Cancer Informatics for Cancer Centers (CI4CC): Building a Community Focused on Sharing Ideas and Best Practices to Improve Cancer Care and Patient Outcomes.

Cancer Informatics for Cancer Centers (CI4CC) is a grassroots, nonprofit 501c3 organization intended to provide a focused national forum for engagement of senior cancer informatics leaders, primarily aimed at academic cancer centers anywhere in the world but with a special emphasis on the 70 National Cancer Institute-funded cancer centers. Although each of the participating cancer centers is structured differently, and leaders' titles vary, we know firsthand there are similarities in both the issues we face and the solutions we achieve. As a consortium, we have initiated a dedicated listserv, an open-initiatives program, and targeted biannual face-to-face meetings. These meetings are a place to review our priorities and initiatives, providing a forum for discussion of the strategic and pragmatic issues we, as informatics leaders, individually face at our respective institutions and cancer centers. Here we provide a brief history of the CI4CC organization and meeting highlights from the latest CI4CC meeting that took place in Napa, California from October 14-16, 2019. The focus of this meeting was "intersections between informatics, data science, and population science." We conclude with a discussion on "hot topics" on the horizon for cancer informatics

Genetic variation in the HLA region is associated with susceptibility to herpes zoster.

Herpes zoster, commonly referred to as shingles, is caused by the varicella zoster virus (VZV). VZV initially manifests as chicken pox, most commonly in childhood, can remain asymptomatically latent in nerve tissues for many years and often re-emerges as shingles. Although reactivation may be related to immune suppression, aging and female sex, most inter-individual variability in re-emergence risk has not been explained to date. We performed a genome-wide association analyses in 22,981 participants (2280 shingles cases) from the electronic Medical Records and Genomics Network. Using Cox survival and logistic regression, we identified a genomic region in the combined and European ancestry groups that has an age of onset effect reaching genome-wide significance (P>1.0 × 10(-8)). This region tags the non-coding gene HCP5 (HLA Complex P5) in the major histocompatibility complex. This gene is an endogenous retrovirus and likely influences viral activity through regulatory functions. Variants in this genetic region are known to be associated with delay in development of AIDS in people infected by HIV. Our study provides further suggestion that this region may have a critical role in viral suppression and could potentially harbor a clinically actionable variant for the shingles vaccine

Simulation Approach to Assess the Precision of Estimates Derived from Linking Survey and Administrative Records

Probabilistic record linkage implies that there is some level of uncertainty related to the classification of pairs as links or non-links vis-à-vis their true match status. As record linkage is usually performed as a preliminary step to developing statistical estimates, the question then is how does this linkage uncertainty propagate to them? In this paper, we develop an approach to estimate the impact of linkage uncertainty on derived estimates by using a re-sampling approach. For each iteration of the re-sampling, pairs are classified as links or non-links by Monte-Carlo assignment to model estimated true match probabilities. By looking at the range of estimates produced in a series of re-samples, we can estimate the distribution of derived statistics under the prevailing incidence of linkage uncertainty. For this analysis we use the results of linking the 2014 National Hospital Care Survey to the National Death Index performed at the National Center for Health Statistics. We assess the precision of hospital-level death rate estimates

Nonsampling errors and their implication for estimates of current cancer treatment using the Medical Expenditure Panel Survey

Survey nonsampling errors refer to the components of total survey error (TSE) that result from failures in data collection and processing procedures. Evaluating nonsampling errors can lead to a better understanding of their sources, which in turn, can inform survey inference and assist in the design of future surveys. Data collected via supplemental questionnaires can provide a means for evaluating nonsampling errors because it may provide additional information on survey nonrespondents and/or measurements of the same concept over repeated trials on the same sampling unit. We used a supplemental questionnaire administered to cancer survivors to explore potential nonsampling errors, focusing primarily on nonresponse and measurement/specification errors. We discuss the implications of our findings in the context of the TSE paradigm and identify areas for future research

