Sheng Wang

Honglin Xiong, Sheng Wang, Yitao Zhu et al.

The recent progress of large language models (LLMs), including ChatGPT and GPT-4, in comprehending and responding to human instructions has been remarkable. Nevertheless, these models typically perform better in English and have not been explicitly trained for the medical domain, resulting in suboptimal precision in diagnoses, drug recommendations, and other medical advice. Additionally, training and deploying a dialogue model is still believed to be impossible for hospitals, hindering the promotion of LLMs. To tackle these challenges, we have collected databases of medical dialogues in Chinese with ChatGPT's help and adopted several techniques to train an easy-deploy LLM. Remarkably, we were able to fine-tune the ChatGLM-6B on a single A100 80G in 13 hours, which means having a healthcare-purpose LLM can be very affordable. DoctorGLM is currently an early-stage engineering attempt and contain various mistakes. We are sharing it with the broader community to invite feedback and suggestions to improve its healthcare-focused capabilities: https://github.com/xionghonglin/DoctorGLM.

Xiangyu Zhao, Zengxin Qi, Sheng Wang et al.

Medical image segmentation methods are generally designed as fully-supervised to guarantee model performance, which require a significant amount of expert annotated samples that are high-cost and laborious. Semi-supervised image segmentation can alleviate the problem by utilizing a large number of unlabeled images along with limited labeled images. However, learning a robust representation from numerous unlabeled images remains challenging due to potential noise in pseudo labels and insufficient class separability in feature space, which undermines the performance of current semi-supervised segmentation approaches. To address the issues above, we propose a novel semi-supervised segmentation method named as Rectified Contrastive Pseudo Supervision (RCPS), which combines a rectified pseudo supervision and voxel-level contrastive learning to improve the effectiveness of semi-supervised segmentation. Particularly, we design a novel rectification strategy for the pseudo supervision method based on uncertainty estimation and consistency regularization to reduce the noise influence in pseudo labels. Furthermore, we introduce a bidirectional voxel contrastive loss to the network to ensure intra-class consistency and inter-class contrast in feature space, which increases class separability in the segmentation. The proposed RCPS segmentation method has been validated on two public datasets and an in-house clinical dataset. Experimental results reveal that the proposed method yields better segmentation performance compared with the state-of-the-art methods in semi-supervised medical image segmentation. The source code is available at https://github.com/hsiangyuzhao/RCPS.

Cai Yang, Addie Woicik, Hoifung Poon et al. · stanford

Language models pre-trained on scientific literature corpora have substantially advanced scientific discovery by offering high-quality feature representations for downstream applications. However, these features are often not interpretable, and thus can reveal limited insights to domain experts. Instead of obtaining features from language models, we propose BLIAM, a literature-based data synthesis approach to directly generate training data points that are interpretable and model-agnostic to downstream applications. The key idea of BLIAM is to create prompts using existing training data and then use these prompts to synthesize new data points. BLIAM performs these two steps iteratively as new data points will define more informative prompts and new prompts will in turn synthesize more accurate data points. Notably, literature-based data augmentation might introduce data leakage since labels of test data points in downstream applications might have already been mentioned in the language model corpus. To prevent such leakage, we introduce GDSC-combo, a large-scale drug combination discovery dataset that was published after the biomedical language model was trained. We found that BLIAM substantially outperforms a non-augmented approach and manual prompting in this rigorous data split setting. BLIAM can be further used to synthesize data points for novel drugs and cell lines that were not even measured in biomedical experiments. In addition to the promising prediction performance, the data points synthesized by BLIAM are interpretable and model-agnostic, enabling in silico augmentation for in vitro experiments.

Fenglin Liu, Bang Yang, Chenyu You et al. · oxford

Gene Ontology (GO) is the primary gene function knowledge base that enables computational tasks in biomedicine. The basic element of GO is a term, which includes a set of genes with the same function. Existing research efforts of GO mainly focus on predicting gene term associations. Other tasks, such as generating descriptions of new terms, are rarely pursued. In this paper, we propose a novel task: GO term description generation. This task aims to automatically generate a sentence that describes the function of a GO term belonging to one of the three categories, i.e., molecular function, biological process, and cellular component. To address this task, we propose a Graph-in-Graph network that can efficiently leverage the structural information of GO. The proposed network introduces a two-layer graph: the first layer is a graph of GO terms where each node is also a graph (gene graph). Such a Graph-in-Graph network can derive the biological functions of GO terms and generate proper descriptions. To validate the effectiveness of the proposed network, we build three large-scale benchmark datasets. By incorporating the proposed Graph-in-Graph network, the performances of seven different sequence-to-sequence models can be substantially boosted across all evaluation metrics, with up to 34.7%, 14.5%, and 39.1% relative improvements in BLEU, ROUGE-L, and METEOR, respectively.

