An algorithm for optimal testing in co-segregation analysis.

Clinical genetic sequencing tests often identify variants of uncertain significance. One source of data that can help classify the pathogenicity of variants is familial cosegregation analysis. Identifying and genotyping relatives for cosegregation analysis can be time consuming and costly. We propose an algorithm that describes a single measure of expected variant information gain from genotyping a single additional relative in a family. Then we explore the performance of this algorithm by comparing actual recruitment strategies used in 35 families who had pursued cosegregation analysis with synthetic pedigrees of possible testing outcomes if the families had pursued an optimized testing strategy instead. For each actual and synthetic pedigree, we calculated the likelihood ratio of pathogenicity as each successive test was added to the pedigree. We analyzed the differences in cosegregation likelihood ratio over time resulting from actual versus optimized testing approaches. Employing the testing strategy indicated by the algorithm would have led to maximal information more rapidly in 30 of the 35 pedigrees (86%). Many clinical and research laboratories are involved in targeted cosegregation analysis. The algorithm we present can facilitate a data driven approach to optimal relative recruitment and genotyping for cosegregation analysis and more efficient variant classification.

Characterizing Websites That Provide Information About Complementary and Integrative Health: Systematic Search and Evaluation of Five Domains.

BACKGROUND: In recent years, there has been an increase in the utilization of complementary and integrative health (CIH) care, and an increase in information-seeking behavior focused on CIH. Thus, understanding the quality of CIH information that is available on the internet is imperative. Although there have been a limited number of studies evaluating the quality of websites providing information about specific CIH-related topics, a broad evaluation of CIH websites has not been conducted. OBJECTIVE: This study was designed to fill that gap. We set out to assess website quality in 5 CIH domains: (1) acupuncture, (2) homeopathy, (3) massage, (4) reiki, and (5) yoga. This study aimed to 1) characterize the websites by type and quality; 2) evaluate website characteristics which may affect readers' perceptions, specifically message content, structural features, and presentation style, and 3) investigate the extent to which harms, benefits and purposes of use are stated on websites. METHODS: This study employed a systematic search strategy to identify websites in each of the target domains to be evaluated. The websites were then classified by type, and a set of checklists focusing on quality, message content, structural features, and presentation style was used to evaluate the websites. Lastly, we performed content analysis to identify harms, benefits, and perceived purposes of use. RESULTS: There were similarities across domains regarding their overall quality and their message content. Across all domains, a high proportion of websites received strong scores in terms of ownership, currency, interactivity and navigability. Scores were more variable concerning authorship, balanced presentation of information and the use of sources of information. However, there were differences regarding their structural features and presentation style. Acupuncture and reiki sites tended to include more external links, and yoga, fewer. There was variation across domains in the extent to which the websites contained domain-specific terminology. Websites tended to provide an extensive list of potential benefits, while reporting of harms was scarce. CONCLUSIONS: This is the first study to perform a multidimensional assessment of websites in multiple CIH domains. This review showed that while there are similarities among websites of different CIH domains, there are also differences. The diverse distribution of website types suggests that, regardless of CIH domain, the public encounters information through many different types of media, and it would be useful to consider how the presentation of this content may differ depending on the medium. The characteristics for which variability exist are areas that warrant greater attention from researchers, policy makers, clinicians and patients. There is also a need to better understand how individuals may interact with CIH websites, and to develop tools to assist people to interpret the CIH-related information that they encounter.