Differential expression analysis identifies a prognostically significant extracellular matrix-enriched gene signature in hyaluronan-positive clear cell renal cell carcinoma.

Hyaluronan (HA) accumulation in clear cell renal cell carcinoma (ccRCC) is associated with poor prognosis; however, its biology and role in tumorigenesis are unknown. RNA sequencing of 48 HA-positive and 48 HA-negative formalin-fixed paraffin-embedded (FFPE) samples was performed to identify differentially expressed genes (DEG). The DEGs were subjected to pathway and gene enrichment analyses. The Cancer Genome Atlas Kidney Renal Clear Cell Carcinoma (TCGA-KIRC) data and DEGs were used for the cluster analysis. In total, 129 DEGs were identified. HA-positive tumors exhibited enhanced expression of genes related to extracellular matrix (ECM) organization and ECM receptor interaction pathways. Gene set enrichment analysis showed that epithelial-mesenchymal transition-associated genes were highly enriched in the HA-positive phenotype. A protein-protein interaction network was constructed, and 17 hub genes were discovered. Heatmap analysis of TCGA-KIRC data identified two prognostic clusters corresponding to HA-positive and HA-negative phenotypes. These clusters were used to verify the expression levels and conduct survival analysis of the hub genes, 11 of which were linked to poor prognosis. These findings enhance our understanding of hyaluronan in ccRCC.

A systematic comparison of data- and knowledge-driven approaches to disease subtype discovery.

Typical clustering analysis for large-scale genomics data combines two unsupervised learning techniques: dimensionality reduction and clustering (DR-CL) methods. It has been demonstrated that transforming gene expression to pathway-level information can improve the robustness and interpretability of disease grouping results. This approach, referred to as biological knowledge-driven clustering (BK-CL) approach, is often neglected, due to a lack of tools enabling systematic comparisons with more established DR-based methods. Moreover, classic clustering metrics based on group separability tend to favor the DR-CL paradigm, which may increase the risk of identifying less actionable disease subtypes that have ambiguous biological and clinical explanations. Hence, there is a need for developing metrics that assess biological and clinical relevance. To facilitate the systematic analysis of BK-CL methods, we propose a computational protocol for quantitative analysis of clustering results derived from both DR-CL and BK-CL methods. Moreover, we propose a new BK-CL method that combines prior knowledge of disease relevant genes, network diffusion algorithms and gene set enrichment analysis to generate robust pathway-level information. Benchmarking studies were conducted to compare the grouping results from different DR-CL and BK-CL approaches with respect to standard clustering evaluation metrics, concordance with known subtypes, association with clinical outcomes and disease modules in co-expression networks of genes. No single approach dominated every metric, showing the importance multi-objective evaluation in clustering analysis. However, we demonstrated that, on gene expression data sets derived from TCGA samples, the BK-CL approach can find groupings that provide significant prognostic value in both breast and prostate cancers.

From insight network to open policy practice: practical experiences.

BACKGROUND: Evidence-informed decision-making and better use of scientific information in societal decisions has been an area of development for decades but is still topical. Decision support work can be viewed from the perspective of information collection, synthesis and flow between decision-makers, experts and stakeholders. Open policy practice is a coherent set of methods for such work. It has been developed and utilised mostly in Finnish and European contexts. METHODS: An overview of open policy practice is given, and theoretical and practical properties are evaluated based on properties of good policy support. The evaluation is based on information from several assessments and research projects developing and applying open policy practice and the authors' practical experiences. The methods are evaluated against their capability of producing quality of content, applicability and efficiency in policy support as well as how well they support close interaction among participants and understanding of each other's views. RESULTS: The evaluation revealed that methods and online tools work as expected, as demonstrated by the assessments and policy support processes conducted. The approach improves the availability of information and especially of relevant details. Experts are ambivalent about the acceptability of openness - it is an important scientific principle, but it goes against many current research and decision-making practices. However, co-creation and openness are megatrends that are changing science, decision-making and the society at large. Against many experts' fears, open participation has not caused problems in performing high-quality assessments. On the contrary, a key challenge is to motivate and help more experts, decision-makers and citizens to participate and share their views. Many methods within open policy practice have also been widely used in other contexts. CONCLUSIONS: Open policy practice proved to be a useful and coherent set of methods. It guided policy processes toward a more collaborative approach, whose purpose was wider understanding rather than winning a debate. There is potential for merging open policy practice with other open science and open decision process tools. Active facilitation, community building and improving the user-friendliness of the tools were identified as key solutions for improving the usability of the method in the future.