Chemical discovery as belief revision

In this paper we describe STAHLp, a system that constructs componential models of chemical substances. STAHLp is a descendent of Zytkow and Simon's (1986) STAHL system, and both use chemical reactions and known componential models in order to construct new chemical models. However, STAHLp employs a more unified and effective strategy for recovering from erroneous inferences, based partly on de Kleer's (1984) assumption-based method of belief revision. This involves recording the underlying source beliefs or premises which lead to each inferred reaction or model. Where Zytkow and Simon's system required multiple methods for detecting errors and recovering from them, STAHLp uses a more powerful representation and additional rules which allow a unified method for error detection and recovery. When given the same initial data, the new system constructs the same historically correct models as STAHL, but it has other capabilities as well. In particular, STAHLp can modify data it has been given if this is necessary to achieve consistent models, and then proceed to construct new models based on the revised data

Theory formation by abduction : initial results of a case study based on the chemical revolution

Abduction is the process of constructing explanations. This chapter suggests that automated abduction is a key to advancing beyond the "routine theory revision" methods developed in early AI research towards automated reasoning systems capable of "world model revision" — dramatic changes in systems of beliefs such as occur in children's cognitive development and in scientific revolutions. The chapter describes a general approach to automating theory revision based upon computational methods for theory formation by abduction. The approach is based on the idea that, when an anomaly is encountered, the best course is often simply to suppress parts of the original theory thrown into question by the contradiction and to derive an explanation of the anomalous observation based on relatively solid, basic principles. This process of looking for explanations of unexpected new phenomena can lead by abductive inference to new hypotheses that can form crucial parts of a revised theory. As an illustration, the chapter shows how some of Lavoisier's key insights during the Chemical Revolution can be viewed as examples of theory formation by abduction

Organising metabolic networks: cycles in flux distributions

Metabolic networks are among the most widely studied biological systems. The topology and interconnections of metabolic reactions have been well described for many species, but are not sufficient to understand how their activity is regulated in living organisms. The principles directing the dynamic organisation of reaction fluxes remain poorly understood. Cyclic structures are thought to play a central role in the homeostasis of biological systems and in their resilience to a changing environment. In this work, we investigate the role of fluxes of matter cycling in metabolic networks. First, we introduce a methodology for the computation of cyclic and acyclic fluxes in metabolic networks, adapted from an algorithm initially developed to study cyclic fluxes in trophic networks. Subsequently, we apply this methodology to the analysis of three metabolic systems, including the central metabolism of wild type and a deletion mutant of Escherichia coli, erythrocyte metabolism and the central metabolism of the bacterium Methylobacterium extorquens. The role of cycles in driving and maintaining the performance of metabolic functions upon perturbations is unveiled through these examples. This methodology may be used to further investigate the role of cycles in living organisms, their pro-activity and organisational invariance, leading to a better understanding of biological entailment and information processing

Reconstruction of an in silico metabolic model of _Arabidopsis thaliana_ through database integration

The number of genome-scale metabolic models has been rising quickly in recent years, and the scope of their utilization encompasses a broad range of applications from metabolic engineering to biological discovery. However the reconstruction of such models remains an arduous process requiring a high level of human intervention. Their utilization is further hampered by the absence of standardized data and annotation formats and the lack of recognized quality and validation standards.

Plants provide a particularly rich range of perspectives for applications of metabolic modeling. We here report the first effort to the reconstruction of a genome-scale model of the metabolic network of the plant _Arabidopsis thaliana_, including over 2300 reactions and compounds. Our reconstruction was performed using a semi-automatic methodology based on the integration of two public genome-wide databases, significantly accelerating the process. Database entries were compared and integrated with each other, allowing us to resolve discrepancies and enhance the quality of the reconstruction. This process lead to the construction of three models based on different quality and validation standards, providing users with the possibility to choose the standard that is most appropriate for a given application. First, a _core metabolic model_ containing only consistent data provides a high quality model that was shown to be stoichiometrically consistent. Second, an _intermediate metabolic model_ attempts to fill gaps and provides better continuity. Third, a _complete metabolic model_ contains the full set of known metabolic reactions and compounds in _Arabidopsis thaliana_.

We provide an annotated SBML file of our core model to enable the maximum level of compatibility with existing tools and databases. We eventually discuss a series of principles to raise awareness of the need to develop coordinated efforts and common standards for the reconstruction of genome-scale metabolic models, with the aim of enabling their widespread diffusion, frequent update, maximum compatibility and convenience of use by the wider research community and industry

Retrosynthetic reaction prediction using neural sequence-to-sequence models

We describe a fully data driven model that learns to perform a retrosynthetic reaction prediction task, which is treated as a sequence-to-sequence mapping problem. The end-to-end trained model has an encoder-decoder architecture that consists of two recurrent neural networks, which has previously shown great success in solving other sequence-to-sequence prediction tasks such as machine translation. The model is trained on 50,000 experimental reaction examples from the United States patent literature, which span 10 broad reaction types that are commonly used by medicinal chemists. We find that our model performs comparably with a rule-based expert system baseline model, and also overcomes certain limitations associated with rule-based expert systems and with any machine learning approach that contains a rule-based expert system component. Our model provides an important first step towards solving the challenging problem of computational retrosynthetic analysis

Identification of students' mental models about the milk transformation in yogurt

A review of the scientific literature reveals that there are still few researches on the conceptions of secondary school students about chemical reactions involving microorganisms, especially those related to the mental models that students use in their explanations. This paper describes a study concerning the different mental models related to the milk transformation into yogurt with 83 students from a Spanish secondary school of 8th and 9th grade (13-16 years) developed in the framework of a research that intends to use the elaboration of this product as a context for the teaching and learning of chemical reactions through modeling approaches. In order to identify the mental models of the students, in this paper we consider the milk transformation into yogurt as a process in which its main components are: the entities involved (milk and bacteria), the interaction between them and the result (yogurt). A simplified school model of this process would involve students considering that bacteria use the sugar in milk to transform it into lactic acid through a chemical reaction to obtain the necessary energy. Using this scheme in interaction with the students' answers, the underlying mental models were identified. Although almost half of the students showed great difficulties explaining the process, five models have been identified. Students often consider the milk transformation into yogurt primarily as a physical process of agglutination or change of state. These models are far from a school model of reference in which the bacteria have a fundamental role in the transformation of milk into yogurt by a chemical reaction.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech