Generalized random set framework for functional enrichment analysis using primary genomics datasets.
BACKGROUND
Functional enrichment analysis using primary genomics datasets is an emerging approach to complement established methods for functional enrichment based on predefined lists of functionally related genes. Currently used methods depend on creating lists of 'significant' and 'non-significant' genes based on ad hoc significance cutoffs. This can lead to loss of statistical power and can introduce biases affecting the interpretation of experimental results.


RESULTS
We developed and validated a new statistical framework, generalized random set (GRS) analysis, for comparing the genomic signatures in two datasets without the need for gene categorization. In our tests, GRS produced correct measures of statistical significance, and it showed dramatic improvement in the statistical power over other methods currently used in this setting. We also developed a procedure for identifying genes driving the concordance of the genomics profiles and demonstrated a dramatic improvement in functional coherence of genes identified in such analysis.


BACKGROUND
GRS can be downloaded as part of the R package CLEAN from http://ClusterAnalysis.org/. An online implementation is available at http://GenomicsPortals.org/.
Freudenberg
Johannes M
JM
Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
Sivaganesan
Siva
S
Phatak
Mukta
M
Shinde
Kaustubh
K
Medvedovic
Mario
M
D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics; D003627:Data Interpretation, Statistical; D004032:Diet; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling / Q000379:methods*; D023281:Genomics / Q000379:methods*; D006801:Humans; D051381:Rats