Tao Shen, Zhihang Hu, Siqi Sun et al.

Accurate prediction of RNA three-dimensional (3D) structure remains an unsolved challenge. Determining RNA 3D structures is crucial for understanding their functions and informing RNA-targeting drug development and synthetic biology design. The structural flexibility of RNA, which leads to scarcity of experimentally determined data, complicates computational prediction efforts. Here, we present RhoFold+, an RNA language model-based deep learning method that accurately predicts 3D structures of single-chain RNAs from sequences. By integrating an RNA language model pre-trained on ~23.7 million RNA sequences and leveraging techniques to address data scarcity, RhoFold+ offers a fully automated end-to-end pipeline for RNA 3D structure prediction. Retrospective evaluations on RNA-Puzzles and CASP15 natural RNA targets demonstrate RhoFold+'s superiority over existing methods, including human expert groups. Its efficacy and generalizability are further validated through cross-family and cross-type assessments, as well as time-censored benchmarks. Additionally, RhoFold+ predicts RNA secondary structures and inter-helical angles, providing empirically verifiable features that broaden its applicability to RNA structure and function studies.

Xin Wang, Sheng Wang, Honglin Xiong et al.

Magnetic resonance (MR) images collected in 2D clinical protocols typically have large inter-slice spacing, resulting in high in-plane resolution and reduced through-plane resolution. Super-resolution technique can enhance the through-plane resolution of MR images to facilitate downstream visualization and computer-aided diagnosis. However, most existing works train the super-resolution network at a fixed scaling factor, which is not friendly to clinical scenes of varying inter-slice spacing in MR scanning. Inspired by the recent progress in implicit neural representation, we propose a Spatial Attention-based Implicit Neural Representation (SA-INR) network for arbitrary reduction of MR inter-slice spacing. The SA-INR aims to represent an MR image as a continuous implicit function of 3D coordinates. In this way, the SA-INR can reconstruct the MR image with arbitrary inter-slice spacing by continuously sampling the coordinates in 3D space. In particular, a local-aware spatial attention operation is introduced to model nearby voxels and their affinity more accurately in a larger receptive field. Meanwhile, to improve the computational efficiency, a gradient-guided gating mask is proposed for applying the local-aware spatial attention to selected areas only. We evaluate our method on the public HCP-1200 dataset and the clinical knee MR dataset to demonstrate its superiority over other existing methods.

Xin Wang, Zhenrong Shen, Zhiyun Song et al.

Magnetic resonance (MR) images collected in 2D scanning protocols typically have large inter-slice spacing, resulting in high in-plane resolution but reduced through-plane resolution. Super-resolution techniques can reduce the inter-slice spacing of 2D scanned MR images, facilitating the downstream visual experience and computer-aided diagnosis. However, most existing super-resolution methods are trained at a fixed scaling ratio, which is inconvenient in clinical settings where MR scanning may have varying inter-slice spacings. To solve this issue, we propose Hierarchical Feature Conditional Diffusion (HiFi-Diff)} for arbitrary reduction of MR inter-slice spacing. Given two adjacent MR slices and the relative positional offset, HiFi-Diff can iteratively convert a Gaussian noise map into any desired in-between MR slice. Furthermore, to enable fine-grained conditioning, the Hierarchical Feature Extraction (HiFE) module is proposed to hierarchically extract conditional features and conduct element-wise modulation. Our experimental results on the publicly available HCP-1200 dataset demonstrate the high-fidelity super-resolution capability of HiFi-Diff and its efficacy in enhancing downstream segmentation performance.

Zhiyun Song, Zengxin Qi, Xin Wang et al.

