Recent breakthroughs in protein structure prediction have opened new avenues for genome-wide drug discovery, yet existing virtual screening methods remain computationally prohibitive. We present DrugCLIP, a contrastive learning framework that achieves ultrafast and accurate virtual screening, up to 10 million times faster than docking, while consistently outperforming various baselines on in silico benchmarks. In wet-lab validations, DrugCLIP achieved a 15% hit rate for norepinephrine transporter, and structures of two identified inhibitors were determined in complex with the target protein. For thyroid hormone receptor interactor 12, a target that lacks holo structures and small-molecule binders, DrugCLIP achieved a 17.5% hit rate using only AlphaFold2-predicted structures. Finally, we released GenomeScreenDB, an open-access database providing precomputed results for ~10,000 human proteins screened against 500 million compounds, pioneering a drug discovery paradigm in the post-AlphaFold era.

Fei Xiao, Liang Pang, Yanyan Lan, Yan Wang, Huawei Shen, Xueqi Cheng. Proceedings of the 2021 Conference on Empirical Methods in Natural Language Processing. 2021.

Most existing visual reasoning tasks, such as CLEVR in VQA, ignore an important factor, i.e., transformation. They are solely defined to test how well machines understand concepts and relations within static settings, like one image. Such state driven visual reasoning has limitations in reflecting the ability to infer the dynamics between different states, which has shown to be equally important for human cognition in Piaget's theory. To tackle this problem, we propose a novel transformation driven visual reasoning (TVR) task. Given both the initial and final states, the target becomes to infer the corresponding intermediate transformation. Following this definition, a new synthetic dataset namely TRANCE is first constructed on the basis of CLEVR, including three levels of settings, i.e., Basic (single-step transformation), Event (multi-step transformation), and View (multi-step transformation with variant views). Next, we build another real dataset called TRANCO based on COIN, to cover the loss of transformation diversity on TRANCE. Inspired by human reasoning, we propose a three-staged reasoning framework called TranNet, including observing, analyzing, and concluding, to test how recent advanced techniques perform on TVR. Experimental results show that the state-of-the-art visual reasoning models perform well on Basic, but are still far from human-level intelligence on Event, View, and TRANCO. We believe the proposed new paradigm will boost the development of machine visual reasoning. More advanced methods and new problems need to be investigated in this direction.

Current natural language understanding (NLU) models have been continuously scaling up, both in terms of model size and input context, introducing more hidden and input neurons. While this generally improves performance on average, the extra neurons do not yield a consistent improvement for all instances. This is because some hidden neurons are redundant, and the noise mixed in input neurons tends to distract the model. Previous work mainly focuses on extrinsically reducing low-utility neurons by additional post- or pre-processing, such as network pruning and context selection, to avoid this problem. Beyond that, can we make the model reduce redundant parameters and suppress input noise by intrinsically enhancing the utility of each neuron? If a model can efficiently utilize neurons, no matter which neurons are ablated (disabled), the ablated submodel should perform no better than the original full model. Based on such a comparison principle between models, we propose a cross-model comparative loss for a broad range of tasks. Comparative loss is essentially a ranking loss on top of the task-specific losses of the full and ablated models, with the expectation that the task-specific loss of the full model is minimal. We demonstrate the universal effectiveness of comparative loss through extensive experiments on 14 datasets from three distinct NLU tasks based on five widely used pre-trained language models and find it particularly superior for models with few parameters or long input.

Community Question Answering (CQA) sites such as Yahoo! Answers and Baidu Knows have emerged as rich knowledge resources for information seekers. However, answers posted to CQA sites often vary a lot in their qualities. User votes from the community may partially reflect the overall quality of the answer, but they are often missing. Hence, automatic selection of "good'' answers becomes a practical research problem that will help us manage the quality of accumulated knowledge. Without loss of generality, a good answer should deliver not only relevant but also trustworthy information that can help resolve the information needs of the posted question, but the latter has received less investigation in the past. In this paper, we propose a novel matching-verification framework for automatic answer selection. The matching component assesses the relevance of a candidate answer to a given question as conventional QA methods. The major enhancement is the verification component, which aims to leverage the wisdom of crowds, e.g., some big information repository, for trustworthiness measurement. Given a question, we take the top retrieved results from the information repository as the supporting evidences to distill the consensus representation. A major challenge is that there is no guarantee that one can always obtain reliable consensus from the wisdom of crowds for a question due to the noisy nature and the limitation of the existing search technology.Therefore, we decompose the trustworthiness measurement into two parts, i.e., a verification score which measures the consistency between a candidate answer and the consensus representation, and a confidence score which measures the reliability of the consensus itself. Empirical studies on three real-world CQA data collections, i.e. YahooQA, QuoraQA and AmazonQA, show that our approach can significantly outperform the state-of-the-art methods on the answer selection task.