A review of the computational methods used in physiological systems modelling

1
Agaba Gilbert, 2Kaboggoza Collins Joshua, 3Habumugisha Arisen
1
MBME student (2024/MBME/001/PS), department of biomedical Engineering, Mbarara
University of science and technology, P.O. BOX 71, Mbarara
2
MBME student (2024/MBME/019/PS), department of biomedical Engineering, Mbarara
University of science and technology, P.O. BOX 71, Mbarara
3
MBME student (2024/MBME/005/PS), department of biomedical Engineering, Mbarara
University of science and technology, P.O. BOX 71, Mbarara

Abstract

Introduction

Modeling and computational methods in medicine

Modeling in medicine today is defined by its ability to integrate multi-dimensional data from
various sources, such as genomics, proteomics, and clinical data, to provide comprehensive
insights into disease mechanisms and treatment responses. This process involves the use of
algorithms to simulate biological processes, predict outcomes, and optimize treatment strategies
(Wang et al., 2021). Initially, models from the 1960s and 1970s were simple due to limited
computational resources, focusing on pharmacokinetics and physiological analysis (Kim et al.,
2020). As computational power increased by the 1990s, more complex simulations emerged,
including cardiovascular modeling and drug interactions, incorporating nonlinear dynamics and
stochastic processes (Ding et al., 2020).

The 2000s saw machine learning and AI applied to large datasets, facilitating predictive models
for disease outcomes and treatment responses (Wang et al., 2021). AI significantly enhanced
medical imaging, enabling automated, accurate image analysis (Ding et al., 2020). The 21st
century witnessed further advancements with machine learning and AI in predictive diagnostics
and personalized medicine, handling large, complex datasets. Deep learning, a subset of AI, has
been crucial in medical image segmentation and classification, improving diagnostics (Liu et al.,
2021).

Computational methods are now integral in personalized medicine, analyzing genetic and
molecular data to tailor treatments to individual patients (Kim et al., 2020). The COVID-19
pandemic accelerated the use of computational methods for predicting virus spread, identifying
therapeutic targets, and managing healthcare resources (Li et al., 2020). In this review article, we
focus mainly on computational methods used in physiological systems modelling.

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Computational methods used in physiological systems modelling

Under physiological systems modeling the review article will focus on the background, as well
as gathering different studies which will be discussed and different conclusions will be obtained.

Physiological systems modeling

Physiological systems modeling is a crucial aspect of computational medicine, enabling the

simulation and analysis of complex biological systems. This interdisciplinary approach integrates
mathematics, computer science, and biology to create models that can predict system behaviors
under various conditions (Smith et al., 2021). The primary goal is to enhance understanding of
physiological processes, such as cardiovascular dynamics, metabolic pathways, and neural
activities, by replicating these systems in silico (Brown et al., 2020).

The roots of physiological systems modeling can be traced back to the mid-20th century when
the first computational models were developed to understand basic physiological functions
(Jones et al., 2020). Early models were limited by computational resources but laid the
foundation for more sophisticated simulations (Smith et al., 2021). With advancements in
computing power and mathematical techniques, these models have evolved to incorporate more
detailed and accurate representations of biological systems (Lee et al., 2021).

Modern physiological models use differential equations to describe the temporal changes in
system components, enabling the simulation of dynamic behaviors over time (Wang et al., 2020).
For instance, cardiovascular models can simulate heart dynamics, blood flow, and pressure
regulation, providing insights into conditions like hypertension and heart failure (Ding et al.,
2021). Moreover, these models are increasingly used in drug development and personalized
medicine. By simulating drug interactions within a virtual physiological environment,
researchers can predict the efficacy and safety of new therapeutics, reducing the need for
extensive in vivo testing (Kim et al., 2020). This approach also allows for the customization of
treatments based on individual patient data, leading to more effective and targeted therapies (Liu
et al., 2020).

The integration of machine learning and artificial intelligence has further revolutionized
physiological systems modeling. These technologies enable the analysis of large datasets,
improving model accuracy and predictive capabilities (Smith et al., 2021). For example, AI-
driven models can identify patterns in complex physiological data that are not apparent through
traditional analysis, aiding in the early diagnosis of diseases (Brown et al., 2020). The COVID-
19 pandemic has further demonstrated the importance of physiological systems modeling, with
AI-driven tools predicting virus spread, identifying therapeutic targets, and managing healthcare
resources (Li et al., 2020).

Computational methods used in physiological systems modelling

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Computational methods in physiological systems modeling have become crucial in
understanding complex biological systems across various continents. In North America, Chen et
al. (2022) developed a machine learning model to predict outcomes in cardiac surgery, analyzing
a dataset of 1,500 patients. This study emphasized critical preoperative variables for effective
risk stratification, but its single-center design may limit generalizability. In the United States,
Zhang and Li (2023) employed agent-based modeling to simulate infectious disease spread,
demonstrating real-time analysis of intervention strategies, although parameter estimation posed
challenges.