Cross-modality synthesis (CMS), super-resolution (SR), and their combination (CMSR) have been extensively studied for magnetic resonance imaging (MRI). Their primary goals are to enhance the imaging quality by synthesizing the desired modality and reducing the slice thickness. Despite the promising synthetic results, these techniques are often tailored to specific tasks, thereby limiting their adaptability to complex clinical scenarios. Therefore, it is crucial to build a unified network that can handle various image synthesis tasks with arbitrary requirements of modality and resolution settings, so that the resources for training and deploying the models can be greatly reduced. However, none of the previous works is capable of performing CMS, SR, and CMSR using a unified network. Moreover, these MRI reconstruction methods often treat alias frequencies improperly, resulting in suboptimal detail restoration. In this paper, we propose a Unified Co-Modulated Alias-free framework (Uni-COAL) to accomplish the aforementioned tasks with a single network. The co-modulation design of the image-conditioned and stochastic attribute representations ensures the consistency between CMS and SR, while simultaneously accommodating arbitrary combinations of input/output modalities and thickness. The generator of Uni-COAL is also designed to be alias-free based on the Shannon-Nyquist signal processing framework, ensuring effective suppression of alias frequencies. Additionally, we leverage the semantic prior of Segment Anything Model (SAM) to guide Uni-COAL, ensuring a more authentic preservation of anatomical structures during synthesis. Experiments on three datasets demonstrate that Uni-COAL outperforms the alternatives in CMS, SR, and CMSR tasks for MR images, which highlights its generalizability to wide-range applications.

Jiahan Li, Tong Chen, Shitong Luo et al.

Peptides, short chains of amino acids, interact with target proteins, making them a unique class of protein-based therapeutics for treating human diseases. Recently, deep generative models have shown great promise in peptide generation. However, several challenges remain in designing effective peptide binders. First, not all residues contribute equally to peptide-target interactions. Second, the generated peptides must adopt valid geometries due to the constraints of peptide bonds. Third, realistic tasks for peptide drug development are still lacking. To address these challenges, we introduce PepHAR, a hot-spot-driven autoregressive generative model for designing peptides targeting specific proteins. Building on the observation that certain hot spot residues have higher interaction potentials, we first use an energy-based density model to fit and sample these key residues. Next, to ensure proper peptide geometry, we autoregressively extend peptide fragments by estimating dihedral angles between residue frames. Finally, we apply an optimization process to iteratively refine fragment assembly, ensuring correct peptide structures. By combining hot spot sampling with fragment-based extension, our approach enables de novo peptide design tailored to a target protein and allows the incorporation of key hot spot residues into peptide scaffolds. Extensive experiments, including peptide design and peptide scaffold generation, demonstrate the strong potential of PepHAR in computational peptide binder design. Source code will be available at https://github.com/Ced3-han/PepHAR.

Yitao Zhu, Yuan Yin, Zhenrong Shen et al.

The growing complexity and scale of visual model pre-training have made developing and deploying multi-task computer-aided diagnosis (CAD) systems increasingly challenging and resource-intensive. Furthermore, the medical imaging community lacks an open-source CAD platform to enable the rapid creation of efficient and extendable diagnostic models. To address these issues, we propose UniCAD, a unified architecture that leverages the robust capabilities of pre-trained vision foundation models to seamlessly handle both 2D and 3D medical images while requiring only minimal task-specific parameters. UniCAD introduces two key innovations: (1) Efficiency: A low-rank adaptation strategy is employed to adapt a pre-trained visual model to the medical image domain, achieving performance on par with fully fine-tuned counterparts while introducing only 0.17% trainable parameters. (2) Plug-and-Play: A modular architecture that combines a frozen foundation model with multiple plug-and-play experts, enabling diverse tasks and seamless functionality expansion. Building on this unified CAD architecture, we establish an open-source platform where researchers can share and access lightweight CAD experts, fostering a more equitable and efficient research ecosystem. Comprehensive experiments across 12 diverse medical datasets demonstrate that UniCAD consistently outperforms existing methods in both accuracy and deployment efficiency. The source code and project page are available at https://mii-laboratory.github.io/UniCAD/.

Bo Jiang, Sheng Wang, Xiao Wang et al.

Recently, Batch DropBlock network (BDB) has demonstrated its effectiveness on person image representation and re-identification task via feature erasing. However, BDB drops the features \textbf{randomly} which may lead to sub-optimal results. In this paper, we propose a novel Self-Thresholding attention guided Adaptive DropBlock network (STADB) for person re-ID which can \textbf{adaptively} erase the most discriminative regions. Specifically, STADB first obtains an attention map by channel-wise pooling and returns a drop mask by thresholding the attention map. Then, the input features and self-thresholding attention guided drop mask are multiplied to generate the dropped feature maps. In addition, STADB utilizes the spatial and channel attention to learn a better feature map and iteratively trains the feature dropping module for person re-ID. Experiments on several benchmark datasets demonstrate that the proposed STADB outperforms many other related methods for person re-ID. The source code of this paper is released at: \textcolor{red}{\url{https://github.com/wangxiao5791509/STADB_ReID}}.

