SimThyr
{{short description|Medical research simulation software}}
{{Infobox software
| name =
| logo = File:SimThyr new 512x512x32.png
| logo alt = SimThyr icon
| screenshot = File:Simthyr 3.1 on openSUSE 11.png
| caption = SimThyr 3.1 on openSUSE 11
| author = Johannes W. Dietrich, Ulla Mitzdorf, Renate Pickardt, Rudolf Hoermann, John E. M. Midgley
| developer = Ruhr University Bochum
| released = {{start date and age|df=yes|paren=yes|2002}}
| latest release version = 4.0.6
| latest release date = {{Start date and age|2022|04|23}}
| operating system = macOS, Windows and Linux
| platform = PowerPC, IA-32, x86-64 and ARM,
m68k (legacy versions only)
| genre = Free scientific application software for physiological simulations
| license = BSD-style
| repo =
| language = British English, German (SimThyr 2.0 or older only)
| qid = Q59421094
| programming language = Pascal and Object Pascal
| engines =
| website =
}}
SimThyr is a free continuous dynamic simulation program for the pituitary-thyroid feedback control system.{{cite journal |last1=Dietrich |first1=JW |last2=Landgrafe |first2=G |last3=Fotiadou |first3=EH |title=TSH and Thyrotropic Agonists: Key Actors in Thyroid Homeostasis. |journal=Journal of Thyroid Research |date=2012 |volume=2012 |pages=351864 |doi=10.1155/2012/351864 |pmid=23365787|pmc=3544290 |doi-access=free }} The open-source program is based on a nonlinear model of thyroid homeostasis.{{cite journal |last1=Hoermann |first1=R |last2=Midgley |first2=JE |last3=Larisch |first3=R |last4=Dietrich |first4=JW |title=Homeostatic Control of the Thyroid-Pituitary Axis: Perspectives for Diagnosis and Treatment. |journal=Frontiers in Endocrinology |date=2015 |volume=6 |pages=177 |doi=10.3389/fendo.2015.00177 |pmid=26635726 |pmc=4653296 |doi-access=free }}{{cite journal |last1=Berberich |first1=Julian |title=Mathematical Modeling of the Pituitary-Thyroid Feedback Loop: Matlab/Simulink Files for Simulation and Sensitivity Analysis |date=13 September 2018 |doi=10.5281/zenodo.1415331 }}{{cite book |last1=Dietrich |first1=Johannes W. |title=Der Hypophysen-Schilddrüsen-Regelkreis : Entwicklung und klinische Anwendung eines nichtlinearen Modells |date=2002 |publisher=Logos-Verlag |location=Berlin |isbn=978-3897228504}} In addition to simulations in the time domain the software supports various methods of sensitivity analysis. Its simulation engine is multi-threaded and supports multiple processor cores. SimThyr provides a GUI, which allows for visualising time series, modifying constant structure parameters of the feedback loop (e.g. for simulation of certain diseases), storing parameter sets as XML files (referred to as "scenarios" in the software) and exporting results of simulations in various formats that are suitable for statistical software. SimThyr is intended for both educational purposes and in-silico research.{{cite book |last1=Dietrich |first1=Johannes W. |last2=Midgley |first2=John E. M. |last3=Hoermann |first3=Rudolf |title=Homeostasis and Allostasis of Thyroid Function |date=2018 |publisher=Frontiers Media SA |location=Lausanne |isbn=9782889455706}}
Mathematical model
The underlying model of thyroid homeostasis is based on fundamental biochemical, physiological and pharmacological principles, e.g. Michaelis-Menten kinetics, non-competitive inhibition and empirically justified kinetic parameters. The model has been validated in healthy controls and in cohorts of patients with hypothyroidism and thyrotoxicosis.{{cite journal |last1=Hoermann |first1=R |last2=Pekker |first2=MJ |last3=Midgley |first3=JEM |last4=Larisch |first4=R |last5=Dietrich |first5=JW |title=Triiodothyronine secretion in early thyroid failure: The adaptive response of central feedforward control. |journal=European Journal of Clinical Investigation |date=February 2020 |volume=50 |issue=2 |pages=e13192 |doi=10.1111/eci.13192 |pmid=31815292|s2cid=208956920 }}
Scientific uses
File:SimThyr in computer resource centre.jpg
