In this paper, we study human sequential behavior by integrating cognitive, evolutionary, and computational approaches. Our work centers around the emergence of shared vocabularies in the Embodied... Show moreIn this paper, we study human sequential behavior by integrating cognitive, evolutionary, and computational approaches. Our work centers around the emergence of shared vocabularies in the Embodied Communication Game (ECG). Here, participant pairs solve a shared task without access to conventional means of communication, enforcing the emergence of a new communication system. This problem is solved typi- cally by negotiating a shared set of sequential signals that acquire meaning through interactions. Individual differences in Personal Need for Structure (PNS) have been found to influence how this process develops. We trained deep neural networks to mimic the emergence of new communicative systems and used hyperparameter optimization to approximate latent human cognitive variables to explain human behavior. We demonstrate that models based on bidirectional LSTM networks are better at capturing human behavior than unidirectional LSTM networks. This suggests that human sequence processing in the ECG is influenced by expected future states. The approximated variables cannot explain the differences in PNS, but we do provide evidence suggesting that random and uncertainty-directed exploration strategies are combined to develop optimal behavior. Show less
Liu, X.; Ye, K.; Vlijmen, H.W.T. van; Emmerich, M.T.M.; IJzerman, A.P.; Westen, G.J.P. van 2021
In polypharmacology drugs are required to bind to multiple specific targets, for example to enhance efficacy or to reduce resistance formation. Although deep learning has achieved a breakthrough in... Show moreIn polypharmacology drugs are required to bind to multiple specific targets, for example to enhance efficacy or to reduce resistance formation. Although deep learning has achieved a breakthrough in de novo design in drug discovery, most of its applications only focus on a single drug target to generate drug-like active molecules. However, in reality drug molecules often interact with more than one target which can have desired (polypharmacology) or undesired (toxicity) effects. In a previous study we proposed a new method named DrugEx that integrates an exploration strategy into RNN-based reinforcement learning to improve the diversity of the generated molecules. Here, we extended our DrugEx algorithm with multi-objective optimization to generate drug-like molecules towards multiple targets or one specific target while avoiding off-targets (the two adenosine receptors, A1AR and A2AAR, and the potassium ion channel hERG in this study). In our model, we applied an RNN as the agent and machine learning predictors as the environment. Both the agent and the environment were pre-trained in advance and then interplayed under a reinforcement learning framework. The concept of evolutionary algorithms was merged into our method such that crossover and mutation operations were implemented by the same deep learning model as the agent. During the training loop, the agent generates a batch of SMILES-based molecules. Subsequently scores for all objectives provided by the environment are used to construct Pareto ranks of the generated molecules. For this ranking a non-dominated sorting algorithm and a Tanimoto-based crowding distance algorithm using chemical fingerprints are applied. Here, we adopted GPU acceleration to speed up the process of Pareto optimization. The final reward of each molecule is calculated based on the Pareto ranking with the ranking selection algorithm. The agent is trained under the guidance of the reward to make sure it can generate desired molecules after convergence of the training process. All in all we demonstrate generation of compounds with a diverse predicted selectivity profile towards multiple targets, offering the potential of high efficacy and low toxicity. Show less
