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Leveraging existing data sets to generate new insights into Alzheimer's disease biology in specific patient subsets.

ABSTRACT: To generate new insights into the biology of Alzheimer's Disease (AD), we developed methods to combine and reuse a wide variety of existing data sets in new ways. We first identified genes consistently associated with AD in each of four separate expression studies, and confirmed this result using a fifth study. We next developed algorithms to search hundreds of thousands of Gene Expression Omnibus (GEO) data sets, identifying a link between an AD-associated gene (NEUROD6) and gender. We therefore stratified patients by gender along with APOE4 status, and analyzed multiple SNP data sets to identify variants associated with AD. SNPs in either the region of NEUROD6 or SNAP25 were significantly associated with AD, in APOE4+ females and APOE4+ males, respectively. We developed algorithms to search Connectivity Map (CMAP) data for medicines that modulate AD-associated genes, identifying hypotheses that warrant further investigation for treating specific AD patient subsets. In contrast to other methods, this approach focused on integrating multiple gene expression datasets across platforms in order to achieve a robust intersection of disease-affected genes, and then leveraging these results in combination with genetic studies in order to prioritize potential genes for targeted therapy.

SUBMITTER: Fowler KD

PROVIDER: S-EPMC4585817 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Leveraging existing data sets to generate new insights into Alzheimer's disease biology in specific patient subsets.

Fowler Kevin D KD Funt Jason M JM Artyomov Maxim N MN Zeskind Benjamin B Kolitz Sarah E SE Towfic Fadi F

Scientific reports 20150923

To generate new insights into the biology of Alzheimer's Disease (AD), we developed methods to combine and reuse a wide variety of existing data sets in new ways. We first identified genes consistently associated with AD in each of four separate expression studies, and confirmed this result using a fifth study. We next developed algorithms to search hundreds of thousands of Gene Expression Omnibus (GEO) data sets, identifying a link between an AD-associated gene (NEUROD6) and gender. We therefor ...[more]

PMID: 26395074

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Project description:IntroductionSince 2008, Egypt has four existing generic bi-annually rotating warning labels (WLs) on 50% of the waterpipe tobacco packs (WTPs). The Ministry of Health Tobacco Control Unit proposed increasing WL size to 80%, removing colours and flavour imagery from WTPs, and plain packaging to help curb the rising epidemic of waterpipe tobacco smoking. Therefore, we measured the perceived efficacy of existing against novel enhanced (generic and waterpipe-specific) WTP WLs and the associated factors among Egyptian waterpipe smokers and nonsmokers.MethodsA purposive quota sample of 2014 adults was surveyed in two rounds using face interviews. At each round, participants were randomly shown one of four existing WLs, then one of four novel WLs. Participants rated the perceived efficacy of existing and novel WLs regarding the salience, depth of processing, affective reactions, credibility, relevance, perceived harm and perceived behavioural control. Data were analysed using Generalized Estimating Equations.ResultsParticipants rated novel WTP WLs with higher mean perceived efficacy scores than existing WLs for all measures, although both sets collectively scored modestly (59.7; 95% CI: 58.9-60.5 vs 53.0; 95% CI: 52.1-54.0, respectively; p<0.001). Relative to the existing WTP WLs, novel WLs were particularly able to induce higher salience, affective reactions, and depth of processing. Relative to the generic novel WTP WLs, waterpipe-specific WLs induced higher relevance, perceived harm, and affective reactions. Nonsmokers scored higher than waterpipe tobacco smokers, specifically for perceived behavioral control (65.0±32.5 vs 43.6±19.8, respectively; p<0.001). WTP WLs featuring proximal risks, such as dental effects (β = 9.70; 95% CI: 7.00-12.40), fetal harm (β = 9.42; 95% CI: 6.75-12.10), or toxic contents (β = 9.14; 95% CI: 6.58-11.70) were strongly associated with participants' perceived efficacy scores. Among other independent factors, rural residence (β = 24.09; 95% CI: 22.21-25.97), being a nonsmoker (β = 10.51; 95% CI: 8.92-12.10), survey round 2 (β = 6.96, 95% CI: 5.73-8.19), the novel WTP WL set (β = 6.68; 95% CI: 6.19-7.17), and having higher education (β = 6.31; 95% CI: 4.34-8.27) were highly associated with participants' perceived efficacy scores.ConclusionsWaterpipe-specific WLs on plain WTPs that feature proximal risks and address different population subgroups need to be developed in conjunction with awareness raising campaigns on WTS harms to reinforce the credibility of WTP WLs. Our findings suggest the proposed WTP WL enhancements by the Tobacco Control Unit may support a more effective WTP labelling policy within a comprehensive waterpipe-specific tobacco control framework.

