UWAFA-GAN: Ultra-Wide-Angle Fluorescein Angiography Transformation via Multi-scale Generation and Registration Enhancement.

Fundus photography, in combination with the ultra-wide-angle fundus (UWF) techniques, becomes an indispensable diagnostic tool in clinical settings by offering a more comprehensive view of the retina. Nonetheless, UWF fluorescein angiography (UWF-FA) necessitates the administration of a fluorescent dye via injection into the patient's hand or elbow unlike UWF scanning laser ophthalmoscopy (UWF-SLO). To mitigate potential adverse effects associated with injections, researchers have proposed the development of cross-modality medical image generation algorithms capable of converting UWF-SLO images into their UWF-FA counterparts. Current image generation techniques applied to fundus photography encounter difficulties in producing high-resolution retinal images, particularly in capturing minute vascular lesions. To address these issues, we introduce a novel conditional generative adversarial network (UWAFA-GAN) to synthesize UWF-FA from UWF-SLO. This approach employs multi-scale generators and an attention transmit module to efficiently extract both global structures and local lesions. Additionally, to counteract the image blurriness issue that arises from training with misaligned data, a registration module is integrated within this framework. Our method performs non-trivially on inception scores and details generation. Clinical user studies further indicate that the UWF-FA images generated by UWAFA-GAN are clinically comparable to authentic images in terms of diagnostic reliability. Empirical evaluations on our proprietary UWF image datasets elucidate that UWAFA-GAN outperforms extant methodologies. The code is accessible at https://github.com/Tinysqua/UWAFA-GAN.

HybAVPnet: a Novel Hybrid Network Architecture for Antiviral Peptides Prediction.

Viruses pose a great threat to human production and life, thus the research and development of antiviral drugs is urgently needed. Antiviral peptides play an important role in drug design and development. Compared with the time-consuming and laborious wet chemical experiment methods, it is critical to use computational methods to predict antiviral peptides accurately and rapidly. However, due to limited data, accurate prediction of antiviral peptides is still challenging and extracting effective feature representations from sequences is crucial for creating accurate models. This study introduces a novel two-step approach, named HybAVPnet, to predict antiviral peptides with a hybrid network architecture based on neural networks and traditional machine learning methods. We adopted a stacking-like structure to capture both the long-term dependencies and local evolution information to achieve a comprehensive and diverse prediction using the predicted labels and probabilities. Using an ensemble technique with the different kinds of features can reduce the variance without increasing the bias. The experimental result shows HybAVPnet can achieve better and more robust performance compared with the state-of-the-art methods, which makes it useful for the research and development of antiviral drugs. Meanwhile, it can also be extended to other peptide recognition problems because of its generalization ability.

Identification of important gene signatures in schizophrenia through feature fusion and genetic algorithm.

Schizophrenia is a debilitating psychiatric disorder that can significantly affect a patient's quality of life and lead to permanent brain damage. Although medical research has identified certain genetic risk factors, the specific pathogenesis of the disorder remains unclear. Despite the prevalence of research employing magnetic resonance imaging, few studies have focused on the gene level and gene expression profile involving a large number of screened genes. However, the high dimensionality of genetic data presents a great challenge to accurately modeling the data. To tackle the current challenges, this study presents a novel feature selection strategy that utilizes heuristic feature fusion and a multi-objective optimization genetic algorithm. The goal is to improve classification performance and identify the key gene subset for schizophrenia diagnostics. Traditional gene screening techniques are inadequate for accurately determining the precise number of key genes associated with schizophrenia. Our innovative approach integrates a filter-based feature selection method to reduce data dimensionality and a multi-objective optimization genetic algorithm for improved classification tasks. By combining the filtering and wrapper methods, our strategy leverages their respective strengths in a deliberate manner, leading to superior classification accuracy and a more efficient selection of relevant genes. This approach has demonstrated significant improvements in classification results across 11 out of 14 relevant datasets. The performance on the remaining three datasets is comparable to the existing methods. Furthermore, visual and enrichment analyses have confirmed the practicality of our proposed method as a promising tool for the early detection of schizophrenia.

