Peter Dittrich

Friedrich Schiller University Jena | FSU · Department of Computer Science

Finding pathways that optimize the formation of a particular target molecule in a chemical reaction network is a key problem in many settings, including reactor systems. Reaction networks are mathematically well represented as hypergraphs, a modeling that facilitates the search for pathways by computational means. We propose to enrich an existing s...

Measuring the dynamics of microbial communities results in high-dimensional measurements of taxa abundances over time and space, which is difficult to analyze due to complex changes in taxonomic compositions. This paper presents a new method to investigate and visualize the intrinsic hierarchical community structure implied by the measurements. The...

An algorithm is presented for computing a reaction-diffusion partial differential equation (PDE) system for all possible subspaces that can hold a persistent solution of the equation. For this, all possible sub-networks of the underlying reaction network that are distributed organizations (DOs) are identified. Recently it has been shown that a pers...

An algorithm is presented for computing for a reaction-diffusion partial differential equation (PDE) system all possible subspaces that can hold a persistent solution of the equation. For this, all possible sub-networks of the underlying reaction network that are distributed organizations (DOs) are identified, because recently it has been shown tha...

It can be expected that medical treatments in the future will be individually tailored for each patient. Here we present a step towards personally addressed drug therapy. We consider multiple myeloma treatment with drugs: bortezomib and dexamethasone. It has been observed that these drugs are effective for some patients and do not help others. We d...

This work provides a mathematical technique for analyzing and comparing infection dynamics models with respect to their potential long-term behavior, resulting in a hierarchy integrating all models. We apply our technique to coupled ordinary and partial differential equation models of SARS-CoV-2 infection dynamics operating on different scales, tha...

Chemical Organization Theory (COT) has been successfully applied to analyze complex reaction networks where species interact and new species can emerge. The COT has been well studied, but is yet to analyze high dimensional systems dynamics over time equivalent to ordinary differential equations. Moreover, spatial effects, such as diffusion and boun...

Designing novel unconventional computing systems often requires the selection of the computational structure as well as choosing the right symbol encoding. Several approaches apply heuristic search and evolutionary algorithms to find both computational structure and symbol encoding, which is time consuming because they depend on each other. Here, w...

Influenza A virus is recognized today as one of the most challenging viruses that threatens both human and animal health worldwide. Understanding the control mechanisms of influenza infection and dynamics is crucial and could result in effective future treatment strategies. Many kinetic models based on differential equations have been developed in...

SRSim combines rule-based reaction network models with spatial particle simulations allowing to simulate the dynamics of large molecular complexes changing according to a set of chemical reaction rules. As the rule can contain patterns of molecular complexes and specific states of certain binding sites, a combinatorially complex or even infinitely...

The complexity of biological models makes methods for their analysis and understanding highly desirable. Here, we demonstrate the orchestration of various novel coarse-graining methods by applying them to the mitotic spindle assembly checkpoint. We begin with a detailed fine-grained spatial model in which individual molecules are simulated moving a...

Theoretical investigation of the kinetics of low-temperature combustion chemistry of propylbenzene Harish Kumar Chakravarty* and Peter Dittrich Institute of Computer Science, Friedrich Schiller University, Jena, 07745, Thuringia, Germany. *Corresponding author: harish.chakravarty@uni-jena.de Numerical kinetic modeling of combustion behaviour of fue...

The project aims at the semantic aspect of biological information. We will develop novel methods to objectively identify and describe semiotic subsystems of living cells. The basic idea relies on the identification of organic codes (as recently reviewed by Barbieri, Naturwissenschaften 95, 577–599, 2008) and on how these codes are physically instan...

The spindle assembly checkpoint (SAC) is an evolutionarily conserved mechanism, exclusively sensitive to the states of kinetochores attached to microtubules. During metaphase, the anaphase-promoting complex/cyclosome (APC/C) is inhibited by the SAC but it rapidly switches to its active form following proper attachment of the final spindle. It had b...

The proper segregation of sister chromatids at onset of anaphase is surveyed by the mitotic spindle assembly checkpoint. The concentration dynamics of the complexes APC:Cdc20 and MCC:APC determine exit from metaphase to anaphase. We have developed a model based on 14 proteins and complexes to describe concentration dynamics by ordinary differential...

