ArticleProceedings of the National Academy of Sciences of the United States of America2005
Effects of threshold choice on biological conclusions reached during analysis of gene expression by DNA microarrays.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed.
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- Cross-study homogeneity of psoriasis gene expression in skin across a large expression range.PloS one · 2013Trial
- Skeletal muscle gene expression in response to resistance exercise: sex specific regulation.BMC genomics · 2010Trial
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- Analytical Considerations of Large-Scale Aptamer-Based Datasets for Translational Applications.Cancers · 2022Review
- Computational identification of protein complexes from network interactions: Present state, challenges, and the way forward.Computational and structural biotechnology journal · 2022Review
- The Role of Tumor Stem Cell Exosomes in Cancer Invasion and Metastasis.Frontiers in oncology · 2022Review
- Estimates of gene ensemble noise highlight critical pathways and predict disease severity in H1N1, COVID-19 and mortality in sepsis patients.Scientific reports · 2021Article
- TMEA: A Thermodynamically Motivated Framework for Functional Characterization of Biological Responses to System Acclimation.Entropy (Basel, Switzerland) · 2020Article
- Gene Set Analysis: Challenges, Opportunities, and Future Research.Frontiers in genetics · 2020Review
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- A Powerful Test for SNP Effects on Multivariate Binary Outcomes using Kernel Machine Regression.Statistics in biosciences · 2018Article
- Robust method for identification of prognostic gene signatures from gene expression profiles.Scientific reports · 2017Article
- Avoiding the pitfalls of gene set enrichment analysis with SetRank.BMC bioinformatics · 2017Article
- A novel pathway analysis approach based on the unexplained disregulation of genes.Proceedings of the IEEE. Institute of Electrical and Electronics Engineers · 2017Article
- Identifying biologically relevant putative mechanisms in a given phenotype comparison.PloS one · 2017Article
- Computational Systems Biology of Psoriasis: Are We Ready for the Age of Omics and Systems Biomarkers?Omics : a journal of integrative biology · 2015Article
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3 authors.
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No grant is acknowledged in the PubMed record.
Abstract
Global analysis of gene expression by using DNA microarrays is employed increasingly to search for differences in biological properties between normal and diseased tissue. In such studies, expression that deviates from defined thresholds commonly is used for creating genetic signatures that characterize disease vs. normality. Although it is axiomatic that the threshold parameters applied to microarray analysis will alter the contents of such genetic signatures, the extent to which threshold choice can affect the fundamental conclusions made from microarray-based studies has not been elucidated. We used GABRIEL (Genetic Analysis By Rules Incorporating Expert Logic), a platform of knowledge-based algorithms for the global analysis of gene expression, together with conventional statistical approaches, to examine the sensitivity of conclusions to threshold choice in recently published microarray-based studies. An analysis of the effects of threshold decisions in one of these studies [Ramaswamy, S., Ross, K. N., Lander, E. S. & Golub, T. R. (2003) Nat. Genet. 33, 49-54], which arrived at the important conclusion that the metastatic potential of primary tumors is encoded by the bulk of cells in the tumor, is the focus of this article. We discovered that support for this conclusion highly depends on the threshold used to create gene expression signatures. We also found that threshold choice dramatically affected the gene function categories represented nonrandomly in signatures. Our results suggest that the robustness of biological conclusions made by using microarray analysis should be routinely assessed by examining the validity of the conclusions by using a range of threshold parameters.
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