scholarly journals A Rarefaction-Based Extension of the LDM for Testing Presence-Absence Associations in the Microbiome

2020 ◽  
Author(s):  
Yi-Juan Hu ◽  
Andrea Lane ◽  
Glen A. Satten

AbstractBackgroundMany methods for testing association between the microbiome and covariates of interest (e.g., clinical outcomes, environmental factors) assume that these associations are driven by changes in the relative abundance of taxa. However, these associations may also result from changes in which taxa are present and which are absent. Analyses of such presence-absence associations face a unique challenge: confounding by library size (total sample read count), which occurs when library size is associated with covariates in the analysis. It is known that rarefaction (subsampling to a common library size) controls this bias, but at the potential cost of information loss as well as the introduction of a stochastic component into the analysis. Currently, there is a need for robust and efficient methods for testing presence-absence associations in the presence of such confounding, both at the community level and at the individual-taxon level, that avoid the drawbacks of rarefaction.MethodsWe have previously developed the linear decomposition model (LDM) that unifies the community-level and taxon-level tests into one framework. Here we present an extension of the LDM for testing presence-absence associations. The extended LDM is a non-stochastic approach that repeatedly applies the LDM to all rarefied taxa count tables, averages the residual sum-of-squares (RSS) terms over the rarefaction replicates, and then forms an F-statistic based on these average RSS terms. We show that this approach compares favorably to averaging the F-statistic from R rarefaction replicates, which can only be calculated stochastically. The flexible nature of the LDM allows discrete or continuous traits or interactions to be tested while allowing confounding covariates to be adjusted for.ResultsOur simulations indicate that our proposed method is robust to any systematic differences in library size and has better power than alternative approaches. We illustrate our method using an analysis of data on inflammatory bowel disease (IBD) in which case samples have systematically smaller library sizes than controls.ConclusionsThe rarefaction-based extension of the LDM performs well for testing presenceabsence associations and should be adopted even when there is no obvious systematic variation in library size.

2021 ◽  
Author(s):  
Yi-Juan Hu ◽  
Glen A. Satten

Abstract Background PERMANOVA [1] is currently the most commonly used method for testing community-level hypotheses about microbiome associations with covariates of interest. PERMANOVA can test for associations that result from changes in which taxa are present or absent by using the Jaccard or unweighted UniFrac distance. However, such presence-absence analyses face a unique challenge: confounding by library size (total sample read count), which occurs when library size is associated with covariates in the analysis. It is known that rarefaction (subsampling to a common library size) controls this bias, but at the potential costs of information loss and the introduction of a stochastic component into the analysis.Methods Here we develop a non-stochastic approach to PERMANOVA presence-absence analyses that aggregates information over all potential rarefaction replicates without actual resampling, when the Jaccard or unweighted UniFrac distance is used. We compare this new approach to three possible ways of aggregating PERMANOVA over multiple rarefactions obtained from resampling: averaging the distance matrix, averaging the (element-wise) squared distance matrix, and averaging the F-statistic.Results Our simulations indicate that our non-stochastic approach is robust to confounding by library size and outperforms each of the stochastic resampling approaches. We also show that, when overdispersion is low, averaging the (element-wise) squared distance outperforms averaging the unsquared distance, currently implemented in the R package vegan. We illustrate our methods using an analysis of data on inflammatory bowel disease (IBD) in which samples from case participants have systematically smaller library sizes than samples from control participants.Conclusions Our extension of PERMANOVA for presence-absence analyses using a non-stochastic approach that aggregates information over all potential rarefaction replicates without actual resampling is robust to confounding by library size and outperforms stochastic resampling approaches.


