Large language models generate functional protein sequences across diverse families.

Deep-learning language models have shown promise in various biotechnological applications, including protein design and engineering. Here we describe ProGen, a language model that can generate protein sequences with a predictable function across large protein families, akin to generating grammatically and semantically correct natural language sentences on diverse topics. The model was trained on 280 million protein sequences from >19,000 families and is augmented with control tags specifying protein properties. ProGen can be further fine-tuned to curated sequences and tags to improve controllable generation performance of proteins from families with sufficient homologous samples. Artificial proteins fine-tuned to five distinct lysozyme families showed similar catalytic efficiencies as natural lysozymes, with sequence identity to natural proteins as low as 31.4%. ProGen is readily adapted to diverse protein families, as we demonstrate with chorismate mutase and malate dehydrogenase.

A Dynamic Frame Selection Framework for Fast Video Recognition.

We introduce AdaFrame, a conditional computation framework that adaptively selects relevant frames on a per-input basis for fast video recognition. AdaFrame, which contains a Long Short-Term Memory augmented with a global memory to provide context information, operates as an agent to interact with video sequences aiming to search over time which frames to use. Trained with policy search methods, at each time step, AdaFrame computes a prediction, decides where to observe next, and estimates a utility, i.e., expected future rewards, of viewing more frames in the future. Exploring predicted utilities at testing time, AdaFrame is able to achieve adaptive lookahead inference so as to minimize the overall computational cost without incurring a degradation in accuracy. We conduct extensive experiments on two large-scale video benchmarks, FCVID and ActivityNet. With a vanilla ResNet-101 model, AdaFrame achieves similar performance of using all frames while only requiring, on average, 8.21 and 8.65 frames on FCVID and ActivityNet, respectively. We also demonstrate AdaFrame is compatible with modern 2D and 3D networks for video recognition. Furthermore, we show, among other things, learned frame usage can reflect the difficulty of making prediction decisions both at instance-level within the same class and at class-level among different categories.

Active Clustering with Model-Based Uncertainty Reduction.

Semi-supervised clustering seeks to augment traditional clustering methods by incorporating side information provided via human expertise in order to increase the semantic meaningfulness of the resulting clusters. However, most current methods are passive in the sense that the side information is provided beforehand and selected randomly. This may require a large number of constraints, some of which could be redundant, unnecessary, or even detrimental to the clustering results. Thus in order to scale such semi-supervised algorithms to larger problems it is desirable to pursue an active clustering method-i.e., an algorithm that maximizes the effectiveness of the available human labor by only requesting human input where it will have the greatest impact. Here, we propose a novel online framework for active semi-supervised spectral clustering that selects pairwise constraints as clustering proceeds, based on the principle of uncertainty reduction. Using a first-order Taylor expansion, we decompose the expected uncertainty reduction problem into a gradient and a step-scale, computed via an application of matrix perturbation theory and cluster-assignment entropy, respectively. The resulting model is used to estimate the uncertainty reduction potential of each sample in the dataset. We then present the human user with pairwise queries with respect to only the best candidate sample. We evaluate our method using three different image datasets (faces, leaves and dogs), a set of common UCI machine learning datasets and a gene dataset. The results validate our decomposition formulation and show that our method is consistently superior to existing state-of-the-art techniques, as well as being robust to noise and to unknown numbers of clusters.