CIMIDx: Prototype for a Cloud-Based System to Support Intelligent Medical Image Diagnosis With Efficiency.

BACKGROUND: The Internet has greatly enhanced health care, helping patients stay up-to-date on medical issues and general knowledge. Many cancer patients use the Internet for cancer diagnosis and related information. Recently, cloud computing has emerged as a new way of delivering health services but currently, there is no generic and fully automated cloud-based self-management intervention for breast cancer patients, as practical guidelines are lacking. OBJECTIVE: We investigated the prevalence and predictors of cloud use for medical diagnosis among women with breast cancer to gain insight into meaningful usage parameters to evaluate the use of generic, fully automated cloud-based self-intervention, by assessing how breast cancer survivors use a generic self-management model. The goal of this study was implemented and evaluated with a new prototype called "CIMIDx", based on representative association rules that support the diagnosis of medical images (mammograms). METHODS: The proposed Cloud-Based System Support Intelligent Medical Image Diagnosis (CIMIDx) prototype includes two modules. The first is the design and development of the CIMIDx training and test cloud services. Deployed in the cloud, the prototype can be used for diagnosis and screening mammography by assessing the cancers detected, tumor sizes, histology, and stage of classification accuracy. To analyze the prototype's classification accuracy, we conducted an experiment with data provided by clients. Second, by monitoring cloud server requests, the CIMIDx usage statistics were recorded for the cloud-based self-intervention groups. We conducted an evaluation of the CIMIDx cloud service usage, in which browsing functionalities were evaluated from the end-user's perspective. RESULTS: We performed several experiments to validate the CIMIDx prototype for breast health issues. The first set of experiments evaluated the diagnostic performance of the CIMIDx framework. We collected medical information from 150 breast cancer survivors from hospitals and health centers. The CIMIDx prototype achieved high sensitivity of up to 99.29%, and accuracy of up to 98%. The second set of experiments evaluated CIMIDx use for breast health issues, using t tests and Pearson chi-square tests to assess differences, and binary logistic regression to estimate the odds ratio (OR) for the predictors' use of CIMIDx. For the prototype usage statistics for the same 150 breast cancer survivors, we interviewed 114 (76.0%), through self-report questionnaires from CIMIDx blogs. The frequency of log-ins/person ranged from 0 to 30, total duration/person from 0 to 1500 minutes (25 hours). The 114 participants continued logging in to all phases, resulting in an intervention adherence rate of 44.3% (95% CI 33.2-55.9). The overall performance of the prototype for the good category, reported usefulness of the prototype (P=.77), overall satisfaction of the prototype (P=.31), ease of navigation (P=.89), user friendliness evaluation (P=.31), and overall satisfaction (P=.31). Positive evaluations given by 100 participants via a Web-based questionnaire supported our hypothesis. CONCLUSIONS: The present study shows that women felt favorably about the use of a generic fully automated cloud-based self- management prototype. The study also demonstrated that the CIMIDx prototype resulted in the detection of more cancers in screening and diagnosing patients, with an increased accuracy rate.

A network of conserved damage survival pathways revealed by a genomic RNAi screen.

Damage initiates a pleiotropic cellular response aimed at cellular survival when appropriate. To identify genes required for damage survival, we used a cell-based RNAi screen against the Drosophila genome and the alkylating agent methyl methanesulphonate (MMS). Similar studies performed in other model organisms report that damage response may involve pleiotropic cellular processes other than the central DNA repair components, yet an intuitive systems level view of the cellular components required for damage survival, their interrelationship, and contextual importance has been lacking. Further, by comparing data from different model organisms, identification of conserved and presumably core survival components should be forthcoming. We identified 307 genes, representing 13 signaling, metabolic, or enzymatic pathways, affecting cellular survival of MMS-induced damage. As expected, the majority of these pathways are involved in DNA repair; however, several pathways with more diverse biological functions were also identified, including the TOR pathway, transcription, translation, proteasome, glutathione synthesis, ATP synthesis, and Notch signaling, and these were equally important in damage survival. Comparison with genomic screen data from Saccharomyces cerevisiae revealed no overlap enrichment of individual genes between the species, but a conservation of the pathways. To demonstrate the functional conservation of pathways, five were tested in Drosophila and mouse cells, with each pathway responding to alkylation damage in both species. Using the protein interactome, a significant level of connectivity was observed between Drosophila MMS survival proteins, suggesting a higher order relationship. This connectivity was dramatically improved by incorporating the components of the 13 identified pathways within the network. Grouping proteins into "pathway nodes" qualitatively improved the interactome organization, revealing a highly organized "MMS survival network." We conclude that identification of pathways can facilitate comparative biology analysis when direct gene/orthologue comparisons fail. A biologically intuitive, highly interconnected MMS survival network was revealed after we incorporated pathway data in our interactome analysis.

An analysis of normalization methods for Drosophila RNAi genomic screens and development of a robust validation scheme.

Genome-wide RNA interference (RNAi) screening allows investigation of the role of individual genes in a process of choice. Most RNAi screens identify a large number of genes with a continuous gradient in the assessed phenotype. Screeners must decide whether to examine genes with the most robust phenotype or the full gradient of genes that cause an effect and how to identify candidate genes. The authors have used RNAi in Drosophila cells to examine viability in a 384-well plate format and compare 2 screens, untreated control and treatment. They compare multiple normalization methods, which take advantage of different features within the data, including quantile normalization, background subtraction, scaling, cellHTS2 (Boutros et al. 2006), and interquartile range measurement. Considering the false-positive potential that arises from RNAi technology, a robust validation method was designed for the purpose of gene selection for future investigations. In a retrospective analysis, the authors describe the use of validation data to evaluate each normalization method. Although no method worked ideally, a combination of 2 methods, background subtraction followed by quantile normalization and cellHTS2, at different thresholds, captures the most dependable and diverse candidate genes. Thresholds are suggested depending on whether a few candidate genes are desired or a more extensive systems-level analysis is sought. The normalization approaches and experimental design to perform validation experiments are likely to apply to those high-throughput screening systems attempting to identify genes for systems-level analysis.