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Systems Biomedicine...
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Systems Biomedicine

A special issue of Processes (ISSN 2227-9717). This special issue belongs to the section "Biological Processes and Systems".

Deadline for manuscript submissions: closed (31 January 2019) | Viewed by 29090

Special Issue Editors

Dr. Ashlee N. Ford Versypt

E-Mail Website
Guest Editor
School of Chemical Engineering, Oklahoma State University, Stillwater, OK 74078, USA
Interests: dynamic physiological processes; disease mechanisms; pharmaceutical treatments; mathematical biology; multiscale modeling
Dr. Belinda S. Akpa

E-Mail Website
Guest Editor
Molecular Biomedical Sciences and Electrical & Computer Engineering, North Carolina State University, Raleigh, NC 27607, USA
Interests: systems physiology; systems pharmacology; multiscale biological models

Special Issue Information

Dear Colleagues,

The term “systems biomedicine”, defined as the study of dynamic systems of the human body as a multiscale integrated whole, is used to distinguish from the term “systems biology”, which primarily focuses on the application of dynamic systems theory and network analysis to molecular biology. Many recent advances in the systems biology field have been made in the past decade. The systems biology quantitative methods for analyzing biological networks such as metabolic networks and cell signaling pathways have yielded a greater understanding of relationships between genetic information and cellular function. However, a gap still exists in tying these genetic and cellular effects to clinically observable properties. As the translational counterpart to systems biology, systems biomedicine seeks to bridge this gap between molecular and cellular systems analysis and clinical medicine. Applying approaches from process systems engineering to mathematically describe the physical and chemical processes that occur in biomedical applications across multiple scales allows for testing of proposed mechanisms for physiological functions or disease progression by simulating complex interdependent interactions that cannot be decoupled easily in experiments. Dynamic behaviors and macroscopically observable properties may emerge from the collective behavior of many cells or interactions between populations of cells and tissues that cannot be explained simply by studying the isolated parts. In this Special Issue we encourage manuscripts that utilize and create process systems engineering tools and experimental or computational/mathematial models to make clinically-relevant predictions of physiological functions and to incorporate interactions between medical therapies and healthy and diseased tissues.

Topics include but are not limited to:

  • Development of new tools to facilitiate single- or multi-scale modeling of biomedical systems
  • Design of validated experimental (animal, 3D tissue mimic, microfluidic, etc.) or computational/mathematical models of physiological and pathophysiological tissues and/or organ systems for biomedical applications
  • Prediction and analysis of physiological or pathophysiological phenomena
  • Optimization of schedules of medical interventions or therapies

Dr. Ashlee N. Ford Versypt
Dr. Belinda S. Akpa
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Processes is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2400 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Systems biomedicine
  • biomedical systems
  • systems pharmacology
  • mathematical biology
  • multiscale systems biology
  • physiology
  • multiscale modeling
  • systems toxicology

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Published Papers (6 papers)

