This paper addresses exact learning of Bayesian network structure from data and expert's knowledge based on score functions that are decomposable. First, it describes useful properties that strongly reduce the time and memory costs of many known methods such as hill-climbing, dynamic programming and sampling variable orderings. Secondly, a branch and bound algorithm is presented that integrates parameter and structural constraints with data in a way to guarantee global optimality with respect to the score function. It is an any-time procedure because, if stopped, it provides the best current solution and an estimation about how far it is from the global solution. We show empirically the advantages of the properties and the constraints, and the applicability of the algorithm to large data sets (up to one hundred variables) that cannot be handled by other current methods (limited to around 30 variables).

Marginal zone B-cell lymphomas (MZLs) have been divided into 3 distinct subtypes (extranodal MZLs of mucosa-associated lymphoid tissue [MALT] type, nodalMZLs, and splenic MZLs). Nevertheless, the relationship between the subtypes is still unclear. We performed a comprehensive analysis of genomic DNA copy number changes in a very large series of MZL cases with the aim of addressing this question. Samples from 218 MZL patients (25 nodal, 57 MALT, 134 splenic, and 2 not better specified MZLs) were analyzed with the Affymetrix Human Mapping 250K SNP arrays, and the data combined with matched gene expression in 33 of 218 cases. MALT lymphoma presented significantly more frequently gains at 3p, 6p, 18p, and del(6q23) (TNFAIP3/A20), whereas splenic MZLs was associated with del(7q31), del(8p). Nodal MZLs did not show statistically significant differences compared with MALT lymphoma while lacking the splenic MZLs-related 7q losses. Gains of 3q and 18q were common to all 3 subtypes. del(8p) was often present together with del(17p) (TP53). Although del(17p) did not determine a worse outcome and del(8p) was only of borderline significance, the presence of both deletions had a highly significant negative impact on the outcome of splenic MZLs. (Blood. 2011;117(5):1595-1604)

Summary Despite recent therapeutic improvements, the clinical course of diffuse large B‐cell lymphoma (DLBCL) still differs considerably among patients. We conducted this retrospective multi‐centre study to evaluate the impact of genomic aberrations detected using a high‐density genome wide‐single nucleotide polymorphism‐based array on clinical outcome in a population of DLBCL patients treated with R‐CHOP‐21 (rituximab, cyclophosphamide, doxorubicine, vincristine and prednisone repeated every 21 d). 166 DNA samples were analysed using the GeneChip Human Mapping 250K NspI. Genomic anomalies were analysed regarding their impact on the clinical course of 124 patients treated with R‐CHOP‐21. Unsupervised clustering was performed to identify genetically related subgroups of patients with different clinical outcomes. Twenty recurrent genetic lesions showed an impact on the clinical course. Loss of genomic material at 8p23.1 showed the strongest statistical significance and was associated with additional aberrations, such as 17p‐ and 15q‐. Unsupervised clustering identified five DLBCL clusters with distinct genetic profiles, clinical characteristics and outcomes. Genetic features and clusters, associated with a different outcome in patients treated with R‐CHOP, have been identified by arrayCGH.