Turning straw into gold : building robustness into gene signature inference

• Main Authors: Goh, Wilson Wen Bin, Wong, Limsoon
• Other Authors: School of Biological Sciences
• Format: Article
• Language: English
• Published: 2020
• Subjects: Science::Biological sciences; Good Analytical Practices; Meta-analysis
• Online Access: https://hdl.handle.net/10356/137542
• Institution: Nanyang Technological University

Reproducible and generalizable gene signatures are essential for clinical deployment, but are hard to come by. The primary issue is insufficient mitigation of confounders: ensuring that hypotheses are appropriate, test statistics and null distributions are appropriate, and so on. To further improve robustness, additional good analytical practices (GAPs) are needed, namely: leveraging existing data and knowledge; careful and systematic evaluation of gene sets, even if they overlap with known sources of confounding; and rigorous testing of inferred signatures against as many published data sets as possible. Here, using a re-examination of a breast cancer data set and 48 published signatures, we illustrate the value of adopting these GAPs.