arXiv subjects

Jacob G. Scott

Publications and source records attributed to Jacob G. Scott.

15 recordsLinked to original sources

arXiv2024

Asymmetric Interactions Shape Survival During Population Range Expansions

An organism that is newly introduced into an existing population has a survival probability that is dependent on both the population density of its environment and the competition it experiences with the members of that population. Expanding populations naturally form regions of high and low density, and simultaneously experience ecological interactions both internally and at the boundary of their range. For this reason, systems of expanding populations are ideal for studying the combination of density and ecological effects. Conservation ecologists have been studying the ability of an invasive species to establish for some time, attributing success to both ecological and spatial factors. Similar behaviors have been observed in spatially structured cell populations, such as those found in cancerous tumors and bacterial biofilms. In these scenarios, novel organisms may be the introduction of a new mutation or bacterial species with some form of drug resistance, leading to the possibility of treatment failure. In order to gain insight into the relationship between population density and ecological interactions, we study an expanding population of interacting wild-type cells and mutant cells. We simulate these interactions in time and study the spatially dependent probability for a mutant to survive or to take over the front of the population wave (gene surfing). Additionally, we develop a mathematical model that describes this survival probability and find agreement when the payoff for the mutant is positive (corresponding to cooperation, exploitation, or commensalism). By knowing the types of interactions, our model provides insight into the spatial distribution of survival probability. Conversely, given a spatial distribution of survival probabilities, our model provides insight into the types of interactions that were involved to generate it.

q-bio.PE↗

arXiv2022

Inferring Density-Dependent Population Dynamics Mechanisms through Rate Disambiguation for Logistic Birth-Death Processes

Density dependence is important in the ecology and evolution of microbial and cancer cells. Typically, we can only measure net growth rates, but the underlying density-dependent mechanisms that give rise to the observed dynamics can manifest in birth processes, death processes, or both. Therefore, we utilize the mean and variance of cell number fluctuations to separately identify birth and death rates from time series that follow stochastic birth-death processes with logistic growth. Our method provides a novel perspective on stochastic parameter identifiability, which we validate by analyzing the accuracy in terms of the discretization bin size. We apply our method to the scenario where a homogeneous cell population goes through three stages: (1) grows naturally to its carrying capacity, (2) is treated with a drug that reduces its carrying capacity, and (3) overcomes the drug effect to restore its original carrying capacity. In each stage, we disambiguate whether it happens through the birth process, death process, or some combination of the two, which contributes to understanding drug resistance mechanisms. In the case of limited data sets, we provide an alternative method based on maximum likelihood and solve a constrained nonlinear optimization problem to identify the most likely density dependence parameter for a given cell number time series. Our methods can be applied to other biological systems at different scales to disambiguate density-dependent mechanisms underlying the same net growth rate.

q-bio.PE↗

arXiv2021

Accessing United States Bulk Patent Data with patentpy and patentr

The United States Patent and Trademark Office (USPTO) provides publicly accessible bulk data files containing information for all patents from 1976 onward. However, the format of these files changes over time and is memory-inefficient, which can pose issues for individual researchers. Here, we introduce the patentpy and patentr packages for the Python and R programming languages. They allow users to programmatically fetch bulk data from the USPTO website and access it locally in a cleaned, rectangular format. Research depending on United States patent data would benefit from the use of patentpy and patentr. We describe package implementation, quality control mechanisms, and present use cases highlighting simple, yet effective, applications of this software.

cs.DL↗

arXiv2020

Exploring complex networks with the ICON R package

We introduce ICON, an R package that contains 1075 complex network datasets in a standard edgelist format. All provided datasets have associated citations and have been indexed by the Colorado Index of Complex Networks - also referred to as ICON. In addition to supplying a large and diverse corpus of useful real-world networks, ICON also implements an S3 generic to work with the network and ggnetwork R packages for network analysis and visualization, respectively. Sample code in this report also demonstrates how ICON can be used in conjunction with the igraph package. Currently, the Comprehensive R Archive Network hosts ICON v0.4.0. We hope that ICON will serve as a standard corpus for complex network research and prevent redundant work that would be otherwise necessary by individual research groups. The open source code for ICON and for this reproducible report can be found at https://github.com/rrrlw/ICON.