2021 ◽  
Author(s):  
Yijuan Hu ◽  
Glen Satten

Background: PERMANOVA is currently the most commonly used method for testing community-level hypotheses about microbiome associations with covariates of interest. PERMANOVA can test for associations that result from changes in which taxa are present or absent by using the Jaccard or unweighted UniFrac distance. However, such presence-absence analyses face a unique challenge: confounding by library size (total sample read count), which occurs when library size is associated with covariates in the analysis. It is known that rarefaction (subsampling to a common library size) controls this bias, but at the potential costs of information loss and the introduction of a stochastic component into the analysis. Methods: Here we develop a non-stochastic approach to PERMANOVA presence-absence analyses that aggregates information over all potential rarefaction replicates without actual resampling, when the Jaccard or unweighted UniFrac distance is used. We compare this new approach to three possible ways of aggregating PERMANOVA over multiple rarefactions obtained from resampling: averaging the distance matrix, averaging the (element-wise) squared distance matrix, and averaging the F-statistic. Results: Our simulations indicate that our non-stochastic approach is robust to confounding by library size and outperforms each of the stochastic resampling approaches. We also show that, when overdispersion is low, averaging the (element-wise) squared distance outperforms averaging the unsquared distance, currently implemented in the R package vegan. We illustrate our methods using an analysis of data on inflammatory bowel disease (IBD) in which samples from case participants have systematically smaller library sizes than samples from control participants.


2020 ◽  
Vol 11 (01) ◽  
Author(s):  
Priyanka Beniwal ◽  
Chandrakala Singh

Aging is a series of processes that begin with life and continue throughout the lifecycle. It represents the closing period in the lifespan, a time when the individual looks back on life, lives on past accomplishments and begins to finish off his life course. It represents the accumulation of changes in person over time. The study aims to investigate the health status of senior citizens. The present study was carried out in Hisar and Sirsa district of Haryana state. A total of 400 elderly equally representing both males and females of age group 65-70 years were selected randomly for the study. Modified inventory developed by Khan and Lal (2011) was used to assess health status of senior citizens. The results of the study elucidated that health status of senior citizens depicted that 54.25 per cent of the total respondents had average health status followed by good (25.25%) and poor health status (20.50%). The most common health problems reported by the senior citizens were joint pains, back pains, blood pressure, and chest pain etc. Gender wise comparison of total sample further pointed out that females were poor in their health against males.


2020 ◽  
Vol 25 (46) ◽  
pp. 4893-4913 ◽  
Author(s):  
Fan Cao ◽  
Jie Liu ◽  
Bing-Xian Sha ◽  
Hai-Feng Pan

: Inflammatory bowel disease (IBD) is a chronic, elusive disorder resulting in relapsing inflammation of intestine with incompletely elucidated etiology, whose two representative forms are ulcerative colitis (UC) and Crohn’s disease (CD). Accumulating researches have revealed that the individual genetic susceptibility, environmental risk elements, intestinal microbial flora, as well as innate and adaptive immune system are implicated in the pathogenesis and development of IBD. Despite remarkable progression of IBD therapy has been achieved by chemical drugs and biological therapies such as aminosalicylates, corticosteroids, antibiotics, anti-tumor necrosis factor (TNF)-α, anti-integrin agents, etc., healing outcome still cannot be obtained, along with inevitable side effects. Consequently, a variety of researches have focused on exploring new therapies, and found that natural products (NPs) isolated from herbs or plants may serve as promising therapeutic agents for IBD through antiinflammatory, anti-oxidant, anti-fibrotic and anti-apoptotic effects, which implicates the modulation on nucleotide- binding domain (NOD) like receptor protein (NLRP) 3 inflammasome, gut microbiota, intestinal microvascular endothelial cells, intestinal epithelia, immune system, etc. In the present review, we will summarize the research development of IBD pathogenesis and current mainstream therapy, as well as the therapeutic potential and intrinsic mechanisms of NPs in IBD.


2021 ◽  
Vol 9 (2) ◽  
pp. 370
Author(s):  
Hyunjoon Park ◽  
Soyoung Yeo ◽  
Seokwon Kang ◽  
Chul Sung Huh

The role of the gut microbiota in the pathogenesis of inflammatory bowel disease (IBD) has been in focus for decades. Although metagenomic observations in patients/animal colitis models have been attempted, the microbiome results were still indefinite and broad taxonomic presumptions were made due to the cross-sectional studies. Herein, we conducted a longitudinal microbiome analysis in a dextran sulfate sodium (DSS)-induced colitis mouse model with a two-factor design based on serial DSS dose (0, 1, 2, and 3%) and duration for 12 days, and four mice from each group were sacrificed at two-day intervals. During the colitis development, a transition of the cecal microbial diversity from the normal state to dysbiosis and dynamic changes of the populations were observed. We identified genera that significantly induced or depleted depending on DSS exposure, and confirmed the correlations of the individual taxa to the colitis severity indicated by inflammatory biomarkers (intestinal bleeding and neutrophil-derived indicators). Of note, each taxonomic population showed its own susceptibility to the changing colitis status. Our findings suggest that an understanding of the individual susceptibility to colitis conditions may contribute to identifying the role of the gut microbes in the pathogenesis of IBD.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Emiru Merdassa Atomssa ◽  
Araya Abrha Medhanyie ◽  
Girmatsion Fisseha

