Kaja Chmielewska | Scientific Achievements



Publications

1. Chmielewska K., Formanowicz D., Formanowicz P.: The effect of cigarette smoking on endothelial damage and atherosclerosis development – modeled and analyzed using Petri nets. Archives of Control Sciences, 27(2), (2017), 211-228. DOI: 10.1515/acsc-2017-0013

2. Chmielewska K., Formanowicz D., Formanowicz P. Modelowanie i analiza uszkodzeń śródbłonka za pomocą sieci Petriego [in] Świerniak A., Krystek J., (Eds.): Automatyzacja procesów dyskretnych, Teoria i zastosowania", Vol II, Wydawnictwo Pracowni Komputerowej Jacka Skalmierskiego, Gliwice, (2016), 41-56.


Conferences and Seminars

ICOLE 2017: International Colloquium Lessach, Lessach, Austria (01-07.10.2017).

Talk: "Modeling and analysis of interleukin 18 influence on cardiovascular system using Petri nets."

Authors: Kaja CHMIELEWSKA1, Dorota FORMANOWICZ2, Piotr FORMANOWICZ1,3
1Institute of Computing Science, Poznan University of Technology, Piotrowo 2, 60-965 Poznan, Poland
2Department of Clinical Biochemistry and Laboratory Medicine, Poznan University of Medical Sciences, Grunwaldzka 6, 60-780 Poznan, Poland
3Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznan, Poland

X Convention of the Polish Bioinformatics Society, Uniejów, Poland (27-29.09.2017).

Poster: "Interleukin 18 influence on the cardiovascular system modeled and analyzed using Petri net-based approach."

Authors: Kaja CHMIELEWSKA1, Dorota FORMANOWICZ2, Piotr FORMANOWICZ1,3
1Institute of Computing Science, Poznan University of Technology, Piotrowo 2, 60-965 Poznan, Poland
2Department of Clinical Biochemistry and Laboratory Medicine, Poznan University of Medical Sciences, Grunwaldzka 6, 60-780 Poznan, Poland
3Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznan, Poland

Abstract: Interleukin 18 is one of the pro-inflammatory cytokines and it plays an important role in stimulation of natural killers and T cells to interferon gamma synthesis in response to activity of different pathogens. IL18 is recognized as very important regulator of innate and adaptive immune responses. Recent studies confirmed that IL18 can be produced by preadipocytes and adipocytes, reflecting the share of fatty tissue in regulation of inflammatory and metabolic processes, which can be engaged in development of atherosclerosis. IL18 can be helpful in prediction of cardiovascular events, however, there is no definitive evidence of an accurate IL18 action mechanism. It became the reason for using systems approach based on Petri nets for the analysis of the influence of IL18 on the cardiovascular system in the human body. The analysis of the model was based mainly on t-invariants.

This research has been partially supported by the Polish National Science Centre grant No. 2012/07/B/ST6/01537.



PIC17: 3rd Meeting of Polish Iron Club, Gdańsk, Poland (15-16.09.2017).

Talk: "Interrelations between vitamin A and iron – modeled and analysed using Petri nets."

Authors: Kaja CHMIELEWSKA1, Dorota FORMANOWICZ2, Piotr FORMANOWICZ1,3
1Institute of Computing Science, Poznan University of Technology, Piotrowo 2, 60-965 Poznan, Poland
2Department of Clinical Biochemistry and Laboratory Medicine, Poznan University of Medical Sciences, Grunwaldzka 6, 60-780 Poznan, Poland
3Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznan, Poland

Abstract: Vitamin A and iron deficiency are major nutritional problems that collectively affect billions of people worldwide. The influence of vitamin A deficiency on body iron status have been widely studied, however, the mechanism of the relationship between vitamin A and iron metabolism remains unclear. The results of the recent studies demonstrate that the HJVBMP6- SMAD signaling pathway, that normally activates the expression of hepcidin in a course of the iron deficiency, is impaired by vitamin A deficiency. To better understand this complex biological phenomenon and to systematize the existing knowledge, a Petri net based model of this complex issue has been created and then analysed. This analysis has been based on t-invariants and MCT sets. It allowed to determine a biological meaning of components of the modeled system and has enabled for an in-depth analysis of the studied phenomenon.

This research has been partially supported by the Polish National Science Centre grant No. 2012/07/B/ST6/01537.



OR17: International Conference on Operations Research, Berlin, Germany (06-08.09.2017).

Talk: "Atherosclerosis development as a complex biological phenomenon studied using Petri nets."

