Deep Neural Encoder-Decoder Model to Relate fMRI Brain Activity with Naturalistic Stimuli

We propose an end-to-end deep neural encoder-decoder model to encode and decode brain activity in response to naturalistic stimuli using functional magnetic resonance imaging (fMRI) data. Leveraging temporally correlated input from consecutive film frames, we employ temporal convolutional layers in our architecture, which effectively allows to bridge the temporal resolution gap between natural movie stimuli and fMRI acquisitions. Our model predicts activity of voxels in and around the visual cortex and performs reconstruction of corresponding visual inputs from neural activity. Finally, we investigate brain regions contributing to visual decoding through saliency maps. We find that the most contributing regions are the middle occipital area, the fusiform area, and the calcarine, respectively employed in shape perception, complex recognition (in particular face perception), and basic visual features such as edges and contrasts. These functions being strongly solicited are in line with the decoder's capability to reconstruct edges, faces, and contrasts. All in all, this suggests the possibility to probe our understanding of visual processing in films using as a proxy the behaviour of deep learning models such as the one proposed in this paper.

PepINVENT: Generative peptide design beyond the natural amino acids

Peptides play a crucial role in the drug design and discovery whether as a therapeutic modality or a delivery agent. Non-natural amino acids (NNAAs) have been used to enhance the peptide properties from binding affinity, plasma stability to permeability. Incorporating novel NNAAs facilitates the design of more effective peptides with improved properties. The generative models used in the field, have focused on navigating the peptide sequence space. The sequence space is formed by combinations of a predefined set of amino acids. However, there is still a need for a tool to explore the peptide landscape beyond this enumerated space to unlock and effectively incorporate de novo design of new amino acids. To thoroughly explore the theoretical chemical space of the peptides, we present PepINVENT, a novel generative AI-based tool as an extension to the small molecule molecular design platform, REINVENT. PepINVENT navigates the vast space of natural and non-natural amino acids to propose valid, novel, and diverse peptide designs. The generative model can serve as a central tool for peptide-related tasks, as it was not trained on peptides with specific properties or topologies. The prior was trained to understand the granularity of peptides and to design amino acids for filling the masked positions within a peptide. PepINVENT coupled with reinforcement learning enables the goal-oriented design of peptides using its chemistry-informed generative capabilities. This study demonstrates PepINVENT's ability to explore the peptide space with unique and novel designs, and its capacity for property optimization in the context of therapeutically relevant peptides. Our tool can be employed for multi-parameter learning objectives, peptidomimetics, lead optimization, and variety of other tasks within the peptide domain.