Inter- and intra-uncertainty based feature aggregation model for semi-supervised histopathology image segmentation

Acquiring pixel-level annotations is often limited in applications such as histology studies that require domain expertise. Various semi-supervised learning approaches have been developed to work with limited ground truth annotations, such as the popular teacher-student models. However, hierarchical prediction uncertainty within the student model (intra-uncertainty) and image prediction uncertainty (inter-uncertainty) have not been fully utilized by existing methods. To address these issues, we first propose a novel inter- and intra-uncertainty regularization method to measure and constrain both inter- and intra-inconsistencies in the teacher-student architecture. We also propose a new two-stage network with pseudo-mask guided feature aggregation (PG-FANet) as the segmentation model. The two-stage structure complements with the uncertainty regularization strategy to avoid introducing extra modules in solving uncertainties and the aggregation mechanisms enable multi-scale and multi-stage feature integration. Comprehensive experimental results over the MoNuSeg and CRAG datasets show that our PG-FANet outperforms other state-of-the-art methods and our semi-supervised learning framework yields competitive performance with a limited amount of labeled data.

MolCAP: Molecular Chemical reActivity pretraining and prompted-finetuning enhanced molecular representation learning

Molecular representation learning (MRL) is a fundamental task for drug discovery. However, previous deep-learning (DL) methods focus excessively on learning robust inner-molecular representations by mask-dominated pretraining framework, neglecting abundant chemical reactivity molecular relationships that have been demonstrated as the determining factor for various molecular property prediction tasks. Here, we present MolCAP to promote MRL, a graph pretraining Transformer based on chemical reactivity (IMR) knowledge with prompted finetuning. Results show that MolCAP outperforms comparative methods based on traditional molecular pretraining framework, in 13 publicly available molecular datasets across a diversity of biomedical tasks. Prompted by MolCAP, even basic graph neural networks are capable of achieving surprising performance that outperforms previous models, indicating the promising prospect of applying reactivity information for MRL. In addition, manual designed molecular templets are potential to uncover the dataset bias. All in all, we expect our MolCAP to gain more chemical meaningful insights for the entire process of drug discovery.

Multi-view deep learning based molecule design and structural optimization accelerates the SARS-CoV-2 inhibitor discovery

In this work, we propose MEDICO, a Multi-viEw Deep generative model for molecule generation, structural optimization, and the SARS-CoV-2 Inhibitor disCOvery. To the best of our knowledge, MEDICO is the first-of-this-kind graph generative model that can generate molecular graphs similar to the structure of targeted molecules, with a multi-view representation learning framework to sufficiently and adaptively learn comprehensive structural semantics from targeted molecular topology and geometry. We show that our MEDICO significantly outperforms the state-of-the-art methods in generating valid, unique, and novel molecules under benchmarking comparisons. In particular, we showcase the multi-view deep learning model enables us to generate not only the molecules structurally similar to the targeted molecules but also the molecules with desired chemical properties, demonstrating the strong capability of our model in exploring the chemical space deeply. Moreover, case study results on targeted molecule generation for the SARS-CoV-2 main protease (Mpro) show that by integrating molecule docking into our model as chemical priori, we successfully generate new small molecules with desired drug-like properties for the Mpro, potentially accelerating the de novo design of Covid-19 drugs. Further, we apply MEDICO to the structural optimization of three well-known Mpro inhibitors (N3, 11a, and GC376) and achieve ~88% improvement in their binding affinity to Mpro, demonstrating the application value of our model for the development of therapeutics for SARS-CoV-2 infection.