Authors: Kaja CHMIELEWSKA1, Dorota FORMANOWICZ2, Piotr FORMANOWICZ1,3
1Institute of Computing Science, Poznan University of Technology, Piotrowo 2, 60-965 Poznan, Poland
2Department of Clinical Biochemistry and Laboratory Medicine, Poznan University of Medical Sciences, Grunwaldzka 6, 60-780 Poznan, Poland
3Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznan, Poland

Abstract: Atherosclerosis is a very complex issue and the use of Petri nets for its modeling and analysis allows to systematize existing knowledge about this phenomenon and for new discoveries. This is especially important because the studied process is very common, the mechanisms that contribute to it are still studied and therefore new data is coming. Based on it, models of this process have been created and then analyzed in detail. Analysis of the models expressed as Petri nets have been based on t-invariants. They correspond to subprocesses occurring in the modeled system which do not change its state. Searching for similarities among t-invariants may lead to identification of subprocesses which interact with each other. This, in turn, may lead to discoveries of some previously unknown properties of the biological system. Such an analysis can be based on clustering of t-invariants. In addition, identification of MCT sets, i.e., sets containing transitions corresponding to exactly the same t-invariants, helps to identify important functional blocks of the system. In this work the application of this methodology to the analysis of processes related to atherosclerosis is presented and discussed.

This research has been partially supported by the Polish National Science Centre grant No. 2012/07/B/ST6/01537.



BIT17: Bioinformatics in Torun, Toruń, Poland (22-24.06.2017).

Poster: "Modeling and analysis of disorders in prothrombotic states as reason of atherosclerosis development using Petri net-based approch."

Authors: Kaja CHMIELEWSKA1, Dorota FORMANOWICZ2, Piotr FORMANOWICZ1,3
1Institute of Computing Science, Poznan University of Technology, Piotrowo 2, 60-965 Poznan, Poland
2Department of Clinical Biochemistry and Laboratory Medicine, Poznan University of Medical Sciences, Grunwaldzka 6, 60-780 Poznan, Poland
3Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznan, Poland

Abstract: Atherosclerosis as one of the cardiovascular diseases (CVDs) is the major cause of morbidities and mortalities worldwide. Furthermore, the knowledge about this multifocal immunoinflammatory disease of arteries is still incomplete. To better understand and to systematize existing expertise systems approach based on Petri nets has been used. Due to the fact that many mechanisms have influence on atherosclerosis development, this research has been focused on selected subprocesses which are disorders in prothrombotic states and the extrinsic pathway of coagulation. Analysis of the proposed model distinguished significant components of modeled system e.g., thrombin (which is main enzyme of coagulation) and tissue factor (which is a specific cellular lipoprotein). These mechanisms and components are closely associated with formation of thrombus, which is one of the contribute risk factor leading to development of atherosclerosis and other cardiovascular diseases. The complex biological process has been modeled using Petri nets and analysis of the proposed model has been based on t-invariants. Analysis allowed to determined biological meaning for the modeled system. Moreover, this systems approach confirmed important roles of disorders in prothrombotic states and coagulation process in atherosclerosis development through thrombus formation. Mechanisms of thrombus formation are leading to progression of narrowing the arterial lumen via rapidly slow-down of blood flow.

This research has been partially supported by the Polish National Science Centre grant No. 2012/07/B/ST6/01537.



Seminar of the Laboratory of Algorithm Design and Programming Systems, Institute of Computing Science, Poznan University of Technology, Poland (22.11.2016).

Talk: "Modeling of interactions of various factors in atherosclerosis."

Authors: Kaja CHMIELEWSKA1, Dorota FORMANOWICZ2, Piotr FORMANOWICZ1,3
1Institute of Computing Science, Poznan University of Technology, Piotrowo 2, 60-965 Poznan, Poland
2Department of Clinical Biochemistry and Laboratory Medicine, Poznan University of Medical Sciences, Grunwaldzka 6, 60-780 Poznan, Poland
3Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznan, Poland



IX Convention of the Polish Bioinformatics Society, Białystok, Poland (28-30.09.2016).

Talk: "From tobacco smoke throught prothrombotic state to atherosclerosis – a systems approach."

