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Table 1 Benchmarking studies of GSA methods

From: Popularity and performance of bioinformatics software: the case of gene set analysis

References

Scope

Size

Criteria

Best performing methods

Naeem et al. [21]

ORA and FCS methods

14 methods

Method’s AUC (evaluated by predicting targets of TFs and miRNAs)

ANOVA, Z-SCORE, and Wilcoxon’s rank sum (WRS)

Tarca et al. [22]

ORA, FCS, and SS methods

16 methods

Prioritization, Sensitivity, and FPR

GLOBALTEST and PLAGE (sensitivity), PADOG and ORA (prioritization), and CAMERA (FPR). Author’s general recommendation: PLAGE, GLOBALTEST, and PADOG

Bayerlova et al. [23]

ORA, FCS, and PT methods

7 methods

Sensitivity and prioritization (for benchmark), and Sensitivity, specificity, and accuracy (for simulations of pathway overlap)

For benchmark: CePaGSA (sensitivity) and PathNet (prioritization). For simulation -original pathways: CePAGSA (sensitivity), WRS (specificity), and WRS (accuracy). For simulation -non-overlapping pathways: KS (sensitivity), and SPIA, CePaORA, CePaGSA, and PathNet (specificity and accuracy)

Jaakkola et al. [24]

ORA, FCS, and PT methods

5 methods

Consistency of significant pathways between datasets, and Sensitivity

SPIA and CePaORA (consistency), and SPIA, CePaORA, and NetGSA (sensitivity). Author’s general recommendation: SPIA

De Meyer et al. [25]

ORA, FCS, and NI methods

4 methods

Prioritization, Sensitivity, and Specificity

PADOG (specificity) and BinoX (sensitivity)

Lim et al. [26]

SS/Pathway-activity methods

13 methods

Classification performance, preservation of data structure, robustness to noise, and reproducibility between pathway databases

ESEA, Pathifier, SAS, and PADOG (classification tasks), Pathifier and PLAGE (data structure), ssGSEA (robustness), and individPath, Pathifier, and SAS (reproducibility). Author’s general recommendation: Pathifier, SAS, and individPath

Nguyen et al. [27]

ORA, FCS, and PT methods

13 methods

In order of importance: Number of biased pathways, Prioritization, Method’s AUC, and sensitivity (evaluated using both disease target pathways and KO data)

GSEA (bias), PADOG (prioritization), ROntoTools (AUC), and CePaGSA (p-values). Author’s general recommendation: ROntoTools

Ma et al. [28]

FCS, PT, and NI methods

9 methods

Ranking of empirical powers

DEGraph, followed by PathNet and NetGSA

Zyla et al. [29]

ORA, FCS, and SS methods

9 methods

Sensitivity, FPR, prioritization, computational time, and reproducibility

PLAGE (sensitivity), ORA and PADOG (specificity/FPR), PADOG (prioritization), and CERNO (reproducibility)

Geistlinger et al. [30]

ORA, FCS, and SS methods

10 methods

Sensitivity, computational time, and phenotype relevance score

Author’s general recommendation: ROAST and GSVA (for self-contained hypothesis). ORA and PADOG (for competitive hypothesis)

  1. Ten benchmark studies from 2012 to 2020, showing a plurality of scopes, sizes, and method recommendations. Details on each study can be found in Additional file 2
  2. ORA, over-representation analysis; FCS, functional class scoring; PT, pathway topology-based; SS, single-sample; NI, network interaction