Multivariate regression analysis of distance matrices for testing associations between gene expression patterns and related variables. Proc Natl Acad Sci USA

Biomedical Sciences Graduate Program and the Polymorphism Research Laboratory, Department of Psychiatry, Moores UCSD Cancer Center, Center for Human Genetics and Genomics, University of California at San Diego, La Jolla, CA 92093, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 01/2007; 103(51):19430-5. DOI: 10.1073/pnas.0609333103
Source: PubMed


A fundamental step in the analysis of gene expression and other high-dimensional genomic data is the calculation of the similarity or distance between pairs of individual samples in a study. If one has collected N total samples and assayed the expression level of G genes on those samples, then an N x N similarity matrix can be formed that reflects the correlation or similarity of the samples with respect to the expression values over the G genes. This matrix can then be examined for patterns via standard data reduction and cluster analysis techniques. We consider an alternative to conventional data reduction and cluster analyses of similarity matrices that is rooted in traditional linear models. This analysis method allows predictor variables collected on the samples to be related to variation in the pairwise similarity/distance values reflected in the matrix. The proposed multivariate method avoids the need for reducing the dimensions of a similarity matrix, can be used to assess relationships between the genes used to construct the matrix and additional information collected on the samples under study, and can be used to analyze individual genes or groups of genes identified in different ways. The technique can be used with any high-dimensional assay or data type and is ideally suited for testing subsets of genes defined by their participation in a biochemical pathway or other a priori grouping. We showcase the methodology using three published gene expression data sets.

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    • "The similarity in species composition among treatments was tested using a multivariate analysis of variance by means of distance matrices, known as Adonis (Legendre and Anderson 1999; Oksanen 2013), using 300 permutations and the Bray-Curtis dissimilarity index as the default (Faith et al. 1987). The Adonis is suitable for small individual sample sizes (Zapala and Schork 2006) and useful for beta diversity studies (Oksanen 2013). Adonis was also used for further paired comparisons between treatments. "
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    ABSTRACT: The mutualism between ants and trophobiont insects is widely known as an interaction where the trophobionts are usually defended from their natural enemies by the ants. Ants can also remove herbivores, causing changes in the arthropod community structure and altering the stability of ecological communities. However, few studies have been conducted in field conditions to test the effects of mutualism on the associated arthropod community. In this study, we tested the hypothesis that the mutualism between trophobiont insects and ants decreases the abundance and species richness of the associated arthropod community, supporting a more stable community. We also investigated whether the abundance of specific arthropod feeding groups is affected by the mutualism and whether plants with and without mutualism form a mosaic with different species composition, increasing overall species richness. Our assumptions were experimentally examined in a system comprising the host plant Psittacanthus robustus, three trophobionts and two tending ants. We showed that, locally, the abundance and species richness of the whole arthropod community did not decrease when mutualism was present, but the feeding group composed by predators was negatively affected by mutualism. Plants with trophobionts but without ants presented the highest stability. At the landscape level, plants with and without mutualism differed in arthropod species composition, suggesting that there was a mosaic formed by plants with and without mutualism, enhancing the overall species richness (or beta diversity). Overall, our results revealed that the mutualism can alter the structure and stability of the surrounding arthropod community.
    Journal of Insect Conservation 06/2015; 19:627-638. DOI:10.1007/s10841-015-9785-2 · 1.72 Impact Factor
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    • "We tested whether treatment (coevolution/evolution) affected the types of mutations observed using permutational analysis of variance (Zapala and Schork 2006). For each gene, every genotype was scored as being mutated (1) or not mutated (0), before the Euclidean distance between each pair of genotypes was calculated (Excoffier et al. 1992). "
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    ABSTRACT: Studies of antagonistic coevolution between hosts and parasites typically focus on resistance and infectivity traits. However, coevolution could also have genome-wide effects on the hosts due to pleiotropy, epistasis or selection for evolvability. Here we investigate these effects in the bacterium Pseudomonas fluorescens SBW25 during ~400 generations of evolution in the presence or absence of bacteriophage (coevolution or evolution treatments respectively). Coevolution resulted in variable phage resistance, lower competitive fitness in the absence of phages, and greater genome-wide divergence both from the ancestor and between replicates, in part due to the evolution of increased mutation rates. Hosts from coevolution and evolution treatments had different suites of mutations. A high proportion of mutations observed in coevolved hosts were associated with a known phage target binding site, the Lipopolysaccharide (LPS), and correlated with altered LPS length and phage resistance. Mutations in evolved bacteria were correlated with higher fitness in the absence of phages. However, the benefits of these growth-promoting mutations were completely lost when these bacteria were subsequently coevolved with phages, indicating that they were not beneficial in the presence of resistance mutations (consistent with negative epistasis). Our results show that in addition to affecting genome-wide evolution in loci not obviously linked to parasite resistance, coevolution can also constrain the acquisition of mutations beneficial for growth in the abiotic environment. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail:
    Molecular Biology and Evolution 02/2015; 32(6). DOI:10.1093/molbev/msv032 · 9.11 Impact Factor
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    • "A simple fix would be an F-test, but it is sensitive to nonnormality (Box, 1953) of data being tested. To address this issue, the distance-based permutation test was developed for between-group comparisons in neuroimaging studies (Anderson and Legendre, 1999; Reiss et al., 2010; Zapala and Schork, 2006), which fits the purpose of the current study. For these reasons, the distance-based permutation test was used to detect differences between specific grouping criteria of interest (heretofore referred to as " group membership " ): either between TD and WRD for a specific ROI, or across the L-OT/F ROIs, as well as initially to confirm that there were no site specific confounds. "
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    ABSTRACT: With the advent of neuroimaging techniques, especially functional MRI (fMRI), studies have mapped brain regions that are associated with good and poor reading, most centrally a region within the left occipito-temporal/fusiform region (L-OT/F) often referred to as the visual word form area (VWFA). Despite an abundance of fMRI studies of the VWFA, research about its structural connectivity has just started. Provided that the VWFA may be connected to distributed regions in the brain, it remains unclear how this network is engaged in constituting a well-tuned reading circuitry in the brain. Here we used diffusion MRI to study the structural connectivity patterns of the putative VWFA and surrounding areas within the L-OT/F in children with typically developing (TD) reading ability and with word recognition deficits (WRD; sometimes referred to as dyslexia). We found that L-OT/F connectivity varied along a posterior-anterior gradient, with specific structural connectivity patterns related to reading ability in the ROIs centered upon the putative VWFA. Findings suggest that the architecture of the VWFA connectivity is fundamentally different between TD and WRD, with TD showing greater connectivity to linguistic regions than WRD, and WRD showing greater connectivity to visual and parahippocampal regions than TD. Findings thus reveal clear structural abnormalities underlying the functional abnormalities in the VWFA in WRD.
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