Chaochao Yan, Sheng Wang, Jinyu Yang et al.

Molecule generation is to design new molecules with specific chemical properties and further to optimize the desired chemical properties. Following previous work, we encode molecules into continuous vectors in the latent space and then decode the vectors into molecules under the variational autoencoder (VAE) framework. We investigate the posterior collapse problem of current RNN-based VAEs for molecule sequence generation. For the first time, we find that underestimated reconstruction loss leads to posterior collapse, and provide both theoretical and experimental evidence. We propose an effective and efficient solution to fix the problem and avoid posterior collapse. Without bells and whistles, our method achieves SOTA reconstruction accuracy and competitive validity on the ZINC 250K dataset. When generating 10,000 unique valid SMILES from random prior sampling, it costs JT-VAE1450s while our method only needs 9s. Our implementation is at https://github.com/chaoyan1037/Re-balanced-VAE.

Zihao Zhao, Sheng Wang, Qian Wang et al.

Obtaining large-scale radiology reports can be difficult for medical images due to various reasons, limiting the effectiveness of contrastive pre-training in the medical image domain and underscoring the need for alternative methods. In this paper, we propose eye-tracking as an alternative to text reports, as it allows for the passive collection of gaze signals without disturbing radiologist's routine diagnosis process. By tracking the gaze of radiologists as they read and diagnose medical images, we can understand their visual attention and clinical reasoning. When a radiologist has similar gazes for two medical images, it may indicate semantic similarity for diagnosis, and these images should be treated as positive pairs when pre-training a computer-assisted diagnosis (CAD) network through contrastive learning. Accordingly, we introduce the Medical contrastive Gaze Image Pre-training (McGIP) as a plug-and-play module for contrastive learning frameworks. McGIP uses radiologist's gaze to guide contrastive pre-training. We evaluate our method using two representative types of medical images and two common types of gaze data. The experimental results demonstrate the practicality of McGIP, indicating its high potential for various clinical scenarios and applications.

Sheng Wang, Ge Sun, Fulong Ma et al.

Evaluating and training autonomous driving systems require diverse and scalable corner cases. However, most existing scene generation methods lack controllability, accuracy, and versatility, resulting in unsatisfactory generation results. Inspired by DragGAN in image generation, we propose DragTraffic, a generalized, interactive, and controllable traffic scene generation framework based on conditional diffusion. DragTraffic enables non-experts to generate a variety of realistic driving scenarios for different types of traffic agents through an adaptive mixture expert architecture. We employ a regression model to provide a general initial solution and a refinement process based on the conditional diffusion model to ensure diversity. User-customized context is introduced through cross-attention to ensure high controllability. Experiments on a real-world driving dataset show that DragTraffic outperforms existing methods in terms of authenticity, diversity, and freedom. Demo videos and code are available at https://chantsss.github.io/Dragtraffic/.

Mengjie Xu, Yitao Zhu, Haotian Jiang et al.

Multi-view object tracking (MVOT) offers promising solutions to challenges such as occlusion and target loss, which are common in traditional single-view tracking. However, progress has been limited by the lack of comprehensive multi-view datasets and effective cross-view integration methods. To overcome these limitations, we compiled a Multi-View object Tracking (MVTrack) dataset of 234K high-quality annotated frames featuring 27 distinct objects across various scenes. In conjunction with this dataset, we introduce a novel MVOT method, Multi-View Integration Tracker (MITracker), to efficiently integrate multi-view object features and provide stable tracking outcomes. MITracker can track any object in video frames of arbitrary length from arbitrary viewpoints. The key advancements of our method over traditional single-view approaches come from two aspects: (1) MITracker transforms 2D image features into a 3D feature volume and compresses it into a bird's eye view (BEV) plane, facilitating inter-view information fusion; (2) we propose an attention mechanism that leverages geometric information from fused 3D feature volume to refine the tracking results at each view. MITracker outperforms existing methods on the MVTrack and GMTD datasets, achieving state-of-the-art performance. The code and the new dataset will be available at https://mii-laboratory.github.io/MITracker/.

Tong Chen, Sheng Wang

With the increasingly available large-scale cancer genomics datasets, machine learning approaches have played an important role in revealing novel insights into cancer development. Existing methods have shown encouraging performance in identifying genes that are predictive for cancer survival, but are still limited in modeling the distribution over genes. Here, we proposed a novel method that can simulate the gene expression distribution at any given time point, including those that are out of the range of the observed time points. In order to model the irregular time series where each patient is one observation, we integrated a neural ordinary differential equation (neural ODE) with cox regression into our framework. We evaluated our method on eight cancer types on TCGA and observed a substantial improvement over existing approaches. Our visualization results and further analysis indicate how our method can be used to simulate expression at the early cancer stage, offering the possibility for early cancer identification.