MSMG-Net: Multi-scale Multi-grained Supervised Metworks for Multi-task Image Manipulation Detection and Localization

With the rapid advances of image editing techniques in recent years, image manipulation detection has attracted considerable attention since the increasing security risks posed by tampered images. To address these challenges, a novel multi-scale multi-grained deep network (MSMG-Net) is proposed to automatically identify manipulated regions. In our MSMG-Net, a parallel multi-scale feature extraction structure is used to extract multi-scale features. Then the multi-grained feature learning is utilized to perceive object-level semantics relation of multi-scale features by introducing the shunted self-attention. To fuse multi-scale multi-grained features, global and local feature fusion block are designed for manipulated region segmentation by a bottom-up approach and multi-level feature aggregation block is designed for edge artifacts detection by a top-down approach. Thus, MSMG-Net can effectively perceive the object-level semantics and encode the edge artifact. Experimental results on five benchmark datasets justify the superior performance of the proposed method, outperforming state-of-the-art manipulation detection and localization methods. Extensive ablation experiments and feature visualization demonstrate the multi-scale multi-grained learning can present effective visual representations of manipulated regions. In addition, MSMG-Net shows better robustness when various post-processing methods further manipulate images.

EOCSA: Predicting Prognosis of Epithelial Ovarian Cancer with Whole Slide Histopathological Images

Ovarian cancer is one of the most serious cancers that threaten women around the world. Epithelial ovarian cancer (EOC), as the most commonly seen subtype of ovarian cancer, has rather high mortality rate and poor prognosis among various gynecological cancers. Survival analysis outcome is able to provide treatment advices to doctors. In recent years, with the development of medical imaging technology, survival prediction approaches based on pathological images have been proposed. In this study, we designed a deep framework named EOCSA which analyzes the prognosis of EOC patients based on pathological whole slide images (WSIs). Specifically, we first randomly extracted patches from WSIs and grouped them into multiple clusters. Next, we developed a survival prediction model, named DeepConvAttentionSurv (DCAS), which was able to extract patch-level features, removed less discriminative clusters and predicted the EOC survival precisely. Particularly, channel attention, spatial attention, and neuron attention mechanisms were used to improve the performance of feature extraction. Then patient-level features were generated from our weight calculation method and the survival time was finally estimated using LASSO-Cox model. The proposed EOCSA is efficient and effective in predicting prognosis of EOC and the DCAS ensures more informative and discriminative features can be extracted. As far as we know, our work is the first to analyze the survival of EOC based on WSIs and deep neural network technologies. The experimental results demonstrate that our proposed framework has achieved state-of-the-art performance of 0.980 C-index. The implementation of the approach can be found at https://github.com/RanSuLab/EOCprognosis.

MechRetro is a chemical-mechanism-driven graph learning framework for interpretable retrosynthesis prediction and pathway planning

Leveraging artificial intelligence for automatic retrosynthesis speeds up organic pathway planning in digital laboratories. However, existing deep learning approaches are unexplainable, like "black box" with few insights, notably limiting their applications in real retrosynthesis scenarios. Here, we propose MechRetro, a chemical-mechanism-driven graph learning framework for interpretable retrosynthetic prediction and pathway planning, which learns several retrosynthetic actions to simulate a reverse reaction via elaborate self-adaptive joint learning. By integrating chemical knowledge as prior information, we design a novel Graph Transformer architecture to adaptively learn discriminative and chemically meaningful molecule representations, highlighting the strong capacity in molecule feature representation learning. We demonstrate that MechRetro outperforms the state-of-the-art approaches for retrosynthetic prediction with a large margin on large-scale benchmark datasets. Extending MechRetro to the multi-step retrosynthesis analysis, we identify efficient synthetic routes via an interpretable reasoning mechanism, leading to a better understanding in the realm of knowledgeable synthetic chemists. We also showcase that MechRetro discovers a novel pathway for protokylol, along with energy scores for uncertainty assessment, broadening the applicability for practical scenarios. Overall, we expect MechRetro to provide meaningful insights for high-throughput automated organic synthesis in drug discovery.