Unconventional computing devices operating on nonlinear chemical media offer an interesting alternative to standard, semiconductor-based computers. In this work we study in-silico a chemical medium composed of communicating droplets that functions as a database classifier. The droplet network can be "programmed" by an externally provided illuminati...

Molecular dynamics simulations yield large amounts of trajectory data. For their durable storage and accessibility an efficient compression algorithm is paramount. State of the art domain-specific algorithms combine quantization, Huffman encoding and occasionally domain knowledge. We propose the high resolution trajectory compression scheme (HRTC)...

In this paper, we present general methods that can be used to explore the information processing potential of a medium composed of oscillating (self-exciting) droplets. Networks of Belousov-Zhabotinsky (BZ) droplets seem especially interesting as chemical reaction-diffusion computers because their time evolution is qualitatively similar to neural n...

Knowledge of metabolic processes is collected in easily accessible online databases which are increasing rapidly in content and detail. Using these databases for the automatic construction of metabolic network models requires high accuracy and consistency. In this bipartite study we evaluate current accuracy and consistency problems using the KEGG...

This chapter addresses three coordinated chronobiological studies demonstrating the convergence of experimental observations, fine-grained spatio-temporal modelling, and predictive simulation. Due to the discrete manner of molecular assembly in cell signalling and gene regulation, we define a framework of membrane systems equipped with discretised...

Large multi-molecular complexes like the kinetochore are lacking of suitable methods to determine their spatial structure. Here, we use and evaluate a novel modeling approach that combines rule-bases reaction network models with spatial molecular geometries. In particular, we introduce a method that allows to study in silico the influence of single...

In this paper, we present general methods that can be used to explore the information processing potential of a medium composed of oscillating (self-exciting) droplets. Networks of Belousov–Zhabotinsky (BZ) droplets seem especially interesting as chemical reaction-diffusion computers because their time evolution is qualitatively similar to neural n...

Belousov-Zhabotinsky (BZ) excitable chemical medium exhibits a rich variety of spatial patterns of excitation. In a sub-excitable light-sensitive chemical medium, an asymmetric disturbing or excitation, causes formation of localized travelling excitation wave-fragments. When two or more wave-fragments collide, they annihilate or merge into new wave...

Motivation: The functioning of many biological processes depends on the appearance of only a small number of a single molecular species. Additionally, the observation of molecular crowding leads to the insight that even a high number of copies of species do not guarantee their interaction. How single particles contribute to stabilizing biological s...

We apply molecular code theory to a rule-based model of the human inner kinetochore and study how complex formation in general can give rise to molecular codes. We analyze 105 reaction networks generated from the rule-based inner kinetochoremodel in two variants: with and without dissociation of complexes. Interestingly, we found codes only when so...

We investigate several evolutionary computation approaches as a mechanism to “program” networks of excitable chemical droplets. For this kind of systems, we assigned a specific task and concentrated on the characteristics of signals representing symbols. Given a Boolean function as target functionality, 2D networks composed of 10 × 10 droplets were...

A common problem in the analysis of biological systems is the combinatorial explosion that emerges from the complexity of multi-protein assemblies. Conventional formalisms, like differential equations, Boolean networks and Bayesian networks, are unsuitable for dealing with the combinatorial explosion, because they are designed for a restricted stat...

Background Systems Biology develops computational models in order to understand biological phenomena. The increasing number and complexity of such “bio-models” necessitate computer support for the overall modelling task. Computer-aided modelling has to be based on a formal semantic description of bio-models. But, even if computational bio-models th...

Shannon's theory of communication has been very successfully applied for the analysis of biological information. However, the theory neglects semantic and pragmatic aspects and thus cannot directly be applied to distinguish between (bio-) chemical systems able to process "meaningful" information from those that do not. Here, we present a formal met...

Effect of network randomization on the semantic capacity. The boxplots shows the relation between semantic capacity and increasing randomization for the artificial chemistry NTOP. With increasing randomizing the semantic capacity decreases on average. Nevertheless, weak to medium randomization, i.e. only parts of the network are randomly rearranged...