Fenglin Liu, Chenyu You, Xian Wu et al.

Medical report generation, which aims to automatically generate a long and coherent report of a given medical image, has been receiving growing research interests. Existing approaches mainly adopt a supervised manner and heavily rely on coupled image-report pairs. However, in the medical domain, building a large-scale image-report paired dataset is both time-consuming and expensive. To relax the dependency on paired data, we propose an unsupervised model Knowledge Graph Auto-Encoder (KGAE) which accepts independent sets of images and reports in training. KGAE consists of a pre-constructed knowledge graph, a knowledge-driven encoder and a knowledge-driven decoder. The knowledge graph works as the shared latent space to bridge the visual and textual domains; The knowledge-driven encoder projects medical images and reports to the corresponding coordinates in this latent space and the knowledge-driven decoder generates a medical report given a coordinate in this space. Since the knowledge-driven encoder and decoder can be trained with independent sets of images and reports, KGAE is unsupervised. The experiments show that the unsupervised KGAE generates desirable medical reports without using any image-report training pairs. Moreover, KGAE can also work in both semi-supervised and supervised settings, and accept paired images and reports in training. By further fine-tuning with image-report pairs, KGAE consistently outperforms the current state-of-the-art models on two datasets.

Jinxin Lv, Zhiwei Wang, Hongkuan Shi et al.

Registration of brain MRI images requires to solve a deformation field, which is extremely difficult in aligning intricate brain tissues, e.g., subcortical nuclei, etc. Existing efforts resort to decomposing the target deformation field into intermediate sub-fields with either tiny motions, i.e., progressive registration stage by stage, or lower resolutions, i.e., coarse-to-fine estimation of the full-size deformation field. In this paper, we argue that those efforts are not mutually exclusive, and propose a unified framework for robust brain MRI registration in both progressive and coarse-to-fine manners simultaneously. Specifically, building on a dual-encoder U-Net, the fixed-moving MRI pair is encoded and decoded into multi-scale deformation sub-fields from coarse to fine. Each decoding block contains two proposed novel modules: i) in Deformation Field Integration (DFI), a single integrated sub-field is calculated, warping by which is equivalent to warping progressively by sub-fields from all previous decoding blocks, and ii) in Non-rigid Feature Fusion (NFF), features of the fixed-moving pair are aligned by DFI-integrated sub-field, and then fused to predict a finer sub-field. Leveraging both DFI and NFF, the target deformation field is factorized into multi-scale sub-fields, where the coarser fields alleviate the estimate of a finer one and the finer field learns to make up those misalignments insolvable by previous coarser ones. The extensive and comprehensive experimental results on both private and public datasets demonstrate a superior registration performance of brain MRI images over progressive registration only and coarse-to-fine estimation only, with an increase by at most 8% in the average Dice.

Qin Wang, Jun Wei, Boyuan Wang et al.

Protein secondary structure prediction (PSSP) is essential for protein function analysis. However, for low homologous proteins, the PSSP suffers from insufficient input features. In this paper, we explicitly import external self-supervised knowledge for low homologous PSSP under the guidance of residue-wise profile fusion. In practice, we firstly demonstrate the superiority of profile over Position-Specific Scoring Matrix (PSSM) for low homologous PSSP. Based on this observation, we introduce the novel self-supervised BERT features as the pseudo profile, which implicitly involves the residue distribution in all native discovered sequences as the complementary features. Further-more, a novel residue-wise attention is specially designed to adaptively fuse different features (i.e.,original low-quality profile, BERT based pseudo profile), which not only takes full advantage of each feature but also avoids noise disturbance. Be-sides, the feature consistency loss is proposed to accelerate the model learning from multiple semantic levels. Extensive experiments confirm that our method outperforms state-of-the-arts (i.e.,4.7%forextremely low homologous cases on BC40 dataset).

Jun Wei, Qin Wang, Zhen Li et al.

