Covering Hierarchical Dirichlet Mixture Models on binary data to enhance genomic stratifications in onco-hematology

by Daniele Dall ’Olio, Eric Sträng, Amin T. Turki, Jesse M. Tettero, Martje Barbus, Renate Schulze-Rath, Javier Martinez Elicegui, Tommaso Matteuzzi, Alessandra Merlotti, Luciana Carota, Claudia Sala, Matteo G. Della Porta, Enrico Giampieri, Jesús María Hernández-Rivas, Lars Bullinger, Gastone Castellani, wit h the HARMONY Healthcare Alliance Consortium Onco-hematological studies are increasingly adopting statistical mixture models to support the advancement of the genomically-driven classification systems for blood cancer. Targeting enhanced patients stratification based on the sole role of molecular biology attracted much interest and contributes to bring personalized medicine closer to reality. In onco-hematology, Hierarchical Dirichlet Mixture Models (HDMM) have become one of the preferred method to cluster the genomics data, that include the presence or absence of gene mutations and cytogenetics anomalies, into components. This work unfolds the standard workflow used in onco-hematology to improve patient stratification and proposes alternative approaches to characterize the components and to assign patient to them, as they are crucial tasks usually supported by a priori clinical knowledge. We propose (a) to compute the parameters of the multinomial components of the HDMM or (b) to estimate the parameters of the HDMM components as if they were Multivariate Fisher ’s Non-Central Hypergeometric (MFNCH) distributions. Then, our approach to perform patients assignmen...
Source: PLoS Computational Biology - Category: Biology Authors: Source Type: research