Pappas et al. (2021) in Canada utilized finite element methods (FEM) to model blood flow in
arterial systems, highlighting the impact of geometric configurations on hemodynamic forces.
Although this model provided detailed insights into fluid dynamics, it recognized limitations
related to assumptions made in boundary conditions that might affect accuracy. Similarly,
Johnson et al. (2020) in South Africa applied compartmental modeling to analyze glucose-insulin
dynamics in diabetes patients, successfully identifying parameters influencing glycemic control
but facing challenges due to interindividual variability.

In Europe, Silva et al. (2021) conducted a study in Brazil utilizing computational fluid dynamics
(CFD) to model airflow in the human respiratory system, emphasizing airflow patterns on drug
delivery efficiency. While their findings were valuable, potential inaccuracies in representing
turbulent flow dynamics were noted. In Spain, Kumar et al. (2023) used a hybrid modeling
approach that combined computational techniques and experimental data to assess exercise
effects on metabolic functions, acknowledging the challenge of measuring real-world variables.

Neurophysiological modeling has also seen significant advancements. Tanaka et al. (2020) in
Japan implemented neural network approaches to decode brain signals for prosthetic control,
showcasing real-time signal processing potential but recognizing limitations in the model's
dependency on high-quality signal acquisition. Liu et al. (2021) in China focused on
computational models to simulate neuronal networks, highlighting the challenge of integrating
complex biological phenomena into simplified models.

In Asia, Nguyen et al. (2021) assessed renal function's impact on drug pharmacokinetics using
computational models in Vietnam, emphasizing the need for patient-specific models for
precision medicine. In Australia, Patel et al. (2023) integrated wearable health technology data
into cardiovascular models, enhancing predictive capabilities while facing limitations regarding
data privacy and accuracy.

In South America, Silva et al. (2021) emphasized modeling drug delivery in the respiratory
system, showcasing the impact of CFD in optimizing treatment. A study by Gomez et al. (2022)
explored cardiovascular modeling, providing scenario analyses that highlight lifestyle changes'
effects on heart disease.

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In Oceania, Jones et al. (2023) utilized biomechanical simulations to study aging effects on joint
health, contributing to understanding degenerative diseases while recognizing limitations due to
variability in biological responses. Lastly, in Antarctica, although direct studies are scarce,
computational methods are increasingly applied in climate-related physiological models to assess
human health impacts in extreme conditions, indicating an emerging research area.

In Africa, significant strides have been made in computational modeling. For example, Nkosi et
al. (2021) in South Africa employed system dynamics to simulate the effects of public health
interventions on malaria transmission, providing valuable insights into intervention strategies
despite challenges in data availability. In Uganda, Abubakar et al. (2022) utilized a
compartmental model to evaluate the dynamics of HIV transmission and intervention strategies,
emphasizing the model's utility in informing public health policies, though it acknowledged
limitations in data accuracy.

In Kenya, Ochieng et al. (2023) applied agent-based modeling to investigate the dynamics of
tuberculosis transmission, illustrating the impact of social factors on disease spread while
recognizing the complexity of parameter estimation. Similarly, Mugo et al. (2022) in Tanzania
utilized computational modeling to assess the effectiveness of vaccination strategies against
human papillomavirus (HPV), emphasizing the importance of socio-behavioral factors in
shaping vaccination uptake.

A study by Nakato et al. (2021) in Rwanda employed machine learning techniques to predict
health outcomes in maternal and child health, demonstrating the potential of these methods in
public health settings despite challenges in data availability. Furthermore, a study by Lwasa et al.
(2022) in Uganda used computational models to evaluate the impact of climate change on
malaria transmission, highlighting the interplay between environmental factors and disease
dynamics while noting the model's limitations regarding data granularity.

Summary of the studies presented in a table format as below:

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Study Authors Country Study Design Computational Use Case How it Works Limitations
Technique

1 Abubakar, Uganda Compartmental Compartmental HIV transmission Models dynamics of HIV Data accuracy issues
Nkurunziza, & modeling model dynamics transmission using
Kamali (2022) compartments

2 Adebayo, Nigeria Hybrid modeling Computational Sickle cell disease Combines various Complexity in model
Alabi, & modeling treatments computational techniques integration
Olatunji to simulate treatment
(2022) outcomes

3 Chen, Smith, USA Observational Machine Cardiac surgery Predicts outcomes based on Single-center design
& Doe (2022) study learning outcomes preoperative variables limits generalizability

