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Jana L. Gevertz

Publications and source records attributed to Jana L. Gevertz.

4 recordsLinked to original sources

Spatial Model Selection and Uncertainty Quantification: Comparing Continuous and Discrete Wound Healing Models

All data-driven modeling tasks (e.g., parameter estimation, uncertainty quantification, and data forecasting) require the selection of a mathematical model. An overlooked aspect of model selection is modality; for example, there are no guidelines on when to use a partial differential equation (PDE) model or an agent-based model (ABM) for spatial processes. To address this, we created a model selection pipeline that uses approximate Bayesian computations to perform parameter estimation, uncertainty quantification, and model selection (using both information criteria and out-of-sample forecasting). Applying the pipeline to artificial datasets (generated from ABMs) reveals that while both modalities yield comparable parameter estimation performance, the ABM estimates exhibit higher uncertainty, and the PDE models compute more than 1,000$\times$ faster. Surprisingly, the mean-field PDE is often selected over the true generative ABM model using both information criteria and data forecasting. Applying the pipeline to public wound healing data indicates that a PDE model with cell pulling and a time delay is the most appropriate model for this data, however, this model has high levels of parametric uncertainty. This methodology establishes a preliminary framework for selecting the appropriate modeling modality for spatial biological data.

q-bio.QM↗

Mentoring Undergraduate Interdisciplinary Mathematics Research Students: Junior Faculty Experiences

To be successful, junior faculty must properly manage their time in the face of expanding responsibilities. One such responsibility is supervising undergraduate research projects. Student research projects (either single or multi-student) can be undertaken as a full-time summer experience, or as a part-time academic year commitment. With many potential undergraduate research formats, and with different types of students, junior faculty may find challenges in forming their research group, establishing a structure that promotes student productivity, picking an appropriate project, or in effectively mentoring their students. This article draws from the authors' experiences to help junior faculty navigate these complexities so that all parties reap the benefits of undergraduate research in interdisciplinary mathematical disciplines.

math.HO↗

Limiting the Development of Anti-Cancer Drug Resistance in a Spatial Model of Micrometastases

While chemoresistance in primary tumors is well-studied, much less is known about the influence of systemic chemotherapy on the development of drug resistance at metastatic sites. In this work, we use a hybrid spatial model of tumor response to a DNA damaging drug to study how the development of chemoresistance in micrometastases depends on the drug dosing schedule. We separately consider cell populations that harbor pre-existing resistance to the drug, and those that acquire resistance during the course of treatment. For each of these independent scenarios, we consider one hypothetical cell line that is responsive to metronomic chemotherapy, and another that with high probability cannot be eradicated by a metronomic protocol. Motivated by experimental work on ovarian cancer xenografts, we consider all possible combinations of a one week treatment protocol, repeated for three weeks, and constrained by the total weekly drug dose. Simulations reveal a small number of fractionated-dose protocols that are at least as effective as metronomic therapy in eradicating micrometastases with acquired resistance (weak or strong), while also being at least as effective on those that harbor weakly pre-existing resistant cells. Given the responsiveness of very different theoretical cell lines to these few fractionated-dose protocols, these may represent more effective ways to schedule chemotherapy with the goal of limiting metastatic tumor progression.

q-bio.TO↗

Emergence of Anti-Cancer Drug Resistance: Exploring the Importance of the Microenvironmental Niche via a Spatial Model

Practically, all chemotherapeutic agents lead to drug resistance. Clinically, it is a challenge to determine whether resistance arises prior to, or as a result of, cancer therapy. Further, a number of different intracellular and microenvironmental factors have been correlated with the emergence of drug resistance. With the goal of better understanding drug resistance and its connection with the tumor microenvironment, we have developed a hybrid discrete-continuous mathematical model. In this model, cancer cells described through a particle-spring approach respond to dynamically changing oxygen and DNA damaging drug concentrations described through partial differential equations. We thoroughly explored the behavior of our self-calibrated model under the following common conditions: a fixed layout of the vasculature, an identical initial configuration of cancer cells, the same mechanism of drug action, and one mechanism of cellular response to the drug. We considered one set of simulations in which drug resistance existed prior to the start of treatment, and another set in which drug resistance is acquired in response to treatment. This allows us to compare how both kinds of resistance influence the spatial and temporal dynamics of the developing tumor, and its clonal diversity. We show that both pre-existing and acquired resistance can give rise to three biologically distinct parameter regimes: successful tumor eradication, reduced effectiveness of drug during the course of treatment (resistance), and complete treatment failure.

q-bio.PE↗