Network model of Figure 1A . (TXT)

Network model of the artificial chemistry NTOP. (TXT)

Reaction network formulation of a gene translation system with amino-acyl-tRNA-synthetases. (PDF)

List of Molecular Codes that can be identified in the merge of the 17 known genetic codes. For the network see Dataset S3. (PDF)

List of all binary molecular codes (including duplicates) identified in the NTOP chemistry. (PDF)

Network model of Figure 1C . (TXT)

Network model of a 2×2 subnetwork of the gene translation chemistry including synthetases. (TXT)

Network model of ethanol combustion. (TXT)

List of all analyzed systems stating their size, density, semantic capacity, the reference of the system, and the method used for analysis. (PDF)

Network model the merge of the 17 known genetic codes as listed at NCBI. (TXT)

Network model of the Martian atmosphere photochemistry. (TXT)

Relation among the code pairs in the NTOP chemistry. Graph illustrating the six code pairs found in the NTOP chemistry. The nodes refer to the closed sets containing the signs and meanings in each individual code pair. The six code pairs are distinguished by color. The graph clearly shows that signs and meanings can be reused in different codes and...

Pseudocode of the closure-base code identifying algorithms, the pathway-based code identifying algorithm and the random network generation algorithm. (PDF)

Mathematical model of the phosphorylation cascade shown in Figure 4C . (PDF)

Network model of hydrogen combustion. (TXT)

Network model of methane combustion. (TXT)

Network model of di methyl ether combustion. (TXT)

Here we review and extend models on different scales for a computing architecture made from networks of excitable chemical droplets. A system of lipid covered droplets containing reagents of the Belousov-Zhabotinsky (BZ) reaction has been used in our experiments as model system to study the signal transmission dynamics of chemical computers and the...

The powerful mathematical tools developed for the study of large scale reaction networks have given rise to applications of this framework beyond the scope of biochemistry. Recently, reaction networks have been suggested as an alternative way to model social phenomena. In this "socio-chemical metaphor" molecular species play the role of agents' dec...

Cycles are abundant in most kinds of networks, especially in biological ones. Here, we investigate their role in the evolution of a chemical reaction system from one self-sustaining composition of molecular species to another and their influence on the stability of these compositions. While it is accepted that, from a topological standpoint, they e...

The orientation of the mitotic spindle with respect to the polarity axis is crucial for the accuracy of asymmetric cell division. In budding yeast, a surveillance mechanism called the spindle position checkpoint (SPOC) prevents exit from mitosis when the mitotic spindle fails to align along the mother-to-daughter polarity axis. SPOC arrest relies u...

Supplementary figures S1-9, Supplementary tables S1-5

Chemical organization theory has been suggested as a new approach to analyze complex reaction networks. Concerning the long-term behavior of the network dynamics we will study its foundations mathematically. Therefore we consider a chemical reactor containing molecules of different species reacting with each other according to a set of reaction rul...

Can we objectively distinguish chemical systems that are able to process meaningful information from those that are not suitable for information processing? Here, we present a formal method to assess the semantic capacity of a chemical reaction network. The semantic capacity of a network can be measured by analyzing the capability of the network to...

We describe some aspects of the relationship between the chemical organisations of a reaction network and the chemical organisations of the fragments of this network. The conjecture is that fragments embeddable in a (feasible) organisation of molecules is a (feasible) organisation of fragments. We show this for a certain type of reaction network. H...

We consider cells as biological systems that process information by means of molecular codes. Many studies analyze cellular information processing exclusively in syntactic terms (e.g., by measuring Shannon entropy of sets of macromolecules), and abstract completely from semantic aspects that are related to the meaning of molecular information. This...

Chemical information processing possesses a variety of valuable properties, such as robustness, concurrency, fault-tolerance and evolvability. However, it is difficult to predict and program a chemical system because the computation emerges as a global phenomenon from microscopic reactions. For programming chemical systems a theoretical method to c...

This article gives an outlook to further research on Organic Computing in the context of chemical-inspired computing. KeywordsSelf-organisation-Chemical computing-Unconventional computing-Rule-based models-Membrane computing-Protocells-Molecular computing

In order to control the dynamics of a system, feedback control (FC for short) is an extremely successful strategy, which is widely applied by engineers. Here we discuss a different strategy of control, called emergent control (EC for short), which can be found in large, distributed systems of components interacting only locally. For comparison we p...

