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  • Publication
    GOexpress: an R/Bioconductor package for the identification and visualisation of robust gene ontology signatures through supervised learning of gene expression data
    Background: Identification of gene expression profiles that differentiate experimental groups is critical for discovery and analysis of key molecular pathways and also for selection of robust diagnostic or prognostic biomarkers. While integration of differential expression statistics has been used to refine gene set enrichment analyses, such approaches are typically limited to single gene lists resulting from simple two-group comparisons or time-series analyses. In contrast, functional class scoring and machine learning approaches provide powerful alternative methods to leverage molecular measurements for pathway analyses, and to compare continuous and multi-level categorical factors. Results: We introduce GOexpress, a software package for scoring and summarising the capacity of gene ontology features to simultaneously classify samples from multiple experimental groups. GOexpress integrates normalised gene expression data (e.g., from microarray and RNA-seq experiments) and phenotypic information of individual samples with gene ontology annotations to derive a ranking of genes and gene ontology terms using a supervised learning approach. The default random forest algorithm allows interactions between all experimental factors, and competitive scoring of expressed genes to evaluate their relative importance in classifying predefined groups of samples. Conclusions: GOexpress enables rapid identification and visualisation of ontology-related gene panels that robustly classify groups of samples and supports both categorical (e.g., infection status, treatment) and continuous (e.g., time-series, drug concentrations) experimental factors. The use of standard Bioconductor extension packages and publicly available gene ontology annotations facilitates straightforward integration of GOexpress within existing computational biology pipelines.
      741Scopus© Citations 21
  • Publication
    Bayesian methods for proteomic biomarker development
    The advent of liquid chromatography mass spectrometry has seen a dramatic increase in the amount of data derived from proteomic biomarker discovery. These experiments have seemingly identified many potential candidate biomarkers. Frustratingly, very few of these candidates have been evaluated and validated sufficiently such that that they have progressed to the stage of routine clinical use. It is becoming apparent that the statistical methods used to evaluate the performance of new candidate biomarkers are a major limitation in their development. Bayesian methods offer some advantages over traditional statistical and machine learning methods. In particular they can incorporate external information into current experiments so as to guide biomarker selection. Further, they can be more robustto over-fitting than other approaches, especially when the number of samples used for discovery is relatively small. In this review we provide an introduction to Bayesian inference and demonstrate some of the advantages of using a Bayesian framework. We summarize how Bayesian methods have been used previously in proteomics and other areas of bioinformatics. Finally, we describe some popular and emerging Bayesian models from the statistical literature and provide a worked tutorial including code snippets to show how these methods may be applied for the evaluation of proteomic biomarkers.
      535Scopus© Citations 15