Dataset Information

Discovering General Multidimensional Associations.

ABSTRACT: When two variables are related by a known function, the coefficient of determination (denoted R2) measures the proportion of the total variance in the observations explained by that function. For linear relationships, this is equal to the square of the correlation coefficient, ?. When the parametric form of the relationship is unknown, however, it is unclear how to estimate the proportion of explained variance equitably--assigning similar values to equally noisy relationships. Here we demonstrate how to directly estimate a generalised R2 when the form of the relationship is unknown, and we consider the performance of the Maximal Information Coefficient (MIC)--a recently proposed information theoretic measure of dependence. We show that our approach behaves equitably, has more power than MIC to detect association between variables, and converges faster with increasing sample size. Most importantly, our approach generalises to higher dimensions, estimating the strength of multivariate relationships (Y against A, B, …) as well as measuring association while controlling for covariates (Y against X controlling for C). An R package named matie ("Measuring Association and Testing Independence Efficiently") is available (http://cran.r-project.org/web/packages/matie/).

SUBMITTER: Murrell B

PROVIDER: S-EPMC4798755 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Publications

Discovering General Multidimensional Associations.

Murrell Ben B Murrell Daniel D Murrell Hugh H

PloS one 20160318 3

When two variables are related by a known function, the coefficient of determination (denoted R2) measures the proportion of the total variance in the observations explained by that function. For linear relationships, this is equal to the square of the correlation coefficient, ρ. When the parametric form of the relationship is unknown, however, it is unclear how to estimate the proportion of explained variance equitably--assigning similar values to equally noisy relationships. Here we demonstrat ...[more]

PMID: 26991498

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Project description:BackgroundThe Health Information Technology for Economic and Clinical Health Act (HITECH) has greatly accelerated the adoption of electronic health records (EHRs) with the promise of better clinical decisions and patients' outcomes. One of the core criteria for "Meaningful Use" of EHRs is to have a problem list that shows the most important health problems faced by a patient. The implementation of problem lists in EHRs has a potential to help practitioners to provide customized care to patients. However, it remains an open question on how to leverage problem lists in different practice settings to provide tailored care, of which the bottleneck lies in the associations between problem list and practice setting.MethodsIn this study, using sampled clinical documents associated with a cohort of patients who received their primary care at Mayo Clinic, we investigated the associations between problem list and practice setting through natural language processing (NLP) and topic modeling techniques. Specifically, after practice settings and problem lists were normalized, statistical χ2 test, term frequency-inverse document frequency (TF-IDF) and enrichment analysis were used to choose representative concepts for each setting. Then Latent Dirichlet Allocations (LDA) were used to train topic models and predict potential practice settings using similarity metrics based on the problem concepts representative of practice settings. Evaluation was conducted through 5-fold cross validation and Recall@k, Precision@k and F1@k were calculated.ResultsOur method can generate prioritized and meaningful problem lists corresponding to specific practice settings. For practice setting prediction, recall increases from 0.719 (k = 2) to 0.931 (k = 10), precision increases from 0.882 (k = 2) to 0.931 (k = 10) and F1 increases from 0.790 (k = 2) to 0.931 (k = 10).ConclusionTo our best knowledge, our study is the first attempting to discover the association between the problem lists and hospital practice settings. In the future, we plan to investigate how to provide more tailored care by utilizing the association between problem list and practice setting revealed in this study.

Project description:A genome-wide association study (GWAS) typically involves examining representative SNPs in individuals from some population. A GWAS data set can concern a million SNPs and may soon concern billions. Researchers investigate the association of each SNP individually with a disease, and it is becoming increasingly commonplace to also analyze multi-SNP associations. Techniques for handling so many hypotheses include the Bonferroni correction and recently developed bayesian methods. These methods can encounter problems. Most importantly, they are not applicable to a complex multi-locus hypothesis which has several competing hypotheses rather than only a null hypothesis. A method that computes the posterior probability of complex hypotheses is a pressing need.We introduce the bayesian network posterior probability (BNPP) method which addresses the difficulties. The method represents the relationship between a disease and SNPs using a directed acyclic graph (DAG) model, and computes the likelihood of such models using a bayesian network scoring criterion. The posterior probability of a hypothesis is computed based on the likelihoods of all competing hypotheses. The BNPP can not only be used to evaluate a hypothesis that has previously been discovered or suspected, but also to discover new disease loci associations. The results of experiments using simulated and real data sets are presented. Our results concerning simulated data sets indicate that the BNPP exhibits both better evaluation and discovery performance than does a p-value based method. For the real data sets, previous findings in the literature are confirmed and additional findings are found.We conclude that the BNPP resolves a pressing problem by providing a way to compute the posterior probability of complex multi-locus hypotheses. A researcher can use the BNPP to determine the expected utility of investigating a hypothesis further. Furthermore, we conclude that the BNPP is a promising method for discovering disease loci associations.

Project description:BACKGROUND: Experimental techniques such as DNA microarray, serial analysis of gene expression (SAGE) and mass spectrometry proteomics, among others, are generating large amounts of data related to genes and proteins at different levels. As in any other experimental approach, it is necessary to analyze these data in the context of previously known information about the biological entities under study. The literature is a particularly valuable source of information for experiment validation and interpretation. Therefore, the development of automated text mining tools to assist in such interpretation is one of the main challenges in current bioinformatics research. RESULTS: We present a method to create literature profiles for large sets of genes or proteins based on common semantic features extracted from a corpus of relevant documents. These profiles can be used to establish pair-wise similarities among genes, utilized in gene/protein classification or can be even combined with experimental measurements. Semantic features can be used by researchers to facilitate the understanding of the commonalities indicated by experimental results. Our approach is based on non-negative matrix factorization (NMF), a machine-learning algorithm for data analysis, capable of identifying local patterns that characterize a subset of the data. The literature is thus used to establish putative relationships among subsets of genes or proteins and to provide coherent justification for this clustering into subsets. We demonstrate the utility of the method by applying it to two independent and vastly different sets of genes. CONCLUSION: The presented method can create literature profiles from documents relevant to sets of genes. The representation of genes as additive linear combinations of semantic features allows for the exploration of functional associations as well as for clustering, suggesting a valuable methodology for the validation and interpretation of high-throughput experimental data.

Dataset Information

Discovering General Multidimensional Associations.

Publications

Discovering General Multidimensional Associations.

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