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DomainRBF: a Bayesian regression approach to the prioritization of candidate domains for complex diseases.

ABSTRACT: BACKGROUND: Domains are basic units of proteins, and thus exploring associations between protein domains and human inherited diseases will greatly improve our understanding of the pathogenesis of human complex diseases and further benefit the medical prevention, diagnosis and treatment of these diseases. Within a given domain-domain interaction network, we make the assumption that similarities of disease phenotypes can be explained using proximities of domains associated with such diseases. Based on this assumption, we propose a Bayesian regression approach named "domainRBF" (domain Rank with Bayes Factor) to prioritize candidate domains for human complex diseases. RESULTS: Using a compiled dataset containing 1,614 associations between 671 domains and 1,145 disease phenotypes, we demonstrate the effectiveness of the proposed approach through three large-scale leave-one-out cross-validation experiments (random control, simulated linkage interval, and genome-wide scan), and we do so in terms of three criteria (precision, mean rank ratio, and AUC score). We further show that the proposed approach is robust to the parameters involved and the underlying domain-domain interaction network through a series of permutation tests. Once having assessed the validity of this approach, we show the possibility of ab initio inference of domain-disease associations and gene-disease associations, and we illustrate the strong agreement between our inferences and the evidences from genome-wide association studies for four common diseases (type 1 diabetes, type 2 diabetes, Crohn's disease, and breast cancer). Finally, we provide a pre-calculated genome-wide landscape of associations between 5,490 protein domains and 5,080 human diseases and offer free access to this resource. CONCLUSIONS: The proposed approach effectively ranks susceptible domains among the top of the candidates, and it is robust to the parameters involved. The ab initio inference of domain-disease associations shows strong agreement with the evidence provided by genome-wide association studies. The predicted landscape provides a comprehensive understanding of associations between domains and human diseases.

SUBMITTER: Zhang W

PROVIDER: S-EPMC3108930 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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DomainRBF: a Bayesian regression approach to the prioritization of candidate domains for complex diseases.

Zhang Wangshu W Chen Yong Y Sun Fengzhu F Jiang Rui R

BMC systems biology 20110419

<h4>Background</h4>Domains are basic units of proteins, and thus exploring associations between protein domains and human inherited diseases will greatly improve our understanding of the pathogenesis of human complex diseases and further benefit the medical prevention, diagnosis and treatment of these diseases. Within a given domain-domain interaction network, we make the assumption that similarities of disease phenotypes can be explained using proximities of domains associated with such disease ...[more]

PMID: 21504591

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Project description:BackgroundThe burden of child under-nutrition still remains a global challenge, with greater severity being faced by low- and middle-income countries, despite the strategies in the Sustainable Development Goals (SDGs). Globally, malnutrition is the one of the most important risk factors associated with illness and death, affecting hundreds of millions of pregnant women and young children. Sub-Saharan Africa is one of the regions in the world struggling with the burden of chronic malnutrition. The 2018 Zambia Demographic and Health Survey (ZDHS) report estimated that 35% of the children under five years of age are stunted. The objective of this study was to analyse the distribution, and associated factors of stunting in Zambia.MethodsWe analysed the relationships between socio-economic, and remote sensed characteristics and anthropometric outcomes in under five children, using Bayesian distributional regression. Georeferenced data was available for 25,852 children from two waves of the ZDHS, 31% observation were from the 2007 and 69% were from the 2013/14. We assessed the linear, non-linear and spatial effects of covariates on the height-for-age z-score.ResultsStunting decreased between 2007 and 2013/14 from a mean z-score of 1.59 (credible interval (CI): -1.63; -1.55) to -1.47 (CI: -1.49; -1.44). We found a strong non-linear relationship for the education of the mother and the wealth of the household on the height-for-age z-score. Moreover, increasing levels of maternal education above the eighth grade were associated with a reduced variation of stunting. Our study finds that remote sensed covariates alone explain little of the variation of the height-for-age z-score, which highlights the importance to collect socio-economic characteristics, and to control for socio-economic characteristics of the individual and the household.ConclusionsWhile stunting still remains unacceptably high in Zambia with remarkable regional inequalities, the decline is lagging behind goal two of the SDGs. This emphasises the need for policies that help to reduce the share of chronic malnourished children within Zambia.

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DomainRBF: a Bayesian regression approach to the prioritization of candidate domains for complex diseases.

Publications

DomainRBF: a Bayesian regression approach to the prioritization of candidate domains for complex diseases.

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