Estimating cell-type-specific DNA methylation effects in heterogeneous cellular populations.

Aim: To develop a method for estimating cell-specific effects in epigenomic association studies in the presence of cell type heterogeneity. Materials & methods: We utilized Monte Carlo Expectation-Maximization algorithm with Metropolis-Hastings sampler to reconstruct the 'missing' cell-specific methylations and to estimate their associations with phenotypes free of confounding by cell type proportions. Results: Simulations showed reliable performance of the method under various settings including when the cell type is rare. Application to a real dataset recapitulated the directly measured cell-specific methylation pattern in whole blood. Conclusion: This work provides a framework to identify important cell groups and account for cell type composition useful for studying the role of epigenetic changes in human traits and diseases.

The lung microbiome in health and disease.

The Human Microbiome Project began 10 years ago, leading to a significant growth in understanding of the role the human microbiome plays in health and disease. In this article, we explain with an emphasis on the lung, the origins of microbiome research. We discuss how 16S rRNA gene sequencing became the first major molecular tool to examine the bacterial communities present within the human body. We highlight the pitfalls of molecular-based studies, such as false findings resulting from contamination, and the limitations of 16S rRNA gene sequencing. Knowledge about the lung microbiome has evolved from initial scepticism to the realisation that it might have a significant influence on many illnesses. We also discuss the lung microbiome in the context of disease by giving examples of important respiratory conditions. In addition, we draw attention to the challenges for metagenomic studies of respiratory samples and the importance of systematic bacterial isolation to enable host-microbiome interactions to be understood. We conclude by discussing how knowledge of the lung microbiome impacts current clinical diagnostics.