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Robust Sampling of Defective Pathways in Multiple Myeloma

Juan Luis Fernández-Martínez, Enrique J. De Andrés-Galiana, Francisco Javier Fernández-Ovies, Ana Cernea, Andrzej Kloczkowski
Published: 21 September 2019
 by  MDPI
International Journal of Molecular Sciences , Volume 20; doi:10.3390/ijms20194681

Abstract: We present the analysis of defective pathways in multiple myeloma (MM) using two recently developed sampling algorithms of the biological pathways: The Fisher’s ratio sampler, and the holdout sampler. We performed the retrospective analyses of different gene expression datasets concerning different aspects of the disease, such as the existing difference between bone marrow stromal cells in MM and healthy controls (HC), the gene expression profiling of CD34+ cells in MM and HC, the difference between hyperdiploid and non-hyperdiploid myelomas, and the prediction of the chromosome 13 deletion, to provide a deeper insight into the molecular mechanisms involved in the disease. Our analysis has shown the importance of different altered pathways related to glycosylation, infectious disease, immune system response, different aspects of metabolism, DNA repair, protein recycling and regulation of the transcription of genes involved in the differentiation of myeloid cells. The main difference in genetic pathways between hyperdiploid and non-hyperdiploid myelomas are related to infectious disease, immune system response and protein recycling. Our work provides new insights on the genetic pathways involved in this complex disease and proposes novel targets for future therapies.
Keywords: multiple myeloma / Genes / pathways / Genetic Signatures / analysis of defective pathways / Fisher’s ratio sampler / holdout sampler / chromosome 13 deletion prediction

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