Multiple studies have employed SimThyr for in silico research on the control of thyroid function.{{cite journal |last1=Ramos |first1=André |last2=Chaves |first2=Rafael |last3=Favero |first3=Elói |title=Simulação baseada em Dinâmica de Sistemas para o ensino da fisiologia do eixo Hipotálamo-hipófise-tireoide no contexto da graduação em medicina |journal=Brazilian Symposium on Computers in Education (Simpósio Brasileiro de Informática Na Educação - SBIE) |date=11 November 2019 |volume=30 |issue=1 |pages=962 |doi=10.5753/cbie.sbie.2019.962 |s2cid=213401607 |language=pt |issn=2316-6533|doi-access=free }}{{cite journal |last1=Ghosh |first1=Devleena |last2=Mandal |first2=Chittaranjan |title=Clustering Based Parameter Estimation of Thyroid Hormone Pathway |journal=IEEE/ACM Transactions on Computational Biology and Bioinformatics |date=2020 |volume=PP |issue=1 |pages=343–354 |doi=10.1109/TCBB.2020.2995589|pmid=32750849 |s2cid=219479222 }}
The original version was developed to check hypotheses about the generation of pulsatile TSH release.{{cite journal |last1=DIETRICH |first1=J. W. |last2=TESCHE |first2=A. |last3=PICKARDT |first3=C. R. |last4=MITZDORF |first4=U. |title=Thyrotropic Feedback Control: Evidence for an Additional Ultrashort Feedback Loop from Fractal Analysis |journal=Cybernetics and Systems |date=2004 |volume=35 |issue=4 |pages=315–331 |doi=10.1080/01969720490443354|s2cid=13421388 }} Later and expanded versions of the software were used to develop the hypothesis of the TSH-T3 shunt in the hypothalamus-pituitary-thyroid axis,{{cite journal |last1=Hoermann |first1=R |last2=Midgley |first2=JE |last3=Larisch |first3=R |last4=Dietrich |first4=JW |title=Integration of Peripheral and Glandular Regulation of Triiodothyronine Production by Thyrotropin in Untreated and Thyroxine-Treated Subjects |journal=Horm Metab Res |date=2015 |volume=47 |issue=9 |pages=674–80 |doi=10.1055/s-0034-1398616 |pmid=25750078|s2cid=9824656 |url=https://zenodo.org/record/918309 }} to assess the validity of calculated parameters of thyroid homeostasis (including SPINA-GT and SPINA-GD){{cite journal |last1=Dietrich |first1=JW |last2=Landgrafe-Mende |first2=G |last3=Wiora |first3=E |last4=Chatzitomaris |first4=A |last5=Klein |first5=HH |last6=Midgley |first6=JE |last7=Hoermann |first7=R |title=Calculated Parameters of Thyroid Homeostasis: Emerging Tools for Differential Diagnosis and Clinical Research. |journal=Frontiers in Endocrinology |date=2016 |volume=7 |pages=57 |doi=10.3389/fendo.2016.00057 |pmid=27375554 |pmc=4899439 |doi-access=free }}{{cite journal |last1=Hoermann |first1=Rudolf |last2=Midgley |first2=John E. M. |last3=Larisch |first3=Rolf |last4=Dietrich |first4=Johannes W. |title=The role of functional thyroid capacity in pituitary thyroid feedback regulation |journal=European Journal of Clinical Investigation |date=October 2018 |volume=48 |issue=10 |pages=e13003 |doi=10.1111/eci.13003 |pmid=30022470|s2cid=51698223 }} and to study allostatic mechanisms leading to non-thyroidal illness syndrome.{{cite journal |last1=Hoermann |first1=R |last2=Midgley |first2=JE |last3=Larisch |first3=R |last4=Dietrich |first4=JW |title=Is pituitary TSH an adequate measure of thyroid hormone-controlled homoeostasis during thyroxine treatment? |journal=European Journal of Endocrinology |date=February 2013 |volume=168 |issue=2 |pages=271–80 |doi=10.1530/EJE-12-0819 |pmid=23184912|s2cid=34158774 |doi-access=free }}{{cite journal |last1=Chatzitomaris |first1=A |last2=Hoermann |first2=R |last3=Midgley |first3=JE |last4=Hering |first4=S |last5=Urban |first5=A |last6=Dietrich |first6=B |last7=Abood |first7=A |last8=Klein |first8=HH |last9=Dietrich |first9=JW |title=Thyroid Allostasis-Adaptive Responses of Thyrotropic Feedback Control to Conditions of Strain, Stress, and Developmental Programming. |journal=Frontiers in Endocrinology |date=2017 |volume=8 |pages=163 |doi=10.3389/fendo.2017.00163 |pmid=28775711|pmc=5517413 |doi-access=free }}{{cite journal |last1=Hoermann |first1=Rudolf |last2=Dietrich |first2=Johannes W. |title=Mechanisms of Health and Disease |journal=Hypothyroidism |date=2025 |pages=67–79 |doi=10.1007/978-981-96-3682-2_6|isbn=978-981-96-3681-5 }}