Abstract Background The prevalence of Intimate partner violence (IPV) is higher in societies with higher acceptance of norms that support IPV. In Ethiopia, the proportion of women’s acceptance of IPV was 69%, posing a central challenge in preventing IPV. The main objective of this study was to assess the individual and community-level factors associated with women’s acceptance of IPV. Methods Two-level mixed-effects logistic regression was applied to the 2011 Ethiopia Demographic and Health Survey data. A total of 16,366 women nested in the 596 clusters were included in the analysis. Results The acceptability of the IPV was estimated to be 69%. Among the individual-level factors: women’s education with secondary and above (AOR = 0.38; 95% CI 0.29–0.52), partner’s education secondary and above (AOR = 0.71; 95% CI 0.54–0.82), women aged 35–49 years (AOR = 0.67; 95% CI 0.54–0.82), fully empowered in household level decision making (AOR = 0.67; 95% CI0.54–0.81), literate (AOR = 0.76; 95% CI 0.62–0.92), and perceived existence of law that prevents IPV (AOR = 0.56; 95% CI 0.50–0.63) were significantly associated with women’s acceptance of IPV. Similarly, rural residence (AOR = 1.93; 95% CI 1.53–2.43) and living in the State region (AOR = 2.37; 95% CI 1.81–3.10) were significantly associated with the women’s acceptance of IPV among the community-level factors. Conclusion Both individual and community-level factors were significant risk factors for the acceptability of intimate partner violence. Women's education, women's age, women’s empowerment, partner education level, perceived existence of the law, and literacy were among individual factors. State region and residence were among community-level risk factors significantly associated women’s acceptance of IPV.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Tsegaye Gebremedhin ◽  
Demiss Mulatu Geberu ◽  
Asmamaw Atnafu

Abstract Background The burden of low coverage of exclusive breastfeeding (EBF) has a significant impact on the health of a newborn and also on the family and social economy in the long term. Even though the prevalence of EBF practices in Ethiopia is low, the practices in the pastoral communities, in particular, are significantly low and affected by individual and community-level factors. Besides, its adverse outcomes are mostly unrecognised. Therefore, this study aimed to assess the individual and community-level factors of low coverage of EBF practices in the emerging regions of Ethiopia. Methods In this analysis, data from 2016 Ethiopian Demographic and Health Survey (EDHS) were used. A two-stage stratified sampling technique was used to identify 1406 children aged 0 to 23 months in the emerging regions of Ethiopia. A multilevel mixed-effect binary logistic regression analysis was used to determine the individual and community level factors associated with exclusive breastfeeding practices. In the final model, variables with a p-value of < 0.05 and Adjusted Odds Ratio (AOR) with 95% Confidence Interval (CI) were found to be statistically significant factors that affect exclusive breastfeeding practices. Results Overall, 17.6% (95% CI: 15.6–19.6) of the children aged 0 to 23 months have received exclusive breastfeeding. Employed mothers (AOR: 0.33, 95% CI: 0.21–0.53), richer household wealth status (AOR: 0.39, 95% CI: 0.16–0.96), mothers undecided to have more children (AOR: 2.29, 95% CI: 1.21–4.29), a child with a history of diarrhoea (AOR: 0.31, 95% CI: 0.16–0.61) were the individual-level factors, whereas Benishangul region (AOR: 2.63, 95% CI: 1.44–4.82) was the community-level factors associated with the exclusive breastfeeding practices. Conclusions Less than one-fifth of the mothers have practised exclusive breastfeeding in the emerging regions of Ethiopia. The individual-level factors such as mother’s employment status, household wealth status, desire for more children, presence of diarrhoea and community-level factors such as region have contributed to the low coverage of exclusive breastfeeding. Therefore, the federal and regional health bureaus and other implementers should emphasise to those emerging regions by creating awareness and strengthening the existing community-based health extension program to enhance exclusive breastfeeding practices.