Project description:Rationale: As donor contributions for HIV/AIDS stagnate globally, national governments must seek ways to improve use of existing resources through interventions to drive efficiency at the facility level. But program managers lack routine information on unit expenditures at points of care, and higher-level planners are unable to assess resource use in the health system. Thus, managers cannot measure current levels of technical efficiency, and are unable to evaluate effectiveness of interventions to increase technical efficiency. Phased Implementation of REMS: FHI 360 developed the Routine Efficiency Monitoring System (REMS)-a relational database leveraging existing budget, expenditure and output data to produce quarterly site-level estimates of unit expenditure per service. Along with the Government of the Republic of Zambia (GRZ) and implementation partner Avencion, we configured REMS to measure technical efficiency of Ministry of Health resources used to deliver HIV/AIDS services in 326 facilities in 17 high-priority districts in Copperbelt and Central Provinces. REMS allocation algorithms were developed through facility assessments, and key informant interviews with MoH staff. Existing IFMIS and DHIS-2 data streams provide recurring flows of expenditure and output data needed to estimate service-specific unit expenditures. Trained users access REMS output through user-friendly dashboards delivered through a web-based application. REMS as a Solution: District health managers use REMS to identify "outlier" facilities to test performance improvement interventions. Provincial and national planners are using REMS to seek savings and ensure that resources are directed to geographic and programmatic areas with highest need. REMS can support reimbursement for social health insurance and provide time-series data on facility-level costs for modeling. Conclusions and Next Steps: REMS gives managers and planners substantially-improved data on how programs transform resources into services. The GRZ is seeking funding to expand REMS nationally, covering all major disease areas. Improved technical efficiency supports the goal of a sustainable HIV/AIDS response.

Project description:An increasing body of literature suggests that both individual and collections of bacteria are associated with the progression of colorectal cancer. As the number of studies investigating these associations increases and the number of subjects in each study increases, a meta-analysis to identify the associations that are the most predictive of disease progression is warranted. We analyzed previously published 16S rRNA gene sequencing data collected from feces and colon tissue. We quantified the odds ratios (ORs) for individual bacterial taxa that were associated with an individual having tumors relative to a normal colon. Among the fecal samples, there were no taxa that had significant ORs associated with adenoma and there were 8 taxa with significant ORs associated with carcinoma. Similarly, among the tissue samples, there were no taxa that had a significant OR associated with adenoma and there were 3 taxa with significant ORs associated with carcinoma. Among the significant ORs, the association between individual taxa and tumor diagnosis was equal to or below 7.11. Because individual taxa had limited association with tumor diagnosis, we trained Random Forest classification models using only the taxa that had significant ORs, using the entire collection of taxa found in each study, and using operational taxonomic units defined based on a 97% similarity threshold. All training approaches yielded similar classification success as measured using the area under the curve. The ability to correctly classify individuals with adenomas was poor, and the ability to classify individuals with carcinomas was considerably better using sequences from feces or tissue.IMPORTANCE Colorectal cancer is a significant and growing health problem in which animal models and epidemiological data suggest that the colonic microbiota have a role in tumorigenesis. These observations indicate that the colonic microbiota is a reservoir of biomarkers that may improve our ability to detect colonic tumors using noninvasive approaches. This meta-analysis identifies and validates a set of 8 bacterial taxa that can be used within a Random Forest modeling framework to differentiate individuals as having normal colons or carcinomas. When models trained using one data set were tested on other data sets, the models performed well. These results lend support to the use of fecal biomarkers for the detection of tumors. Furthermore, these biomarkers are plausible candidates for further mechanistic studies into the role of the gut microbiota in tumorigenesis.

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Leveraging existing data sets to generate new insights into Alzheimer's disease biology in specific patient subsets.

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Leveraging existing data sets to generate new insights into Alzheimer's disease biology in specific patient subsets.

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