MiDReG: Mining developmentally regulated genes using Boolean implications
Debashis Sahoo1, Jun Seita3, Deepta Bhattacharya3, Irving L. Weissman 3, Sylvia K. Plevritis 4, David L. Dill2
1Dept. of Electrical Engineering, 2Dept. of Computer Science,
3Institute for Stem Cell Biology and Regenerative Medicine, 4Department of Radiology, Stanford, CA
Introduction MiDReG prediction algorithm
It is hard to discover genes that are developmentally regulated
using traditional approaches e.g. Genetics and Biochemistry.
We present a new algorithm called “MiDReG” to discover
developmentally regulated genes using large repositories of
publicly available microarray data.
Our method uses conserved Boolean implications mined from
a diverse collections of microarrays across different species.
MiDReG predicted 62 genes on B cell development.
The results were validated using qPCR on 13 different stages of
B cell development.
33/62 genes have knockout phenotypes in the literature and B X B
18/33 genes have defects in B cell function and B cell
The MiDReG algorithm predicted 52 B cell precursor genes
using KIT, CD19 and AICDA.
qPCR results for Pax5, Syk, Il21r, SpiB and Fcrlm1 are consistent
with the prediction.
MiDReG uses Boolean implications to predict genes related to
B cell development
Knockouts of the predicted genes have defects in B cell
function and differentiation
MiDReG can be directly applied to other less well-characterized
qPCR result of 16 genes
including the control
genes: KIT and CD19. Acknowledgement and references
CEL files are downloaded from GEO and normalized using
RMA. Test:Median1 <Median2
× × The authors gratefully acknowledge funding from the National Institutes of Health, award 5U56CA112973 (to
Each probeset is assigned a threshold. S.K.P) and 5R01CA086065 (to I.L.W.). D.B was supported by a fellowship from the National Institutes of
Boolean implications are discovered using a pair of probesets
10/14 pass (FDR 14%)
× × Health (5K01DK078318), J.S. was supported by a fellowship from the California Institute of Regenerative
. Sahoo D, Dill DL, Gentles AJ, Tibshirani R, Plevritis SK. (2008). Boolean implication
A Boolean implication is conserved if it holds between networks derived from large scale, whole genome microarray datasets. Genome Biology
homologous genes from human and mouse.