Introduction

1. Introduction • 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 18/33 genes have defects in B cell function and B cell differentiation. Conclusion • 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 developmental pathway Acknowledgement and references The authors gratefully acknowledge funding from the National Institutes of Health, award 5U56CA112973 (to S.K.P) and 5R01CA086065 (to I.L.W.). D.B was supported by a fellowship from the National Institutes of Health (5K01DK078318), J.S. was supported by a fellowship from the California Institute of Regenerative Medicine. [1]Sahoo D, Dill DL, Gentles AJ, Tibshirani R, Plevritis SK. (2008). Boolean implication networks derived from large scale, whole genome microarray datasets. Genome Biology (In Press). MiDReG: Mining developmentally regulated genes using Boolean implications Debashis Sahoo1, Jun Seita3, Deepta Bhattacharya3, Irving L. Weissman3, Sylvia K. Plevritis4, David L. Dill2 1Dept. of Electrical Engineering, 2Dept. of Computer Science, 3Institute for Stem Cell Biology and Regenerative Medicine, 4Department of Radiology, Stanford, CA A A X B X B MiDReG prediction algorithm Results Boolean implications • 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. qPCR result of 16 genes including the control genes: KIT and CD19. Test: Median1 < Median2 10/14 pass (FDR 14%) × × • CEL files are downloaded from GEO and normalized using RMA. • Each probeset is assigned a threshold. • Boolean implications are discovered using a pair of probesets [1]. • A Boolean implication is conserved if it holds between homologous genes from human and mouse. × ×