Dataset Information

Clustering of Expression Data in Chronic Lymphocytic Leukemia Reveals New Molecular Subdivisions.

ABSTRACT: Although the identification of inherent structure in chronic lymphocytic leukemia (CLL) gene expression data using class discovery approaches has not been extensively explored, the natural clustering of patient samples can reveal molecular subdivisions that have biological and clinical implications. To explore this, we preprocessed raw gene expression data from two published studies, combined the data to increase the statistical power, and performed unsupervised clustering analysis. The clustering analysis was replicated in 4 independent cohorts. To assess the biological significance of the resultant clusters, we evaluated their prognostic value and identified cluster-specific markers. The clustering analysis revealed two robust and stable subgroups of CLL patients in the pooled dataset. The subgroups were confirmed by different methodological approaches (non-negative matrix factorization NMF clustering and hierarchical clustering) and validated in different cohorts. The subdivisions were related with differential clinical outcomes and markers associated with the microenvironment and the MAPK and BCR signaling pathways. It was also found that the cluster markers were independent of the immunoglobulin heavy chain variable (IGVH) genes mutational status. These findings suggest that the microenvironment can influence the clinical behavior of CLL, contributing to prognostic differences. The workflow followed here provides a new perspective on differences in prognosis and highlights new markers that should be explored in this context.

SUBMITTER: Yepes S

PROVIDER: S-EPMC4565688 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Clustering of Expression Data in Chronic Lymphocytic Leukemia Reveals New Molecular Subdivisions.

Yepes Sally S Torres Maria Mercedes MM Andrade Rafael E RE

PloS one 20150910 9

Although the identification of inherent structure in chronic lymphocytic leukemia (CLL) gene expression data using class discovery approaches has not been extensively explored, the natural clustering of patient samples can reveal molecular subdivisions that have biological and clinical implications. To explore this, we preprocessed raw gene expression data from two published studies, combined the data to increase the statistical power, and performed unsupervised clustering analysis. The clusteri ...[more]

PMID: 26355846

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Project description:BackgroundAlthough the etiology of chronic lymphocytic leukemia (CLL), the most common type of adult leukemia, is still unclear, strong evidence implicates antigen involvement in disease ontogeny and evolution. Primary and 3D structure analysis has been utilised in order to discover indications of antigenic pressure. The latter has been mostly based on the 3D models of the clonotypic B cell receptor immunoglobulin (BcR IG) amino acid sequences. Therefore, their accuracy is directly dependent on the quality of the model construction algorithms and the specific methods used to compare the ensuing models. Thus far, reliable and robust methods that can group the IG 3D models based on their structural characteristics are missing.ResultsHere we propose a novel method for clustering a set of proteins based on their 3D structure focusing on 3D structures of BcR IG from a large series of patients with CLL. The method combines techniques from the areas of bioinformatics, 3D object recognition and machine learning. The clustering procedure is based on the extraction of 3D descriptors, encoding various properties of the local and global geometrical structure of the proteins. The descriptors are extracted from aligned pairs of proteins. A combination of individual 3D descriptors is also used as an additional method. The comparison of the automatically generated clusters to manual annotation by experts shows an increased accuracy when using the 3D descriptors compared to plain bioinformatics-based comparison. The accuracy is increased even more when using the combination of 3D descriptors.ConclusionsThe experimental results verify that the use of 3D descriptors commonly used for 3D object recognition can be effectively applied to distinguishing structural differences of proteins. The proposed approach can be applied to provide hints for the existence of structural groups in a large set of unannotated BcR IG protein files in both CLL and, by logical extension, other contexts where it is relevant to characterize BcR IG structural similarity. The method does not present any limitations in application and can be extended to other types of proteins.

Dataset Information

Clustering of Expression Data in Chronic Lymphocytic Leukemia Reveals New Molecular Subdivisions.

Publications

Clustering of Expression Data in Chronic Lymphocytic Leukemia Reveals New Molecular Subdivisions.

Similar Datasets

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