2018 ◽  
Vol 63 (05) ◽  
pp. 1385-1403 ◽  
Author(s):  
KITAE SOHN ◽  
ILLOONG KWON

Trust was found to promote entrepreneurship in the US. We investigated whether this was true in a developing country, Indonesia. We failed to replicate this; this failure was true whether trust was estimated at the individual or community level or whether ordinary least squares (OLS) or two stage least squares (2SLS) was employed. We reconciled the difference between our results and those for the US by arguing that the weak enforcement of property rights in developing countries and the consequent hold-up problem make it more efficient for entrepreneurs to produce generic goods than relationship-specific goods—producing generic goods does not depend on trust.


2018 ◽  
Vol 11 (6) ◽  
pp. 496-506 ◽  
Author(s):  
Peter Austin Morton Ntenda ◽  
Jane Flora Kazambwe

Abstract Background Overweight and obesity are well-known risk factors for non-communicable diseases such as cardiovascular disease, diabetes, some cancers and musculoskeletal disorders. In Malawi, the proportion of women who are overweight/obese has doubled, from 10% in 1992 to 21% in 2015–16. Therefore we aimed to explore the individual- and community-level factors associated with overweight and obesity among non-pregnant women of child-bearing age. Methods Secondary analysis of the 2015–16 Malawi Demographic and Health Survey was conducted. Overweight was defined as a body mass index (BMI) of 25 to &lt;30 kg/m2, while obesity was defined as a BMI ≥30 kg/m2. Two-level multilevel multivariable logistic regression models were constructed using a logit-link function with a binomial distribution on 7326 women living in 850 different communities. Results At the individual level, the adjusted multilevel regression results showed that women 15–19 y of age as well as women from the poorest households had reduced odds of being overweight/obese. However, women with white collar jobs and women who were affiliated with the Church of Central Africa Presbyterian and the Roman Catholic church had increased odds of being overweight/obese. At the community level, women from urban areas and women who resided in communities with a low percentage of media exposure had increased odds of being overweight or obese. While women from poor communities had reduced odds of being overweight and obese, the proportion change in variance showed that 56, 77 and 78% of total variations in the odds of overweight, obese and overweight/obese across the communities were explained by both individual- and community-level factors. The median odds ratio showed that the likelihood of maternal overweight, obese and overweight/obese increased by 63, 39 and 84% when the women moved from low- to high-risk neighbourhoods. Conclusions Older women, Christian women, women with white collar jobs and women from the richest households should be targeted during policy formulation. At the community level, media coverage should be spread evenly so that health awareness messages, consequences and means of overweight and obesity prevention are getting to the targeted women. Our study revealed evidence of clustering effects of overweight and obesity at the community level, hence neighbourhood variations with respect to maternal overweight and obesity should be taken into account when designing nutritional policies.


2021 ◽  
Author(s):  
András Hajdu ◽  
György Terdik ◽  
Attila Tiba ◽  
Henrietta Tomán

AbstractEnsemble-based methods are highly popular approaches that increase the accuracy of a decision by aggregating the opinions of individual voters. The common point is to maximize accuracy; however, a natural limitation occurs if incremental costs are also assigned to the individual voters. Consequently, we investigate creating ensembles under an additional constraint on the total cost of the members. This task can be formulated as a knapsack problem, where the energy is the ensemble accuracy formed by some aggregation rules. However, the generally applied aggregation rules lead to a nonseparable energy function, which takes the common solution tools—such as dynamic programming—out of action. We introduce a novel stochastic approach that considers the energy as the joint probability function of the member accuracies. This type of knowledge can be efficiently incorporated in a stochastic search process as a stopping rule, since we have the information on the expected accuracy or, alternatively, the probability of finding more accurate ensembles. Experimental analyses of the created ensembles of pattern classifiers and object detectors confirm the efficiency of our approach over other pruning ones. Moreover, we propose a novel stochastic search method that better fits the energy, which can be incorporated in other stochastic strategies as well.


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