Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Nov 21;25(1):362.
doi: 10.1186/s12859-024-05981-6.

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

Affiliations

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

Aideen McCabe et al. BMC Bioinformatics. .

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: High-grade serous ovarian cancer; Molecular classification; Prostate cancer; Shiny application; Transcriptomics.

PubMed Disclaimer

Conflict of interest statement

Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: SSM and GPQ are share-holders of generatR Ltd trading as BlokBio, a cloud genomics data analysis company. All other authors have no competing interests.

Figures

Fig. 1
Fig. 1
Overview of ClassifieR 2.0. A. Visual abstract of ClassifieRp and ClassifieRov. B. Screenshot of the graphical user interface (GUI) of ClassifieRp data input page. C. Schematic overview of ClassifieRp architecture and sub-functions
Fig. 2
Fig. 2
ClassifieRp use case conducted on demo data obtained from prostate cancer gene expression dataset (GSE116918) [29]. A. Patient subgroup table and frequency bar plot from sigInfer. B. Boxplot of Fibroblast scores from the MCP-counter R package for the patient subgroups 1 and 2 from sigInfer. C. Boxplot of MYC TF activity scores from the DoRothEA R package for the patient subgroups 1 and 2 from sigInfer. D. Boxplot of androgen receptor (AR) TF activity scores from the DoRothEA R package for the patient subgroups 1 and 2 from sigInfer. E. Kaplan–Meier survival curves from the surviveR application for time to metastatic disease of the patient subgroups 1 and 2 from sigInfer
Fig. 3
Fig. 3
ClassifieRov use case conducted on demo data obtained from GSE14764 [37]. A. Interactive boxplot from the Complete Report tab showing distribution of MYC TF-activity scores amongst consensusOV molecular subgroups. B. Interactive boxplot from the Complete Report tab showing distribution of MCP-Counter scores for T cells amongst consensusOV molecular subgroups. C. Updated heatmap with sample annotations for MCP-Counter scores. D. Boxplots showing enrichment score distribution of the MSigDB epithelial-to-mesenchymal transition signature obtained from MSigDB across molecular subtypes. DIF_consensus (differentiated), IMR_consensus (immunoreactive), MES_consensus (mesenchymal) and PRO_consensus (proliferative)

Similar articles

References

    1. Prat A, Pineda E, Adamo B, Galván P, Fernández A, Gaba L, et al. Clinical implications of the intrinsic molecular subtypes of breast cancer. The Breast. 2015;1(24):S26-35. - PubMed
    1. Guinney J, Dienstmann R, Wang X, de Reyniès A, Schlicker A, Soneson C, et al. The consensus molecular subtypes of colorectal cancer. Nat Med. 2015;21(11):1350–6. - PMC - PubMed
    1. Bijlsma MF, Sadanandam A, Tan P, Vermeulen L. Molecular subtypes in cancers of the gastrointestinal tract. Nat Rev Gastroenterol Hepatol. 2017;14(6):333–42. - PubMed
    1. Collisson EA, Bailey P, Chang DK, Biankin AV. Molecular subtypes of pancreatic cancer. Nat Rev Gastroenterol Hepatol. 2019;16(4):207–20. - PubMed
    1. Chen GM, Kannan L, Geistlinger L, Kofia V, Safikhani Z, Gendoo DM, et al. Consensus on molecular subtypes of high-grade serous ovarian carcinoma. Clin Cancer Res Off J Am Assoc Cancer Res. 2018;24(20):5037–47. - PMC - PubMed

LinkOut - more resources