Random forests-based differential analysis of gene sets for gene expression data

Gene ◽  
2013 ◽  
Vol 518 (1) ◽  
pp. 179-186 ◽  
Author(s):  
Huey-Miin Hsueh ◽  
Da-Wei Zhou ◽  
Chen-An Tsai
2020 ◽  
Vol 15 ◽  
Author(s):  
Chen-An Tsai ◽  
James J. Chen

Background: Gene set enrichment analyses (GSEA) provide a useful and powerful approach to identify differentially expressed gene sets with prior biological knowledge. Several GSEA algorithms have been proposed to perform enrichment analyses on groups of genes. However, many of these algorithms have focused on identification of differentially expressed gene sets in a given phenotype. Objective: In this paper, we propose a gene set analytic framework, Gene Set Correlation Analysis (GSCoA), that simultaneously measures within and between gene sets variation to identify sets of genes enriched for differential expression and highly co-related pathways. Methods: We apply co-inertia analysis to the comparisons of cross-gene sets in gene expression data to measure the costructure of expression profiles in pairs of gene sets. Co-inertia analysis (CIA) is one multivariate method to identify trends or co-relationships in multiple datasets, which contain the same samples. The objective of CIA is to seek ordinations (dimension reduction diagrams) of two gene sets such that the square covariance between the projections of the gene sets on successive axes is maximized. Simulation studies illustrate that CIA offers superior performance in identifying corelationships between gene sets in all simulation settings when compared to correlation-based gene set methods. Result and Conclusion: We also combine between-gene set CIA and GSEA to discover the relationships between gene sets significantly associated with phenotypes. In addition, we provide a graphical technique for visualizing and simultaneously exploring the associations of between and within gene sets and their interaction and network. We then demonstrate integration of within and between gene sets variation using CIA and GSEA, applied to the p53 gene expression data using the c2 curated gene sets. Ultimately, the GSCoA approach provides an attractive tool for identification and visualization of novel associations between pairs of gene sets by integrating co-relationships between gene sets into gene set analysis.


2008 ◽  
Vol 6 ◽  
pp. CIN.S606 ◽  
Author(s):  
Attila Frigyesi ◽  
Mattias Höglund

Non-negative matrix factorization (NMF) is a relatively new approach to analyze gene expression data that models data by additive combinations of non-negative basis vectors (metagenes). The non-negativity constraint makes sense biologically as genes may either be expressed or not, but never show negative expression. We applied NMF to five different microarray data sets. We estimated the appropriate number metagens by comparing the residual error of NMF reconstruction of data to that of NMF reconstruction of permutated data, thus finding when a given solution contained more information than noise. This analysis also revealed that NMF could not factorize one of the data sets in a meaningful way. We used GO categories and pre defined gene sets to evaluate the biological significance of the obtained metagenes. By analyses of metagenes specific for the same GO-categories we could show that individual metagenes activated different aspects of the same biological processes. Several of the obtained metagenes correlated with tumor subtypes and tumors with characteristic chromosomal translocations, indicating that metagenes may correspond to specific disease entities. Hence, NMF extracts biological relevant structures of microarray expression data and may thus contribute to a deeper understanding of tumor behavior.


2013 ◽  
Vol 6 (1) ◽  
Author(s):  
Kristina M Hettne ◽  
André Boorsma ◽  
Dorien A M van Dartel ◽  
Jelle J Goeman ◽  
Esther de Jong ◽  
...  

2004 ◽  
Vol 3 (1) ◽  
pp. 1-29 ◽  
Author(s):  
Jörg Rahnenführer ◽  
Francisco S Domingues ◽  
Jochen Maydt ◽  
Thomas Lengauer

We present a statistical approach to scoring changes in activity of metabolic pathways from gene expression data. The method identifies the biologically relevant pathways with corresponding statistical significance. Based on gene expression data alone, only local structures of genetic networks can be recovered. Instead of inferring such a network, we propose a hypothesis-based approach. We use given knowledge about biological networks to improve sensitivity and interpretability of findings from microarray experiments.Recently introduced methods test if members of predefined gene sets are enriched in a list of top-ranked genes in a microarray study. We improve this approach by defining scores that depend on all members of the gene set and that also take pairwise co-regulation of these genes into account. We calculate the significance of co-regulation of gene sets with a nonparametric permutation test. On two data sets the method is validated and its biological relevance is discussed. It turns out that useful measures for co-regulation of genes in a pathway can be identified adaptively.We refine our method in two aspects specific to pathways. First, to overcome the ambiguity of enzyme-to-gene mappings for a fixed pathway, we introduce algorithms for selecting the best fitting gene for a specific enzyme in a specific condition. In selected cases, functional assignment of genes to pathways is feasible. Second, the sensitivity of detecting relevant pathways is improved by integrating information about pathway topology. The distance of two enzymes is measured by the number of reactions needed to connect them, and enzyme pairs with a smaller distance receive a higher weight in the score calculation.


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