Anne Condon

Chenwei Zhang, Khanh Dao Duc, Anne Condon

Synthetic biologists and molecular programmers design novel nucleic acid reactions, with many potential applications. Good visualization tools are needed to help domain experts make sense of the complex outputs of folding pathway simulations of such reactions. Here we present ViDa, a new approach for visualizing DNA reaction folding trajectories over the energy landscape of secondary structures. We integrate a deep graph embedding model with common dimensionality reduction approaches, to map high-dimensional data onto 2D Euclidean space. We assess ViDa on two well-studied and contrasting DNA hybridization reactions. Our preliminary results suggest that ViDa's visualization successfully separates trajectories with different folding mechanisms, thereby providing useful insight to users, and is a big improvement over the current state-of-the-art in DNA kinetics visualization.

Chenwei Zhang, Anne Condon, Khanh Dao Duc

Generating synthetic cryogenic electron microscopy 3D density maps from molecular structures has potential important applications in structural biology. Yet existing simulation-based methods cannot mimic all the complex features present in experimental maps, such as secondary structure elements. As an alternative, we propose struc2mapGAN, a novel data-driven method that employs a generative adversarial network to produce improved experimental-like density maps from molecular structures. More specifically, struc2mapGAN uses a nested U-Net architecture as the generator, with an additional L1 loss term and further processing of raw training experimental maps to enhance learning efficiency. While struc2mapGAN can promptly generate maps after training, we demonstrate that it outperforms existing simulation-based methods for a wide array of tested maps and across various evaluation metrics.

Chenwei Zhang, Jordan Lovrod, Boyan Beronov et al.

Visualization tools can help synthetic biologists and molecular programmers understand the complex reactive pathways of nucleic acid reactions, which can be designed for many potential applications and can be modelled using a continuous-time Markov chain (CTMC). Here we present ViDa, a new visualization approach for DNA reaction trajectories that uses a 2D embedding of the secondary structure state space underlying the CTMC model. To this end, we integrate a scattering transform of the secondary structure adjacency, a variational autoencoder, and a nonlinear dimensionality reduction method. We augment the training loss with domain-specific supervised terms that capture both thermodynamic and kinetic features. We assess ViDa on two well-studied DNA hybridization reactions. Our results demonstrate that the domain-specific features lead to significant quality improvements over the state-of-the-art in DNA state space visualization, successfully separating different folding pathways and thus providing useful insights into dominant reaction mechanisms.