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| 2. |
- Spjuth, Ola, 1977-, et al.
(författare)
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E-Science technologies in a workflow for personalized medicine using cancer screening as a case study
- 2017
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Ingår i: JAMIA Journal of the American Medical Informatics Association. - : Oxford University Press. - 1067-5027 .- 1527-974X. ; 24:5, s. 950-957
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Tidskriftsartikel (refereegranskat)abstract
- Objective: We provide an e-Science perspective on the workflow from risk factor discovery and classification of disease to evaluation of personalized intervention programs. As case studies, we use personalized prostate and breast cancer screenings.Materials and Methods: We describe an e-Science initiative in Sweden, e-Science for Cancer Prevention and Control (eCPC), which supports biomarker discovery and offers decision support for personalized intervention strategies. The generic eCPC contribution is a workflow with 4 nodes applied iteratively, and the concept of e-Science signifies systematic use of tools from the mathematical, statistical, data, and computer sciences.Results: The eCPC workflow is illustrated through 2 case studies. For prostate cancer, an in-house personalized screening tool, the Stockholm-3 model (S3M), is presented as an alternative to prostate-specific antigen testing alone. S3M is evaluated in a trial setting and plans for rollout in the population are discussed. For breast cancer, new biomarkers based on breast density and molecular profiles are developed and the US multicenter Women Informed to Screen Depending on Measures (WISDOM) trial is referred to for evaluation. While current eCPC data management uses a traditional data warehouse model, we discuss eCPC-developed features of a coherent data integration platform.Discussion and Conclusion: E-Science tools are a key part of an evidence-based process for personalized medicine. This paper provides a structured workflow from data and models to evaluation of new personalized intervention strategies. The importance of multidisciplinary collaboration is emphasized. Importantly, the generic concepts of the suggested eCPC workflow are transferrable to other disease domains, although each disease will require tailored solutions.
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| 3. |
- Leu, Monica, et al.
(författare)
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NordicDB : a Nordic pool and portal for genome-wide control data
- 2010
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Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 18:12, s. 1322-1326
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Tidskriftsartikel (refereegranskat)abstract
- A cost-efficient way to increase power in a genetic association study is to pool controls from different sources. The genotyping effort can then be directed to large case series. The Nordic Control database, NordicDB, has been set up as a unique resource in the Nordic area and the data are available for authorized users through the web portal (http://www.nordicdb.org). The current version of NordicDB pools together high-density genome-wide SNP information from similar to 5000 controls originating from Finnish, Swedish and Danish studies and shows country-specific allele frequencies for SNP markers. The genetic homogeneity of the samples was investigated using multidimensional scaling (MDS) analysis and pairwise allele frequency differences between the studies. The plot of the first two MDS components showed excellent resemblance to the geographical placement of the samples, with a clear NW-SE gradient. We advise researchers to assess the impact of population structure when incorporating NordicDB controls in association studies. This harmonized Nordic database presents a unique genome-wide resource for future genetic association studies in the Nordic countries. European Journal of Human Genetics (2010) 18, 1322-1326; doi: 10.1038/ejhg.2010.112; published online 28 July 2010
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| 4. |
- Sjolander, Arvid, et al.
(författare)
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Sensitivity Analysis for Principal Stratum Direct Effects, with an Application to a Study of Physical Activity and Coronary Heart Disease
- 2009
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Ingår i: Biometrics. - : Wiley. - 0006-341X .- 1541-0420. ; 65:2, s. 514-520
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Tidskriftsartikel (refereegranskat)abstract
- In many studies, the aim is to learn about the direct exposure effect, that is, the effect not mediated through an intermediate variable. For example, in circulation disease studies it may be of interest to assess whether a suitable level of physical activity can prevent disease, even if it fails to prevent obesity. It is well known that stratification on the intermediate may introduce a so-called posttreatment selection bias. To handle this problem, we use the framework of principal stratification (Frangakis and Rubin, 2002, Biometrics 58, 21-29) to define a causally relevant estimand-the principal stratum direct effect (PSDE). The PSDE is not identified in our setting. We propose a method of sensitivity analysis that yields a range of plausible values for the causal estimand. We compare our work to similar methods proposed in the literature for handling the related problem of ""truncation by death."".
