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MiDReG uses two gene expression-based seed conditions that mark the initial and the terminal stages of a given differentiation pathway and combines the statistically inferred Boolean implications from these seed conditions to identify the relevant genes. The method was validated by applying it to B-cell development. The algorithm predicted 62 genes that are expressed after the KIT+ progenitor cell stage and remain expressed through CD19+ and AICDA+ germinal center B cells. qRT-PCR of 14 of these genes on sorted B-cell progenitors confirmed that the expression of 10 genes is indeed stably established during B-cell differentiation. Review of the published literature of knockout mice revealed that of the predicted genes, 63.4% have defects in B-cell differentiation and function and 22% have a role in the B cell according to other experiments, and the remaining 14.6% are not characterized. Therefore, our method identified novel gene candidates for future examination of their role in B-cell development. These data demonstrate the power of MiDReG in predicting functionally important intermediate genes in a given developmental pathway that is defined by a mutually exclusive gene expression pattern.<\/jats:p>","DOI":"10.1073\/pnas.0913635107","type":"journal-article","created":{"date-parts":[[2010,3,15]],"date-time":"2010-03-15T23:59:34Z","timestamp":1268697574000},"page":"5732-5737","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":59,"title":["MiDReG: A method of mining developmentally regulated genes using Boolean implications"],"prefix":"10.1073","volume":"107","author":[{"given":"Debashis","family":"Sahoo","sequence":"first","affiliation":[{"name":"Department of Electrical Engineering, Stanford University, Stanford, CA, 94305;"},{"name":"Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, CA, 94305;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Seita","sequence":"additional","affiliation":[{"name":"Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, CA, 94305;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepta","family":"Bhattacharya","sequence":"additional","affiliation":[{"name":"Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, CA, 94305;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew A.","family":"Inlay","sequence":"additional","affiliation":[{"name":"Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, CA, 94305;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irving L.","family":"Weissman","sequence":"additional","affiliation":[{"name":"Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, CA, 94305;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia K.","family":"Plevritis","sequence":"additional","affiliation":[{"name":"Department of Radiology, Stanford University, CA, 94305; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David L.","family":"Dill","sequence":"additional","affiliation":[{"name":"Department of Computer Science, Stanford University, CA, 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2010,3,15]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-008-9867-6"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-0436.2003.700606.x"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1210\/mend.16.6.0865"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.0010028"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2008-9-10-r157"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.174.1.63"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.4.1502"},{"key":"e_1_3_3_8_2","first-page":"157","article-title":"C-kit is expressed by primitive human hematopoietic cells that give rise to colony-forming cells in stroma-dependent or cytokine-supplemented culture","volume":"22","author":"Simmons PJ","year":"1994","unstructured":"PJ Simmons, et al., C-kit is expressed by primitive human hematopoietic cells that give rise to colony-forming cells in stroma-dependent or cytokine-supplemented culture. 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