Biosimulation

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Biosimulation is a computer-aided mathematical simulation of biological processes and systems and thus is an integral part of systems biology. Due to the complexity of biological systems simplified models are often used, which should only be as complex as necessary.

The aim of biosimulations is model-based prediction of the behaviour and the dynamics of biological systems e.g. the response of an organ or a single cell towards a chemical. However the quality of model-based predictions strongly depends on the quality of the model, which in turn is defined by the quality of the data and the profoundness of the knowledge.

Pharmacy

Biosimulation is becoming increasingly important for drug development. [1] Since on average only 11% of all drug candidates are approved, [2] it is anticipated that biosimulation may be the tool to predict whether a candidate drug will fail in the development process e.g. in clinical trials due to adverse side effects, bad pharmacokinetics or even toxicity. The early prediction if a drug will fail in animals or humans would be a key to reduce both drug development costs and the amount of required animal experiments and clinical trials. The latter is also in line with the so-called "3Rs" which refer to the principle of reduction and replacement of animal experiments as well as to the refinement of the methodology in cases where animal tests are still necessary. [3] In a future scenario, biosimulation would change the way substances are tested, in which in vivo and in vitro tests are substituted by tests in silico. [4]

Due to the importance of biosimulation in drug development a number of research projects exist which aim for simulating metabolism, toxicity, pharmacodynamic and pharmacokinetics of a drug candidate. Some of the research projects are listed below:

Moreover, a few software tools already exist, which aim for predicting the toxicity of a substance or even try to simulate the virtual patient (Entelos). A few of these software tools are listed below:

Related Research Articles

<span class="mw-page-title-main">Bioinformatics</span> Computational analysis of large, complex sets of biological data

Bioinformatics is an interdisciplinary field of science that develops methods and software tools for understanding biological data, especially when the data sets are large and complex. Bioinformatics uses biology, chemistry, physics, computer science, computer programming, information engineering, mathematics and statistics to analyze and interpret biological data. The subsequent process of analyzing and interpreting data is referred to as computational biology.

<i>In vitro</i> Latin term meaning outside a natural biological environment

In vitro studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in biology and its subdisciplines are traditionally done in labware such as test tubes, flasks, Petri dishes, and microtiter plates. Studies conducted using components of an organism that have been isolated from their usual biological surroundings permit a more detailed or more convenient analysis than can be done with whole organisms; however, results obtained from in vitro experiments may not fully or accurately predict the effects on a whole organism. In contrast to in vitro experiments, in vivo studies are those conducted in living organisms, including humans, known as clinical trials, and whole plants.

<span class="mw-page-title-main">Pharmacology</span> Branch of biology concerning drugs

Pharmacology is a branch of medicine, biology, and pharmaceutical sciences concerned with drug or medication action, where a drug may be defined as any artificial, natural, or endogenous molecule which exerts a biochemical or physiological effect on the cell, tissue, organ, or organism. It is the science of drugs including their origin, composition, pharmacokinetics, therapeutic use, and toxicology. More specifically, it is the study of the interactions that occur between a living organism and chemicals that affect normal or abnormal biochemical function. If substances have medicinal properties, they are considered pharmaceuticals.

<span class="mw-page-title-main">Toxicology</span> Study of substances harmful to living organisms

Toxicology is a scientific discipline, overlapping with biology, chemistry, pharmacology, and medicine, that involves the study of the adverse effects of chemical substances on living organisms and the practice of diagnosing and treating exposures to toxins and toxicants. The relationship between dose and its effects on the exposed organism is of high significance in toxicology. Factors that influence chemical toxicity include the dosage, duration of exposure, route of exposure, species, age, sex, and environment. Toxicologists are experts on poisons and poisoning. There is a movement for evidence-based toxicology as part of the larger movement towards evidence-based practices. Toxicology is currently contributing to the field of cancer research, since some toxins can be used as drugs for killing tumor cells. One prime example of this is ribosome-inactivating proteins, tested in the treatment of leukemia.

