Dataset Information

A mixed-modeling framework for analyzing multitask whole-brain network data.

ABSTRACT: The emerging area of brain network analysis considers the brain as a system, providing profound insight into links between system-level properties and health outcomes. Network science has facilitated these analyses and our understanding of how the brain is organized. While network science has catalyzed a paradigmatic shift in neuroscience, methods for statistically analyzing networks have lagged behind. To address this for cross-sectional network data, we developed a mixed-modeling framework that enables quantifying the relationship between phenotype and connectivity patterns, predicting connectivity structure based on phenotype, simulating networks to gain a better understanding of topological variability, and thresholding individual networks leveraging group information. Here we extend this comprehensive approach to enable studying system-level brain properties across multiple tasks. We focus on rest-to-task network changes, but this extension is equally applicable to the assessment of network changes for any repeated task paradigm. Our approach allows (a) assessing population network differences in changes between tasks, and how these changes relate to health outcomes; (b) assessing individual variability in network differences in changes between tasks, and how this variability relates to health outcomes; and (c) deriving more accurate and precise estimates of the relationships between phenotype and health outcomes within a given task.

SUBMITTER: Simpson SL

PROVIDER: S-EPMC6370463 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A mixed-modeling framework for analyzing multitask whole-brain network data.

Simpson Sean L SL Bahrami Mohsen M Laurienti Paul J PJ

Network neuroscience (Cambridge, Mass.) 20190201 2

The emerging area of brain network analysis considers the brain as a system, providing profound insight into links between system-level properties and health outcomes. Network science has facilitated these analyses and our understanding of how the brain is organized. While network science has catalyzed a paradigmatic shift in neuroscience, methods for statistically analyzing networks have lagged behind. To address this for cross-sectional network data, we developed a mixed-modeling framework tha ...[more]

PMID: 30793084

Similar Datasets

Project description:Most small-molecule drug candidates fail before entering the market, frequently because of unexpected toxicity. Often, toxicity is detected only late in drug development, because many types of toxicities, especially idiosyncratic adverse drug reactions (IADRs), are particularly hard to predict and detect. Moreover, drug-induced liver injury (DILI) is the most frequent reason drugs are withdrawn from the market and causes 50% of acute liver failure cases in the United States. A common mechanism often underlies many types of drug toxicities, including both DILI and IADRs. Drugs are bioactivated by drug-metabolizing enzymes into reactive metabolites, which then conjugate to sites in proteins or DNA to form adducts. DNA adducts are often mutagenic and may alter the reading and copying of genes and their regulatory elements, causing gene dysregulation and even triggering cancer. Similarly, protein adducts can disrupt their normal biological functions and induce harmful immune responses. Unfortunately, reactive metabolites are not reliably detected by experiments, and it is also expensive to test drug candidates for potential to form DNA or protein adducts during the early stages of drug development. In contrast, computational methods have the potential to quickly screen for covalent binding potential, thereby flagging problematic molecules and reducing the total number of necessary experiments. Here, we train a deep convolution neural network-the XenoSite reactivity model-using literature data to accurately predict both sites and probability of reactivity for molecules with glutathione, cyanide, protein, and DNA. On the site level, cross-validated predictions had area under the curve (AUC) performances of 89.8% for DNA and 94.4% for protein. Furthermore, the model separated molecules electrophilically reactive with DNA and protein from nonreactive molecules with cross-validated AUC performances of 78.7% and 79.8%, respectively. On both the site- and molecule-level, the model's performances significantly outperformed reactivity indices derived from quantum simulations that are reported in the literature. Moreover, we developed and applied a selectivity score to assess preferential reactions with the macromolecules as opposed to the common screening traps. For the entire data set of 2803 molecules, this approach yielded totals of 257 (9.2%) and 227 (8.1%) molecules predicted to be reactive only with DNA and protein, respectively, and hence those that would be missed by standard reactivity screening experiments. Site of reactivity data is an underutilized resource that can be used to not only predict if molecules are reactive, but also show where they might be modified to reduce toxicity while retaining efficacy. The XenoSite reactivity model is available at http://swami.wustl.edu/xenosite/p/reactivity.

Project description:BackgroundIn medical informatics, psychology, market research and many other fields, researchers often need to analyze and model ranking data. However, there is no statistical software that provides tools for the comprehensive analysis of ranking data. Here, we present pmr, an R package for analyzing and modeling ranking data with a bundle of tools. The pmr package enables descriptive statistics (mean rank, pairwise frequencies, and marginal matrix), Analytic Hierarchy Process models (with Saaty's and Koczkodaj's inconsistencies), probability models (Luce model, distance-based model, and rank-ordered logit model), and the visualization of ranking data with multidimensional preference analysis.ResultsExamples of the use of package pmr are given using a real ranking dataset from medical informatics, in which 566 Hong Kong physicians ranked the top five incentives (1: competitive pressures; 2: increased savings; 3: government regulation; 4: improved efficiency; 5: improved quality care; 6: patient demand; 7: financial incentives) to the computerization of clinical practice. The mean rank showed that item 4 is the most preferred item and item 3 is the least preferred item, and significance difference was found between physicians' preferences with respect to their monthly income. A multidimensional preference analysis identified two dimensions that explain 42% of the total variance. The first can be interpreted as the overall preference of the seven items (labeled as "internal/external"), and the second dimension can be interpreted as their overall variance of (labeled as "push/pull factors"). Various statistical models were fitted, and the best were found to be weighted distance-based models with Spearman's footrule distance.ConclusionsIn this paper, we presented the R package pmr, the first package for analyzing and modeling ranking data. The package provides insight to users through descriptive statistics of ranking data. Users can also visualize ranking data by applying a thought multidimensional preference analysis. Various probability models for ranking data are also included, allowing users to choose that which is most suitable to their specific situations.

Dataset Information

A mixed-modeling framework for analyzing multitask whole-brain network data.

Publications

A mixed-modeling framework for analyzing multitask whole-brain network data.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure