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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

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

[…] 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 […]


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

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

[…] 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 […]


Empirical pathway analysis, without permutation

PMCID: 3677738
PMID: 23428933
DOI: 10.1093/biostatistics/kxt004

[…] acknowledge correlation via permutation have vastly superior type i error control properties compared with methods that assume no correlation, and include gene set enrichment analysis (gsea) () and significance analysis of function and expression (safe) (). the globaltest of offers a non-resampling approach, in which the correlation structures are parametrically modeled., the safe procedure […]


Microarray analysis of peripheral blood lymphocytes from ALS patients and the SAFE detection of the KEGG ALS pathway

PMCID: 3219589
PMID: 22027401
DOI: 10.1186/1755-8794-4-74

[…] possibly relevant to als pathogenesis., differentially expressed genes were determined by limma (linear models for microarray) and sam (significance analysis of microarrays) analyses. the safe (significance analysis of function and expression) procedure was used to identify molecular pathway perturbations. proteasome inhibition assays were conducted on cultured peripheral blood mononuclear […]


Gene expression in nontumoral liver tissue and recurrence free survival in hepatitis C virus positive hepatocellular carcinoma

PMCID: 2856554
PMID: 20380719
DOI: 10.1186/1476-4598-9-74

[…] procedure., hcc: hepatocellular carcinoma; hcv: hepatitis c virus; fdr: false discovery rate; go: gene ontology; kegg: kyoto encyclopedia of genes and genomes; rfs: recurrence-free survival; safe: significance analysis of function and expression., the authors declare that they have no competing interests., mt participated in the design of the study, carried out the molecular and statistical […]


Statistical methods for gene set co expression analysis

PMCID: 2781749
PMID: 19689953
DOI: 10.1093/bioinformatics/btp502

[…] label permutations. details of this type of approach are given in subramanian et al. (), who proposed the gene set enrichment analysis (gsea), and barry et al. (), who proposed a framework for the significance analysis of function and expression (safe). the single study gsca approach is most similar to gsea (or safe) in that a single statistic is calculated for each gene set and calibrated via […]

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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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