SimThyr was also used to show that the release rate of thyrotropin is controlled by multiple factors other than T4 and that the relation between free T4 and TSH may be different in euthyroidism, hypothyroidism and thyrotoxicosis.{{cite journal |last1=Midgley |first1=JE |last2=Hoermann |first2=R |last3=Larisch |first3=R |last4=Dietrich |first4=JW |title=Physiological states and functional relation between thyrotropin and free thyroxine in thyroid health and disease: in vivo and in silico data suggest a hierarchical model. |journal=Journal of Clinical Pathology |date=April 2013 |volume=66 |issue=4 |pages=335–42 |doi=10.1136/jclinpath-2012-201213 |pmid=23423518 |s2cid=46291947 |url=https://jcp.bmj.com/content/66/4/335.long |accessdate=4 December 2018|url-access=subscription }}
Public perception, reception and discussion of the software
SimThyr is free and open-source software. This ensures the source code to be available, which facilitates scientific discussion and reviewing of the underlying model.{{cite web |last1=Gezelter |first1=Dan |title=SimThyr – simulation software for pituitary thyroid feedback {{!}} The OpenScience Project |url=http://openscience.org/simthyr-simulation-software-for-pituitary-thyroid-feedback/ |website=The OpenScience Project |accessdate=6 February 2019 |archive-url=https://web.archive.org/web/20190404101222/http://openscience.org/simthyr-simulation-software-for-pituitary-thyroid-feedback/ |archive-date=4 April 2019}}{{cite web |last1=Glensbo |first1=Henrik |title=Fokus i 2020 - stofskiftesygdom.dk |url=https://www.stofskiftesygdom.dk/fokus-i-2020/ |website=www.stofskiftesygdom.dk |date=31 December 2019 |publisher=Stofskiftesygdom |accessdate=2 April 2020}} Additionally, the fact that it is freely available may result in economical benefits.{{cite book |last1=Lupínek |first1=Jiří |title=Freeware simulační a vizualizační nástroje pro GNU/Linux |date=2012 |publisher=Západočeská univerzita v Plzni |hdl=11025/5282 |language=cs}}{{cite journal |last1=Arslan |first1=M. Oguz |title=Özgür ve Açık Kaynak Yazılımın Ekonomik Faydaları: Saglık Sektörü Için Bir Degerlendirme [Economic Benefits of Free and Open Source Software: An Evaluation for Health Sector.] |journal=Hacettepe Sağlık İdaresi Dergisi |date=2014 |volume=17 |pages=119–31 |url=https://www.researchgate.net/publication/274947660}}
The software provides an editor that enables users to modify most structure parameters of the information processing structure.{{citation |last1=Dietrich |first1=J. W. |title=SimThyr 4.0 Handbook and Reference |date=2017 |publisher=figshare |doi=10.6084/m9.figshare.4902098}} This functionality fosters simulation of several functional diseases of the thyroid and the pituitary gland. Parameter sets may be stored as MIRIAM- and MIASE-compliant XML files.
On the other hand, the complexity of the user interface and the lack of the ability to model treatment effects have been criticized.{{cite thesis |last1=Han |first1=Simon Xian He |title=THYROSIM: A Web Application for Human Thyroid System Regulation Education and Research |date=2013 |publisher=UCLA |location=Los Angeles |url=https://escholarship.org/uc/item/59f4r28p |language=en}}
See also
References
{{Reflist|2}}
External links
{{Library resources box|by=no|onlinebooks=no|about=yes|wikititle=SimThyr}}
- {{Official website|http://simthyr.sourceforge.net}} of the SimThyr project
- [https://doi.org/10.5281/zenodo.1303822 Curated information at Zenodo]
- [http://scicrunch.org/browse/resources/SCR_014351 Curated information at SciCrunch]
{{Authority control}}
Category:Free science software
Category:Free biosimulation software
Category:Free software programmed in Pascal
Category:Scientific simulation software
Category:Science software for macOS
Category:Science software for Windows
Category:Mathematical and theoretical biology
Category:Computational biology
Category:Cross-platform software