A Bioinformatics View on Acute Myeloid Leukemia Surface Molecules by Combined Bayesian and ABC Analysis

Abstract

"Big omics data" provoke the challenge of extracting meaningful information with clinical benefit. Here, we propose a two-step approach, an initial unsupervised inspection of the structure of the high dimensional data followed by supervised analysis of gene expression levels, to reconstruct the surface patterns on different subtypes of acute myeloid leukemia (AML). First, Bayesian methodology was used, focusing on surface molecules encoded by cluster of differentiation (CD) genes to assess whether AML is a homogeneous group or segregates into clusters. Gene expressions of 390 patient samples measured using microarray technology and 150 samples measured via RNA-Seq were compared. Beyond acute promyelocytic leukemia (APL), a well-known AML subentity, the remaining AML samples were separated into two distinct subgroups. Next, we investigated which CD molecules would best distinguish each AML subgroup against APL, and validated discriminative molecules of both datasets by searching the scientific literature. Surprisingly, a comparison of both omics analyses revealed that CD339 was the only overlapping gene differentially regulated in APL and other AML subtypes. In summary, our two-step approach for gene expression analysis revealed two previously unknown subgroup distinctions in AML based on surface molecule expression, which may guide the differentiation of subentities in a given clinical-diagnostic context.

Keywords: Bayesian machine learning; CD genes; cluster of differentiation genes; gene expressions; leukemia.

Figure 1

Ward clustering applied to the RNA-Seq data revealed a cluster structure of three groups $G_k$, $k=1,2,3$, one consisting only of APL and two of AML with the FAB classification of Table 1 which also depicts the colors of this figure. Clustering and dendrogram generation were computed with the R package “FCPS” available on the Comprehensive R Archive Network (CRAN) [19].

Figure 2

Dendrogram of Ward clustering applied to microarray np-AML patient samples revealed two subgroups (magenta and red). Clustering and dendrogram generation were computed with the R package “FCPS”, available on CRAN. The dataset provided normal controls in addition to APL. Both diagnostic entities were not used in the clustering.