Weakly supervised object localization (WSOL) aims to localize objects by only utilizing image-level labels. Class activation maps (CAMs) are the commonly used features to achieve WSOL. However, previous CAM-based methods did not take full advantage of the shallow features, despite their importance for WSOL. Because shallow features are easily buried in background noise through conventional fusion. In this paper, we propose a simple but effective Shallow feature-aware Pseudo supervised Object Localization (SPOL) model for accurate WSOL, which makes the utmost of low-level features embedded in shallow layers. In practice, our SPOL model first generates the CAMs through a novel element-wise multiplication of shallow and deep feature maps, which filters the background noise and generates sharper boundaries robustly. Besides, we further propose a general class-agnostic segmentation model to achieve the accurate object mask, by only using the initial CAMs as the pseudo label without any extra annotation. Eventually, a bounding box extractor is applied to the object mask to locate the target. Experiments verify that our SPOL outperforms the state-of-the-art on both CUB-200 and ImageNet-1K benchmarks, achieving 93.44% and 67.15% (i.e., 3.93% and 2.13% improvement) Top-5 localization accuracy, respectively.

Yifan Wang, Suyao Tang, Yuntong Lei et al.

Heterogeneous information network has been widely used to alleviate sparsity and cold start problems in recommender systems since it can model rich context information in user-item interactions. Graph neural network is able to encode this rich context information through propagation on the graph. However, existing heterogeneous graph neural networks neglect entanglement of the latent factors stemming from different aspects. Moreover, meta paths in existing approaches are simplified as connecting paths or side information between node pairs, overlooking the rich semantic information in the paths. In this paper, we propose a novel disentangled heterogeneous graph attention network DisenHAN for top-$N$ recommendation, which learns disentangled user/item representations from different aspects in a heterogeneous information network. In particular, we use meta relations to decompose high-order connectivity between node pairs and propose a disentangled embedding propagation layer which can iteratively identify the major aspect of meta relations. Our model aggregates corresponding aspect features from each meta relation for the target user/item. With different layers of embedding propagation, DisenHAN is able to explicitly capture the collaborative filtering effect semantically. Extensive experiments on three real-world datasets show that DisenHAN consistently outperforms state-of-the-art approaches. We further demonstrate the effectiveness and interpretability of the learned disentangled representations via insightful case studies and visualization.

Jiaxiang Wu, Shitong Luo, Tao Shen et al.

Accurate protein structure prediction from amino-acid sequences is critical to better understanding the protein function. Recent advances in this area largely benefit from more precise inter-residue distance and orientation predictions, powered by deep neural networks. However, the structure optimization procedure is still dominated by traditional tools, e.g. Rosetta, where the structure is solved via minimizing a pre-defined statistical energy function (with optional prediction-based restraints). Such energy function may not be optimal in formulating the whole conformation space of proteins. In this paper, we propose a fully-differentiable approach for protein structure optimization, guided by a data-driven generative network. This network is trained in a denoising manner, attempting to predict the correction signal from corrupted distance matrices between Ca atoms. Once the network is well trained, Langevin dynamics based sampling is adopted to gradually optimize structures from random initialization. Extensive experiments demonstrate that our EBM-Fold approach can efficiently produce high-quality decoys, compared against traditional Rosetta-based structure optimization routines.

Liangzhen Zheng, Haidong Lan, Tao Shen et al.

Protein structure prediction has been a grand challenge for over 50 years, owing to its broad scientific and application interests. There are two primary types of modeling algorithms, template-free modeling and template-based modeling. The latter one is suitable for easy prediction tasks and is widely adopted in computer-aided drug discoveries for drug design and screening. Although it has been several decades since its first edition, the current template-based modeling approach suffers from two critical problems: 1) there are many missing regions in the template-query sequence alignment, and 2) the accuracy of the distance pairs from different regions of the template varies, and this information is not well introduced into the modeling. To solve these two problems, we propose a structural optimization process based on template modeling, introducing two neural network models to predict the distance information of the missing regions and the accuracy of the distance pairs of different regions in the template modeling structure. The predicted distances and residue pairwise-specific deviations are incorporated into the potential energy function for structural optimization, which significantly improves the qualities of the original template modeling decoys.

Linchao Bao, Xiangkai Lin, Yajing Chen et al.

