Retro-fallback: retrosynthetic planning in an uncertain world

Retrosynthesis is the task of proposing a series of chemical reactions to create a desired molecule from simpler, buyable molecules. While previous works have proposed algorithms to find optimal solutions for a range of metrics (e.g. shortest, lowest-cost), these works generally overlook the fact that we have imperfect knowledge of the space of possible reactions, meaning plans created by the algorithm may not work in a laboratory. In this paper we propose a novel formulation of retrosynthesis in terms of stochastic processes to account for this uncertainty. We then propose a novel greedy algorithm called retro-fallback which maximizes the probability that at least one synthesis plan can be executed in the lab. Using in-silico benchmarks we demonstrate that retro-fallback generally produces better sets of synthesis plans than the popular MCTS and retro* algorithms.Comment: 39 pages (including appendices). Currently undergoing peer revie

Ontology based model framework for conceptual design of treatment flow sheets

The primary objective of wastewater treatment is the removal of pollutants to meet given legal effluent standards. To further reduce operators costs additional recovery of resources and energy is desired by industrial and municipal wastewater treatment. Hence the objective in early stage of planning of treatment facilities lies in the identification and evaluation of promising configurations of treatment units. Obviously this early stage of planning may best be supported by software tools to be able to deal with a variety of different treatment configurations. In chemical process engineering various design tools are available that automatically identify feasible process configurations for the purpose to obtain desired products from given educts. In contrast, the adaptation of these design tools for the automatic generation of treatment unit configurations (process chains) to achieve preset effluent standards is hampered by the following three reasons. First, pollutants in wastewater are usually not defined as chemical substances but by compound parameters according to equal properties (e.g. all particulate matter). Consequently the variation of a single compound parameter leads to a change of related parameters (e.g. relation between Chemical Oxygen Demand and Total Suspended Solids). Furthermore, mathematical process models of treatment processes are tailored towards fractions of compound parameters. This hampers the generic representation of these process models which in turn is essential for automatic identification of treatment configurations. Second, treatment technologies for wastewater treatment rely on a variety of chemical, biological, and physical phenomena. Approaches to mathematically describe these phenomena cover a wide range of modeling techniques including stochastic, conceptual or deterministic approaches. Even more the consideration of temporal and spatial resolutions differ. This again hampers a generic representation of process models. Third, the automatic identification of treatment configurations may either be achieved by the use of design rules or by permutation of all possible combinations of units stored within a database of treatment units. The first approach depends on past experience translated into design rules. Hence, no innovative new treatment configurations can be identified. The second approach to identify all possible configurations collapses by extremely high numbers of treatment configurations that cannot be mastered. This is due to the phenomena of combinatorial explosion. It follows therefrom that an appropriate planning algorithm should function without the need of additional design rules and should be able to identify directly feasible configurations while discarding those impractical. This work presents a planning tool for the identification and evaluation of treatment configurations that tackles the before addressed problems. The planning tool comprises two major parts. An external declarative knowledge base and the actual planning tool that includes a goal oriented planning algorithm. The knowledge base describes parameters for wastewater characterization (i.e. material model) and a set of treatment units represented by process models (i.e. process model). The formalization of the knowledge base is achieved by the Web Ontology Language (OWL). The developed data model being the organization structure of the knowledge base describes relations between wastewater parameters and process models to enable for generic representation of process models. Through these parameters for wastewater characterization as well as treatment units can be altered or added to the knowledge base without the requirement to synchronize already included parameter representations or process models. Furthermore the knowledge base describes relations between parameters and properties of water constituents. This allows to track changes of all wastewater parameters which result from modeling of removal efficiency of applied treatment units. So far two generic treatment units have been represented within the knowledge base. These are separation and conversion units. These two raw types have been applied to represent different types of clarifiers and biological treatment units. The developed planning algorithm is based on a Means-Ends Analysis (MEA). This is a goal oriented search algorithm that posts goals from wastewater state and limit value restrictions to select those treatment units only that are likely to solve the treatment problem. Regarding this, all treatment units are qualified according to postconditions that describe the effect of each unit. In addition, units are also characterized by preconditions that state the application range of each unit. The developed planning algorithm furthermore allows for the identification of simple cycles to account for moving bed reactor systems (e.g. functional unit of aeration tank and clarifier). The evaluation of identified treatment configurations is achieved by total estimated cost of each configuration. The planning tool has been tested on five use cases. Some use cases contained multiple sources and sinks. This showed the possibility to identify water reuse capabilities as well as to identify solutions that go beyond end of pipe solutions. Beyond the originated area of application, the planning tool may be used for advanced interrogations. Thereby the knowledge base and planning algorithm may be further developed to address the objectives to identify configurations for any type of material and energy recovery

