Using MMRFBiolinks R-Package for Discovering Prognostic Markers in Multiple Myeloma.

Abstract

Multiple myeloma (MM) is the second most frequent hematological malignancy in the world although the related pathogenesis remains unclear. Gene profiling studies, commonly carried out through next-generation sequencing (NGS) and Microarrays technologies, represent powerful tools for discovering prognostic markers in MM. NGS technologies have made great leaps forward both economically and technically gaining in popularity. As NGS techniques becomes simpler and cheaper, researchers choose NGS over microarrays for more of their genomic applications. However, Microarrays still provide significant benefits with respect to NGS. For instance, RNA-Seq requires more complex bioinformatic analysis with respect to Microarray as well as it lacks of standardized protocols for analysis. Therefore, a synergy between the two technologies may be well expected in the future. In order to take up this challenge, a valid tool for integrative analysis of MM data retrieved through NGS techniques is MMRFBiolinks, a new R package for integrating and analyzing datasets from the Multiple Myeloma Research Foundation (MMRF) CoMMpass (Clinical Outcomes in MM to Personal Assessment of Genetic Profile) study, available at MMRF Researcher Gateway (MMRF-RG), and at the National Cancer Institute Genomic Data Commons (NCI-GDC) Data Portal. Instead of developing a completely new package from scratch, we decided to leverage TC-GABiolinks, an R/Bioconductor package, because it provides some useful methods to access and analyze MMRF-CoMMpass data. An integrative analysis workflow based on the usage of MMRFBiolinks is illustrated.In particular, it leads towards a comparative analysis of RNA-Seq data stored at GDC Data Portal that allows to carry out a Kaplan Meier (KM ) Survival Analysis and an enrichment analysis for a Differential Gene Expression (DGE) gene set.Furthermore, it deals with MMRF-RG data for analyzing the correlation between canonical variants and treatment outcome as well as treatment class. In order to show the potential of the workflow, we present two case studies. The former deals with data of MM Bone Marrow sample types available at GDC Data Portal. The latter deals with MMRF-RG data for analyzing the correlation between canonical variants in a gene set obtained from the case study 1 and the treatment outcome as well as the treatment class.