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| 5. |
- Christoffersen, Benjamin, et al.
(författare)
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Quasi-Monte Carlo Methods for Binary Event Models with Complex Family Data
- 2023
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Ingår i: Journal of Computational And Graphical Statistics. - : Informa UK Limited. - 1061-8600 .- 1537-2715. ; 32:4, s. 1393-1401
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Tidskriftsartikel (refereegranskat)abstract
- The generalized linear mixed model for binary outcomes with the probit link function is used in many fields but has a computationally challenging likelihood when there are many random effects. We extend a previously used importance sampler, making it much faster in the context of estimating heritability and related effects from family data by adding a gradient and a Hessian approximation and making a faster implementation. Additionally, a graph-based method is suggested to simplify the likelihood when there are thousands of individuals in each family. Simulation studies show that the resulting method is orders of magnitude faster, has a negligible efficiency loss, and confidence intervals with nominal coverage. We also analyze data from a large study of obsessive-compulsive disorder based on Swedish multi-generational data. In this analysis, the proposed method yielded similar results to a previous analysis, but was much faster. Supplementary materials for this article are available online.
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| 6. |
- Grünewald, Maria, et al.
(författare)
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A Stochastic EM type algorithm for estimation in data with ascertainment on continuous outcomes
- 2008
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Outcome dependent sampling probabilities can be used to increase efficiency in observational studies. For continuous outcomes appropriate consideration of sampling design in estimating parameters of interest is often computationally cumbersome. In this article we suggest a Stochastic EM type algorithm for estimation. The computational complexity of the likelihood is avoided by filling in missing data so that the full data likelihood can be used. The method is not restricted to any specific distribution of the data and can be used for a broad range of statistical models.
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| 7. |
- Grünewald, Maria, 1976-, et al.
(författare)
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A Stochastic EM Type Algorithm for Parameter Estimation in Models with Continuous Outcomes, under Complex Ascertainment
- 2010
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Ingår i: The International Journal of Biostatistics. - : Walter de Gruyter GmbH. - 1557-4679. ; 6:1, s. Article 23-
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Tidskriftsartikel (refereegranskat)abstract
- Outcome-dependent sampling probabilities can be used to increase efficiency in observational studies. For continuous outcomes, appropriate consideration of sampling design in estimating parameters of interest is often computationally cumbersome. In this article, we suggest a Stochastic EM type algorithm for estimation when ascertainment probabilities are known or estimable. The computational complexity of the likelihood is avoided by filling in missing data so that an approximation of the full data likelihood can be used. The method is not restricted to any specific distribution of the data and can be used for a broad range of statistical models.
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| 8. |
- Grünewald, Maria, 1976-
(författare)
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Design and analysis of response selective samples in observational studies
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Outcome dependent sampling may increase efficiency in observational studies. It is however not always obvious how to sample efficiently, and how to analyze the resulting data without introducing bias. This thesis describes a general framework for efficiency calculations in multistage sampling, with focus on what is sometimes referred to as ascertainment sampling. A method for correcting for the sampling scheme in analysis of ascertainment samples is also presented. Simulation based methods are used to overcome computational issues in both efficiency calculations and analysis of data.
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| 9. |
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| 10. |
- Sjölander, Arvid, et al.
(författare)
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Fine Mapping of Disease Genes Using Tagging SNPs
- 2007
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Ingår i: Annals of Human Genetics. - : Wiley. - 1469-1809 .- 0003-4800. ; 71:6, s. 815-827
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Tidskriftsartikel (refereegranskat)abstract
- We describe a haplotype clustering approach for localising a disease mutation within a fixed genomic region, which supplements tagging SNP (tSNP) information with (external) information on linkage disequilibrium. By applying our method to simulated data based on the coalescent, and on real haplotype data, we demonstrate that there are situations where significant gains can be made by incorporating tagged SNPs into the analysis. The issues we explore are important not only to these types of studies, but also to studies that select tSNPs based on (external) HapMap phase II data, and those that use genome-wide markers.
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