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Testing Proximity of Genomic Regions to Transcription Start Sites and Enhancers Complements Gene Set Enrichment Testing
Large sets of genomic regions are generated by the initial analysis of various genome-wide sequencing data, such as ChIP-seq and ATAC-seq experiments. Gene set enrichment (GSE) methods are commonly employed to determine the pathways associated with them. Given the pathways and other gene sets (e.g.,...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7069355/ https://www.ncbi.nlm.nih.gov/pubmed/32211031 http://dx.doi.org/10.3389/fgene.2020.00199 |
Sumario: | Large sets of genomic regions are generated by the initial analysis of various genome-wide sequencing data, such as ChIP-seq and ATAC-seq experiments. Gene set enrichment (GSE) methods are commonly employed to determine the pathways associated with them. Given the pathways and other gene sets (e.g., GO terms) of significance, it is of great interest to know the extent to which each is driven by binding near transcription start sites (TSS) or near enhancers. Currently, no tool performs such an analysis. Here, we present a method that addresses this question to complement GSE methods for genomic regions. Specifically, the new method tests whether the genomic regions in a gene set are significantly closer to a TSS (or to an enhancer) than expected by chance given the total list of genomic regions, using a non-parametric test. Combining the results from a GSE test with our novel method provides additional information regarding the mode of regulation of each pathway, and additional evidence that the pathway is truly enriched. We illustrate our new method with a large set of ENCODE ChIP-seq data, using the chipenrich Bioconductor package. The results show that our method is a powerful complementary approach to help researchers interpret large sets of genomic regions. |
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