<i>In silico</i> Latin phrase referring to computer simulations

In biology and other experimental sciences, an in silico experiment is one performed on computer or via computer simulation. The phrase is pseudo-Latin for 'in silicon', referring to silicon in computer chips. It was coined in 1987 as an allusion to the Latin phrases in vivo, in vitro, and in situ, which are commonly used in biology. The latter phrases refer, respectively, to experiments done in living organisms, outside living organisms, and where they are found in nature.

<span class="mw-page-title-main">Vaccine trial</span> Clinical trial

A vaccine trial is a clinical trial that aims at establishing the safety and efficacy of a vaccine prior to it being licensed.

<span class="mw-page-title-main">Physiologically based pharmacokinetic modelling</span>

Physiologically based pharmacokinetic (PBPK) modeling is a mathematical modeling technique for predicting the absorption, distribution, metabolism and excretion (ADME) of synthetic or natural chemical substances in humans and other animal species. PBPK modeling is used in pharmaceutical research and drug development, and in health risk assessment for cosmetics or general chemicals.

The Virtual Physiological Human (VPH) is a European initiative that focuses on a methodological and technological framework that, once established, will enable collaborative investigation of the human body as a single complex system. The collective framework will make it possible to share resources and observations formed by institutions and organizations, creating disparate but integrated computer models of the mechanical, physical and biochemical functions of a living human body.

Pharmacokinetics, sometimes abbreviated as PK, is a branch of pharmacology dedicated to determining the fate of substances administered to a living organism. The substances of interest include any chemical xenobiotic such as: pharmaceutical drugs, pesticides, food additives, cosmetics, etc. It attempts to analyze chemical metabolism and to discover the fate of a chemical from the moment that it is administered up to the point at which it is completely eliminated from the body. Pharmacokinetics is the study of how an organism affects a drug, whereas pharmacodynamics (PD) is the study of how the drug affects the organism. Both together influence dosing, benefit, and adverse effects, as seen in PK/PD models.

Evolution in Variable Environment (EVE) is a computer program designed to simulate microbial cellular behavior in various environments. The prediction of cellular responses is a rapidly evolving topic in systems biology and computational biology. The goal is to predict the behavior a particular organism in response to a set of environmental stimuli in silico. Such predictions can have a significant impact on preventive medicine, biotechnology, and microbe re-engineering. Computational prediction of behavior has two major components: the integration and simulation of vast biological networks and the creation of external stimuli. Current limitations of the method are: lack of comprehensive experimental data on the various cellular subsystems and inadequate computational algorithms.

<span class="mw-page-title-main">Phases of clinical research</span> Clinical trial stages using human subjects

The phases of clinical research are the stages in which scientists conduct experiments with a health intervention to obtain sufficient evidence for a process considered effective as a medical treatment. For drug development, the clinical phases start with testing for drug safety in a few human subjects, then expand to many study participants to determine if the treatment is effective. Clinical research is conducted on drug candidates, vaccine candidates, new medical devices, and new diagnostic assays.

In silico medicine is the application of in silico research to problems involving health and medicine. It is the direct use of computer simulation in the diagnosis, treatment, or prevention of a disease. More specifically, in silico medicine is characterized by modeling, simulation, and visualization of biological and medical processes in computers with the goal of simulating real biological processes in a virtual environment.

In vitro to in vivo extrapolation (IVIVE) refers to the qualitative or quantitative transposition of experimental results or observations made in vitro to predict phenomena in vivo, biological organisms.

Quantitative systems pharmacology (QSP) is a discipline within biomedical research that uses mathematical computer models to characterize biological systems, disease processes and drug pharmacology. QSP can be viewed as a sub-discipline of pharmacometrics that focuses on modeling the mechanisms of drug pharmacokinetics (PK), pharmacodynamics (PD), and disease processes using a systems pharmacology point of view. QSP models are typically defined by systems of ordinary differential equations (ODE) that depict the dynamical properties of the interaction between the drug and the biological system.

