Protein-ligand structure prediction is an essential task in drug discovery, predicting the binding interactions between small molecules (ligands) and target proteins (receptors). Recent advances have incorporated deep learning techniques to improve the accuracy of protein-ligand structure prediction. Nevertheless, the experimental validation of docking conformations remains costly, it raises concerns regarding the generalizability of these deep learning-based methods due to the limited training data. In this work, we show that by pre-training on a large-scale docking conformation generated by traditional physics-based docking tools and then fine-tuning with a limited set of experimentally validated receptor-ligand complexes, we can obtain a protein-ligand structure prediction model with outstanding performance. Specifically, this process involved the generation of 100 million docking conformations for protein-ligand pairings, an endeavor consuming roughly 1 million CPU core days. The proposed model, HelixDock, aims to acquire the physical knowledge encapsulated by the physics-based docking tools during the pre-training phase. HelixDock has been rigorously benchmarked against both physics-based and deep learning-based baselines, demonstrating its exceptional precision and robust transferability in predicting binding confirmation. In addition, our investigation reveals the scaling laws governing pre-trained protein-ligand structure prediction models, indicating a consistent enhancement in performance with increases in model parameters and the volume of pre-training data. Moreover, we applied HelixDock to several drug discovery-related tasks to validate its practical utility. HelixDock demonstrates outstanding capabilities on both cross-docking and structure-based virtual screening benchmarks.
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Machine-learning models consist of kernels, which are algorithms applying operations on tensors -- data indexed by a linear combination of natural numbers. Examples of kernels include convolutions, transpositions, and vectorial products. There are many ways to implement a kernel. These implementations form the kernel's optimization space. Kernel scheduling is the problem of finding the best implementation, given an objective function -- typically execution speed. Kernel optimizers such as Ansor, Halide, and AutoTVM solve this problem via search heuristics, which combine two phases: exploration and exploitation. The first step evaluates many different kernel optimization spaces. The latter tries to improve the best implementations by investigating a kernel within the same space. For example, Ansor combines kernel generation through sketches for exploration and leverages an evolutionary algorithm to exploit the best sketches. In this work, we demonstrate the potential to reduce Ansor's search time while enhancing kernel quality by incorporating Droplet Search, an AutoTVM algorithm, into Ansor's exploration phase. The approach involves limiting the number of samples explored by Ansor, selecting the best, and exploiting it with a coordinate descent algorithm. By applying this approach to the first 300 kernels that Ansor generates, we usually obtain better kernels in less time than if we let Ansor analyze 10,000 kernels. This result has been replicated in 20 well-known deep-learning models (AlexNet, ResNet, VGG, DenseNet, etc.) running on four architectures: an AMD Ryzen 7 (x86), an NVIDIA A100 tensor core, an NVIDIA RTX 3080 GPU, and an ARM A64FX. A patch with this combined approach was approved in Ansor in February 2024. As evidence of the generality of this search methodology, a similar patch, achieving equally good results, was submitted to TVM's MetaSchedule in June 2024.
3D reconstruction of the liver for volumetry is important for qualitative analysis and disease diagnosis. Liver volumetry using ultrasound (US) scans, although advantageous due to less acquisition time and safety, is challenging due to the inherent noisiness in US scans, blurry boundaries, and partial liver visibility. We address these challenges by using the segmentation masks of a few incomplete sagittal-plane US scans of the liver in conjunction with a statistical shape model (SSM) built using a set of CT scans of the liver. We compute the shape parameters needed to warp this canonical SSM to fit the US scans through a parametric regression network. The resulting 3D liver reconstruction is accurate and leads to automatic liver volume calculation. We evaluate the accuracy of the estimated liver volumes with respect to CT segmentation volumes using RMSE. Our volume computation is statistically much closer to the volume estimated using CT scans than the volume computed using Childs' method by radiologists: p-value of 0.094 (>0.05) says that there is no significant difference between CT segmentation volumes and ours in contrast to Childs' method. We validate our method using investigations (ablation studies) on the US image resolution, the number of CT scans used for SSM, the number of principal components, and the number of input US scans. To the best of our knowledge, this is the first automatic liver volumetry system using a few incomplete US scans given a set of CT scans of livers for SSM.
Weakly-supervised medical image segmentation is a challenging task that aims to reduce the annotation cost while keep the segmentation performance. In this paper, we present a novel framework, SimTxtSeg, that leverages simple text cues to generate high-quality pseudo-labels and study the cross-modal fusion in training segmentation models, simultaneously. Our contribution consists of two key components: an effective Textual-to-Visual Cue Converter that produces visual prompts from text prompts on medical images, and a text-guided segmentation model with Text-Vision Hybrid Attention that fuses text and image features. We evaluate our framework on two medical image segmentation tasks: colonic polyp segmentation and MRI brain tumor segmentation, and achieve consistent state-of-the-art performance.
The precise prediction of molecular properties is essential for advancements in drug development, particularly in virtual screening and compound optimization. The recent introduction of numerous deep learning-based methods has shown remarkable potential in enhancing molecular property prediction (MPP), especially improving accuracy and insights into molecular structures. Yet, two critical questions arise: does the integration of domain knowledge augment the accuracy of molecular property prediction and does employing multi-modal data fusion yield more precise results than unique data source methods? To explore these matters, we comprehensively review and quantitatively analyze recent deep learning methods based on various benchmarks. We discover that integrating molecular information significantly improves molecular property prediction (MPP) for both regression and classification tasks. Specifically, regression improvements, measured by reductions in root mean square error (RMSE), are up to 4.0%, while classification enhancements, measured by the area under the receiver operating characteristic curve (ROC-AUC), are up to 1.7%. We also discover that enriching 2D graphs with 1D SMILES boosts multi-modal learning performance for regression tasks by up to 9.1%, and augmenting 2D graphs with 3D information increases performance for classification tasks by up to 13.2%, with both enhancements measured using ROC-AUC. The two consolidated insights offer crucial guidance for future advancements in drug discovery.
