Wenxian Shi

Zhenqiao Song, Yunlong Zhao, Wenxian Shi et al.

Proteins are macromolecules responsible for essential functions in almost all living organisms. Designing reasonable proteins with desired functions is crucial. A protein's sequence and structure are strongly correlated and they together determine its function. In this paper, we propose NAEPro, a model to jointly design Protein sequence and structure based on automatically detected functional sites. NAEPro is powered by an interleaving network of attention and equivariant layers, which can capture global correlation in a whole sequence and local influence from nearest amino acids in three dimensional (3D) space. Such an architecture facilitates effective yet economic message passing at two levels. We evaluate our model and several strong baselines on two protein datasets, $β$-lactamase and myoglobin. Experimental results show that our model consistently achieves the highest amino acid recovery rate, TM-score, and the lowest RMSD among all competitors. These findings prove the capability of our model to design protein sequences and structures that closely resemble their natural counterparts. Furthermore, in-depth analysis further confirms our model's ability to generate highly effective proteins capable of binding to their target metallocofactors. We provide code, data and models in Github.

Zhenqiao Song, Yunlong Zhao, Yufei Song et al.

Designing novel proteins with desired functions is crucial in biology and chemistry. However, most existing work focus on protein sequence design, leaving protein sequence and structure co-design underexplored. In this paper, we propose GeoPro, a method to design protein backbone structure and sequence jointly. Our motivation is that protein sequence and its backbone structure constrain each other, and thus joint design of both can not only avoid nonfolding and misfolding but also produce more diverse candidates with desired functions. To this end, GeoPro is powered by an equivariant encoder for three-dimensional (3D) backbone structure and a protein sequence decoder guided by 3D geometry. Experimental results on two biologically significant metalloprotein datasets, including $β$-lactamases and myoglobins, show that our proposed GeoPro outperforms several strong baselines on most metrics. Remarkably, our method discovers novel $β$-lactamases and myoglobins which are not present in protein data bank (PDB) and UniProt. These proteins exhibit stable folding and active site environments reminiscent of those of natural proteins, demonstrating their excellent potential to be biologically functional.

Wenxian Shi, Hao Zhou, Ning Miao et al.

Deep generative models are commonly used for generating images and text. Interpretability of these models is one important pursuit, other than the generation quality. Variational auto-encoder (VAE) with Gaussian distribution as prior has been successfully applied in text generation, but it is hard to interpret the meaning of the latent variable. To enhance the controllability and interpretability, one can replace the Gaussian prior with a mixture of Gaussian distributions (GM-VAE), whose mixture components could be related to hidden semantic aspects of data. In this paper, we generalize the practice and introduce DEM-VAE, a class of models for text generation using VAEs with a mixture distribution of exponential family. Unfortunately, a standard variational training algorithm fails due to the mode-collapse problem. We theoretically identify the root cause of the problem and propose an effective algorithm to train DEM-VAE. Our method penalizes the training with an extra dispersion term to induce a well-structured latent space. Experimental results show that our approach does obtain a meaningful space, and it outperforms strong baselines in text generation benchmarks. The code is available at https://github.com/wenxianxian/demvae.

Wenxian Shi, Yuxuan Song, Hao Zhou et al.

Deep neural networks often have a huge number of parameters, which posts challenges in deployment in application scenarios with limited memory and computation capacity. Knowledge distillation is one approach to derive compact models from bigger ones. However, it has been observed that a converged heavy teacher model is strongly constrained for learning a compact student network and could make the optimization subject to poor local optima. In this paper, we propose ProKT, a new model-agnostic method by projecting the supervision signals of a teacher model into the student's parameter space. Such projection is implemented by decomposing the training objective into local intermediate targets with an approximate mirror descent technique. The proposed method could be less sensitive with the quirks during optimization which could result in a better local optimum. Experiments on both image and text datasets show that our proposed ProKT consistently achieves superior performance compared to other existing knowledge distillation methods.

Rong Ye, Wenxian Shi, Hao Zhou et al.

How to generate descriptions from structured data organized in tables? Existing approaches using neural encoder-decoder models often suffer from lacking diversity. We claim that an open set of templates is crucial for enriching the phrase constructions and realizing varied generations. Learning such templates is prohibitive since it often requires a large paired <table, description> corpus, which is seldom available. This paper explores the problem of automatically learning reusable "templates" from paired and non-paired data. We propose the variational template machine (VTM), a novel method to generate text descriptions from data tables. Our contributions include: a) we carefully devise a specific model architecture and losses to explicitly disentangle text template and semantic content information, in the latent spaces, and b)we utilize both small parallel data and large raw text without aligned tables to enrich the template learning. Experiments on datasets from a variety of different domains show that VTM is able to generate more diversely while keeping a good fluency and quality.

Ning Miao, Hao Zhou, Chengqi Zhao et al.

Neural models for text generation require a softmax layer with proper token embeddings during the decoding phase. Most existing approaches adopt single point embedding for each token. However, a word may have multiple senses according to different context, some of which might be distinct. In this paper, we propose KerBS, a novel approach for learning better embeddings for text generation. KerBS embodies two advantages: (a) it employs a Bayesian composition of embeddings for words with multiple senses; (b) it is adaptive to semantic variances of words and robust to rare sentence context by imposing learned kernels to capture the closeness of words (senses) in the embedding space. Empirical studies show that KerBS significantly boosts the performance of several text generation tasks.