Domain adaptation based self-correction model for COVID-19 infection segmentation in CT images

The capability of generalization to unseen domains is crucial for deep learning models when considering real-world scenarios. However, current available medical image datasets, such as those for COVID-19 CT images, have large variations of infections and domain shift problems. To address this issue, we propose a prior knowledge driven domain adaptation and a dual-domain enhanced self-correction learning scheme. Based on the novel learning schemes, a domain adaptation based self-correction model (DASC-Net) is proposed for COVID-19 infection segmentation on CT images. DASC-Net consists of a novel attention and feature domain enhanced domain adaptation model (AFD-DA) to solve the domain shifts and a self-correction learning process to refine segmentation results. The innovations in AFD-DA include an image-level activation feature extractor with attention to lung abnormalities and a multi-level discrimination module for hierarchical feature domain alignment. The proposed self-correction learning process adaptively aggregates the learned model and corresponding pseudo labels for the propagation of aligned source and target domain information to alleviate the overfitting to noises caused by pseudo labels. Extensive experiments over three publicly available COVID-19 CT datasets demonstrate that DASC-Net consistently outperforms state-of-the-art segmentation, domain shift, and coronavirus infection segmentation methods. Ablation analysis further shows the effectiveness of the major components in our model. The DASC-Net enriches the theory of domain adaptation and self-correction learning in medical imaging and can be generalized to multi-site COVID-19 infection segmentation on CT images for clinical deployment.

RA-UNet: A hybrid deep attention-aware network to extract liver and tumor in CT scans

Automatic extraction of liver and tumor from CT volumes is a challenging task due to their heterogeneous and diffusive shapes. Recently, 2D and 3D deep convolutional neural networks have become popular in medical image segmentation tasks because of the utilization of large labeled datasets to learn hierarchical features. However, 3D networks have some drawbacks due to their high cost on computational resources. In this paper, we propose a 3D hybrid residual attention-aware segmentation method, named RA-UNet, to precisely extract the liver volume of interests (VOI) and segment tumors from the liver VOI. The proposed network has a basic architecture as a 3D U-Net which extracts contextual information combining low-level feature maps with high-level ones. Attention modules are stacked so that the attention-aware features change adaptively as the network goes "very deep" and this is made possible by residual learning. This is the first work that an attention residual mechanism is used to process medical volumetric images. We evaluated our framework on the public MICCAI 2017 Liver Tumor Segmentation dataset and the 3DIRCADb dataset. The results show that our architecture outperforms other state-of-the-art methods. We also extend our RA-UNet to brain tumor segmentation on the BraTS2018 and BraTS2017 datasets, and the results indicate that RA-UNet achieves good performance on a brain tumor segmentation task as well.

DUNet: A deformable network for retinal vessel segmentation

Automatic segmentation of retinal vessels in fundus images plays an important role in the diagnosis of some diseases such as diabetes and hypertension. In this paper, we propose Deformable U-Net (DUNet), which exploits the retinal vessels' local features with a U-shape architecture, in an end to end manner for retinal vessel segmentation. Inspired by the recently introduced deformable convolutional networks, we integrate the deformable convolution into the proposed network. The DUNet, with upsampling operators to increase the output resolution, is designed to extract context information and enable precise localization by combining low-level feature maps with high-level ones. Furthermore, DUNet captures the retinal vessels at various shapes and scales by adaptively adjusting the receptive fields according to vessels' scales and shapes. Three public datasets DRIVE, STARE and CHASE_DB1 are used to train and test our model. Detailed comparisons between the proposed network and the deformable neural network, U-Net are provided in our study. Results show that more detailed vessels are extracted by DUNet and it exhibits state-of-the-art performance for retinal vessel segmentation with a global accuracy of 0.9697/0.9722/0.9724 and AUC of 0.9856/0.9868/0.9863 on DRIVE, STARE and CHASE_DB1 respectively. Moreover, to show the generalization ability of the DUNet, we used another two retinal vessel data sets, one is named WIDE and the other is a synthetic data set with diverse styles, named SYNTHE, to qualitatively and quantitatively analyzed and compared with other methods. Results indicates that DUNet outperforms other state-of-the-arts.