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Research

21 pages, 3426 KiB  
Article
Single-Cell Receptor Quantification of an In Vitro Coculture Angiogenesis Model Reveals VEGFR, NRP1, Tie2, and PDGFR Regulation and Endothelial Heterogeneity
by Si Chen and P. I. Imoukhuede
Processes 2019, 7(6), 356; https://doi.org/10.3390/pr7060356 - 10 Jun 2019
Cited by 6 | Viewed by 4249
Abstract
Angiogenesis, the formation of new blood vessels from pre-existing ones, is essential for both normal development and numerous pathologies. Systems biology has offered a unique approach to study angiogenesis by profiling tyrosine kinase receptors (RTKs) that regulate angiogenic processes and computationally modeling RTK [...] Read more.
Angiogenesis, the formation of new blood vessels from pre-existing ones, is essential for both normal development and numerous pathologies. Systems biology has offered a unique approach to study angiogenesis by profiling tyrosine kinase receptors (RTKs) that regulate angiogenic processes and computationally modeling RTK signaling pathways. Historically, this systems biology approach has been applied on ex vivo angiogenesis assays, however, these assays are difficult to quantify and limited in their potential of temporal analysis. In this study, we adopted a simple two-dimensional angiogenesis assay comprised of human umbilical vein endothelial cells (HUVECs) and human dermal fibroblasts (HDFs) and examined temporal dynamics of a panel of six RTKs and cell heterogeneity up to 17 days. We observed ~2700 VEGFR1 (vascular endothelial growth factor receptor 1) per cell on 24-h-old cocultured HDF plasma membranes, which do not express VEGFR when cultured alone. We observed 4000–8100 VEGFR2 per cell on cocultured HUVEC plasma membranes throughout endothelial tube formation. We showed steady increase of platelet-derived growth factor receptors (PDGFRs) on cocultured HDF plasma membranes, and more interestingly, 1900–2900 PDGFRβ per plasma membrane were found on HUVECs within the first six hours of coculturing. These quantitative findings will offer us insights into molecular regulation during angiogenesis and help assess in vitro tube formation models and their physiological relevance. Full article
(This article belongs to the Special Issue Systems Biomedicine )
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15 pages, 9422 KiB  
Article
A Glucose-Dependent Pharmacokinetic/ Pharmacodynamic Model of ACE Inhibition in Kidney Cells
by Minu R. Pilvankar, Hui Ling Yong and Ashlee N. Ford Versypt
Processes 2019, 7(3), 131; https://doi.org/10.3390/pr7030131 - 4 Mar 2019
Cited by 1 | Viewed by 4808
Abstract
Diabetic kidney disease (DKD) is a major cause of renal failure. Podocytes are terminally differentiated renal epithelial cells that are key targets of damage due to DKD. Podocytes express a glucose-stimulated local renin-angiotensin system (RAS) that produces angiotensin II (ANG II). Local RAS [...] Read more.
Diabetic kidney disease (DKD) is a major cause of renal failure. Podocytes are terminally differentiated renal epithelial cells that are key targets of damage due to DKD. Podocytes express a glucose-stimulated local renin-angiotensin system (RAS) that produces angiotensin II (ANG II). Local RAS differs from systemic RAS, which has been studied widely. Hyperglycemia increases the production of ANG II by podocyte cells, leading to podocyte injury. Angiotensin-converting enzyme (ACE) is involved in the production of ANG II, and ACE inhibitors are drugs used to suppress elevated ANG II concentration. As systemic RAS differs from the local RAS in podocytes, ACE inhibitor drugs should act differently in local versus systemic contexts. Experimental and computational studies have considered the pharmacokinetics (PK) and pharmacodynamics (PD) of ACE inhibition of the systemic RAS. Here, a PK/PD model for ACE inhibition is developed for the local RAS in podocytes. The model takes constant or dynamic subject-specific glucose concentration input to predict the ANG II concentration and the corresponding effects of drug doses locally and systemically. The model is developed for normal and impaired renal function in combination with different glucose conditions, thus enabling the study of various pathophysiological conditions. Parameter uncertainty is also analyzed. Such a model can improve the study of the effects of drugs at the cellular level and can aid in development of therapeutic approaches to slow the progression of DKD. Full article
(This article belongs to the Special Issue Systems Biomedicine )
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19 pages, 11986 KiB  
Article
Information Extraction from Retinal Images with Agent-Based Technology
by Pablo Chamoso, Sara Rodríguez, Luis García-Ortiz and Juan Manuel Corchado
Processes 2018, 6(12), 254; https://doi.org/10.3390/pr6120254 - 6 Dec 2018
Cited by 2 | Viewed by 3822
Abstract
The study of retinal vessels can provide information on a wide range of illnesses in the human body. Numerous works have already focused on this new field of research and several medical software programs have been proposed to facilitate the close examination of [...] Read more.
The study of retinal vessels can provide information on a wide range of illnesses in the human body. Numerous works have already focused on this new field of research and several medical software programs have been proposed to facilitate the close examination of retinal vessels. Some allow for the automatic extraction of information and can be combined with other clinical tools for effective diagnosis and further medical studies. This article proposes an Agent-based Virtual Organizations (VO) System which applies a novel methodology for taking measurements from fundus images and extracting information on the retinal vessel caliber. A case study was conducted to evaluate the performance of the developed system, and the fundus images of different patients were used to extract information. Its performance was compared with that of similar tools. Full article
(This article belongs to the Special Issue Systems Biomedicine )
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18 pages, 2010 KiB  
Article
Multicellular Models Bridging Intracellular Signaling and Gene Transcription to Population Dynamics
by Mohammad Aminul Islam, Satyaki Roy, Sajal K. Das and Dipak Barua
