Reproducible Research: A Bioinformatics Case Study

While scientific research and the methodologies involved have gone through substantial technological evolution the technology involved in the publication of the results of these endeavors has remained relatively stagnant. Publication is largely done in the same manner today as it was fifty years ago. Many journals have adopted electronic formats, however, their orientation and style is little different from a printed document. The documents tend to be static and take little advantage of computational resources that might be available. Recent work, Gentleman and Temple Lang (2004), suggests a methodology and basic infrastructure that can be used to publish documents in a substantially different way. Their approach is suitable for the publication of papers whose message relies on computation. Stated quite simply, Gentleman and Temple Lang propose a paradigm where documents are mixtures of code and text. Such documents may be self-contained or they may be a component of a compendium which provides the infrastructure needed to provide access to data and supporting software. These documents, or compendiums, can be processed in a number of different ways. One transformation will be to replace the code with its output -- thereby providing the familiar, but limited, static document. In this paper we apply these concepts to a seminal paper in bioinformatics, namely The Molecular Classification of Cancer, Golub et al. (1999). The authors of that paper have generously provided data and other information that have allowed us to largely reproduce their results. Rather than reproduce this paper exactly we demonstrate that such a reproduction is possible and instead concentrate on demonstrating the usefulness of the compendium concept itself

Bioinformatics Software Engineering

Abstracts not available for BookReview

Peer Observation is a Key Ingredient to Effectiveness in Staff Development

The relationship between peer observation and instructional improvement was investigated. Fifteen middle level teachers from a variety of disciplines participated in the study. Teachers were taped and assessed prior to the study as well as afterward. Teachers also responded to a questionnaire to determine their perceptions of the practicality and usefulness of peer observation. Participants were divided into two groups: an experimental group of eight teachers (four teams of two) and a control group of seven teachers. All fifteen teachers participated in a training review of instructional techniques. In addition those teachers in the experimental group attended three training sessions where they (1) learned the rationale behind peer coaching and a brief historical perspective; (2) were shown how to preconference, take notes, collect and label data, and plan the final conference; and (3) practiced taking notes and labelling. Each member of the experimental group participated in two rotations of peer observation. Analysis of data collected indicated that teachers who participated in peer observation seemed more successful in improving their instructional technique

Extensions to Gene Set Enrichment

Motivation: Gene Set Enrichment Analysis (GSEA) has been developed recently to capture moderate but coordinated changes in the expression of sets of functionally related genes. We propose number of extensions to GSEA, which uses different statistics to describe the association between genes and phenotype of interest. We make use of dimension reduction procedures, such as principle component analysis to identify gene sets containing coordinated genes. We also address the problem of overlapping among gene sets in this paper. Results: We applied our methods to the data come from a clinical trial in acute lymphoblastic leukemia (ALL) [1]. We identified interesting gene sets using different statistics. We find that gender may have effects on the gene expression in addition to the phenotype effects. Investigating overlap among interesting gene sets indicate that overlapping could alter the interpretation of the significant results

Loss of angiotensin II receptor expression in dopamine neurons in Parkinson’s disease correlates with pathological progression and is accompanied by increases in Nox4- and 8-OH guanosine-related nucleic acid oxidation and caspase-3 activation

In rodent models of Parkinsons disease (PD), dopamine neuron loss is accompanied by increased expression of angiotensin II (AngII), its type 1 receptor (AT1), and NADPH oxidase (Nox) in the nigral dopamine neurons and microglia. AT1 blockers (ARBs) stymie such oxidative damage and neuron loss. Whether changes in the AngII/AT1/Nox4 axis contribute to Parkinson neuropathogenesis is unknown. Here, we studied the distribution of AT1 and Nox4 in dopamine neurons in two nigral subregions: the less affected calbindin-rich matrix and the first-affected calbindin-poor nigrosome 1 of three patients, who were clinically asymptomatic, but had nigral dopamine cell loss and Braak stages consistent with a neuropathological diagnosis of PD (prePD). For comparison, five clinically- and neuropathologically-confirmed PD patients and seven age-matched control patients (AMC) were examined.AT1 and Nox4 immunoreactivity was noted in dopamine neurons in both the matrix and the nigrosome 1. The total cellular levels of AT1 in surviving dopamine neurons in the matrix and nigrosome 1 declined from AMC>prePD>PD, suggesting that an AngII/AT1/Nox4 axis orders neurodegenerative progression. In this vein, the loss of dopamine neurons was paralleled by a decline in total AT1 per surviving dopamine neuron. Similarly, AT1 in the nuclei of surviving neurons in the nigral matrix declined with disease progression, i.e., AMC>prePD>PD. In contrast, in nigrosome 1, the expression of nuclear AT1 was unaffected and similar in all groups. The ratio of nuclear AT1 to total AT1 (nuclear + cytoplasmic + membrane) in dopamine neurons increased stepwise from AMC to prePD to PD. The proportional increase in nuclear AT1 in dopamine neurons in nigrosome 1 of prePD and PD patients was accompanied by elevated nuclear expression of Nox4, oxidative damage to DNA, and caspase-3-mediated cell loss.Our observations are consistent with the idea that AngII/AT1/Nox4 axis-mediated oxidative stress gives rise to the dopamine neuron dysfunction and loss characteristic of the neuropathological and clinical manifestations of PD and suggest that the chance for a neuron to survive increases in association with lower total as well as nuclear AT1 expression. Our results support the need for further evaluation of ARBs as disease-modifying agents in PD

Making the most of high-throughput protein-interaction data

Better methods of statistical analysis could make large-scale protein-interaction data more useful

The Regional Security Crisis in the Andes: Patterns of State Response

The instability, corruption, displacement of people, and violence generated by Colombia\u27s unholy trinity of narcotics traffickers, insurgents, and paramilitaries is spilling over into virtually all of northern South America and Panama. Thus, the stability and political sovereignty of the region are being compromised. And, at the same time, progress toward achieving the Free Trade Area of the Americas (FTAA) and the economic integration of the Western Hemisphere by 2005 is being severely threatened. The author outlines some of the detail and implications of the regional security crisis in the Andes and makes recommendations for U.S. civil-military involvement in the hemispheric security arena. She argues for the United States to lead in the articulation of strategic objectives, while designing a defensible and feasible policy that critical elements in North America, Central and South America, Europe, and Japan can understand and support. She specifically argues for the U.S. military to build stronger and more cooperative security relationships within the circle of affected states around Colombia.https://press.armywarcollege.edu/monographs/1836/thumbnail.jp