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Mayhew, M. B.

Publications and source records attributed to Mayhew, M. B..

2 recordsLinked to original sources

Flexible Analysis of Electronic Medical Record Data with Composite Mixture Models

The widespread adoption of electronic medical records (EMRs) in healthcare has provided vast new amounts of data for statistical machine learning researchers in their efforts to model and predict patient health status, potentially enabling novel advances in treatment. In the case of sepsis, a debilitating, dysregulated host response to infection, extracting subtle, uncataloged clinical phenotypes from the EMR with statistical machine learning methods has the potential to impact patient diagnosis and treatment early in the course of their hospitalization. However, there are significant barriers that must be overcome to extract these insights from EMR data. First, EMR datasets consist of both static and dynamic observations of discrete and continuous-valued variables, many of which may be missing, precluding the application of standard multivariate analysis techniques. Second, clinical populations observed via EMRs and relevant to the study and management of conditions like sepsis are often heterogeneous; properly accounting for this heterogeneity is critical. Here, we describe an unsupervised, probabilistic framework called a composite mixture model that can simultaneously accommodate the wide variety of observations frequently observed in EMR datasets, characterize heterogeneous clinical populations, and handle missing observations. We demonstrate the efficacy of our approach on a large-scale sepsis cohort, developing novel techniques built on our model-based clusters to track patient mortality risk over time and identify physiological trends and distinct subgroups of the dataset associated with elevated risk of mortality during hospitalization.\n\nAbbreviations

bioinformatics

Characterization of Dependencies Between Growth and Division in Budding Yeast

Cell growth and division are processes vital to the proliferation and development of life. Coordination between these two processes has been recognized for decades in a variety of organisms. In the budding yeast Saccharomyces cerevisiae, this coordination or size control appears as an inverse correlation between cell size and the rate of cell-cycle progression, routinely observed in G1 prior to cell division commitment. Beyond this point, cells are presumed to complete S/G2/M at similar rates and in a size-independent manner. As such, studies of dependence between growth and division have focused on G1. Moreover, coordination between growth and division has commonly been analyzed within the cycle of a single cell without accounting for correlations in growth and division characteristics between cycles of related cells. In a comprehensive analysis of three published time-lapse microscopy datasets, we analyze both intra-and inter-cycle dependencies between growth and division, revisiting assumptions about the coordination between these two processes. Interestingly, we find evidence (1) that S/G2/M durations are systematically longer in daughters than in mothers, (2) of dependencies between S/G2/M and size at budding that echo the classical G1 dependencies, and, (3) in contrast with recent bacterial studies, of negative dependencies between size at birth and size accumulated during the cell cycle. In addition, we develop a novel hierarchical model to uncover inter-cycle dependencies, and we find evidence for such dependencies in cells growing in sugar-poor environments. Our analysis highlights the need for experimentalists and modelers to account for new sources of cell-to-cell variation in growth and division, and our model provides a formal statistical framework for the continued study of dependencies between biological processes.

bioinformatics