Markush structure reconstruction
A prototype for their reconstruction from image and text into a searchable, context sensitive grammar based extension of SMILES
Today publications are digitally available which enables researchers to search the text and often also the content of tables. On the contrary, images cannot be searched which is not a problem for most fields, but in chemistry most of the information are contained in images, especially structure diagrams. Next to the "normal" chemical structures, which represent exactly one molecule, there also exist generic structures, so called Markush structures. These contain variable parts and additional textual information which enable them to represent several molecules at once. This can vary between just a few and up to thousands or even millions. This ability lead to a spread of Markush structures in patents, because it enables patents to protect entire families of molecules at once. Next to the prevention of an enumeration of all structures it also has the advantage that, if a Markush structure is used in a patent, it is much harder to determine whether a specific structure is protected by it or not. To solve the question about the protection of a structure, it is necessary to search the patents. Appropriate databases for this task already do exist, but are filled manually. An automatic processing does not yet exist. In this project a Markush structure reconstruction prototype is developed which is able to reconstruct bitmaps including Markush structures (meaning a depiction of the structure and a text part describing the generic parts) into a digital format and save them in the newly developed context-free grammar based file format extSMILES. This format is searchable due to its context-free grammar based design. To be able to develop a Markush structure reconstruction prototype, an in depth analysis of the concept of Markush structures and their requirements for a reconstruction process was performed. Thereby it is stated, that the common connection table concept of the existing file formats is not able to store Markush structures. Especially challenging are conditions for most of the formats. Thus, a context-free grammar based file format is developed, which extends the SMILES format. This extSMILES called format assures the searchability of the results by its context-free grammar based concept, and is able to store all information contained in Markush structures. In addition it is generic, extendable and easily understandable. The developed prototype for the Markush structure reconstruction uses ext- SMILES as output format and is based on the chemical structure recognition tool chemoCR and the Unstructured Information Management Architecture UIMA. For chemoCR modules are developed which enable it to recognize and assemble Markush structures as well as to return the reconstruction result in extSMILES. For UIMA on the other hand, a pipeline is developed, which is able to analyse and translate the input text files to extSMILES. The results of both tools then are combined and presented in chemoCR. An evaluation of the prototype is performed on a representative set of twelve structures of interest and low image quality which contain all typical Markush elements. Trivial structures containing only one R-group are not evaluated. Due to the challenging nature of the images, no Markush structure could be correctly reconstructed. But by regarding the assumption, that R-group definitions which are described by natural language are excluded from the task, and under the condition that the core structure reconstruction is improved, the rate of success can be increased to 58.4%.
Sankt Augustin, Hochschule Bonn-Rhein-Sieg, Master Thesis, 2009