cs.SI↗

arXiv2020

Controlling the speed and trajectory of evolution with counterdiabatic driving

The pace and unpredictability of evolution are critically relevant in a variety of modern challenges: combating drug resistance in pathogens and cancer, understanding how species respond to environmental perturbations like climate change, and developing artificial selection approaches for agriculture. Great progress has been made in quantitative modeling of evolution using fitness landscapes, allowing a degree of prediction for future evolutionary histories. Yet fine-grained control of the speed and the distributions of these trajectories remains elusive. We propose an approach to achieve this using ideas originally developed in a completely different context: counterdiabatic driving to control the behavior of quantum states for applications like quantum computing and manipulating ultra-cold atoms. Implementing these ideas for the first time in a biological context, we show how a set of external control parameters (i.e. varying drug concentrations / types, temperature, nutrients) can guide the probability distribution of genotypes in a population along a specified path and time interval. This level of control, allowing empirical optimization of evolutionary speed and trajectories, has myriad potential applications, from enhancing adaptive therapies for diseases, to the development of thermotolerant crops in preparation for climate change, to accelerating bioengineering methods built on evolutionary models, like directed evolution of biomolecules.

cond-mat.stat-mech↗

arXiv2019

A flat persistence diagram for improved visualization of persistent homology

Visualization in the emerging field of topological data analysis has progressed from persistence barcodes and persistence diagrams to display of two-parameter persistent homology. Although persistence barcodes and diagrams have permitted insight into the geometry underlying complex datasets, visualization of even single-parameter persistent homology has significant room for improvement. Here, we propose a modification to the conventional persistence diagram - the flat persistence diagram - that more efficiently displays information relevant to persistent homology and simultaneously corrects for visual bias present in the former. Flat persistence diagrams display equivalent information as their predecessor, while providing researchers with an intuitive horizontal reference axis in contrast to the usual diagonal reference line. Reducing visual bias through the use of appropriate graphical displays not only provides more accurate, but also deeper insights into the topology that underlies complex datasets. Introducing flat persistence diagrams into widespread use would bring researchers one step closer to practical application of topological data analysis.

stat.AP↗

arXiv2018

Optimizing adaptive cancer therapy: dynamic programming and evolutionary game theory

Recent clinical trials have shown that the adaptive drug therapy can be more efficient than a standard MTD-based policy in treatment of cancer patients. The adaptive therapy paradigm is not based on a preset schedule; instead, the doses are administered based on the current state of tumor. But the adaptive treatment policies examined so far have been largely ad hoc. In this paper we propose a method for systematically optimizing the rules of adaptive policies based on an Evolutionary Game Theory model of cancer dynamics. Given a set of treatment objectives, we use the framework of dynamic programming to find the optimal treatment strategies. In particular, we optimize the total drug usage and time to recovery by solving a Hamilton-Jacobi-Bellman equation based on a mathematical model of tumor evolution. We compare adaptive/optimal treatment strategy with MTD-based treatment policy. We show that optimal treatment strategies can dramatically decrease the total amount of drugs prescribed as well as increase the fraction of initial tumour states from which the recovery is possible. We also examine the optimization trade-offs between the total administered drugs and recovery time. The adaptive therapy combined with optimal control theory is a promising concept in the cancer treatment and should be integrated into clinical trial design.