TDFFM: Transformer and Deep Forest Fusion Model for Predicting Coronavirus 3C-Like Protease Cleavage Sites.

COVID-19, caused by the highly contagious SARS-CoV-2 virus, is distinguished by its positive-sense, single-stranded RNA genome. A thorough understanding of SARS-CoV-2 pathogenesis is crucial for halting its proliferation. Notably, the 3C- like protease of the coronavirus (denoted as 3CLpro) is instrumental in the viral replication process. Precise delineation of 3CLpro cleavage sites is imperative for elucidating the transmission dynamics of SARS-CoV-2. While machine learning tools have been deployed to identify potential 3CLpro cleavage sites, these existing methods often fall short in terms of accuracy. To improve the performances of these predictions, we propose a novel analytical framework, the Transformer and Deep Forest Fusion Model (TDFFM). Within TDFFM, we utilize the AAindex and the BLOSUM62 matrix to encode protein sequences. These encoded features are subsequently input into two distinct components: a Deep Forest, which is an effective decision tree ensemble methodology, and a Transformer equipped with a Multi-Level Attention Model (TMLAM). The integration of the attention mechanism allows our model to more accurately identify positive samples, thus enhancing the overall predictive performance. Evaluation on a test set demonstrates that our TDFFM achieves an accuracy of 0.955, an AUC of 0.980, and an F1-score of 0.367, substantiating the model's superior prediction capabilities.

Automated molecular structure segmentation from documents using ChemSAM.

Chemical structure segmentation constitutes a pivotal task in cheminformatics, involving the extraction and abstraction of structural information of chemical compounds from text-based sources, including patents and scientific articles. This study introduces a deep learning approach to chemical structure segmentation, employing a Vision Transformer (ViT) to discern the structural patterns of chemical compounds from their graphical representations. The Chemistry-Segment Anything Model (ChemSAM) achieves state-of-the-art results on publicly available benchmark datasets and real-world tasks, underscoring its effectiveness in accurately segmenting chemical structures from text-based sources. Moreover, this deep learning-based approach obviates the need for handcrafted features and demonstrates robustness against variations in image quality and style. During the detection phase, a ViT-based encoder-decoder model is used to identify and locate chemical structure depictions on the input page. This model generates masks to ascertain whether each pixel belongs to a chemical structure, thereby offering a pixel-level classification and indicating the presence or absence of chemical structures at each position. Subsequently, the generated masks are clustered based on their connectivity, and each mask cluster is updated to encapsulate a single structure in the post-processing workflow. This two-step process facilitates the effective automatic extraction of chemical structure depictions from documents. By utilizing the deep learning approach described herein, it is demonstrated that effective performance on low-resolution and densely arranged molecular structural layouts in journal articles and patents is achievable.

Sketch-Supervised Histopathology Tumour Segmentation: Dual CNN-Transformer With Global Normalised CAM.

Deep learning methods are frequently used in segmenting histopathology images with high-quality annotations nowadays. Compared with well-annotated data, coarse, scribbling-like labelling is more cost-effective and easier to obtain in clinical practice. The coarse annotations provide limited supervision, so employing them directly for segmentation network training remains challenging. We present a sketch-supervised method, called DCTGN-CAM, based on a dual CNN-Transformer network and a modified global normalised class activation map. By modelling global and local tumour features simultaneously, the dual CNN-Transformer network produces accurate patch-based tumour classification probabilities by training only on lightly annotated data. With the global normalised class activation map, more descriptive gradient-based representations of the histopathology images can be obtained, and inference of tumour segmentation can be performed with high accuracy. Additionally, we collect a private skin cancer dataset named BSS, which contains fine and coarse annotations for three types of cancer. To facilitate reproducible performance comparison, experts are also invited to label coarse annotations on the public liver cancer dataset PAIP2019. On the BSS dataset, our DCTGN-CAM segmentation outperforms the state-of-the-art methods and achieves 76.68 % IOU and 86.69 % Dice scores on the sketch-based tumour segmentation task. On the PAIP2019 dataset, our method achieves a Dice gain of 8.37 % compared with U-Net as the baseline network.