Processes 2018, 6(11), 217; https://doi.org/10.3390/pr6110217 - 4 Nov 2018
Cited by 1 | Viewed by 3531
Abstract
Cell signaling and gene transcription occur at faster time scales compared to cellular death, division, and evolution. Bridging these multiscale events in a model is computationally challenging. We introduce a framework for the systematic development of multiscale cell population models. Using message passing [...] Read more.
Cell signaling and gene transcription occur at faster time scales compared to cellular death, division, and evolution. Bridging these multiscale events in a model is computationally challenging. We introduce a framework for the systematic development of multiscale cell population models. Using message passing interface (MPI) parallelism, the framework creates a population model from a single-cell biochemical network model. It launches parallel simulations on a single-cell model and treats each stand-alone parallel process as a cell object. MPI mediates cell-to-cell and cell-to-environment communications in a server-client fashion. In the framework, model-specific higher level rules link the intracellular molecular events to cellular functions, such as death, division, or phenotype change. Cell death is implemented by terminating a parallel process, while cell division is carried out by creating a new process (daughter cell) from an existing one (mother cell). We first demonstrate these capabilities by creating two simple example models. In one model, we consider a relatively simple scenario where cells can evolve independently. In the other model, we consider interdependency among the cells, where cellular communication determines their collective behavior and evolution under a temporally evolving growth condition. We then demonstrate the framework’s capability by simulating a full-scale model of bacterial quorum sensing, where the dynamics of a population of bacterial cells is dictated by the intercellular communications in a time-evolving growth environment. Full article
(This article belongs to the Special Issue Systems Biomedicine )
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17 pages, 545 KiB  
Article
Eden Model Simulation of Re-Epithelialization and Angiogenesis of an Epidermal Wound
by Ephraim Agyingi, Luke Wakabayashi, Tamas Wiandt and Sophia Maggelakis
Processes 2018, 6(11), 207; https://doi.org/10.3390/pr6110207 - 25 Oct 2018
Cited by 4 | Viewed by 4117
Abstract
Among the vital processes of cutaneous wound healing are epithelialization and angiogenesis. The former leads to the successful closure of the wound while the latter ensures that nutrients are delivered to the wound region during and after healing is completed. These processes are [...] Read more.
Among the vital processes of cutaneous wound healing are epithelialization and angiogenesis. The former leads to the successful closure of the wound while the latter ensures that nutrients are delivered to the wound region during and after healing is completed. These processes are regulated by various cytokines and growth factors that subtend their proliferation and migration into the wound region until full healing is attained. Wound epithelialization can be enhanced by the administration of epidermal stem cells (ESC) or impaired by the presence of an infection. This paper uses the Eden model of a growing cluster to independently simulate the processes of epithelialization and angiogenesis in a cutaneous wound for different geometries. Further, simulations illustrating bacterial infection are provided. Our simulation results demonstrate contraction and closure for any wound geometry due to a collective migration of epidermal cells from the wound edge in fractal form and the diffusion of capillary sprouts with the laying down of capillary blocks behind moving tips into the wound area. Full article
(This article belongs to the Special Issue Systems Biomedicine )
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21 pages, 1042 KiB  
Article
A Multicellular Vascular Model of the Renal Myogenic Response
by Maria-Veronica Ciocanel, Tracy L. Stepien, Ioannis Sgouralis and Anita T. Layton
Processes 2018, 6(7), 89; https://doi.org/10.3390/pr6070089 - 17 Jul 2018
Cited by 2 | Viewed by 7268
Abstract
The myogenic response is a key autoregulatory mechanism in the mammalian kidney. Triggered by blood pressure perturbations, it is well established that the myogenic response is initiated in the renal afferent arteriole and mediated by alterations in muscle tone and vascular diameter that [...] Read more.
The myogenic response is a key autoregulatory mechanism in the mammalian kidney. Triggered by blood pressure perturbations, it is well established that the myogenic response is initiated in the renal afferent arteriole and mediated by alterations in muscle tone and vascular diameter that counterbalance hemodynamic perturbations. The entire process involves several subcellular, cellular, and vascular mechanisms whose interactions remain poorly understood. Here, we model and investigate the myogenic response of a multicellular segment of an afferent arteriole. Extending existing work, we focus on providing an accurate—but still computationally tractable—representation of the coupling among the involved levels. For individual muscle cells, we include detailed Ca2+ signaling, transmembrane transport of ions, kinetics of myosin light chain phosphorylation, and contraction mechanics. Intercellular interactions are mediated by gap junctions between muscle or endothelial cells. Additional interactions are mediated by hemodynamics. Simulations of time-independent pressure changes reveal regular vasoresponses throughout the model segment and stabilization of a physiological range of blood pressures (80–180 mmHg) in agreement with other modeling and experimental studies that assess steady autoregulation. Simulations of time-dependent perturbations reveal irregular vasoresponses and complex dynamics that may contribute to the complexity of dynamic autoregulation observed in vivo. The ability of the developed model to represent the myogenic response in a multiscale and realistic fashion, under feasible computational load, suggests that it can be incorporated as a key component into larger models of integrated renal hemodynamic regulation. Full article
(This article belongs to the Special Issue Systems Biomedicine )
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