iSubGen generates integrative disease subtypes by pairwise similarity assessment.

There are myriad types of biomedical data-molecular, clinical images, and others. When a group of patients with the same underlying disease exhibits similarities across multiple types of data, this is called a subtype. Existing subtyping approaches struggle to handle diverse data types with missing information.

A polygenic two-hit hypothesis for prostate cancer.

Prostate cancer is one of the most heritable cancers. Hundreds of germline polymorphisms have been linked to prostate cancer diagnosis and prognosis. Polygenic risk scores can predict genetic risk of a prostate cancer diagnosis.

Ocean Literacy and Surfing: Understanding How Interactions in Coastal Ecosystems Inform Blue Space User's Awareness of the Ocean.

Intergovernmental policy is targeting public ocean literacy to help achieve the societal changes needed to reach a sustainable ocean agenda within a 10-year timeframe. To create a culture of care for the ocean, which is under threat from Anthropocentric pressures, informed ocean citizens are central to upholding meaningful actions and best practices. This research focuses on recreational ocean users, specifically surfers and how their blue space activities may inform understanding of ocean processes and human-ocean interconnections.

Systematic Assessment of Tumor Purity and Its Clinical Implications.

Purpose: The tumor microenvironment is complex, comprising heterogeneous cellular populations. As molecular profiles are frequently generated using bulk tissue sections, they represent an admixture of multiple cell types (including immune, stromal, and cancer cells) interacting with each other. Therefore, these molecular profiles are confounded by signals emanating from many cell types.

Integrative pathway enrichment analysis of multivariate omics data.

Multi-omics datasets represent distinct aspects of the central dogma of molecular biology. Such high-dimensional molecular profiles pose challenges to data interpretation and hypothesis generation. ActivePathways is an integrative method that discovers significantly enriched pathways across multiple datasets using statistical data fusion, rationalizes contributing evidence and highlights associated genes.

Landscape of transcriptomic interactions between breast cancer and its microenvironment.

Solid tumours comprise mixtures of tumour cells (TCs) and tumour-adjacent cells (TACs), and the intricate interconnections between these diverse populations shape the tumour's microenvironment. Despite this complexity, clinical genomic profiling is typically performed from bulk samples, without distinguishing TCs from TACs. To better understand TC-TAC interactions, we computationally distinguish their transcriptomes in 1780 primary breast tumours.

The Proteogenomic Landscape of Curable Prostate Cancer.

DNA sequencing has identified recurrent mutations that drive the aggressiveness of prostate cancers. Surprisingly, the influence of genomic, epigenomic, and transcriptomic dysregulation on the tumor proteome remains poorly understood. We profiled the genomes, epigenomes, transcriptomes, and proteomes of 76 localized, intermediate-risk prostate cancers.

BPG: Seamless, automated and interactive visualization of scientific data.

Background: We introduce BPG, a framework for generating publication-quality, highly-customizable plots in the R statistical environment.

Results: This open-source package includes multiple methods of displaying high-dimensional datasets and facilitates generation of complex multi-panel figures, making it suitable for complex datasets. A web-based interactive tool allows online figure customization, from which R code can be downloaded for integration with computational pipelines.

Prediction of early breast cancer patient survival using ensembles of hypoxia signatures.

Background: Biomarkers are a key component of precision medicine. However, full clinical integration of biomarkers has been met with challenges, partly attributed to analytical difficulties. It has been shown that biomarker reproducibility is susceptible to data preprocessing approaches.

The Evolutionary Landscape of Localized Prostate Cancers Drives Clinical Aggression.

The majority of newly diagnosed prostate cancers are slow growing, with a long natural life history. Yet a subset can metastasize with lethal consequences. We reconstructed the phylogenies of 293 localized prostate tumors linked to clinical outcome data.

Mapping genomic and transcriptomic alterations spatially in epithelial cells adjacent to human breast carcinoma.

Almost all genomic studies of breast cancer have focused on well-established tumours because it is technically challenging to study the earliest mutational events occurring in human breast epithelial cells. To address this we created a unique dataset of epithelial samples ductoscopically obtained from ducts leading to breast carcinomas and matched samples from ducts on the opposite side of the nipple. Here, we demonstrate that perturbations in mRNA abundance, with increasing proximity to tumour, cannot be explained by copy number aberrations.

VennDiagramWeb: a web application for the generation of highly customizable Venn and Euler diagrams.

Background: Visualization of data generated by high-throughput, high-dimensionality experiments is rapidly becoming a rate-limiting step in computational biology. There is an ongoing need to quickly develop high-quality visualizations that can be easily customized or incorporated into automated pipelines. This often requires an interface for manual plot modification, rapid cycles of tweaking visualization parameters, and the generation of graphics code.

Ensemble analyses improve signatures of tumour hypoxia and reveal inter-platform differences.

Background: The reproducibility of transcriptomic biomarkers across datasets remains poor, limiting clinical application. We and others have suggested that this is in-part caused by differential error-structure between datasets, and their incomplete removal by pre-processing algorithms.

Methods: To test this hypothesis, we systematically assessed the effects of pre-processing on biomarker classification using 24 different pre-processing methods and 15 distinct signatures of tumour hypoxia in 10 datasets (2,143 patients).

Validating reference genes within a mouse model system of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxicity.

Background: Quantitative real-time PCR (qPCR) is the "gold-standard" technique for measuring mRNA abundances. To correctly compare samples and generate biologically valid results, qPCR data usually require comprehensive normalization to account for sample content variation between reactions. The most common normalization approaches use one or more endogenous controls (reference or house-keeping genes) to adjust the measured levels of experimental genes appropriately.