Authors: Kaja CHMIELEWSKA1, Dorota FORMANOWICZ2, Piotr FORMANOWICZ1,3
1Institute of Computing Science, Poznan University of Technology, Piotrowo 2, 60-965 Poznan, Poland
2Department of Clinical Biochemistry and Laboratory Medicine, Poznan University of Medical Sciences, Grunwaldzka 6, 60-780 Poznan, Poland
3Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznan, Poland

Abstract: Smoking is a one of the contributing risk factors for the development of cardiovascular diseases (CVDs). Cigarette smoke secretes many particles playing an important role in harmful processes, some of them are: nicotine, carbon monoxide (CO), reactive oxygen (ROS) and others. These particles lead to endothelial dysfunction, inflammation (in response to endothelial damage chemokines are released and monocytes adhesion occurs what leads to macrophage stimulation), modification of lipid profile (it causes increase of low density lipoproteins (LDL) level), respiratory burst, LDL oxidation, increase of nitric oxide (NO) bioavailability, vascular smooth muscle cells (VSMC) proliferation, prothrombotic states and a lot of other processes. All of these mechanisms influence on, inter alia, atherosclerosis progress. For better understanding how smoking influence prothrombotic state and promotes atherosclerosis, Petri net based model of this process has been proposed. Analysis of the net structure and determining some unknown relationships among processes in the modeled biological system has been based on clusters of t-invariants. Particular attention has been paid to influence on disease progress caused by smoking, because both active smoking and passive smoking contribute to morbidity which is associated with CVDs.

This research has been partially supported by the Polish National Science Centre grant No. 2012/07/B/ST6/01537.



KKAPD: XX National Conference of Discrete Processes Automation, Zakopane, Poland (21-24.09.2016).

Talk: "Modeling and analysis of endothelial damage using Petri nets."

Authors: Kaja CHMIELEWSKA1, Dorota FORMANOWICZ2, Piotr FORMANOWICZ1,3
1Institute of Computing Science, Poznan University of Technology, Piotrowo 2, 60-965 Poznan, Poland
2Department of Clinical Biochemistry and Laboratory Medicine, Poznan University of Medical Sciences, Grunwaldzka 6, 60-780 Poznan, Poland
3Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznan, Poland

Abstract: Damage to the vascular endothelium, which is one of the major causes of atherosclerotic plaque formation is a complex and dynamic process depending on many factors. The impact of these factors is diverse and addicted to quantitative and qualitative changes of other factors. Therefore, to fully understand the processes underlying this phenomenon, they must be analyzed in a holistic manner, taking into account as many as possible variables. This approach was applied to the current project. model of endothelial damage by using the theory of Petri nets has been proposed . This model consists of 63 places and 94 transitions, 8481 t-invariants and 19 MCT sets. Analysis of the clusters of the t-invariants, determined the biological sense of the modeled process and at revealed that inflammation and oxidative stress plays a key role in this process.

This research has been partially supported by the Polish National Science Centre grant No. 2012/07/B/ST6/01537.



BIT16: Bioinformatics in Torun, Toruń, Poland (16-18.06.2016).

Poster: "Selected aspects of the participation of tobacco smoke in the development of atherosclerosis modeled and analyzed using Petri nets."

Authors: Kaja CHMIELEWSKA1, Dorota FORMANOWICZ2, Piotr FORMANOWICZ1,3
1Institute of Computing Science, Poznan University of Technology, Piotrowo 2, 60-965 Poznan, Poland
2Department of Clinical Biochemistry and Laboratory Medicine, Poznan University of Medical Sciences, Grunwaldzka 6, 60-780 Poznan, Poland
3Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznan, Poland

Abstract: Endothelial dysfunction is induced by a various factors, some of them are: high blood pressure, high glucose level (in diabetes), high low-density lipoprotein level (LDL) and smoking in the wider sense of the term. For a better understanding of the influence of cigarette smoking on endothelial damage, stimulating inflammation and prothrombotic states a model of this complex biological process has been presented. The proposed model has been built using Petri nets. This Petri net structure includes indirect effect of cigarette smoke on impairment of endothelial function, caused by among others changing the lipid profile (it leads to increase the amount of LDL and then to the LDL oxidation, which in result promotes atherosclerosis), decrease the amount of tetrahydrobiopterin (BH4) (it has influence on inhibition of nitric oxide (NO) synthesis, because BH4 is a cofactor for endothelial nitric oxide synthase, which is necessary for NO synthesis), increase the amount of many other important factors, which influence on the development of unwanted processes (oxidative stress, oxidation of LDL, proliferation of vascular smooth muscle cells). In addition, smoking stimulates inflammation and prothrombotic states, which lead to the development of atherosclerosis. For this reason, the model includes the harmful effects of macrophages (which stimulates development of plaque) and dual role of NO (which is dependent on the amount of this molecule). The analysis of the proposed model has been based mainly on t-invariants. To determine the biological sense of the model, analysis of cluster of t-invariants has been performed.

This research has been partially supported by the Polish National Science Centre grant No. 2012/07/B/ST6/01537.