<span class="mw-page-title-main">Uwe Marx</span>

Uwe Marx is a German physician and biotechnologist, and one of the world’s leading researchers in the fields of organ-on-a-chip technology and antibody production.

Leon Aarons is an Australian chemist who researches and teaches in the areas of pharmacodynamics and pharmacokinetics. He lives in the United Kingdom and from 1976 has been a professor of pharmacometrics at the University of Manchester. In the interest of promoting the effective development of drugs, the main focus of his work is optimizing pharmacological models, the design of clinical studies, and data analysis and interpretation in the field of population pharmacokinetics. From 1985 to 2010 Aarons was an editor emeritus of the Journal of Pharmacokinetics and Pharmacodynamics and is a former executive editor of the British Journal of Clinical Pharmacology.

<span class="mw-page-title-main">SAAM II</span> Compartmental and kinetic modeling software

SAAM II is a proprietary and US NIH-funded software that was developed by SAAM Institute in 1997 at the University of Washington in Seattle. SAAM II is a computer program for tracer and pharmacokinetic studies. It is used for compartmental modeling and noncompartmental analysis. Compared to similar software, compartmental models are constructed graphically allowing the quick run of simple systems or the creation of complex structures. The main uses are in metabolic diseases and pharmacokinetics.

Herbert M. Sauro works in the field of metabolic control analysis and systems biology.

libRoadRunner is a C/C++ software library that supports simulation of SBML based models.. It uses LLVM to generate extremely high-performance code and is the fastest SBML-based simulator currently available. Its main purpose is for use as a reusable library that can be hosted by other applications, particularly on large compute clusters for doing parameter optimization where performance is critical. It also has a set of Python bindings that allow it to be easily used from Python.

References

  1. ↑ M. Bertau, E. Mosekilde, H.V. Westerhoff (Edts.): Biosimulation in Drug Development. 1st Edition Wiley-VCH, Weinheim 2008
  2. ↑ I. Kola, J. Landis: Can the pharmaceutical industry reduce attrition rates? In:Nat.Rev.Drug Discov. Nr. 3, 2004, S.711-715
  3. ↑ J. Richmond: The 3Rs - Past, Present and Future. In:Scand.J.Lab.Anim.Sci Vol. 2(27), 2000, S. 84-92
  4. ↑ Models that take drugs. In:The Economist (US) June 11, 2005
  5. ↑ Bilal Shaikh, Gnaneswara Marupilla, Mike Wilson, Michael L Blinov, Ion I Moraru, Jonathan R Karr, RunBioSimulations: an extensible web application that simulates a wide range of computational modeling frameworks, algorithms, and formats, Nucleic Acids Research, Volume 49, Issue W1, 2 July 2021, Pages W597–W602, https://doi.org/10.1093/nar/gkab411
  6. ↑ Choi, Kiri; Medley, J. Kyle; Cannistra, Caroline; König, Matthias; Smith, Lucian; Stocking, Kaylene; Sauro, Herbert M. (2 June 2016). "Tellurium: A Python Based Modeling and Reproducibility Platform for Systems Biology". p. 054601. bioRxiv   10.1101/054601 .
  7. ↑ Choi, Kiri; Medley, J. Kyle; König, Matthias; Stocking, Kaylene; Smith, Lucian; Gu, Stanley; Sauro, Herbert M. (September 2018). "Tellurium: An extensible python-based modeling environment for systems and synthetic biology". Biosystems. 171: 74–79. doi:10.1016/j.biosystems.2018.07.006. PMC   6108935 . PMID   30053414.
  8. ↑ Vedani, A.; Dobler, M.; Smieško, M. (2012). "Biograf 3R - Computational Alternatives to Animal Testing - Home". Toxicology and Applied Pharmacology. Biograf.ch. 261 (2): 142–153. doi:10.1016/j.taap.2012.03.018. PMID   22521603 . Retrieved 2013-05-22.
  9. ↑ "Lhasa Limited Home Page". Lhasalimited.org. Retrieved 2013-05-22.
  10. ↑ Archived July 3, 2009, at the Wayback Machine
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