Metro: Memory-Enhanced Transformer for Retrosynthetic Planning via Reaction Tree

Retrosynthetic planning plays a critical role in drug discovery and organic chemistry. Starting from a target molecule as the root node, it aims to find a complete reaction tree subject to the constraint that all leaf nodes belong to a set of starting materials. The multi-step reactions are crucial because they determine the flow chart in the production of the Organic Chemical Industry. However, existing datasets lack curation of tree-structured multi-step reactions, and fail to provide such reaction trees, limiting models' understanding of organic molecule transformations. In this work, we first develop a benchmark curated for the retrosynthetic planning task, which consists of 124,869 reaction trees retrieved from the public USPTO-full dataset. On top of that, we propose Metro: Memory-Enhanced Transformer for RetrOsynthetic planning. Specifically, the dependency among molecules in the reaction tree is captured as context information for multi-step retrosynthesis predictions through transformers with a memory module. Extensive experiments show that Metro dramatically outperforms existing single-step retrosynthesis models by at least 10.7% in top-1 accuracy. The experiments demonstrate the superiority of exploiting context information in the retrosynthetic planning task. Moreover, the proposed model can be directly used for synthetic accessibility analysis, as it is trained on reaction trees with the shortest depths. Our work is the first step towards a brand new formulation for retrosynthetic planning in the aspects of data construction, model design, and evaluation. Code is available at https://github.com/SongtaoLiu0823/metro

Search Problems in Mission Planning and Navigation of Autonomous Aircraft

An architecture for the control of an autonomous aircraft is presented. The architecture is a hierarchical system representing an anthropomorphic breakdown of the control problem into planner, navigator, and pilot systems. The planner system determines high level global plans from overall mission objectives. This abstract mission planning is investigated by focusing on the Traveling Salesman Problem with variations on local and global constraints. Tree search techniques are applied including the breadth first, depth first, and best first algorithms. The minimum-column and row entries for the Traveling Salesman Problem cost matrix provides a powerful heuristic to guide these search techniques. Mission planning subgoals are directed from the planner to the navigator for planning routes in mountainous terrain with threats. Terrain/threat information is abstracted into a graph of possible paths for which graph searches are performed. It is shown that paths can be well represented by a search graph based on the Voronoi diagram of points representing the vertices of mountain boundaries. A comparison of Dijkstra's dynamic programming algorithm and the A* graph search algorithm from artificial intelligence/operations research is performed for several navigation path planning examples. These examples illustrate paths that minimize a combination of distance and exposure to threats. Finally, the pilot system synthesizes the flight trajectory by creating the control commands to fly the aircraft

Quantum Machine Learning Technique for Automatic Retrosynthetic Reaction Pathway Search Method

Retrosynthetic analysis often involves evaluating many potential candidate reaction pathways and molecules at multiple stages of the reaction, resulting in complex retrosynthesis trees that need to be searched and parsed efficiently. Computational approaches could significantly aid the chemist in  solving different aspects of the retrosynthesis problem, such as the graph-theoretic search methodologies for efficient tree traversal to identify feasible reaction pathways, dictionary-based methods to evaluate a large search space of precursors, and chemistry-driven heuristics to eliminate practically infeasible routes. In this research, a new single-step retrosynthesis prediction method of the Retro TRAE SMILES-based translation technique is proposed. Accordingly, quantum computing with tree-tensor network topology is presented to construct an automatic data-driven end-to-end retrosynthetic route planning system (Auto-Syn-Route), which is presented based on the heuristic scoring function. AutoSynRoute successfully reproduced published synthesis routes for the four case products. The model is trained in an end-to-end and fully data-driven fashion. Unlike previous models translating the SMILES strings of reactants and products, a new way of representing a chemical reaction based on molecular fragments is introduced. It is demonstrated that the new approach yields better prediction results than current state-of-the-art computational methods. The new approach resolves the major drawbacks of existing retrosynthetic methods such as generating invalid SMILES strings. The proposed method is implemented using Python software. The proposed approach predicts highly similar reactant molecules with an accuracy of 68%. In addition, the proposed method yields more robust predictions than existing methods. However, the experiments demonstrate that the proposed scheme significantly improves the success rate of solving the retrosynthetic problem by 97% while maintaining the performance of the quantum tree tensor for predicting valid reactions

Monitoring using Heterogeneous Autonomous Agents.

This dissertation studies problems involving different types of autonomous agents observing objects of interests in an area. Three types of agents are considered: mobile agents, stationary agents, and marsupial agents, i.e., agents capable of deploying other agents or being deployed themselves. Objects can be mobile or stationary. The problem of a mobile agent without fuel constraints revisiting stationary objects is formulated. Visits to objects are dictated by revisit deadlines, i.e., the maximum time that can elapse between two visits to the same object. The problem is shown to be NP-complete and heuristics are provided to generate paths for the agent. Almost periodic paths are proven to exist. The efficacy of the heuristics is shown through simulation. A variant of the problem where the agent has a finite fuel capacity and purchases fuel is treated. Almost periodic solutions to this problem are also shown to exist and an algorithm to compute the minimal cost path is provided. A problem where mobile and stationary agents cooperate to track a mobile object is formulated, shown to be NP-hard, and a heuristic is given to compute paths for the mobile agents. Optimal configurations for the stationary agents are then studied. Several methods are provided to optimally place the stationary agents; these methods are the maximization of Fisher information, the minimization of the probability of misclassification, and the minimization of the penalty incurred by the placement. A method to compute optimal revisit deadlines for the stationary agents is given. The placement methods are compared and their effectiveness shown using numerical results. The problem of two marsupial agents, one carrier and one passenger, performing a general monitoring task using a constrained optimization formulation is stated. Necessary conditions for optimal paths are provided for cases accounting for constrained release of the passenger, termination conditions for the task, as well as retrieval and constrained retrieval of the passenger. A problem involving two marsupial agents collecting information about a stationary object while avoiding detection is then formulated. Necessary conditions for optimal paths are provided and rectilinear motion is demonstrated to be optimal for both agents.PhDAerospace EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/111439/1/jfargeas_1.pd