Impact of outdated gene annotations on pathway enrichment analysis

  title={Impact of outdated gene annotations on pathway enrichment analysis},
  author={Lina Wadi and Mona Meyer and Joel Weiser and Lincoln D. Stein and J{\"u}ri Reimand},
  journal={Nature Methods},
To the Editor: Pathway enrichment analysis is a common technique for interpreting gene lists derived from high-throughput experiments1. Its success depends on the quality of gene annotations. We analyzed the evolution of pathway knowledge and annotations over the past seven years and found that the use of outdated resources has strongly affected practical genomic analysis and recent literature: 67% of ~3,900 publications we surveyed in 2015 referenced outdated software that captured only 26% of… 

Monitoring changes in the Gene Ontology and their impact on genomic data analysis

GOTrack gives users access to gene- and term-level information on annotations for nine model organisms as well as an interactive tool that measures the stability of enrichment results over time for user-provided “hit lists” of genes.

Using BioPAX-Parser (BiP) to enrich lists of genes or proteins with pathway data

BiP identified some well-known pathways related to the investigated cancer type, validated by the available literature, and shows that BiP provides more stable enrichment results than other tools.

WocEA: The visualization of functional enrichment results in word clouds.

Pathway enrichment analysis approach based on topological structure and updated annotation of pathway

A novel topology‐based pathway enrichment analysis (TPEA) method, which integrated topological properties and global upstream/downstream positions of genes in pathways, was proposed, which was more stable than that of the other tools in analyzing different data sets of the same cancer.

Nine quick tips for pathway enrichment analysis

Nine quick tips to avoid common mistakes and to out a complete, sound, thorough PEA, which can produce relevant and robust results are proposed.

Evaluating the predictive accuracy of curated biological pathways in a public knowledgebase

This study highlights the potential of pathway databases such as Reactome in modeling genetic perturbations, promoting standardization of experimental pathway activity readout and supporting hypothesis-driven research by revealing relationships between pathway inputs and outputs that have not yet been directly experimentally tested.

Comprehensive functional analysis of large lists of genes and proteins.

Pathway enrichment analysis and visualization of omics data using g:Profiler, GSEA, Cytoscape and EnrichmentMap

This protocol describes pathway enrichment analysis of gene lists from RNA-seq and other genomics experiments using g:Profiler, GSEA, Cytoscape and EnrichmentMap software, and describes innovative visualization techniques.

Pathway and Network Analysis of Differentially Expressed Genes in Transcriptomes.

This chapter demonstrates several recent computational workflows, including gene set enrichment and topology-based methods, for analysis of the DE pathways and gene networks from transcriptome-wide sequencing data.

Interpretation of biological experiments changes with evolution of the Gene Ontology and its annotations

It is suggested that GO evolution may have affected the interpretation and possibly reproducibility of experiments over time and researchers must exercise caution when interpreting GO enrichment analyses and should reexamine previous analyses with the most recent GO version.



Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources

By following this protocol, investigators are able to gain an in-depth understanding of the biological themes in lists of genes that are enriched in genome-scale studies.

g:Profiler—a web-based toolset for functional profiling of gene lists from large-scale experiments

G:Profiler has a simple, user-friendly web interface with powerful visualisation for capturing Gene Ontology, pathway, or transcription factor binding site enrichments down to individual gene levels.

PANTHER in 2013: modeling the evolution of gene function, and other gene attributes, in the context of phylogenetic trees

The current PANTHER process as a whole, as well as the website tools for analysis of user-uploaded data are described, which include stable database identifiers for inferred ancestral genes, which are used to associate inferred gene attributes with particular genes in the common ancestral genomes of extant species.

Gene Ontology: tool for the unification of biology

The goal of the Gene Ontology Consortium is to produce a dynamic, controlled vocabulary that can be applied to all eukaryotes even as knowledge of gene and protein roles in cells is accumulating and changing.

Pathway and network analysis of cancer genomes

An overview of pathway and network analysis methods that group genes and illuminate the processes involved in tumor biology are provided and where they guide mechanistic and translational investigations are shown.

Comprehensive identification of mutational cancer driver genes across 12 tumor types

The combination of complementary methods allows identifying a comprehensive and reliable list of cancer driver genes and the methodology presented here open new avenues to better understand the mechanisms of tumorigenesis.

Targeting Notch, Hedgehog, and Wnt pathways in cancer stem cells: clinical update

An update on the latest advances in the clinical development of treatment strategies targeting cancer stem cells with rational combinations of agents to inhibit possible compensatory escape mechanisms is provided.

Brain Tumor Initiating Cells Adapt to Restricted Nutrition through Preferential Glucose Uptake

It is reported that nutrient restriction contributes to tumor progression by enriching for brain tumor initiating cells ( BTICs) owing to preferential BTIC survival and to adaptation of non-BTICs through acquisition of BTIC features.

N at ur e A m er ic a, In c. A ll rig ht s re se rv ed . np g © 2 01 6 N at ur e A m er

  • Nat. Rev. Clin. Oncol
  • 2015