Accounting for Errors in Data Improves Divergence Time Estimates in Single-cell Cancer Evolution

Single-cell sequencing provides a new way to explore the evolutionary history of cells. Compared to traditional bulk sequencing, where a population of heterogeneous cells is pooled to form a single observation, single-cell sequencing isolates and amplifies genetic material from individual cells, thereby preserving the information about the origin of the sequences. However, single-cell data are more error-prone than bulk sequencing data due to the limited genomic material available per cell. Here, we present error and mutation models for evolutionary inference of single-cell data within a mature and extensible Bayesian framework, BEAST2. Our framework enables integration with biologically informative models such as relaxed molecular clocks and population dynamic models. Our simulations show that modeling errors increase the accuracy of relative divergence times and substitution parameters. We reconstruct the phylogenetic history of a colorectal cancer patient and a healthy patient from single-cell DNA sequencing data. We find that the estimated times of terminal splitting events are shifted forward in time compared to models which ignore errors. We observed that not accounting for errors can overestimate the phylogenetic diversity in single-cell DNA sequencing data. We estimate that 30–50% of the apparent diversity can be attributed to error. Our work enables a full Bayesian approach capable of accounting for errors in the data within the integrative Bayesian software framework BEAST2.     

Relationship of trace metals to the alcohol-effect in citric acid synthesis by Aspergillus fonsecaeus

Summary Synthesis of citric acid by Aspergillus fonsecaeus in a basal medium supplemented with trace metals (iron, zinc, copper, and manganese) and methanol has been investigated. Methanol was found to be stimulatory to acid synthesis when manganese or manganese and iron were present. No other mineral tested could be substituted for manganese in the presence of the alcohol. However, comparable yields of citric acid could be obtained if methanol were deleted, the concentration of iron increased and zinc substituted for manganese.This investigation was conducted under a contract with the United States Department of Agriculture, authorized by the Research and Marketing Act, and administered through the Northern Regional Research Laboratory.