High-throughput sequencing of T- and B-cell receptors makes it possible to track immune repertoires across time, in different tissues, in acute and chronic diseases and in healthy individuals. However, quantitative comparison between repertoires is confounded by variability in the read count of each receptor clonotype due to sampling, library preparation, and expression noise. We review methods for accounting for both biological and experimental noise and present an easy-to-use python package that implements and generalizes a previously developed Bayesian method.
View Article and Find Full Text PDFFinding the right amount of deliberation, between insufficient and excessive, is a hard decision making problem that depends on the value we place on our time. Average-reward, putatively encoded by tonic dopamine, serves in existing reinforcement learning theory as the opportunity cost of time, including deliberation time. Importantly, this cost can itself vary with the environmental context and is not trivial to estimate.
View Article and Find Full Text PDFHigh-throughput sequencing of B- and T-cell receptors makes it possible to track immune repertoires across time, in different tissues, and in acute and chronic diseases or in healthy individuals. However, quantitative comparison between repertoires is confounded by variability in the read count of each receptor clonotype due to sampling, library preparation, and expression noise. Here, we present a general Bayesian approach to disentangle repertoire variations from these stochastic effects.
View Article and Find Full Text PDFCortical circuits operate in an inhibition-dominated regime of spiking activity. Recently, it was found that spiking circuit models in this regime can, despite disordered connectivity and asynchronous irregular activity, exhibit a locally stable dynamics that may be used for neural computation. The lack of existing mathematical tools has precluded analytical insight into this phase.
View Article and Find Full Text PDFT cell receptor (TCR) repertoire data contain information about infections that could be used in disease diagnostics and vaccine development, but extracting that information remains a major challenge. Here we developed a statistical framework to detect TCR clone proliferation and contraction from longitudinal repertoire data. We applied this framework to data from three pairs of identical twins immunized with the yellow fever vaccine.
View Article and Find Full Text PDFVaccination induces "public" antibody clonotypes common to all individuals of a species, that may mediate universal protection against pathogens. Only few studies tried to trace back the origin of these public B-cell clones. Here we used Illumina sequencing and computational modeling to unveil the mechanisms shaping the structure of the fish memory antibody response against an attenuated Viral Hemorrhagic Septicemia rhabdovirus.
View Article and Find Full Text PDFThe study of biological invasions of ecological systems has much to offer research on within-host systems, particularly for understanding infections and developing therapies using biological agents. Thanks to the ground-work established in other fields, such as community ecology and evolutionary biology, and to modern methods of measurement and quantification, the study of microbiomes has quickly become a field at the forefront of modern systems biology. Investigations of host-associated microbiomes (e.
View Article and Find Full Text PDFPLoS Comput Biol
December 2015
The response of a neuronal population over a space of inputs depends on the intrinsic properties of its constituent neurons. Two main modes of single neuron dynamics-integration and resonance-have been distinguished. While resonator cell types exist in a variety of brain areas, few models incorporate this feature and fewer have investigated its effects.
View Article and Find Full Text PDFCortical neurons operate within recurrent neuronal circuits. Dissecting their operation is key to understanding information processing in the cortex and requires transparent and adequate dynamical models of circuit function. Convergent evidence from experimental and theoretical studies indicates that strong feedback inhibition shapes the operating regime of cortical circuits.
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