Dataset Information

Testing Proximity of Genomic Regions to Transcription Start Sites and Enhancers Complements Gene Set Enrichment Testing.

ABSTRACT: 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.

SUBMITTER: Lee C

PROVIDER: S-EPMC7069355 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Testing Proximity of Genomic Regions to Transcription Start Sites and Enhancers Complements Gene Set Enrichment Testing.

Lee Christopher C Wang Kai K Qin Tingting T Sartor Maureen A MA

Frontiers in genetics 20200306

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 an ...[more]

PMID: 32211031

Similar Datasets

Project description:BackgroundGene set enrichment testing has helped bridge the gap from an individual gene to a systems biology interpretation of microarray data. Although gene sets are defined a priori based on biological knowledge, current methods for gene set enrichment testing treat all genes equal. It is well-known that some genes, such as those responsible for housekeeping functions, appear in many pathways, whereas other genes are more specialized and play a unique role in a single pathway. Drawing inspiration from the field of information retrieval, we have developed and present here an approach to incorporate gene appearance frequency (in KEGG pathways) into two current methods, Gene Set Enrichment Analysis (GSEA) and logistic regression-based LRpath framework, to generate more reproducible and biologically meaningful results.ResultsTwo breast cancer microarray datasets were analyzed to identify gene sets differentially expressed between histological grade 1 and 3 breast cancer. The correlation of Normalized Enrichment Scores (NES) between gene sets, generated by the original GSEA and GSEA with the appearance frequency of genes incorporated (GSEA-AF), was compared. GSEA-AF resulted in higher correlation between experiments and more overlapping top gene sets. Several cancer related gene sets achieved higher NES in GSEA-AF as well. The same datasets were also analyzed by LRpath and LRpath with the appearance frequency of genes incorporated (LRpath-AF). Two well-studied lung cancer datasets were also analyzed in the same manner to demonstrate the validity of the method, and similar results were obtained.ConclusionsWe introduce an alternative way to integrate KEGG PATHWAY information into gene set enrichment testing. The performance of GSEA and LRpath can be enhanced with the integration of appearance frequency of genes. We conclude that, generally, gene set analysis methods with the integration of information from KEGG PATHWAY performs better both statistically and biologically.

Dataset Information

Testing Proximity of Genomic Regions to Transcription Start Sites and Enhancers Complements Gene Set Enrichment Testing.

Publications

Testing Proximity of Genomic Regions to Transcription Start Sites and Enhancers Complements Gene Set Enrichment Testing.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets