DNA Copy Number Analysis in Gastrointestinal Stromal Tumors Using Gene Expression Microarrays

We report a method, Expression-Microarray Copy Number Analysis (ECNA) for the detection of copy number changes using Affymetrix Human Genome U133 Plus 2.0 arrays, starting with as little as 5 ng input genomic DNA. An analytical approach was developed using DNA isolated from cell lines containing various X-chromosome numbers, and validated with DNA from cell lines with defined deletions and amplifications in other chromosomal locations. We applied this method to examine the copy number changes in DNA from 5 frozen gastrointestinal stromal tumors (GIST). We detected known copy number aberrations consistent with previously published results using conventional or BAC-array CGH, as well as novel changes in GIST tumors. These changes were concordant with results from Affymetrix 100K human SNP mapping arrays. Gene expression data for these GIST samples had previously been generated on U133A arrays, allowing us to explore correlations between chromosomal copy number and RNA expression levels. One of the novel aberrations identified in the GIST samples, a previously unreported gain on 1q21.1 containing the PEX11B gene, was confirmed in this study by FISH and was also shown to have significant differences in expression pattern when compared to a control sample. In summary, we have demonstrated the use of gene expression microarrays for the detection of genomic copy number aberrations in tumor samples. This method may be used to study copy number changes in other species for which RNA expression arrays are available, e.g. other mammals, plants, etc., and for which SNPs have not yet been mapped

Common issues, different approaches: strategies for community–academic partnership development

BAIARDI JM, BRUSH BL and LAPIDES S. Nursing Inquiry 2010; 17 : 289–296 Common issues, different approaches: strategies for community–academic partnership development Communities around the United States face many challenging health problems whose complexity makes them increasingly unresponsive to traditional single-solution approaches. Multiple approaches have considered ways to understand these health issues and devise interventions that work. One such approach is community-based participatory research. This article describes the development of a new collaborative partnership between a school of nursing and an urban social service agency using community-based participatory research as a framework. We describe the partnership’s evolution and process of data collection and analysis and evaluate the outcomes of both. We argue that community-based participatory research involves partnerships at its core whose members, both as individuals and part of the collaboration, must be committed and nimble in the face of shifting and challenging health and social problems, recognize common issues and concerns across the boundaries of community and academia, and respect each other’s different approaches and expertise.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79191/1/j.1440-1800.2010.00509.x.pd

Deficiencies in Vadose Zone Understanding at the INEEL

Subsurface contamination in the vadose zone, that portion of the subsurface pathway between land surface and an underlying aquifer, poses environmental problems at the Idaho National Engineering and Environmental Laboratory (INEEL) in eastern Idaho and across the U.S. Department of Energy complex. Assessing potential adverse impacts from these contaminated sites requires an understanding of the mechanisms controlling contaminant transport. Currently, vadose zone experts at the INEEL cannot with confidence predict the movement of water and contaminants in the complex, heterogeneous, fractured subsurface at the INEEL, especially within the vadose zone. In the draft version (Revision 1) of the Vadose Zone Deficiencies document, deficiencies in scientific understanding of flow and transport processes in the vadose zone at the INEEL were identified and grouped into 13 categories and recommendations were provided to address each of the deficiencies. The draft document provided the basis for an INEEL Vadose Zone Workshop that was conducted October 20 and 21, 1999, in Idaho Falls, Idaho. The workshop was conducted to group and rank the previously identified deficiencies and for the subsequent development of science plans to address the deficiencies that limit reliable predictions of water and contaminant movement in the subsurface. The workshop participants, comprising INEEL and scientists and project managers and non-INEEL scientists knowledgeable about the vadose zone, developed science- and technology-based recommendations derived through a series of technical sessions at the workshop. In this document, the final version of the Vadose Zone Deficiencies document, the draft document has been incorporated, largely intact, as well as the results from the workshop. The workshop participants grouped the deficiencies in vadose zone understanding at the INEEL into seven categories. These seven categories will be the focus areas of five science plans that are being developed to address the deficiencies. This document lays the foundation for the INEEL Site-wide vadose zone roadmap

Resolving deconvolution ambiguity in gene alternative splicing

Abstract Background For many gene structures it is impossible to resolve intensity data uniquely to establish abundances of splice variants. This was empirically noted by Wang et al. in which it was called a "degeneracy problem". The ambiguity results from an ill-posed problem where additional information is needed in order to obtain an unique answer in splice variant deconvolution. Results In this paper, we analyze the situations under which the problem occurs and perform a rigorous mathematical study which gives necessary and sufficient conditions on how many and what type of constraints are needed to resolve all ambiguity. This analysis is generally applicable to matrix models of splice variants. We explore the proposal that probe sequence information may provide sufficient additional constraints to resolve real-world instances. However, probe behavior cannot be predicted with sufficient accuracy by any existing probe sequence model, and so we present a Bayesian framework for estimating variant abundances by incorporating the prediction uncertainty from the micro-model of probe responsiveness into the macro-model of probe intensities. Conclusion The matrix analysis of constraints provides a tool for detecting real-world instances in which additional constraints may be necessary to resolve splice variants. While purely mathematical constraints can be stated without error, real-world constraints may themselves be poorly resolved. Our Bayesian framework provides a generic solution to the problem of uniquely estimating transcript abundances given additional constraints that themselves may be uncertain, such as regression fit to probe sequence models. We demonstrate the efficacy of it by extensive simulations as well as various biological data.</p

Expression Analysis and provided on this web-site.

ABSTRACT. This is supplemental data extracted from the paper Robust Estimators fo