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Biomedical subjects

Richard Miller

Publications and source records attributed to Richard Miller.

2 recordsLinked to original sources

Proportionality-based association metrics in count compositional data.

Compositional data comprise vectors that describe the constituent parts of a whole. Data arising from various -omics platforms such as 16S and RNA sequencing are compositional in nature. In this kind of data, correlations between features on raw counts have no meaningful interpretation. Metrics of proportionality were formulated to address this problem. However, an inherent bias arises when these metrics are calculated empirically on count-based measures due to variability in read depths. We quantify the bias introduced by empirically calculating proportionality-based association metrics in count data. Additionally, we propose a means of estimating these metrics within a logit-normal multinomial model in pursuit of more accurate estimates. The model-based estimates are shown to outperform empirical estimates in simulated data and are applied to a mouse embryonic stem cell single-cell sequencing dataset, as well as a pediatric-onset multiple sclerosis metagenomic dataset.

Animals

Extensive longevity and DNA virus-driven adaptation in nearctic Myotis bats.

The genus Myotis is one of the largest clades of bats, and exhibits some of the most extreme variation in lifespans among mammals alongside unique adaptations to viral tolerance and immune defense. To study the evolution of longevity-associated traits and infectious disease, we generated cell lines and near-complete genome assemblies for 8 closely related species of Myotis. Using genome-wide screens of positive selection, analyses of structural variation, and functional experiments in primary cells, we identify new patterns of adaptation contributing to longevity, cancer resistance, and viral interactions in bats. We show that the recurrent evolution of longevity seen in Myotis leads to some of the highest predicted increases in cancer risk across mammals and demonstrate a unique DNA damage response in primary cells of the long-lived M. lucifugus. We also find evidence of abundant adaptation in response to DNA viruses - but not RNA viruses - in Myotis and other bats in sharp contrast with other mammals, potentially contributing to the role of bats as reservoirs of zoonoses. Together, our results demonstrate how genomics and primary cells derived from diverse taxa uncover the molecular bases of extreme adaptations in non-model organisms.

Aging