Learners in a Changing Learning Landscape: Reflections from an Instructional Design Perspective

Van Merriënboer, J. J. G., & Stoyanov, S. (2008). Learners in a changing learning landscape: Reflections from an instructional design perspective. In J. Visser & M. Visser-Valfrey (Eds.), Learners in a changing learning landscape: Reflections from a dialogue on new roles and expectations (pp. 69-90). Dordrecht, The Netherlands: Springer.Both learners and teachers find themselves in a learning landscape that is rapidly changing, along with fast societal and technological developments. This paper discusses the new learning landscape from an instructional design perspective. First, with regard to what is learned, people more than ever need flexible problem-solving and reasoning skills allowing them to deal with new, unfamiliar problem situations in their professional and everyday life. Second, with regard to the context in which learning takes place, learning in technology-rich, informal and professional 24/7 settings is becoming general practice. And third, with regard to the learners themselves, they can more often be characterized as lifelong learners who are mature, bring relevant prior knowledge, and have very heterogeneous expectations and perceptions of learning. High-quality instructional design research should focus on the question which instructional methods and media-method combinations are effective, efficient and appealing in this new learning landscape. Some innovative instructional methods that meet this requirement are discussed

Cross-domain neurobiology data integration and exploration

<p>Abstract</p> <p>Background</p> <p>Understanding the biomedical implications of data from high throughput experiments requires solutions for effective cross-scale and cross-domain data exploration. However, existing solutions do not provide sufficient support for linking molecular level data to neuroanatomical structures, which is critical for understanding high level neurobiological functions.</p> <p>Results</p> <p>Our work integrates molecular level data with high level biological functions and we present results using anatomical structure as a scaffold. Our solution also allows the sharing of intermediate data exploration results with other web applications, greatly increasing the power of cross-domain data exploration and mining.</p> <p>Conclusions</p> <p>The Flex-based PubAnatomy web application we developed enables highly interactive visual exploration of literature and experimental data for understanding the relationships between molecular level changes, pathways, brain circuits and pathophysiological processes. The prototype of PubAnatomy is freely accessible at:[<url>http://brainarray.mbni.med.umich.edu/Brainarray/prototype/PubAnatomy</url>]</p

Detectable Clonal Mosaicism from Birth to Old Age and its Relationship to Cancer

Clonal mosaicism for large chromosomal anomalies (duplications, deletions and uniparental disomy) was detected using SNP microarray data from over 50,000 subjects recruited for genome-wide association studies. This detection method requires a relatively high frequency of cells (>5–10%) with the same abnormal karyotype (presumably of clonal origin) in the presence of normal cells. The frequency of detectable clonal mosaicism in peripheral blood is low (<0.5%) from birth until 50 years of age, after which it rises rapidly to 2–3% in the elderly. Many of the mosaic anomalies are characteristic of those found in hematological cancers and identify common deleted regions that pinpoint the locations of genes previously associated with hematological cancers. Although only 3% of subjects with detectable clonal mosaicism had any record of hematological cancer prior to DNA sampling, those without a prior diagnosis have an estimated 10-fold higher risk of a subsequent hematological cancer (95% confidence interval = 6–18)

Development of multiplex real-time PCR assays for identification of members of the Anopheles funestus species group