CDNet: Contrastive Disentangled Network for Fine-Grained Image Categorization of Ocular B-Scan Ultrasound.

Precise and rapid categorization of images in the B-scan ultrasound modality is vital for diagnosing ocular diseases. Nevertheless, distinguishing various diseases in ultrasound still challenges experienced ophthalmologists. Thus a novel contrastive disentangled network (CDNet) is developed in this work, aiming to tackle the fine-grained image categorization (FGIC) challenges of ocular abnormalities in ultrasound images, including intraocular tumor (IOT), retinal detachment (RD), posterior scleral staphyloma (PSS), and vitreous hemorrhage (VH). Three essential components of CDNet are the weakly-supervised lesion localization module (WSLL), contrastive multi-zoom (CMZ) strategy, and hyperspherical contrastive disentangled loss (HCD-Loss), respectively. These components facilitate feature disentanglement for fine-grained recognition in both the input and output aspects. The proposed CDNet is validated on our ZJU Ocular Ultrasound Dataset (ZJUOUSD), consisting of 5213 samples. Furthermore, the generalization ability of CDNet is validated on two public and widely-used chest X-ray FGIC benchmarks. Quantitative and qualitative results demonstrate the efficacy of our proposed CDNet, which achieves state-of-the-art performance in the FGIC task.

Self-supervised learning mechanism for identification of eyelid malignant melanoma in pathologic slides with limited annotation.

Purpose: The lack of finely annotated pathologic data has limited the application of deep learning systems (DLS) to the automated interpretation of pathologic slides. Therefore, this study develops a robust self-supervised learning (SSL) pathology diagnostic system to automatically detect malignant melanoma (MM) in the eyelid with limited annotation. Design: Development of a self-supervised diagnosis pipeline based on a public dataset, then refined and tested on a private, real-world clinical dataset. Subjects: A. Patchcamelyon (PCam)-a publicly accessible dataset for the classification task of patch-level histopathologic images. B. The Second Affiliated Hospital, Zhejiang University School of Medicine (ZJU-2) dataset - 524,307 patches (small sections cut from pathologic slide images) from 192 H&E-stained whole-slide-images (WSIs); only 72 WSIs were labeled by pathologists. Methods: Patchcamelyon was used to select a convolutional neural network (CNN) as the backbone for our SSL-based model. This model was further developed in the ZJU-2 dataset for patch-level classification with both labeled and unlabeled images to test its diagnosis ability. Then the algorithm retrieved information based on patch-level prediction to generate WSI-level classification results using random forest. A heatmap was computed for visualizing the decision-making process. Main outcome measures: The area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity were used to evaluate the performance of the algorithm in identifying MM. Results: ResNet50 was selected as the backbone of the SSL-based model using the PCam dataset. This algorithm then achieved an AUC of 0.981 with an accuracy, sensitivity, and specificity of 90.9, 85.2, and 96.3% for the patch-level classification of the ZJU-2 dataset. For WSI-level diagnosis, the AUC, accuracy, sensitivity, and specificity were 0.974, 93.8%, 75.0%, and 100%, separately. For every WSI, a heatmap was generated based on the malignancy probability. Conclusion: Our diagnostic system, which is based on SSL and trained with a dataset of limited annotation, can automatically identify MM in pathologic slides and highlight MM areas in WSIs by a probabilistic heatmap. In addition, this labor-saving and cost-efficient model has the potential to be refined to help diagnose other ophthalmic and non-ophthalmic malignancies.

SuccSPred2.0: A Two-Step Model to Predict Succinylation Sites Based on Multifeature Fusion and Selection Algorithm.