The construction of molecular-scale machines requires novel paradigms for their programming. Here, we assume a scenario of distributed devices that process in-formation by chemical reactions and that communicate by exchanging molecules. Programming such a distributed system requires specifing reaction rules as well as exchange rules. Here, we prese...

The simulator software SRSim is presented here. It is constructed from the molecular dynamics simulator LAMMPS and a set of extensions for modeling rule-based reaction systems. The aim of this software is coping with reaction networks that are combinatorially complex as well as spatially inhomogeneous. On the one hand, there is a combinatorial expl...

In membrane computing, a relatively simple set of reaction rules usually implies a complex "constructive" dynamics, in which novel molecular species appear and present species vanish. Chemical organization theory is a new approach that deals with such systems by describing chemical computing as a transition between organizations, which are closed a...

Analysing genome-scale in silico models with stoichiometry-based methods is computationally demanding. The current algorithms to compute chemical organizations in chemical reaction networks are limited to small-scale networks, prohibiting a thorough analysis of large models. Here, we introduce a parallelized version of the constructive algorithm to...

C++ source files to compile SRSim, including the slightly modified LAMMPS sources.

Additional text discussing how to convert macroscopic kinetic rates from non-spatial biomodels to the microscopic reaction rates that are applicable only, when two reacting particles are already within the geometric tolerance values. Also, possible sources for inaccuracies as the use of the refractory time will be discussed.

Contains the source files for the simulations presented in the Results Section. Makefiles to run the simulations are readily included.

We suggest a new type of modeling approach for the coarse grained, particle-based spatial simulation of combinatorially complex chemical reaction systems. In our approach molecules possess a location in the reactor as well as an orientation and geometry, while the reactions are carried out according to a list of implicitly specified reaction rules....

As living materials, post-harvested fruits and vegetables continue their metabolic activity, exhibiting progres- sive biochemical changes. Optimisation of environmental conditions during storage of these fresh commodi- ties is required in order to increase their shelf life. In this work we use P systems to abstract molecular inter- actions that occ...

The construction of molecular-scale machines requires novel paradigms for their programming. Here, we assume a scenario of distributed devices that process in-formation by chemical reactions and that communicate by exchanging molecules. Programming such a distributed system requires specifing reaction rules as well as exchange rules. Here, we prese...

Using Chemical Organisation Theory [1] we present here an analysis of two classical models of artificial chemistries: a system equivalent to AlChemy [2], and the Automata Chemistry [3]. We show that Chemical Organisation Theory is able to explain why AlChemy was unable to evolve, while the Automata Chemistry would produce a stream of novelty that w...

Studying semantics is strongly connected to studying codes that link signs to meanings. Here we suggest a formal method to identify organic codes at a molecular level. We define a molecular organic code with respect to a given reaction network as a mapping between two sets of molecular species called signs and meanings, respectively, such that (a)...

The mitotic spindle assembly checkpoint (MSAC) is an important regulatory mechanism of the cell cycle, ensuring proper chromosome segregation in mitosis. It delays the transition to anaphase until all chromosomes are properly attached to the mitotic spindle by emitting a diffusible “wait anaphase”-signal from unattached kinetochores. Current models...

Systems Biology reconstructs biological phenomena in order to develop explana- tory models of living systems. These mod- els are represented precisely in terms of mathematical expressions. However, the meaning of a model usually is not formally specified but only described in natural lan- guage. Here, we discuss a framework for specifying the meani...

Biocomputing emerged as a promising paradigm capable of coping efficiently with challenges of programming decentralized but concerted reaction systems. The chemical programming metaphor subsumes different encoding techniques into molecular or spatial structures in conjunction with artificial reaction networks. Here, a variety of supplementary assum...

The increasing number and complexity of biomodels makes automatic procedures for checking the models' properties and quality necessary. Approaches like elementary mode analysis, flux balance analysis, deficiency analysis and chemical organization theory (OT) require only the stoichiometric structure of the reaction network for derivation of valuabl...

Author Summary The development of organs, their position, and boundaries in multicellular organisms are defined by genes that can sustain their own activation over long periods of time, termed genetic switches. A good case in point is provided by the genetic machinery controlling the development of flowers in higher plants. In Arabidopsis thaliana...