q-bio.QM↗

arXiv2017

Evolutionary dynamics of incubation periods

The incubation period of a disease is the time between an initiating pathologic event and the onset of symptoms. For typhoid fever, polio, measles, leukemia and many other diseases, the incubation period is highly variable. Some affected people take much longer than average to show symptoms, leading to a distribution of incubation periods that is right skewed and often approximately lognormal. Although this statistical pattern was discovered more than sixty years ago, it remains an open question to explain its ubiquity. Here we propose an explanation based on evolutionary dynamics on graphs. For simple models of a mutant or pathogen invading a network-structured population of healthy cells, we show that skewed distributions of incubation periods emerge for a wide range of assumptions about invader fitness, competition dynamics, and network structure. The skewness stems from stochastic mechanisms associated with two classic problems in probability theory: the coupon collector and the random walk. Unlike previous explanations that rely crucially on heterogeneity, our results hold even for homogeneous populations. Thus, we predict that two equally healthy individuals subjected to equal doses of equally pathogenic agents may, by chance alone, show remarkably different time courses of disease.

q-bio.PE↗

arXiv2017

Takeover times for a simple model of network infection

We study a stochastic model of infection spreading on a network. At each time step a node is chosen at random, along with one of its neighbors. If the node is infected and the neighbor is susceptible, the neighbor becomes infected. How many time steps $T$ does it take to completely infect a network of $N$ nodes, starting from a single infected node? An analogy to the classic "coupon collector" problem of probability theory reveals that the takeover time $T$ is dominated by extremal behavior, either when there are only a few infected nodes near the start of the process or a few susceptible nodes near the end. We show that for $N \gg 1$, the takeover time $T$ is distributed as a Gumbel for the star graph; as the sum of two Gumbels for a complete graph and an Erdős-Rényi random graph; as a normal for a one-dimensional ring and a two-dimensional lattice; and as a family of intermediate skewed distributions for $d$-dimensional lattices with $d \ge 3$ (these distributions approach the sum of two Gumbels as $d$ approaches infinity). Connections to evolutionary dynamics, cancer, incubation periods of infectious diseases, first-passage percolation, and other spreading phenomena in biology and physics are discussed.

q-bio.PE↗

arXiv2016

Cancer treatment scheduling and dynamic heterogeneity in social dilemmas of tumour acidity and vasculature

Background: Tumours are diverse ecosystems with persistent heterogeneity in various cancer hallmarks like self-sufficiency of growth factor production for angiogenesis and reprogramming of energy-metabolism for aerobic glycolysis. This heterogeneity has consequences for diagnosis, treatment, and disease progression. Methods: We introduce the double goods game to study the dynamics of these traits using evolutionary game theory. We model glycolytic acid production as a public good for all tumour cells and oxygen from vascularization via VEGF production as a club good benefiting non-glycolytic tumour cells. This results in three viable phenotypic strategies: glycolytic, angiogenic, and aerobic non-angiogenic. Results: We classify the dynamics into three qualitatively distinct regimes: (1) fully glycolytic, (2) fully angiogenic, or (3) polyclonal in all three cell types. The third regime allows for dynamic heterogeneity even with linear goods, something that was not possible in prior public good models that considered glycolysis or growth-factor production in isolation. Conclusion: The cyclic dynamics of the polyclonal regime stress the importance of timing for anti-glycolysis treatments like lonidamine. The existence of qualitatively different dynamic regimes highlights the order effects of treatments. In particular, we consider the potential of vascular renormalization as a neoadjuvant therapy before follow up with interventions like buffer therapy.