In industrial scenarios, there is widespread use of collaborative robots (cobots), and growing interest is directed at evaluating and measuring the impact of some characteristics of the cobot on the human factor. In the present pilot study, the effect that the production rhythm (C1 - Slow, C2 - Fast, C3 - Adapted to the participant's pace) of a cobot has on the Experiential Locus of Control (ELoC) and the emotional state of 31 participants has been examined. The operators' performance, the degree of basic internal Locus of Control, and the attitude towards the robots were also considered. No difference was found regarding the emotional state and the ELoC in the three conditions, but considering the other psychological variables, a more complex situation emerges. Overall, results seem to indicate a need to consider the person's psychological characteristics to offer a differentiated and optimal interaction experience.
Large language models have been flourishing in the natural language processing (NLP) domain, and their potential for recommendation has been paid much attention to. Despite the intelligence shown by the recommendation-oriented finetuned models, LLMs struggle to fully understand the user behavior patterns due to their innate weakness in interpreting numerical features and the overhead for long context, where the temporal relations among user behaviors, subtle quantitative signals among different ratings, and various side features of items are not well explored. Existing works only fine-tune a sole LLM on given text data without introducing that important information to it, leaving these problems unsolved. In this paper, we propose ELCoRec to Enhance Language understanding with CoPropagation of numerical and categorical features for Recommendation. Concretely, we propose to inject the preference understanding capability into LLM via a GAT expert model where the user preference is better encoded by parallelly propagating the temporal relations, and rating signals as well as various side information of historical items. The parallel propagation mechanism could stabilize heterogeneous features and offer an informative user preference encoding, which is then injected into the language models via soft prompting at the cost of a single token embedding. To further obtain the user's recent interests, we proposed a novel Recent interaction Augmented Prompt (RAP) template. Experiment results over three datasets against strong baselines validate the effectiveness of ELCoRec. The code is available at //anonymous.4open.science/r/CIKM_Code_Repo-E6F5/README.md.
Understanding causality helps to structure interventions to achieve specific goals and enables predictions under interventions. With the growing importance of learning causal relationships, causal discovery tasks have transitioned from using traditional methods to infer potential causal structures from observational data to the field of pattern recognition involved in deep learning. The rapid accumulation of massive data promotes the emergence of causal search methods with brilliant scalability. Existing summaries of causal discovery methods mainly focus on traditional methods based on constraints, scores and FCMs, there is a lack of perfect sorting and elaboration for deep learning-based methods, also lacking some considers and exploration of causal discovery methods from the perspective of variable paradigms. Therefore, we divide the possible causal discovery tasks into three types according to the variable paradigm and give the definitions of the three tasks respectively, define and instantiate the relevant datasets for each task and the final causal model constructed at the same time, then reviews the main existing causal discovery methods for different tasks. Finally, we propose some roadmaps from different perspectives for the current research gaps in the field of causal discovery and point out future research directions.
Many tasks in natural language processing can be viewed as multi-label classification problems. However, most of the existing models are trained with the standard cross-entropy loss function and use a fixed prediction policy (e.g., a threshold of 0.5) for all the labels, which completely ignores the complexity and dependencies among different labels. In this paper, we propose a meta-learning method to capture these complex label dependencies. More specifically, our method utilizes a meta-learner to jointly learn the training policies and prediction policies for different labels. The training policies are then used to train the classifier with the cross-entropy loss function, and the prediction policies are further implemented for prediction. Experimental results on fine-grained entity typing and text classification demonstrate that our proposed method can obtain more accurate multi-label classification results.
We propose a novel attention gate (AG) model for medical imaging that automatically learns to focus on target structures of varying shapes and sizes. Models trained with AGs implicitly learn to suppress irrelevant regions in an input image while highlighting salient features useful for a specific task. This enables us to eliminate the necessity of using explicit external tissue/organ localisation modules of cascaded convolutional neural networks (CNNs). AGs can be easily integrated into standard CNN architectures such as the U-Net model with minimal computational overhead while increasing the model sensitivity and prediction accuracy. The proposed Attention U-Net architecture is evaluated on two large CT abdominal datasets for multi-class image segmentation. Experimental results show that AGs consistently improve the prediction performance of U-Net across different datasets and training sizes while preserving computational efficiency. The code for the proposed architecture is publicly available.
Object detection typically assumes that training and test data are drawn from an identical distribution, which, however, does not always hold in practice. Such a distribution mismatch will lead to a significant performance drop. In this work, we aim to improve the cross-domain robustness of object detection. We tackle the domain shift on two levels: 1) the image-level shift, such as image style, illumination, etc, and 2) the instance-level shift, such as object appearance, size, etc. We build our approach based on the recent state-of-the-art Faster R-CNN model, and design two domain adaptation components, on image level and instance level, to reduce the domain discrepancy. The two domain adaptation components are based on H-divergence theory, and are implemented by learning a domain classifier in adversarial training manner. The domain classifiers on different levels are further reinforced with a consistency regularization to learn a domain-invariant region proposal network (RPN) in the Faster R-CNN model. We evaluate our newly proposed approach using multiple datasets including Cityscapes, KITTI, SIM10K, etc. The results demonstrate the effectiveness of our proposed approach for robust object detection in various domain shift scenarios.
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