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Biology subjects

Boettcher, L.

Publications and source records attributed to Boettcher, L..

2 recordsLinked to original sources

Learning dynamical systems with biochemically informed neural ordinary differential equations

Ordinary differential equation models of biochemical reactions are often formulated as stoichiometric systems in which the dynamics arise from a collection of interacting processes. A central challenge is that the functional form of each process is rarely known a priori and may be difficult to infer from data. We propose biochemically informed neural ordinary differential equations (BINODEs), a neural-ODE framework that retains the stoichiometric structure of mechanistic models while representing individual processes by neural networks. In BINODEs, the outputs of neural network processes (NNPs) are mapped to state derivatives through a linear layer analogous to a stoichiometric matrix. This architecture allows biological side information, such as process-specific inputs, sign constraints, and monotonicity assumptions, to be built directly into the model. We characterize the approximation properties of NNPs for several standard biochemical rate laws and show that the proposed framework recovers both trajectories and process-level structure in Monod, Lotka-Volterra, pharmacokinetic, and ultradian endocrine models. These results suggest that BINODEs offer a useful compromise between mechanistic interpretability and data-driven flexibility for modeling partially known biochemical or biological dynamical systems.

systems biology↗

Mathematical Characterization of Private and Public Immune Repertoire Sequences

Diverse T and B cell repertoires play an important role in mounting effective immune responses against a wide range of pathogens and malignant cells. The number of unique T and B cell clones is characterized by T and B cell receptors (TCRs and BCRs), respectively. Although receptor sequences are generated probabilistically by recombination processes, clinical studies found a high degree of sharing of TCRs and BCRs among different individuals. In this work, we formulate a mathematical and statistical framework to quantify receptor distributions. We define information-theoretic metrics for comparing the frequency of sampled sequences observed across different individuals. Using synthetic and empirical TCR amino acid sequence data, we perform simulations to compare theoretical predictions of this clonal commonality across individuals with corresponding observations. Thus, we quantify the concept of "publicness" or "privateness" of T cell and B cell clones. Our methods can also be used to study the effect of different sampling protocols on the expected commonality of clones and on the confidence levels of this overlap. We also quantify the information loss associated with grouping together certain receptor sequences, as is done in spectratyping.

bioinformatics↗