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Tao, L.

Publications and source records attributed to Tao, L..

74 records · Page 5Linked to original sources

A common goodness-of-fit framework for neural population models using marked point process time-rescaling

A critical component of any statistical modeling procedure is the ability to assess the goodness-of-fit between a model and observed data. For neural spike train models of individual neurons, many goodness-of-fit measures rely on the time-rescaling theorem to assess the statistical properties of rescaled spike times. Recently, there has been increasing interest in statistical models that describe the simultaneous spiking activity of neuron populations, either in a single brain region or across brain regions. Classically, such models have used spike sorted data to describe relationships between the identified neurons, but more recently clusterless modeling methods have been used to describe population activity using a single model. Here we develop a generalization of the time-rescaling theorem that enables comprehensive goodness-of-fit analysis for either of these classes of population models. We use the theory of marked point processes to model population spiking activity, and show that under the correct model, each spike can be rescaled individually to generate a uniformly distributed set of events in time and the space of spike marks. After rescaling, multiple well-established goodness-of-fit procedures and statistical tests are available. We demonstrate the application of these methods both to simulated data and real population spiking in rat hippocampus.

neuroscience↗

A duplex MIPs-based biological-computational cell lineage discovery platform

Cell lineage analysis aims to uncover the developmental history of an organism back to its cell of origin1. Recently, novel in vivo methods and technologies utilizing genome editing enabled important insights into the cell lineages of animals2-8. In contrast, human cell lineage remains restricted to retrospective approaches, which still lack in resolution and cost-efficient solutions. Here we demonstrate a scalable platform for human cell lineage tracing based on Short Tandem Repeats (STRs) targeted by duplex Molecular Inversion Probes (MIPs). With this platform we accurately reproduced a known lineage of DU145 cell lines cells9 and reconstructed lineages of healthy and metastatic single cells from a melanoma patient. The reconstructed trees matched the anatomical and SNV references while adding further refinements. Our platform allowed to faithfully recapitulate lineages of developmental tissue formation in cells from healthy donors. In summary, our lineage discovery platform can profile informative STR somatic mutations efficiently and we provide a solid, high-resolution lineage reconstruction even in challenging low-mutation-rate healthy single cells.

systems biology↗