ترغب بنشر مسار تعليمي؟ اضغط هنا

Statistical Methods and Workflow for Analyzing Human Metabolomics Data

95   0   0.0 ( 0 )
 نشر من قبل Susan Cheng
 تاريخ النشر 2017
والبحث باللغة English




اسأل ChatGPT حول البحث

High-throughput metabolomics investigations, when conducted in large human cohorts, represent a potentially powerful tool for elucidating the biochemical diversity and mechanisms underlying human health and disease. Large-scale metabolomics data, generated using targeted or nontargeted platforms, are increasingly more common. Appropriate statistical analysis of these complex high-dimensional data is critical for extracting meaningful results from such large-scale human metabolomics studies. Herein, we consider the main statistical analytical approaches that have been employed in human metabolomics studies. Based on the lessons learned and collective experience to date in the field, we propose a step-by-step framework for pursuing statistical analyses of human metabolomics data. We discuss the range of options and potential approaches that may be employed at each stage of data management, analysis, and interpretation, and offer guidance on analytical considerations that are important for implementing an analysis workflow. Certain pervasive analytical challenges facing human metabolomics warrant ongoing research. Addressing these challenges will allow for more standardization in the field and lead to analytical advances in metabolomics investigations with the potential to elucidate novel mechanisms underlying human health and disease.



قيم البحث

اقرأ أيضاً

Background. Emerging technologies now allow for mass spectrometry based profiling of up to thousands of small molecule metabolites (metabolomics) in an increasing number of biosamples. While offering great promise for revealing insight into the patho genesis of human disease, standard approaches have yet to be established for statistically analyzing increasingly complex, high-dimensional human metabolomics data in relation to clinical phenotypes including disease outcomes. To determine optimal statistical approaches for metabolomics analysis, we sought to formally compare traditional statistical as well as newer statistical learning methods across a range of metabolomics dataset types. Results. In simulated and experimental metabolomics data derived from large population-based human cohorts, we observed that with an increasing number of study subjects, univariate compared to multivariate methods resulted in a higher false discovery rate due to substantial correlations among metabolites. In scenarios wherein the number of assayed metabolites increases, as in the application of nontargeted versus targeted metabolomics measures, multivariate methods performed especially favorably across a range of statistical operating characteristics. In nontargeted metabolomics datasets that included thousands of metabolite measures, sparse multivariate models demonstrated greater selectivity and lower potential for spurious relationships. Conclusion. When the number of metabolites was similar to or exceeded the number of study subjects, as is common with nontargeted metabolomics analysis of relatively small sized cohorts, sparse multivariate models exhibited the most robust statistical power with more consistent results. These findings have important implications for the analysis of metabolomics studies of human disease.
A number of recent emerging applications call for studying data streams, potentially infinite flows of information updated in real-time. When multiple co-evolving data streams are observed, an important task is to determine how these streams depend o n each other, accounting for dynamic dependence patterns without imposing any restrictive probabilistic law governing this dependence. In this paper we argue that flexible least squares (FLS), a penalized version of ordinary least squares that accommodates for time-varying regression coefficients, can be deployed successfully in this context. Our motivating application is statistical arbitrage, an investment strategy that exploits patterns detected in financial data streams. We demonstrate that FLS is algebraically equivalent to the well-known Kalman filter equations, and take advantage of this equivalence to gain a better understanding of FLS and suggest a more efficient algorithm. Promising experimental results obtained from a FLS-based algorithmic trading system for the S&P 500 Futures Index are reported.
This review outlines concepts of mathematical statistics, elements of probability theory, hypothesis tests and point estimation for use in the analysis of modern astronomical data. Least squares, maximum likelihood, and Bayesian approaches to statist ical inference are treated. Resampling methods, particularly the bootstrap, provide valuable procedures when distributions functions of statistics are not known. Several approaches to model selection and good- ness of fit are considered. Applied statistics relevant to astronomical research are briefly discussed: nonparametric methods for use when little is known about the behavior of the astronomical populations or processes; data smoothing with kernel density estimation and nonparametric regression; unsupervised clustering and supervised classification procedures for multivariate problems; survival analysis for astronomical datasets with nondetections; time- and frequency-domain times series analysis for light curves; and spatial statistics to interpret the spatial distributions of points in low dimensions. Two types of resources are presented: about 40 recommended texts and monographs in various fields of statistics, and the public domain R software system for statistical analysis. Together with its sim 3500 (and growing) add-on CRAN packages, R implements a vast range of statistical procedures in a coherent high-level language with advanced graphics.
84 - Sean Simmons , Cenk Sahinalp , 2016
The projected increase of genotyping in the clinic and the rise of large genomic databases has led to the possibility of using patient medical data to perform genomewide association studies (GWAS) on a larger scale and at a lower cost than ever befor e. Due to privacy concerns, however, access to this data is limited to a few trusted individuals, greatly reducing its impact on biomedical research. Privacy preserving methods have been suggested as a way of allowing more people access to this precious data while protecting patients. In particular, there has been growing interest in applying the concept of differential privacy to GWAS results. Unfortunately, previous approaches for performing differentially private GWAS are based on rather simple statistics that have some major limitations. In particular, they do not correct for population stratification, a major issue when dealing with the genetically diverse populations present in modern GWAS. To address this concern we introduce a novel computational framework for performing GWAS that tailors ideas from differential privacy to protect private phenotype information, while at the same time correcting for population stratification. This framework allows us to produce privacy preserving GWAS results based on two of the most commonly used GWAS statistics: EIGENSTRAT and linear mixed model (LMM) based statistics. We test our differentially private statistics, PrivSTRAT and PrivLMM, on both simulated and real GWAS datasets and find that they are able to protect privacy while returning meaningful GWAS results.
To analyse a very large data set containing lengthy variables, we adopt a sequential estimation idea and propose a parallel divide-and-conquer method. We conduct several conventional sequential estimation procedures separately, and properly integrate their results while maintaining the desired statistical properties. Additionally, using a criterion from the statistical experiment design, we adopt an adaptive sample selection, together with an adaptive shrinkage estimation method, to simultaneously accelerate the estimation procedure and identify the effective variables. We confirm the cogency of our methods through theoretical justifications and numerical results derived from synthesized data sets. We then apply the proposed method to three real data sets, including those pertaining to appliance energy use and particulate matter concentration.
التعليقات
جاري جلب التعليقات جاري جلب التعليقات
سجل دخول لتتمكن من متابعة معايير البحث التي قمت باختيارها
mircosoft-partner

هل ترغب بارسال اشعارات عن اخر التحديثات في شمرا-اكاديميا