Bioinformatics Seminars

Bioinformatics Seminar

Time: 10:45am Tuesdays.
Level 7 Seminar Room 2, WEHI1

12 June 2018

FRY: A fast and accurate approach to identifying biological pathways

Goknur Giner
WEHI Bioinformatics

Gene set tests help researchers identify significantly enriched biological pathways in the concept of differential expression. A plethora of methods in the literature differs in many aspects. Most gene set tests permute gene labels to evaluate p-values. Such calculation, however, assumes independence of genes and can inflate the false discovery rate even for small correlations. To keep the correlation structure unchanged we can permute the samples instead of genes, yet this method can only be used with simple experimental designs with a few replicates. To overcome aforementioned limitations, one of the most flexible, powerful and robust gene set tests is ROAST in limma package. ROAST uses residual space rotation as a sort of continuous version of sample permutation. Like permutation tests, it protects against false positives caused by correlations between genes in the set. Unlike permutation tests, it is applicable to all designs.

This talk will cover the different statistical approaches to popular gene set analysis pipelines and present the gene set test FRY in detail. FRY is a very fast approximation to the complete ROAST method. FRY preserves most of the advantages of ROAST but also provides high-resolution exact p-values very quickly. In particular, it is able to distinguish the most significant sets in large collections and to yield statistically significant results after adjustment for multiple testing.

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