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Mediation analysis is an important tool for studying causal associations in biomedical and other scientific areas and has recently gained attention in microbiome studies. Using a microbiome study of acute myeloid leukemia (AML) patients, we…

The intricate interplay between host organisms and their gut microbiota has catalyzed research into the microbiome's role in disease, shedding light on novel aspects of disease pathogenesis. However, the mechanisms through which the…

Methodology · Statistics 2024-02-20 Lei Fang , Yue Wang , Chenglong Ye

The role of the microbiome in disease pathogenesis is an emerging field with strong evidence suggesting that dysbiosis is associated with precancerous and cancerous states. Microbiome data present substantial challenges for causal mediation…

Methodology · Statistics 2026-05-07 Seungjun Ahn , Quran Wu , Alicia Yang , Zhigang Li

The gut microbiome plays a crucial role in human health, yet the mechanisms underlying host-microbiome interactions remain unclear, limiting its translational potential. Recent microbiome multiomics studies, particularly paired…

Methodology · Statistics 2025-04-09 Haoran Shi , Yue Wang , Dan Cheng

The human microbiome can contribute to pathogeneses of many complex diseases by mediating disease-leading causal pathways. However, standard mediation analysis methods are not adequate to analyze the microbiome as a mediator due to the…

Bacterial Vaginosis (BV) affects nearly 23-29% of women worldwide and increases risk of miscarriage, preterm birth, and sexually transmitted infections. It involves a shift in the vaginal microbiome from Lactobacillus dominance to a diverse…

Applications · Statistics 2025-07-29 Debarghya Nandi , Soumya Sahu , Supriya Mehta , Dulal K. Bhaumik

Biological sequencing data consist of read counts, e.g. of specified taxa and often exhibit sparsity (zero-count inflation) and overdispersion (extra-Poisson variability). As most sequencing techniques provide an arbitrary total count,…

Applications · Statistics 2024-07-01 Noora Kartiosuo , Jaakko Nevalainen , Olli Raitakari , Katja Pahkala , Kari Auranen

Microbiota contribute to many dimensions of host phenotype, including disease. To link specific microbes to specific phenotypes, microbiome-wide association studies compare microbial abundances between two groups of samples. Abundance…

Applications · Statistics 2018-01-31 Rajita Menon , Vivek Ramanan , Kirill S. Korolev

Analyzing multivariate count data generated by high-throughput sequencing technology in microbiome research studies is challenging due to the high-dimensional and compositional structure of the data and overdispersion. In practice,…

Applications · Statistics 2023-11-03 Jingyan Fu , Matthew D. Koslovsky , Andreas M. Neophytou , Marina Vannucci

The so-called gut-brain axis has stimulated extensive research on microbiomes. One focus is to assess the association between certain clinical outcomes and the relative abundances of gut microbes, which can be presented as sub-compositional…

Methodology · Statistics 2020-06-02 Xiaokang Liu , Xiaomei Cong , Gen Li , Kendra Maas , Kun Chen

In many social mammals, early life social adversity and social integration largely predict individual health, lifespan and reproductive success. Efforts in identifying the physiological mechanisms mediating the relationship between the…

Populations and Evolution · Quantitative Biology 2022-01-25 Alice Baniel , Marie J. E. Charpentier

The intestinal microbiota plays important roles in digestion and resistance against entero-pathogens. As with other ecosystems, its species composition is resilient against small disturbances but strong perturbations such as antibiotics can…

Quantitative Methods · Quantitative Biology 2015-06-04 Vanni Bucci , Serena Bradde , Giulio Biroli , Joao B. Xavier

In epidemiological research, causal models incorporating potential mediators along a pathway are crucial for understanding how exposures influence health outcomes. This work is motivated by integrated epidemiological and blood biomarker…

Methodology · Statistics 2024-11-28 Youngho Bae , Chanmin Kim , Fenglei Wang , Qi Sun , Kyu Ha Lee

Often linear regression is used to perform mediation analysis. However, in many instances, the underlying relationships may not be linear, as in the case of placental-fetal hormones and fetal development. Although, the exact functional form…

Methodology · Statistics 2023-10-16 Qing Yin , Jong-Hyeon Jeong , Xu Qin , Shyamal D Peddada , Jennifer Adibi

Microorganisms play critical roles in human health and disease. It is well known that microbes live in diverse communities in which they interact synergistically or antagonistically. Thus for estimating microbial associations with clinical…

Mediation analysis allows one to use observational data to estimate the importance of each potential mediating pathway involved in the causal effect of an exposure on an outcome. However, current approaches to mediation analysis with…

In mediation analysis, the effect of an exposure (or treatment) on an outcome variable is decomposed into two components: a direct effect, which pertains to an immediate influence of the exposure on the outcome, and an indirect effect,…

Methodology · Statistics 2017-10-04 Marco Geraci , Alessandra Mattei

Recent studies suggest that the microbiome can be an important mediator in the effect of a treatment on an outcome. Microbiome data generated from sequencing experiments contain the relative abundance of a large number of microbial taxa…

Methodology · Statistics 2021-09-03 Qilin Hong , Guanhua Chen , Zheng-Zheng Tang

One of the major research questions regarding human microbiome studies is the feasibility of designing interventions that modulate the composition of the microbiome to promote health and cure disease. This requires extensive understanding…

Methodology · Statistics 2021-11-18 Matthew D. Koslovsky , Kristi L. Hoffman , Carrie R. Daniel , Marina Vannucci

With advances in high-resolution mass spectrometry technologies, metabolomics data are increasingly used to investigate biological mechanisms underlying associations between exposures and health outcomes in clinical and epidemiological…

Applications · Statistics 2025-03-19 Yuzi Zhang , Donghai Liang , Youran Tan , Anne L. Dunlop , Howard H. Chang
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