BACKGROUND: The malaria vector and non-vector species of the Anopheles funestus group are morphologically very similar and accurate identification is required as part of effective control strategies. In the past, this has relied on morphological and cytogenetic methods but these have been largely superseded by a robust allele-specific PCR (AS-PCR). One disadvantage of AS-PCR is the requirement for post-PCR processing by gel electrophoresis of PCR products. In this study, three new high-throughput 'closed-tube' assays were developed and compared with the previously described AS-PCR technique. METHODS: Protocols for three fluorescence-based assays based on Melt Curve Analysis (MCA), High Resolution Melt (HRM) and TaqMan SNP genotyping were developed to detect and discriminate Anopheles parensis, Anopheles leesoni, Anopheles vaneedeni, Anopheles rivulorum and An. funestus s.s. The sensitivity and specificity of these assays were compared with the widely used AS-PCR in a blind trial using DNA extracted from wild-caught mosquitoes. RESULTS: The TaqMan assay proved to be the most sensitive and specific of the three new assays. The MCA and HRM assays initially gave promising results, but were more sensitive to both DNA quality and quantity and consequently showed a higher rate of incorrect identifications. CONCLUSION: The TaqMan assay proved to be the most robust of the three protocols tested in this study. This assay very effectively identified all five members of the An. funestus group using fluorescently-labeled probes with distinct emission and excitation spectra allowing their independent detection in a single reaction. This method is at least as sensitive and specific as the gold standard AS-PCR approach and because it has no requirement for post-PCR processing is simpler and more rapid to run. The one disadvantage of the TaqMan assay is the cost of this assay, both in terms of initial capital outlay and running cost per sample, which is higher than AS-PCR. However, the cost of both the real-time PCR machine and fluorescently labelled probes required is falling and in the future the cost of this assay is likely to become closer to that of standard PCR

Genome-wide association study of Tourette Syndrome

Tourette Syndrome (TS) is a developmental disorder that has one of the highest familial recurrence rates among neuropsychiatric diseases with complex inheritance. However, the identification of definitive TS susceptibility genes remains elusive. Here, we report the first genome-wide association study (GWAS) of TS in 1285 cases and 4964 ancestry-matched controls of European ancestry, including two European-derived population isolates, Ashkenazi Jews from North America and Israel, and French Canadians from Quebec, Canada. In a primary meta-analysis of GWAS data from these European ancestry samples, no markers achieved a genome-wide threshold of significance (p<5 × 10−8); the top signal was found in rs7868992 on chromosome 9q32 within COL27A1 (p=1.85 × 10−6). A secondary analysis including an additional 211 cases and 285 controls from two closely-related Latin-American population isolates from the Central Valley of Costa Rica and Antioquia, Colombia also identified rs7868992 as the top signal (p=3.6 × 10−7 for the combined sample of 1496 cases and 5249 controls following imputation with 1000 Genomes data). This study lays the groundwork for the eventual identification of common TS susceptibility variants in larger cohorts and helps to provide a more complete understanding of the full genetic architecture of this disorder

Blood Lead Levels and Death from All Causes, Cardiovascular Disease, and Cancer: Results from the NHANES III Mortality Study

BACKGROUND: Analyses of mortality data for participants examined in 1976–1980 in the second National Health and Nutrition Examination Survey (NHANES II) suggested an increased risk of mortality at blood lead levels > 20 μg/dL. Blood lead levels have decreased markedly since the late 1970s. In NHANES III, conducted during 1988–1994, few adults had levels > 20 μg/dL. OBJECTIVE: Our objective in this study was to determine the risk of mortality in relation to lower blood lead levels observed for adult participants of NHANES III. METHODS: We analyzed mortality information for 9,757 participants who had a blood lead measurement and who were ≥ 40 years of age at the baseline examination. Using blood lead levels categorized as < 5, 5 to < 10, and ≥ 10 μg/dL, we determined the relative risk of mortality from all causes, cancer, and cardiovascular disease through Cox proportional hazard regression analysis. RESULTS: Using blood lead levels < 5 μg/dL as the referent, we determined that the relative risk of mortality from all causes was 1.24 [95% confidence interval (CI), 1.05–1.48] for those with blood levels of 5–9 μg/dL and 1.59 (95% CI, 1.28–1.98) for those with blood levels ≥ 10 μg/dL (p for trend < 0.001). The magnitude of risk was similar for deaths due to cardiovascular disease and cancer, and tests for trend were statistically significant (p < 0.01) for both causes of death. CONCLUSION: In a nationally representative sample of the U.S. population, blood lead levels as low as 5–9 μg/dL were associated with an increased risk of death from all causes, cardiovascular disease, and cancer