q-bio.PE↗

arXiv2015

Edge effects in game theoretic dynamics of spatially structured tumours

Background: Analysing tumour architecture for metastatic potential usually focuses on phenotypic differences due to cellular morphology or specific genetic mutations, but often ignore the cell's position within the heterogeneous substructure. Similar disregard for local neighborhood structure is common in mathematical models. Methods: We view the dynamics of disease progression as an evolutionary game between cellular phenotypes. A typical assumption in this modeling paradigm is that the probability of a given phenotypic strategy interacting with another depends exclusively on the abundance of those strategies without regard local heterogeneities. We address this limitation by using the Ohtsuki-Nowak transform to introduce spatial structure to the go vs. grow game. Results: We show that spatial structure can promote the invasive (go) strategy. By considering the change in neighbourhood size at a static boundary -- such as a blood-vessel, organ capsule, or basement membrane -- we show an edge effect that allows a tumour without invasive phenotypes in the bulk to have a polyclonal boundary with invasive cells. We present an example of this promotion of invasive (EMT positive) cells in a metastatic colony of prostate adenocarcinoma in bone marrow. Interpretation: Pathologic analyses that do not distinguish between cells in the bulk and cells at a static edge of a tumour can underestimate the number of invasive cells. We expect our approach to extend to other evolutionary game models where interaction neighborhoods change at fixed system boundaries.

q-bio.PE↗

arXiv2013

A filter-flow perspective of hematogenous metastasis offers a non-genetic paradigm for personalized cancer therapy

Research into mechanisms of hematogenous metastasis has largely become genetic in focus, attempting to understand the molecular basis of `seed-soil' relationships. Preceeding this biological mechanism is the physical process of dissemination of circulating tumour cells (CTCs). We utilize a `filter-flow' paradigm to show that assumptions about CTC dynamics strongly affect metastatic efficiency: without data on CTC dynamics, any attempt to predict metastatic spread in individual patients is impossible.

q-bio.TO↗

arXiv2013

Intrinsic cell factors that influence tumourigenicity in cancer stem cells - towards hallmarks of cancer stem cells

Since the discovery of a cancer initiating side population in solid tumours, studies focussing on the role of so-called cancer stem cells in cancer initiation and progression have abounded. The biological interrogation of these cells has yielded volumes of information about their behaviour, but there has, as of yet, not been many actionable generalised theoretical conclusions. To address this point, we have created a hybrid, discrete/continuous computational cellular automaton model of a generalised stem-cell driven tissue and explored the phenotypic traits inherent in the inciting cell and the resultant tissue growth. We identify the regions in phenotype parameter space where these initiating cells are able to cause a disruption in homeostasis, leading to tissue overgrowth and tumour formation. As our parameters and model are non-specific, they could apply to any tissue cancer stem-cell and do not assume specific genetic mutations. In this way, our model suggests that targeting these phenotypic traits could represent generalizable strategies across cancer types and represents a first attempt to identify the hallmarks of cancer stem cells.

q-bio.TO↗

arXiv2013

Mathematical modeling of the metastatic process

Mathematical modeling in cancer has been growing in popularity and impact since its inception in 1932. The first theoretical mathematical modeling in cancer research was focused on understanding tumor growth laws and has grown to include the competition between healthy and normal tissue, carcinogenesis, therapy and metastasis. It is the latter topic, metastasis, on which we will focus this short review, specifically discussing various computational and mathematical models of different portions of the metastatic process, including: the emergence of the metastatic phenotype, the timing and size distribution of metastases, the factors that influence the dormancy of micrometastases and patterns of spread from a given primary tumor.

q-bio.TO↗

arXiv2013

A Markov chain model of evolution in asexually reproducing populations: insight and analytical tractability in the evolutionary process

The evolutionary process has been modelled in many ways using both stochastic and deterministic models. We develop an algebraic model of evolution in a population of asexually reproducing organisms in which we represent a stochastic walk in phenotype space, constrained to the edges of an underlying graph representing the genotype, with a time-homogeneous Markov Chain. We show its equivalence to a more standard, explicit stochastic model and show the algebraic model's superiority in computational efficiency. Because of this increase in efficiency, we offer the ability to simulate the evolution of much larger populations in more realistic genotype spaces. Further, we show how the algebraic properties of the Markov Chain model can give insight into the evolutionary process and allow for analysis using familiar linear algebraic methods.

q-bio.PE↗