Temporal and spatial patterns of gene profiles during chondrogenic differentiation.

Clustering analysis based on temporal profile of genes may provide new insights in particular biological processes or conditions. We report such an integrative clustering analysis which is based on the expression patterns but is also influenced by temporal changes. The proposed platform is illustrated with a temporal gene expression dataset comprised of pellet culture-conditioned human primary chondrocytes and human bone marrow-derived mesenchymal stem cells (MSCs). We derived three clusters in each cell type and compared the content of these classes in terms of temporal changes. We further considered the induced biological processes and the gene-interaction networks formed within each cluster and discuss their biological significance. Our proposed methodology provides a consistent tool that facilitates both the statistical and biological validation of temporal profiles through spatial gene network profiles.

Nonparametric network design and analysis of disease genes in oral cancer progression.

Biological networks in living organisms can be seen as the ultimate means of understanding the underlying mechanisms in complex diseases, such as oral cancer. During the last decade, many algorithms based on high-throughput genomic data have been developed to unravel the complexity of gene network construction and their progression in time. However, the small size of samples compared to the number of observed genes makes the inference of the network structure quite challenging. In this study, we propose a framework for constructing and analyzing gene networks from sparse experimental temporal data and investigate its potential in oral cancer. We use two network models based on partial correlations and kernel density estimation, in order to capture the genetic interactions. Using this network construction framework on real clinical data of the tissue and blood at different time stages, we identified common disease-related structures that may decipher the association between disease state and biological processes in oral cancer. Our study emphasizes an altered MET (hepatocyte growth factor receptor) network during oral cancer progression. In addition, we demonstrate that the functional changes of gene interactions during oral cancer progression might be particularly useful for patient categorization at the time of diagnosis and/or at follow-up periods.

Identification of altered MET network in oral cancer progression based on nonparametric network design.

Oral cancer is characterized by multiple genetic events such as alterations of a number of oncogenes and tumour suppressor genes. The aim of this study is to identify genes and their functional interactions that may play a crucial role on a specific disease-state, especially during oral cancer progression. We examine gene interaction networks on blood genomic data, obtained from twenty three oral cancer patients at four different time stages. We generate the gene-gene networks from sparse experimental temporal data using two methods, Partial Correlations and Kernel Density Estimation, in order to capture genetic interactions. The network study reveals an altered MET (hepatocyte growth factor receptor) network during oral cancer progression, which is further analyzed in relation to other studies.