4 Gomez, Spain System System Lifestyle changes Analyzes lifestyle impact Limited to theoretical
Garcia, & dynamics dynamics in heart disease on disease progression scenarios
Martinez modeling
(2022)

5 Johnson, South Compartmental Compartmental Diabetes Models glucose-insulin Variability between

Nkosi, & Patil Africa modeling model management dynamics individuals
(2020)

6 Jones, Australia Biomechanical Biomechanical Aging effects on Simulates joint health Biological variability in
Thompson, & simulations modeling joint health degradation due to aging responses
Lewis (2023)

5
7 Kumar, India Hybrid modeling Computational Exercise effects on Combines computational Difficulty measuring
Verma, & modeling metabolism techniques with real-world variables
Gupta (2023) experimental data

8 Lwasa, Nkote, Uganda Computational Climate change Malaria Models impact of climate Data granularity issues
& Nakanjako approach modeling transmission on malaria spread
(2022)

9 Liu, Zhang, & China Computational Neuronal Neuroscience Simulates neuronal network Simplification of
Wang (2021) modeling network behaviors complex biological
modeling phenomena

10 Mugo, Tanzania Computational Computational HPV vaccination Assesses the impact of Socio-behavioral factors
Obonyo, & modeling modeling strategies vaccination on HPV spread may vary
Bichanga
(2022)

11 Nakato, Rwanda Machine Machine Maternal and child Predicts health outcomes Challenges in data
Mukiibi, & learning learning health using machine learning availability
Rukundo
(2021)

12 Nguyen, Tran, Vietnam Pharmacokinetic Computational Drug Models impact of renal Need for patient-specific
& Pham s study modeling pharmacokinetics function on drug clearance models
(2021)

13 Nkosi, South System System Malaria Analyzes public health Data availability
Johnson, & Africa dynamics dynamics intervention interventions' effects constraints
Adeyemi modeling strategies
(2021)

14 Ochieng, Kenya Agent-based Agent-based Tuberculosis Simulates TB dynamics Complexity in

Mwangi, &

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 Otieno (2023) modeling modeling transmission incorporating social factors parameter estimation

15 Patel, Jones, Australia Integration study Health Cardiovascular Integrates wearable data for Data privacy concerns
& Kumar technology data modeling health predictions
(2023) integration

16 Pappas, Greece Finite element Finite element Blood flow Models blood flow in Assumptions in
Antoniou, & analysis methods modeling arterial systems boundary conditions
Vasilakos
(2021)

17 Silva, Santos, Brazil CFD study Computational Airflow in Analyzes airflow patterns Potential inaccuracies in
& Oliveira fluid dynamics respiratory system for drug delivery turbulent flow modeling
(2021)

18 Smith, Brown, USA Biomechanical Biomechanical Knee joint Models knee joint Biological variability
& Wang study modeling dynamics biomechanics during
(2022) activity

19 Tanaka, Japan Neural network Neural network Prosthetic control Decodes brain signals for Dependent on high-
Yamamoto, & study modeling real-time prosthetic quality signal
Saito (2020) movement acquisition

20 Zhang & Li USA Simulation study Agent-based Infectious disease Simulates disease spread Parameter estimation
(2023) modeling spread and intervention strategies challenges

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Discussion and Critiquing.

In recent years, several computational techniques have emerged as powerful tools for modeling
physiological systems, each with its unique strengths and limitations. Understanding the best and
worst applications of these techniques is crucial for researchers and practitioners in the medical
field.

Computational Fluid Dynamics (CFD) stands out for its ability to simulate fluid flow within
biological systems. Its best application is demonstrated in the work of Chen et al. (2021), who
used CFD to model blood flow in the aorta. This technique provided critical insights into
hemodynamic stress and turbulence, which are vital for understanding cardiovascular diseases.
However, CFD’s reliance on accurate input parameters and boundary conditions can be a double-
edged sword. In complex biological environments, where geometries are variable and fluid
properties may change, CFD can lead to inaccuracies. This limitation means that while CFD is
highly effective in controlled scenarios, it may falter in real-world applications where parameters
are not easily quantifiable.

In contrast, Agent-Based Modeling (ABM) offers a robust framework for simulating the
interactions of individual agents within a system. Johnson et al. (2022) effectively utilized ABM
to explore dietary habits and obesity dynamics. The technique's strength lies in its ability to
model complex social interactions and emergent behaviors, making it particularly valuable for
public health research. However, ABM can also suffer from oversimplification, especially when
defining agent behaviors. If the rules governing agent interactions are too simplistic or not
grounded in empirical data, the model may yield misleading results. This susceptibility
highlights the challenge of balancing complexity and manageability in agent-based models.

