Analysis of sites of newly integrated DNA in cellular genomes is important to several fields, but methods for analyzing and visualizing these datasets are still under development. Here, we describe tools for data analysis and visualization that take as input integration site data from our INSPIIRED pipeline. Paired-end sequencing allows inference of the numbers of transduced cells as well as the distributions of integration sites in target genomes. We present interactive heatmaps that allow comparison of distributions of integration sites to (...) genomic features and that support numerous user-defined statistical tests. To summarize integration site data from human gene therapy samples, we developed a reproducible report format that catalogs sample population structure, longitudinal dynamics, and integration frequency near cancer-associated genes. We also introduce a novel summary statistic, the UC50, which provides a single number summarizing possible clonal expansion. Using these tools, we characterize ongoing longitudinal characterization of a patient from the first trial to treat severe combined immunodeficiency-X1, showing successful reconstitution for 15 years accompanied by persistence of a cell clone with an integration site near the cancer-associated gene CCND2. Software is available at https://github.com/BushmanLab/INSPIIRED. (shrink)

Background Physicians face competing values of truth-telling and beneficence when deception may be employed in patient care. The purposes of this study were to assess resident physicians' attitudes towards lying, explore lie types and reported reasons for lying. Method After obtaining institutional review board review and receiving exempt status, posts written by Loma Linda University resident physicians in response to forum questions in required online courses were collected from 2002 to 2007. Responses were blinded and manually coded by two investigators (...) using NVivo software. Qualitative and quantitative analyses of the data were performed with links to various attributes. A 95% binomial proportion CI was used to analyse the attribute data. Results The study found that the majority of residents would disclose the truth about medical errors. Similarly, many residents would disclose the truth regarding unanticipated events, especially if the error was serious enough to result in a malpractice suit. However, many residents would not reveal a near miss event because they believe it has no impact on patient health. Some residents would deceive the insurance company for additional patient benefits. Of those willing to lie, only a small group gave self-serving reasons. Conclusions This study demonstrates that the ethical issues related to deception that trouble attending physicians also exist at the resident physician level. Residents primarily lie for altruistic reasons and rarely for egoistic or self-serving purposes that may or may not result in harm to patients, insurance companies and/or physicians themselves. (shrink)