Software Tools and Approaches for Compound Identification of LC-MS/MS Data in Metabolomics.

The annotation of small molecules remains a major challenge in untargeted mass spectrometry-based metabolomics. We here critically discuss structured elucidation approaches and software that are designed to help during the annotation of unknown compounds. Only by elucidating unknown metabolites first is it possible to biologically interpret complex systems, to map compounds to pathways and to create reliable predictive metabolic models for translational and clinical research. These strategies include the construction and quality of tandem mass spectral databases such as the coalition of MassBank repositories and investigations of MS/MS matching confidence. We present in silico fragmentation tools such as MS-FINDER, CFM-ID, MetFrag, ChemDistiller and CSI:FingerID that can annotate compounds from existing structure databases and that have been used in the CASMI (critical assessment of small molecule identification) contests. Furthermore, the use of retention time models from liquid chromatography and the utility of collision cross-section modelling from ion mobility experiments are covered. Workflows and published examples of successfully annotated unknown compounds are included

Towards Molecule Generation with Heterogeneous States via Reinforcement Learning

De novo molecular design and generation are frequently prescribed in the field of chemistry and biology, for it plays a critical role in maintaining the prosperity of the chemical industry and benefiting the drug discovery. Nowadays, many significant problems in this field are based on the philosophy of designing molecular structures towards specific desired properties. This research is very meaningful in both medical and AI fields, which can benefits novel drug discovery for some diseases. However, It remains a challenging task due to the large size of chemical space. In recent years, reinforcement learning-based methods leverage graphs to represent molecules and generate molecules as a decision making process. However, this vanilla graph representation may neglect the intrinsic context information with molecules and limits the generation performance accordingly. In this paper, we propose to augment the original graph states with the SMILES context vectors. As a result, SMILES representations are easily processed by a simple language model such that the general semantic features of a molecule can be extracted; and the graph representations perform better in handling the topology relationship of each atom. Moreover, we propose a framework that combines supervised learning and reinforcement learning algorithm to take a solid consideration of these two heterogeneous state representations of a molecule, which can fuse the information from both of them and extract more comprehensive features so that more sophisticated decisions can be made by the policy network. Our model also introduces two attention mechanisms, i.e., action-attention, and graph-attention, to further improve the performance. We conduct our experiments on a practical dataset, ZINC, and the experiment results demonstrate that our framework can outperform other baselines in the learning performance of molecule generation and chemical property optimization