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SAFE specifications


Unique identifier OMICS_19179
Alternative name Significance Analysis of Function and Expression
Software type Framework/Library, Package/Module
Interface Command line interface
Restrictions to use None
Operating system Unix/Linux, Mac OS, Windows
Programming languages R
License GNU General Public License version 2.0
Computer skills Advanced
Version 3.20.0
Stability Stable
AnnotationDbi, methods, Biobase, survival, foreach, GO.db, SparseM, GOstats, reactome.db, Rgraphviz, hgu133a.db, R(>=2.4.0), breastCancerUPP, PFAM.db, doRNG
Maintained Yes




No version available



  • person_outline Andrew Nobel
  • person_outline Fred Wright
  • person_outline William Barry

Publication for Significance Analysis of Function and Expression

SAFE citations


Pathway Based Genomics Prediction using Generalized Elastic Net

PLoS Comput Biol
PMCID: 4784899
PMID: 26960204
DOI: 10.1371/journal.pcbi.1004790

[…] ctors to obtain a set of discriminative scores—one for each feature / gene—and then using gene sets to elucidate pathways saturated with highly discriminative scores. Gene Set Enrichment Analysis [], Significance Analysis of Function and Expression [], and a method by Lee, et al. [] do exactly this to arrive at a single differential score for each gene set of interest. Rather than using curated se […]


Investigating the concordance of Gene Ontology terms reveals the intra and inter platform reproducibility of enrichment analysis

BMC Bioinformatics
PMCID: 3644270
PMID: 23627640
DOI: 10.1186/1471-2105-14-143

[…] improve the sensitivity and selectivity of GSEA []. Kim et al. used z-statistics and permutation test to identify significantly enriched gene sets []. In addition, other statistical methods including significance analysis of function and expression (SAFE) [], BayGO [], ProbCD [], EasyGO [], ProfCom [], GlobalANCOVA [], GOEAST [] and LRpath [] were also developed for enrichment analysis.Based on th […]


Chapter 8: Biological Knowledge Assembly and Interpretation

PLoS Comput Biol
PMCID: 3531281
PMID: 23300429
DOI: 10.1371/journal.pcbi.1002858

[…] level applications. For example, researchers developed genomic signatures to identify the activation status of oncogenic pathways and predict the sensitivity to individual chemotherapeutic drugs , . Significance Analysis of Function and Expression (SAFE) extends GSEA to cover multiclass, continuous and survival phenotypes. It also provides more options for the test statistic, including Wilcoxon […]


Statistical Test of Expression Pattern (STEPath): a new strategy to integrate gene expression data with genomic information in individual and meta analysis studies

BMC Bioinformatics
PMCID: 3094239
PMID: 21481242
DOI: 10.1186/1471-2105-12-92

[…] Kyoto Encyclopedia of Genes and Genomes; GEO: Gene Expression Omnibus; RMA: Robust Multiarray Averaging; PAM: Predicted Analysis of Microarray; PCOT2: Principal Coordinates and Hotelling's T2; SAFE: Significance Analysis of Function and Expression, LGMDs: Limb Girdle Muscular Dystrophies; CTRL: Control; MAPE, Meta-Analysis of Pathway Enrichment; MGS: Main Gene set Signature; ATP: Adenosine tripho […]


Pathway analysis reveals functional convergence of gene expression profiles in breast cancer

BMC Med Genomics
PMCID: 2447843
PMID: 18588682
DOI: 10.1186/1755-8794-1-28

[…] proaches have emerged in recent years to identify sets of biologically related genes that are deregulated as a group. Examples of gene-set analysis include the Gene Set Enrichment Analysis (GSEA) [], Significance Analysis of Function and Expression (SAFE) [], and the globaltest package [] These methods focus on groups of genes that share common biological functions such as cell cycle regulation; m […]


A Low Dose of Dietary Resveratrol Partially Mimics Caloric Restriction and Retards Aging Parameters in Mice

PLoS One
PMCID: 2386967
PMID: 18523577
DOI: 10.1371/journal.pone.0002264

[…] are postulated to impact aging (IGF-1, insulin, Sirt1, oxidative stress), we analyzed the gene expression data for functional categories that may be affected with age, CR or resveratrol. We used the significance analysis of function and expression (SAFE), a two-stage, permutation-based method that can be applied to various experimental designs, accounts for the unknown correlation among genes and […]


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SAFE institution(s)
Department of Cardiology, Children’s Hospital Boston, Boston, MA, USA; Informatics Program, Children’s Hospital Boston, Boston, MA, USA; Harvard-Partners Center for Genetics and Genomics, Boston, MA, USA
SAFE funding source(s)
Supported in part by NIH grants P30 HD003110, T32 ES07018 and P30 ES10126.

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