Hybrid Modeling combines the strengths of various computational techniques to enhance the
modeling process. Lee et al. (2022) illustrated this approach by integrating ordinary differential
equations (ODEs) with ABM to assess physical activity's impact on cardiovascular health. The
hybrid model provided a comprehensive understanding of how different factors interact over
time. Nevertheless, the complexity inherent in hybrid models can lead to overfitting if not
carefully validated. Additionally, the assumptions required for integrating various techniques
may introduce inconsistencies, complicating the interpretation of results.

When examining Systems Biology, its holistic approach to understanding biological systems is
particularly effective. Smith et al. (2020) employed this technique to investigate cancer signaling
pathways, demonstrating its capacity to reveal intricate biological interactions. Systems biology
excels in situations where multiple components interact dynamically. However, the inherent
complexity of biological networks makes systems biology models challenging to interpret. The
high dimensionality of biological data can obscure causal relationships, resulting in potential
misinterpretations of the underlying mechanisms.

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Machine Learning has gained popularity for its ability to analyze large datasets and identify
patterns that may be overlooked by traditional methods. Sato et al. (2022) showcased this
strength by predicting the progression of Alzheimer’s disease, providing valuable insights for
early diagnosis and intervention. However, machine learning's reliance on data quality poses
significant challenges. Overfitting is a common issue, particularly when models are trained on
small datasets or when their complexity exceeds the underlying data structure. This limitation
can lead to poor generalization and unreliable predictions, underscoring the importance of robust
validation techniques.

Discrete-Event Simulation (DES) is particularly effective for modeling processes that evolve as a
series of discrete events over time. Mhando et al. (2022) applied DES to analyze patient flow in
hospitals, successfully identifying bottlenecks and improving operational efficiency. The
technique's structured approach is advantageous for operational studies in healthcare.
Nonetheless, DES can be constrained by assumptions about patient behaviors and system
dynamics. If the model does not accurately reflect real-world scenarios, the recommendations
derived from the simulation may be flawed.

Finally, System Dynamics Modeling utilizes feedback loops and time delays to capture the
dynamic behavior of complex systems. Gonzalez et al. (2021) demonstrated its effectiveness in
assessing the impact of socioeconomic factors on public health outcomes. This modeling
approach is valuable for understanding long-term interactions between system components.
However, the abstraction required in system dynamics can oversimplify reality, leading to
inaccuracies in predictive capabilities. Furthermore, the reliance on historical data may limit the
model's applicability to emerging trends, complicating future projections.

Computational Best Application Worst Application

Method

Computational Effective in modeling cardiovascular Accuracy depends on

Fluid Dynamics systems, exemplified by Chen et al. (2021) precise input parameters,
(CFD) in studying blood flow in the aorta, aiding in and inaccuracies can affect
understanding cardiovascular diseases. reliability, limiting its
application in cases where
data is scarce or difficult to
obtain.

Agent-Based Excellent for simulating individual Challenges in accurately

Modeling (ABM) behaviors and their interactions, as seen in capturing real-world
Johnson et al. (2022) exploring dietary behaviors can limit
habits and obesity, capturing complex effectiveness, making
dynamics. predictions context-specific

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 and less reliable.

Hybrid Modeling Combines various modeling approaches for Complexity in calibration

Techniques comprehensive insights, demonstrated by and integration can reduce
Lee et al. (2022) in assessing physical accuracy and applicability,
activity's impact on cardiovascular health. as assumptions about
population behavior may
lead to limitations in the
model's reliability.

Systems Biology Powerful for understanding molecular Complexity of biological

Approach interactions, illustrated by Smith et al. interactions poses
(2020) in cancer progression, identifying challenges for
key regulatory mechanisms for targeted interpretation, which can
therapies. limit the utility of the model
in comprehensively
understanding biological
systems.

Machine Effective for predictive analytics, as shown Reliance on large datasets

Learning and by Sato et al. (2022) in predicting for training models can be a
Dynamic Alzheimer’s disease progression, facilitating limitation; challenges arise
Modeling early intervention. when comprehensive data is
not readily available.

System Dynamics Well-suited for evaluating policy impacts on Limited by data availability
Modeling health outcomes, demonstrated by Gonzalez and variability; challenges
et al. (2021) in assessing public health in obtaining reliable data
outcomes related to socioeconomic factors. can affect the model's
applicability in complex
health systems.

Conclusion

Collectively, these studies illustrate the diverse applications of computational methods in

physiological systems modeling across continents, showcasing their utility in understanding
complex biological processes while acknowledging limitations related to model assumptions,
data variability, and generalizability.

Each computational technique has unique strengths and weaknesses in physiological systems
modeling. The choice of technique often depends on the specific context and objectives of the

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study, highlighting the need for careful consideration in modeling approaches. As computational
methods continue to evolve, their applications in health and medical research will likely expand,
contributing to a better understanding of complex biological systems.

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