Protein succinylation is a novel type of post-translational modification in recent decade years. It played an important role in biological structure and functions verified by experiments. However, it is time consuming and laborious for the wet experimental identification of succinylation sites. Traditional technology cannot adapt to the rapid growth of the biological sequence data sets. In this study, a new computational method named SuccSPred2.0 was proposed to identify succinylation sites in the protein sequences based on multifeature fusion and maximal information coefficient (MIC) method. SuccSPred2.0 was implemented based on a two-step strategy. At first, high-dimension features were reduced by linear discriminant analysis to prevent overfitting. Subsequently, MIC method was employed to select the important features binding classifiers to predict succinylation sites. From the compared experiments on 10-fold cross-validation and independent test data sets, SuccSPred2.0 obtained promising improvements. Comparative experiments showed that SuccSPred2.0 was superior to previous tools in identifying succinylation sites in the given proteins.

i2APP: A Two-Step Machine Learning Framework For Antiparasitic Peptides Identification.

Parasites can cause enormous damage to their hosts. Studies have shown that antiparasitic peptides can inhibit the growth and development of parasites and even kill them. Because traditional biological methods to determine the activity of antiparasitic peptides are time-consuming and costly, a method for large-scale prediction of antiparasitic peptides is urgently needed. We propose a computational approach called i2APP that can efficiently identify APPs using a two-step machine learning (ML) framework. First, in order to solve the imbalance of positive and negative samples in the training set, a random under sampling method is used to generate a balanced training data set. Then, the physical and chemical features and terminus-based features are extracted, and the first classification is performed by Light Gradient Boosting Machine (LGBM) and Support Vector Machine (SVM) to obtain 264-dimensional higher level features. These features are selected by Maximal Information Coefficient (MIC) and the features with the big MIC values are retained. Finally, the SVM algorithm is used for the second classification in the optimized feature space. Thus the prediction model i2APP is fully constructed. On independent datasets, the accuracy and AUC of i2APP are 0.913 and 0.935, respectively, which are better than the state-of-arts methods. The key idea of the proposed method is that multi-level features are extracted from peptide sequences and the higher-level features can distinguish well the APPs and non-APPs.

ME-ACP: Multi-view neural networks with ensemble model for identification of anticancer peptides.

Cancer remains one of the most threatening diseases, which kills millions of lives every year. As a promising perspective for cancer treatments, anticancer peptides (ACPs) overcome a lot of disadvantages of traditional treatments. However, it is time-consuming and expensive to identify ACPs through conventional experiments. Hence, it is urgent and necessary to develop highly effective approaches to accurately identify ACPs in large amounts of protein sequences. In this work, we proposed a novel and effective method named ME-ACP which employed multi-view neural networks with ensemble model to identify ACPs. Firstly, we employed residue level and peptide level features preliminarily with ensemble models based on lightGBMs. Then, the outputs of lightGBM classifiers were fed into a hybrid deep neural network (HDNN) to identify ACPs. The experiments on independent test datasets demonstrated that ME-ACP achieved competitive performance on common evaluation metrics.

MD-UNET: Multi-input dilated U-shape neural network for segmentation of bladder cancer.

Accurate segmentation of the tumour area is crucial for the treatment and prognosis of patients with bladder cancer. However, the complex information from the MRI image poses an important challenge for us to accurately segment the lesion, for example, the high distinction among people, size of bladder variation and noise interference. Based on the above issues, we propose an MD-Unet network structure, which uses multi-scale images as the input of the network, and combines max-pooling with dilated convolution to increase the receptive field of the convolutional network. The results show that the proposed network can obtain higher precision than the existing models for the bladder cancer dataset. The MD-Unet can achieve state-of-art performance compared with other methods.

EnACP: An Ensemble Learning Model for Identification of Anticancer Peptides.

