Ayush Varshney

Ayush Varshney, Katherine L. Bouman, Berthy T. Feng

Ill-posed imaging inverse problems remain challenging due to the ambiguity in mapping degraded observations to clean images. Diffusion-based generative priors have recently shown promise, but typically rely on computationally intensive iterative sampling or per-instance optimization. Amortized variational inference frameworks address this inefficiency by learning a direct mapping from measurements to posteriors, enabling fast posterior sampling without requiring the optimization of a new posterior for every new set of measurements. However, they still struggle to reconstruct fine details and complex textures. To address this, we extend the amortized framework by injecting spatially adaptive perturbations to measurements during training, guided by uncertainty estimates, to emphasize learning in the most uncertain regions. Experiments on deblurring and super-resolution demonstrate that our method achieves superior or competitive performance to previous diffusion-based approaches, delivering more realistic reconstructions without the computational cost of iterative refinement.

Rohit Dilip, Ayush Varshney, David Van Valen

Tokenization is a promising path to multi-modal models capable of jointly understanding protein sequences, structure, and function. Existing protein structure tokenizers create tokens by pooling information from local neighborhoods, an approach that limits their performance on generative and representation tasks. In this work, we present a method for global tokenization of protein structures in which successive tokens contribute increasing levels of detail to a global representation. This change resolves several issues with generative models based on local protein tokenization: it mitigates error accumulation, provides embeddings without sequence-reduction operations, and allows task-specific adaptation of a tokenized sequence's information content. We validate our method on reconstruction, generative, and representation tasks and demonstrate that it matches or outperforms existing models based on local protein structure tokenizers. We show how adaptive tokens enable inference criteria based on information content, which boosts designability. We validate representations generated from our tokenizer on CATH classification tasks and demonstrate that non-linear probing on our tokenized sequences outperforms equivalent probing on representations from other tokenizers. Finally, we demonstrate how our method supports zero-shot protein shrinking and affinity maturation.

Rohit Dilip, Evan Zhang, Ayush Varshney et al.

Protein structure tokenizers enable the creation of multimodal models of protein structure, sequence, and function. Current approaches to protein structure tokenization rely on bespoke components that are invariant to spatial symmetries, but that are challenging to optimize and scale. We present Kanzi, a flow-based tokenizer for tokenization and generation of protein structures. Kanzi consists of a diffusion autoencoder trained with a flow matching loss. We show that this approach simplifies several aspects of protein structure tokenizers: frame-based representations can be replaced with global coordinates, complex losses are replaced with a single flow matching loss, and SE(3)-invariant attention operations can be replaced with standard attention. We find that these changes stabilize the training of parameter-efficient models that outperform existing tokenizers on reconstruction metrics at a fraction of the model size and training cost. An autoregressive model trained with Kanzi outperforms similar generative models that operate over tokens, although it does not yet match the performance of state-of-the-art continuous diffusion models. Code is available here: https://github.com/rdilip/kanzi/.