can be used to derive both singular and meta-centric views of MB predictions, across samples and across MB subtypes.

Conclusions: Our MM2S package can be used to generate predictions without having to rely on an external web server or additional sources. Our open-source package facilitates and extends the MM2S algorithm in diverse computational and bioinformatics contexts. The package is available on CRAN, at the following URL: https://cran.r-project.org/web/packages/MM2S/, as well as on Github at the following URLs: https://github.com/DGendoo and https://github.com/bhklab.