We present a fully automatic system that can produce high-fidelity, photo-realistic 3D digital human heads with a consumer RGB-D selfie camera. The system only needs the user to take a short selfie RGB-D video while rotating his/her head, and can produce a high quality head reconstruction in less than 30 seconds. Our main contribution is a new facial geometry modeling and reflectance synthesis procedure that significantly improves the state-of-the-art. Specifically, given the input video a two-stage frame selection procedure is first employed to select a few high-quality frames for reconstruction. Then a differentiable renderer based 3D Morphable Model (3DMM) fitting algorithm is applied to recover facial geometries from multiview RGB-D data, which takes advantages of a powerful 3DMM basis constructed with extensive data generation and perturbation. Our 3DMM has much larger expressive capacities than conventional 3DMM, allowing us to recover more accurate facial geometry using merely linear basis. For reflectance synthesis, we present a hybrid approach that combines parametric fitting and CNNs to synthesize high-resolution albedo/normal maps with realistic hair/pore/wrinkle details. Results show that our system can produce faithful 3D digital human faces with extremely realistic details. The main code and the newly constructed 3DMM basis is publicly available.

Ruoyu Li, Sheng Wang, Feiyun Zhu et al.

Graph Convolutional Neural Networks (Graph CNNs) are generalizations of classical CNNs to handle graph data such as molecular data, point could and social networks. Current filters in graph CNNs are built for fixed and shared graph structure. However, for most real data, the graph structures varies in both size and connectivity. The paper proposes a generalized and flexible graph CNN taking data of arbitrary graph structure as input. In that way a task-driven adaptive graph is learned for each graph data while training. To efficiently learn the graph, a distance metric learning is proposed. Extensive experiments on nine graph-structured datasets have demonstrated the superior performance improvement on both convergence speed and predictive accuracy.

Sheng Wang, Zhen Li, Yizhou Yu et al.

Computational elucidation of membrane protein (MP) structures is challenging partially due to lack of sufficient solved structures for homology modeling. Here we describe a high-throughput deep transfer learning method that first predicts MP contacts by learning from non-membrane proteins (non-MPs) and then predicting three-dimensional structure models using the predicted contacts as distance restraints. Tested on 510 non-redundant MPs, our method has contact prediction accuracy at least 0.18 better than existing methods, predicts correct folds for 218 MPs (TMscore at least 0.6), and generates three-dimensional models with RMSD less than 4 Angstrom and 5 Angstrom for 57 and 108 MPs, respectively. A rigorous blind test in the continuous automated model evaluation (CAMEO) project shows that our method predicted high-resolution three-dimensional models for two recent test MPs of 210 residues with RMSD close to 2 Angstrom. We estimated that our method could predict correct folds for between 1,345 and 1,871 reviewed human multi-pass MPs including a few hundred new folds, which shall facilitate the discovery of drugs targeting at membrane proteins.

Sheng Wang, Siqi Sun, Zhen Li et al.

Recently exciting progress has been made on protein contact prediction, but the predicted contacts for proteins without many sequence homologs is still of low quality and not very useful for de novo structure prediction. This paper presents a new deep learning method that predicts contacts by integrating both evolutionary coupling (EC) and sequence conservation information through an ultra-deep neural network formed by two deep residual networks. This deep neural network allows us to model very complex sequence-contact relationship as well as long-range inter-contact correlation. Our method greatly outperforms existing contact prediction methods and leads to much more accurate contact-assisted protein folding. Tested on three datasets of 579 proteins, the average top L long-range prediction accuracy obtained our method, the representative EC method CCMpred and the CASP11 winner MetaPSICOV is 0.47, 0.21 and 0.30, respectively; the average top L/10 long-range accuracy of our method, CCMpred and MetaPSICOV is 0.77, 0.47 and 0.59, respectively. Ab initio folding using our predicted contacts as restraints can yield correct folds (i.e., TMscore>0.6) for 203 test proteins, while that using MetaPSICOV- and CCMpred-predicted contacts can do so for only 79 and 62 proteins, respectively. Further, our contact-assisted models have much better quality than template-based models. Using our predicted contacts as restraints, we can (ab initio) fold 208 of the 398 membrane proteins with TMscore>0.5. By contrast, when the training proteins of our method are used as templates, homology modeling can only do so for 10 of them. One interesting finding is that even if we do not train our prediction models with any membrane proteins, our method works very well on membrane protein prediction. Finally, in recent blind CAMEO benchmark our method successfully folded 5 test proteins with a novel fold.

Sheng Wang, Jian Peng, Jianzhu Ma et al.

