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Yunbei Pan

Publications and source records attributed to Yunbei Pan.

4 recordsLinked to original sources

HIPNO: Symmetry-Aware Physics-Informed Neural Operators for Noninvasive Hemodynamic Inference

Continuous hemodynamic monitoring guides treatment decisions in surgery and intensive care. However, gold-standard signals are only measured in severe cases due to risks associated with invasive measurement. In this work, we introduce HIPNO (Hemodynamic Inference via Physics-informed Neural Operators) to recover hemodynamic state from ubiquitous, non-invasive signals and expand access to advanced monitoring. HIPNO addresses a problem of scale symmetry in physics-informed hemodynamic inference, where different combinations of flow, resistance, and compliance can generate the same observed pressure. We identify the symmetry group of the observation model and parameterize the network in its quotient space. For the 3-element Windkessel model, the quotient coordinates are the compliance-normalized flow $U=Q/C$, the decay time constant $\tau_{WK}=R_2 C$, and the characteristic-impedance coordinate $\kappa=R_1 C$. Across 945499 intraoperative windows from 2562 patients, HIPNO predicts $\tau_{wave}$, a proxy for vascular decay derived from pressure, with 32% lower error on the log scale than a population baseline while preserving mean arterial pressure accuracy. Because vascular decay and flow drive occupy separate coordinates, counterfactual perturbations produce the expected directional responses in at least 90% of windows in almost all prespecified scenarios, a separation unavailable to pressure-only baselines. The coordinates are also used as inputs to a calibration model for monitored cardiac output. Finally, the formulation identifies the external compliance or flow reference required to recover absolute physical scale.

q-bio.QM

Effective population sizes for asymmetrically regulated birth-death processes

In multispecies birth-death processes, how population regulation -- through suppressed replication, elevated mortality, or both -- affects macroscopic stochastic dynamics has escaped detailed analysis. Here, we show that the distribution of regulation mechanisms can be invisible in deterministic or mean-field dynamics but play a significant role in the diffusive evolution of population frequencies. By introducing a tunable regulation partitioning parameter $\alpha_i$ and projecting a $d$-species birth-death process onto a $(d{-}1)$-dimensional Moran process, we find a regulation-mechanism-dependent diffusion tensor. For the simple two-species case, we derive exact fixation times and probabilities to show how different regulation mechanisms stochastically favors a more birth-regulated species, even under complete deterministic neutrality. Our model also allows us to define an $\alpha$-dependent effective population size $N_{\rm e}(\alpha)$ among neutral species, generalizing its classical interpretation. For near-neutral populations or populations that are heterogeneous in their regulation mechanism, we used perturbation theory to calculate the spectral gap, identifying it with a diversity loss timescale which can also be interpreted as setting an effective population size. Our results are particularly applicable to interacting subpopulations of T cells ("clones") which are near-neutral, are regulated through proliferation and apoptosis, and lose diversity with time.

q-bio.PE

CEI: A Clonal Expansion Identifier for T-cell receptor clones following SARS-CoV-2 vaccination

Each T cell typically carries a specific T-cell receptor (TCR) that determines its specificity against an epitope presented by the HLA complex on a target cell. Antigenic challenge triggers the expansion of reactive cells within a diverse pool of T cells with randomly generated receptors, a process that results in epitope-driven shifts of TCR frequencies over time. Here, we analyze the effects of SARS-CoV-2 vaccination on the TCR populations in peripheral blood drawn from seven COVID-naive individuals, before vaccines were widely available. To identify SARS-CoV-2 vaccine-associated TCR sequences among the $\sim 10^{5}-10^{6}$ TCR sequences sampled before and after vaccination, we develop statistical criteria to detect significant increases in abundance of positive TCR clones. Application of our statistical methods shows a robust identification of TCR sequences that respond to SARS-CoV-2 vaccination in vivo, illustrating the feasibility of quantifying the clone-specific dynamics of T-cell abundance changes following immunological perturbations.

q-bio.QM

How heterogeneous thymic output and homeostatic proliferation shape naive T cell receptor clone abundance distributions

The set of T cells that express the same T cell receptor (TCR) sequence represents a T cell clone. The number of different naive T cell clones in an organism reflects the number of different T cell receptors (TCRs) arising from recombination of the V(D)J gene segments during T cell development in the thymus. TCR diversity and more specifically, the clone abundance distribution is an important factor in immune function. Specific recombination patterns occur more frequently than others while subsequent interactions between TCRs and self-antigens are known to trigger proliferation and sustain naive T cell survival. These processes are TCR-dependent, leading to clone-dependent thymic export and naive T cell proliferation rates. Using a mean-field approximation to the solution of a regulated birth-death-immigration model and a modification arising from sampling, we systematically quantify how TCR-dependent heterogeneities in immigration and proliferation rates affect the shape of clone abundance distributions (the number of different clones that are represented by a specific number of cells, or "clone counts"). By comparing predicted clone counts derived from our heterogeneous birth-death-immigration model with experimentally sampled clone abundances, we show that although heterogeneity in immigration rates causes very little change to predicted clone-counts, significant heterogeneity in proliferation rates is necessary to generate the observed abundances with reasonable physiological parameter values. Our analysis provides constraints among physiological parameters that are necessary to yield predictions that qualitatively match the data. Assumptions of the model and potentially other important mechanistic factors are discussed.

q-bio.PE