iBBiG: iterative binary bi-clustering of gene sets.
BACKGROUND
Meta-analysis of genomics data seeks to identify genes associated with a biological phenotype across multiple datasets; however, merging data from different platforms by their features (genes) is challenging. Meta-analysis using functionally or biologically characterized gene sets simplifies data integration is biologically intuitive and is seen as having great potential, but is an emerging field with few established statistical methods.


RESULTS
We transform gene expression profiles into binary gene set profiles by discretizing results of gene set enrichment analyses and apply a new iterative bi-clustering algorithm (iBBiG) to identify groups of gene sets that are coordinately associated with groups of phenotypes across multiple studies. iBBiG is optimized for meta-analysis of large numbers of diverse genomics data that may have unmatched samples. It does not require prior knowledge of the number or size of clusters. When applied to simulated data, it outperforms commonly used clustering methods, discovers overlapping clusters of diverse sizes and is robust in the presence of noise. We apply it to meta-analysis of breast cancer studies, where iBBiG extracted novel gene set-phenotype association that predicted tumor metastases within tumor subtypes.


BACKGROUND
Implemented in the Bioconductor package iBBiG  CONTACT:  aedin@jimmy.harvard.edu.
Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
Daniel
D
Gusenleitner
Eleanor A
EA
Howe
Stefan
S
Bentink
John
J
Quackenbush
Aedín C
AC
Culhane
D000465:Algorithms; D001943:Breast Neoplasms / Q000235:genetics; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods*; D003198:Computer Simulation; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D023281:Genomics / Q000379:methods*; D006801:Humans; D010641:Phenotype