Protein secondary structure (SS) prediction is important for studying protein structure and function. When only the sequence (profile) information is used as input feature, currently the best predictors can obtain ~80% Q3 accuracy, which has not been improved in the past decade. Here we present DeepCNF (Deep Convolutional Neural Fields) for protein SS prediction. DeepCNF is a Deep Learning extension of Conditional Neural Fields (CNF), which is an integration of Conditional Random Fields (CRF) and shallow neural networks. DeepCNF can model not only complex sequence-structure relationship by a deep hierarchical architecture, but also interdependency between adjacent SS labels, so it is much more powerful than CNF. Experimental results show that DeepCNF can obtain ~84% Q3 accuracy, ~85% SOV score, and ~72% Q8 accuracy, respectively, on the CASP and CAMEO test proteins, greatly outperforming currently popular predictors. As a general framework, DeepCNF can be used to predict other protein structure properties such as contact number, disorder regions, and solvent accessibility.

Sheng Wang, Siqi Sun, Jinbo Xu

Deep Convolutional Neural Networks (DCNN) has shown excellent performance in a variety of machine learning tasks. This manuscript presents Deep Convolutional Neural Fields (DeepCNF), a combination of DCNN with Conditional Random Field (CRF), for sequence labeling with highly imbalanced label distribution. The widely-used training methods, such as maximum-likelihood and maximum labelwise accuracy, do not work well on highly imbalanced data. To handle this, we present a new training algorithm called maximum-AUC for DeepCNF. That is, we train DeepCNF by directly maximizing the empirical Area Under the ROC Curve (AUC), which is an unbiased measurement for imbalanced data. To fulfill this, we formulate AUC in a pairwise ranking framework, approximate it by a polynomial function and then apply a gradient-based procedure to optimize it. We then test our AUC-maximized DeepCNF on three very different protein sequence labeling tasks: solvent accessibility prediction, 8-state secondary structure prediction, and disorder prediction. Our experimental results confirm that maximum-AUC greatly outperforms the other two training methods on 8-state secondary structure prediction and disorder prediction since their label distributions are highly imbalanced and also have similar performance as the other two training methods on the solvent accessibility prediction problem which has three equally-distributed labels. Furthermore, our experimental results also show that our AUC-trained DeepCNF models greatly outperform existing popular predictors of these three tasks.

Wu-Jun Li, Sheng Wang, Wang-Cheng Kang

Recent years have witnessed wide application of hashing for large-scale image retrieval. However, most existing hashing methods are based on hand-crafted features which might not be optimally compatible with the hashing procedure. Recently, deep hashing methods have been proposed to perform simultaneous feature learning and hash-code learning with deep neural networks, which have shown better performance than traditional hashing methods with hand-crafted features. Most of these deep hashing methods are supervised whose supervised information is given with triplet labels. For another common application scenario with pairwise labels, there have not existed methods for simultaneous feature learning and hash-code learning. In this paper, we propose a novel deep hashing method, called deep pairwise-supervised hashing(DPSH), to perform simultaneous feature learning and hash-code learning for applications with pairwise labels. Experiments on real datasets show that our DPSH method can outperform other methods to achieve the state-of-the-art performance in image retrieval applications.

Jianzhu Ma, Sheng Wang, Zhiyong Wang et al.

Sequence-based protein homology detection has been extensively studied and so far the most sensitive method is based upon comparison of protein sequence profiles, which are derived from multiple sequence alignment (MSA) of sequence homologs in a protein family. A sequence profile is usually represented as a position-specific scoring matrix (PSSM) or an HMM (Hidden Markov Model) and accordingly PSSM-PSSM or HMM-HMM comparison is used for homolog detection. This paper presents a new homology detection method MRFalign, consisting of three key components: 1) a Markov Random Fields (MRF) representation of a protein family; 2) a scoring function measuring similarity of two MRFs; and 3) an efficient ADMM (Alternating Direction Method of Multipliers) algorithm aligning two MRFs. Compared to HMM that can only model very short-range residue correlation, MRFs can model long-range residue interaction pattern and thus, encode information for the global 3D structure of a protein family. Consequently, MRF-MRF comparison for remote homology detection shall be much more sensitive than HMM-HMM or PSSM-PSSM comparison. Experiments confirm that MRFalign outperforms several popular HMM or PSSM-based methods in terms of both alignment accuracy and remote homology detection and that MRFalign works particularly well for mainly beta proteins. For example, tested on the benchmark SCOP40 (8353 proteins) for homology detection, PSSM-PSSM and HMM-HMM succeed on 48% and 52% of proteins, respectively, at superfamily level, and on 15% and 27% of proteins, respectively, at fold level. In contrast, MRFalign succeeds on 57.3% and 42.5% of proteins at superfamily and fold level, respectively. This study implies that long-range residue interaction patterns are very helpful for sequence-based homology detection. The software is available for download at http://raptorx.uchicago.edu/download/.