skip to main content
US FlagAn official website of the United States government
dot gov icon
Official websites use .gov
A .gov website belongs to an official government organization in the United States.
https lock icon
Secure .gov websites use HTTPS
A lock ( lock ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Attention:

The NSF Public Access Repository (PAR) system and access will be unavailable from 11:00 PM ET on Friday, May 16 until 2:00 AM ET on Saturday, May 17 due to maintenance. We apologize for the inconvenience.


Title: The Generalized Fisher's Combination and Accurate P -Value Calculation under Dependence
Abstract Combining dependent tests of significance has broad applications but the related p-value calculation is challenging. For Fisher's combination test, current p-value calculation methods (eg, Brown's approximation) tend to inflate the type I error rate when the desired significance level is substantially less than 0.05. The problem could lead to significant false discoveries in big data analyses. This paper provides two main contributions. First, it presents a general family of Fisher type statistics, referred to as the GFisher, which covers many classic statistics, such as Fisher's combination, Good's statistic, Lancaster's statistic, weighted Z-score combination, and so forth. The GFisher allows a flexible weighting scheme, as well as an omnibus procedure that automatically adapts proper weights and the statistic-defining parameters to a given data. Second, the paper presents several new p-value calculation methods based on two novel ideas: moment-ratio matching and joint-distribution surrogating. Systematic simulations show that the new calculation methods are more accurate under multivariate Gaussian, and more robust under the generalized linear model and the multivariate t-distribution. The applications of the GFisher and the new p-value calculation methods are demonstrated by a gene-based single nucleotide polymorphism (SNP)-set association study. Relevant computation has been implemented to an R package GFisher available on the Comprehensive R Archive Network.  more » « less
Award ID(s):
2113570 1812082
PAR ID:
10485788
Author(s) / Creator(s):
;
Publisher / Repository:
Oxford University Press
Date Published:
Journal Name:
Biometrics
Volume:
79
Issue:
2
ISSN:
0006-341X
Format(s):
Medium: X Size: p. 1159-1172
Size(s):
p. 1159-1172
Sponsoring Org:
National Science Foundation
More Like this
  1. Two-sample testing is a fundamental problem in statistics. While many powerful nonparametric methods exist for both the univariate and multivariate context, it is comparatively less common to see a framework for determining which data features lead to rejection of the null. In this paper, we propose a new nonparametric two-sample test named AUGUST, which incorporates a framework for interpretation while maintaining power comparable to existing methods. AUGUST tests for inequality in distribution up to a predetermined resolution using symmetry statistics from binary expansion. Designed for univariate and low to moderate-dimensional multivariate data, this construction allows us to understand distributional differences as a combination of fundamental orthogonal signals. Asymptotic theory for the test statistic facilitates p-value computation and power analysis, and an efficient algorithm enables computation on large data sets. In empirical studies, we show that our test has power comparable to that of popular existing methods, as well as greater power in some circumstances. We illustrate the interpretability of our method using NBA shooting data. 
    more » « less
  2. Schwartz, Russell (Ed.)
    Abstract Summary PERMANOVA (permutational multivariate analysis of variance based on distances) has been widely used for testing the association between the microbiome and a covariate of interest. Statistical significance is established by permutation, which is computationally intensive for large sample sizes. As large-scale microbiome studies, such as American Gut Project (AGP), become increasingly popular, a computationally efficient version of PERMANOVA is much needed. To achieve this end, we derive the asymptotic distribution of the PERMANOVA pseudo-F statistic and provide analytical P-value calculation based on chi-square approximation. We show that the asymptotic P-value is close to the PERMANOVA P-value even under a moderate sample size. Moreover, it is more accurate and an order-of-magnitude faster than the permutation-free method MDMR. We demonstrated the use of our procedure D-MANOVA on the AGP dataset. Availability and implementation D-MANOVA is implemented by the dmanova function in the CRAN package GUniFrac. Supplementary information Supplementary data are available at Bioinformatics online. 
    more » « less
  3. Abstract Due to the hierarchical structure of the tree of life, closely related species often resemble each other more than distantly related species; a pattern termed phylogenetic signal. Numerous univariate statistics have been proposed as measures of phylogenetic signal for single phenotypic traits, but the study of phylogenetic signal for multivariate data, as is common in modern biology, remains challenging. Here, we introduce a new method to explore phylogenetic signal in multivariate phenotypes. Our approach decomposes the data into linear combinations with maximal (or minimal) phylogenetic signal, as measured by Blomberg’s K. The loading vectors of these phylogenetic components or K-components can be biologically interpreted, and scatterplots of the scores can be used as a low-dimensional ordination of the data that maximally (or minimally) preserves phylogenetic signal. We present algebraic and statistical properties, along with 2 new summary statistics, KA and KG, of phylogenetic signal in multivariate data. Simulation studies showed that KA and KG have higher statistical power than the previously suggested statistic Km⁢u⁢l⁢t, especially if phylogenetic signal is low or concentrated in a few trait dimensions. In 2 empirical applications to vertebrate cranial shape (crocodyliforms and papionins), we found statistically significant phylogenetic signal concentrated in a few trait dimensions. The finding that phylogenetic signal can be highly variable across the dimensions of multivariate phenotypes has important implications for current maximum likelihood approaches to phylogenetic signal in multivariate data. 
    more » « less
  4. Abstract BackgroundCells progressing from an early state to a developed state give rise to lineages in cell differentiation. Knowledge of these lineages is central to developmental biology. Each biological lineage corresponds to a trajectory in a dynamical system. Emerging single-cell technologies such as single-cell RNA sequencing can capture molecular abundance in diverse cell types in a developing tissue. Many computational methods have been developed to infer trajectories from single-cell data. However, to our knowledge, none of the existing methods address the problem of determining the existence of a trajectory in observed data before attempting trajectory inference. ResultsWe introduce a method to identify the existence of a trajectory using three graph-based statistics. A permutation test is utilized to calculate the empirical distribution of the test statistic under the null hypothesis that a trajectory does not exist. Finally, ap-value is calculated to quantify the statistical significance for the presence of trajectory in the data. ConclusionsOur work contributes new statistics to assess the level of uncertainty in trajectory inference to increase the understanding of biological system dynamics. 
    more » « less
  5. Abstract It is well known that the power spectrum is not able to fully characterize the statistical properties of non-Gaussian density fields. Recently, many different statistics have been proposed to extract information from non-Gaussian cosmological fields that perform better than the power spectrum. The Fisher matrix formalism is commonly used to quantify the accuracy with which a given statistic can constrain the value of the cosmological parameters. However, these calculations typically rely on the assumption that the sampling distribution of the considered statistic follows a multivariate Gaussian distribution. In this work, we follow Sellentin & Heavens and use two different statistical tests to identify non-Gaussianities in different statistics such as the power spectrum, bispectrum, marked power spectrum, and wavelet scattering transform (WST). We remove the non-Gaussian components of the different statistics and perform Fisher matrix calculations with theGaussianizedstatistics using Quijote simulations. We show that constraints on the parameters can change by a factor of ∼2 in some cases. We show with simple examples how statistics that do not follow a multivariate Gaussian distribution can achieve artificially tight bounds on the cosmological parameters when using the Fisher matrix formalism. We think that the non-Gaussian tests used in this work represent a powerful tool to quantify the robustness of Fisher matrix calculations and their underlying assumptions. We release the code used to compute the power spectra, bispectra, and WST that can be run on both CPUs and GPUs. 
    more » « less