Showing papers by "Wenyi Wang published in 2012"

Slow down to stay alive: HER4 protects against cellular stress and confers chemoresistance in neuroblastoma.

Abstract: BACKGROUND: Neuroblastoma (NBL) is a common pediatric solid tumor, and outcomes for patients with advanced neuroblastoma remain poor despite extremely aggressive treatment. Chemotherapy resistance at relapse contributes heavily to treatment failure. The poor survival of patients with high-risk NBL prompted this investigation into novel treatment options with the objective of gaining a better understanding of resistance mechanisms. On the basis of previous work and on data from publicly available studies, the authors hypothesized that human epidermal growth factor receptor 4 (Her4) contributes to resistance. METHODS: Her4 expression was reduced with small-hairpin RNA (shRNA) to over express intracellular HER4, and the authors tested its impact on tumor cell survival under various culture conditions. The resulting changes in gene expression after HER4 knockdown were measured by using a messenger RNA (mRNA) array. RESULTS: HER4 expression was up-regulated in tumor spheres compared with the expression in monolayer culture. With HER4 knockdown, NBL cells became less resistant to anoikis and serum starvation. Moreover, HER4 knockdown increased the chemosensitivity of NBL cells to cisplatin, doxorubicin, etoposide, and activated ifosfamide. In mRNA array analysis, HER4 knockdown predominately altered genes related to cell cycle regulation. In NBL spheres compared with monolayers, cell proliferation was decreased, and cyclin D expression was reduced. HER4 knockdown reversed cyclin D suppression. Overexpressed intracellular HER4 slowed the cell cycle and induced chemoresistance. CONCLUSIONS: The current results indicated that HER4 protects NBL cells from multiple exogenous apoptotic stimuli, including anoikis, nutrient deficiency, and cytotoxic chemotherapy. The intracellular fragment of HER4 was sufficient to confer this phenotype. HER4 functions as a cell cycle suppressor, maintaining resistance to cellular stress. The current findings indicate that HER4 overexpression may be associated with refractory disease, and HER4 may be an important therapeutic target. Cancer 2012. © 2012 American Cancer Society.

Integrating multi-platform genomic data using hierarchical Bayesian relevance vector machines

Abstract: We present a statistical framework, hierarchical relevance vector machine (H-RVM), for improved prediction of scalar outcomes using interacting high-dimensional input covariates from different sources. We illustrate our methodology for integrating genomic data from multiple platforms to predict observed clinical phenotypes. H-RVM is a hierarchical Bayesian generalization of the relevance vector machine and its learning algorithm is a special case of the computationally efficient variational method of hierarchic kernel learning frame-work. We apply H-RVM to data from the Cancer Genome Atlas based Glioblastoma study to predict imaging-based tumor volume by integrating gene and miRNA expression data and show that H-RVM performs much better in prediction as compared to competing methods.

SRMA: an R package for resequencing array data analysis.

Abstract: Summary: Sequencing by hybridization to oligonucleotides has evolved into an inexpensive, reliable and fast technology for targeted sequencing. Hundreds of human genes can now be sequenced within a day using a single hybridization to a resequencing microarray. However, several issues inherent to these arrays (e.g. cross-hybridization, variable probe/target affinity) cause sequencing errors and have prevented more widespread applications. We developed an R package for resequencing microarray data analysis that integrates a novel statistical algorithm, sequence robust multi-array analysis (SRMA), for rare variant detection with high sensitivity (false negative rate, FNR 5%) and accuracy (false positive rate, FPR 1×10−5). The SRMA package consists of five modules for quality control, data normalization, single array analysis, multi-array analysis and output analysis. The entire workflow is efficient and identifies rare DNA single nucleotide variations and structural changes such as gene deletions with high accuracy and sensitivity. Availability: http://cran.r-project.org/, http://odin.mdacc.tmc.edu/~wwang7/SRMAIndex.html Contact: gro.nosrednadm@7gnaww Supplementary information: Supplementary data are available at Bioinformatics online.