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We propose a new framework for integrative analysis of genome-wide sequencing data by considering diverse genetic information. This approach is applied to study follicular lymphoma (FL), a disease for which little is known about the contribution of regulatory gene mutations. Results from a test FL cohort revealed three novel highly recurrent regulatory mutation blocks near important genes implicated in FL, <jats:italic>BCL6<\/jats:italic> and <jats:italic>BCL2<\/jats:italic>. Similar findings were detected in a validation FL cohort. We also found transcription factors (TF) whose binding may be disturbed by these mutations in FL: disruption of FOX TF family near the <jats:italic>BCL6<\/jats:italic> promoter may result in reduced <jats:italic>BCL6<\/jats:italic> expression, which then increases <jats:italic>BCL2<\/jats:italic> expression over that caused by <jats:italic>BCL2<\/jats:italic> gene translocation. Knockdown experiments of two TF hits (<jats:italic>FOXD2<\/jats:italic> or <jats:italic>FOXD3<\/jats:italic>) were performed in human B lymphocytes verifying that they modulate <jats:italic>BCL6<\/jats:italic>\/<jats:italic>BCL2<\/jats:italic> according to the computationally predicted effects of the SNVs on TF binding. Overall, our proposed integrative analysis facilitates non-coding driver identification and the new findings may enhance the understanding of FL.<\/jats:p>","DOI":"10.1038\/s41598-017-07226-4","type":"journal-article","created":{"date-parts":[[2017,7,26]],"date-time":"2017-07-26T16:20:33Z","timestamp":1501086033000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Integrative whole-genome sequence analysis reveals roles of regulatory mutations in BCL6 and BCL2 in follicular lymphoma"],"prefix":"10.1038","volume":"7","author":[{"given":"Kirill","family":"Batmanov","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magnar","family":"Bj\u00f8r\u00e5s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Delabie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junbai","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,8,1]]},"reference":[{"key":"7226_CR1","doi-asserted-by":"publisher","first-page":"1113","DOI":"10.1038\/ng.2764","volume":"45","author":"K Chang","year":"2013","unstructured":"Chang, K. et al. 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