ClassifieR 2.0: expanding interactive gene expression-based stratification to prostate and high-grade serous ovarian cancer

Abstract

Abstract Background Advances in transcriptional profiling methods have enabled the discovery of molecular subtypes within and across traditional tissue-based cancer classifications. Such molecular subgroups hold potential for improving patient outcomes by guiding treatment decisions and revealing physiological distinctions and targetable pathways. Computational methods for stratifying transcriptomic data into molecular subgroups are increasingly abundant. However, assigning samples to these subtypes and other transcriptionally inferred predictions is time-consuming and requires significant bioinformatics expertise. To address this need, we recently reported “ClassifieR,” a flexible, interactive cloud application for the functional annotation of colorectal and breast cancer transcriptomes. Here, we report “ClassifieR 2.0” which introduces additional modules for the molecular subtyping of prostate and high-grade serous ovarian cancer (HGSOC). Results ClassifieR 2.0 introduces ClassifieRp and ClassifieRov, two specialised modules specifically designed to address the challenges of prostate and HGSOC molecular classification. ClassifieRp includes sigInfer, a method we developed to infer commercial prognostic prostate gene expression signatures from publicly available gene-lists or indeed any user-uploaded gene-list. ClassifieRov utilizes consensus molecular subtyping methods for HGSOC, including tools like consensusOV, for accurate ovarian cancer stratification. Both modules include functionalities present in the original ClassifieR framework for estimating cellular composition, predicting transcription factor (TF) activity and single sample gene set enrichment analysis (ssGSEA). Conclusions ClassifieR 2.0 combines molecular subtyping of prostate cancer and HGSOC with commonly used sample annotation tools in a single, user-friendly platform, allowing scientists without bioinformatics training to explore prostate and HGSOC transcriptional data without the need for extensive bioinformatics knowledge or manual data handling to operate various packages. Our sigInfer method within ClassifieRp enables the inference of commercially available gene signatures for prostate cancer, while ClassifieRov incorporates consensus molecular subtyping for HGSOC. Overall, ClassifieR 2.0 aims to make molecular subtyping more accessible to the wider research community. This is crucial for increased understanding of the molecular heterogeneity of these cancers and developing personalised treatment strategies.

Keywords

• Molecular classification
• Shiny application
• High-grade serous ovarian cancer
• Prostate cancer
• Transcriptomics