As cancer remains one of the main threats of human life, developing efficient cancer treatments is urgent. Anticancer peptides, which could overcome the significant side effects and poor results of traditional cancer treatments, have become a new potential alternative these years. However, identifying anticancer peptides by experimental methods is time consuming and resource consuming, it is of great significance to develop effective computational tools to quickly and accurately identify potential anticancer peptides from amino acid sequences. For most current computational methods, feature representation plays a key role in their final successes. This study proposes a novel fast and accurate approach to identify anticancer peptides using diversified feature representations and ensemble learning method. For the feature representations, the information is encoded from multidimensional feature spaces, including sequence composition, sequence-order, physicochemical properties, etc. In order to better model the potential relationships of peptides, multiple ensemble classifiers, LightGBMs, are applied to detect the different feature sets at first. Then the obtained multiple outputs are used as inputs of the support vector machine classifier, which effectively identifies anticancer peptides. Experimental results on cross validation and independent test sets demonstrate that our method can achieve better or comparable performances compared with other state-of-the-art methods.

Author Correction: Multi-label Learning for Predicting the Activities of Antimicrobial Peptides.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

MUSTv2: An Improved De Novo Detection Program for Recently Active Miniature Inverted Repeat Transposable Elements (MITEs).

Background Miniature inverted repeat transposable element (MITE) is a short transposable element, carrying no protein-coding regions. However, its high proliferation rate and sequence-specific insertion preference renders it as a good genetic tool for both natural evolution and experimental insertion mutagenesis. Recently active MITE copies are those with clear signals of Terminal Inverted Repeats (TIRs) and Direct Repeats (DRs), and are recently translocated into their current sites. Their proliferation ability renders them good candidates for the investigation of genomic evolution. Results This study optimizes the C++ code and running pipeline of the MITE Uncovering SysTem (MUST) by assuming no prior knowledge of MITEs required from the users, and the current version, MUSTv2, shows significantly increased detection accuracy for recently active MITEs, compared with similar programs. The running speed is also significantly increased compared with MUSTv1. We prepared a benchmark dataset, the simulated genome with 150 MITE copies for researchers who may be of interest. Conclusions MUSTv2 represents an accurate detection program of recently active MITE copies, which is complementary to the existing template-based MITE mapping programs. We believe that the release of MUSTv2 will greatly facilitate the genome annotation and structural analysis of the bioOMIC big data researchers.

Multi-label Learning for Predicting the Activities of Antimicrobial Peptides.

Antimicrobial peptides (AMPs) are peptide antibiotics with a broad spectrum of antimicrobial activities. Activity prediction of AMPs from their amino acid sequences is of great therapeutic importance but imposes challenges on prediction methods due to label interactions. In this paper we propose a novel multi-label learning model to address this problem. A weighted K-nearest neighbor classifier is adopted for efficient representation learning of the sequence data. A multiple linear regression model is then employed to learn a mapping from the classifier score vectors to the target labels, with label correlations considered. Several popular multi-label learning algorithms and feature extraction methods were tested on a comprehensive, up-to-date AMP dataset with twelve biological activities covered and its filtered version with five activities covered. The experimental results showed that our proposed method has competitive performance with previous works and could be used as a powerful engine for activity prediction of AMPs.

hMuLab: A Biomedical Hybrid MUlti-LABel Classifier Based on Multiple Linear Regression.

Many biomedical classification problems are multi-label by nature, e.g., a gene involved in a variety of functions and a patient with multiple diseases. The majority of existing classification algorithms assumes each sample with only one class label, and the multi-label classification problem remains to be a challenge for biomedical researchers. This study proposes a novel multi-label learning algorithm, hMuLab, by integrating both feature-based and neighbor-based similarity scores. The multiple linear regression modeling techniques make hMuLab capable of producing multiple label assignments for a query sample. The comparison results over six commonly-used multi-label performance measurements suggest that hMuLab performs accurately and stably for the biomedical datasets, and may serve as a complement to the existing literature.

Rectified-Linear-Unit-Based Deep Learning for Biomedical Multi-label Data.

Disease diagnosis is one of the major data mining questions by the clinicians. The current diagnosis models usually have a strong assumption that one patient has only one disease, i.e. a single-label data mining problem. But the patients, especially when at the late stages, may have more than one disease and require a multi-label diagnosis. The multi-label data mining is much more difficult than a single-label one, and very few algorithms have been developed for this situation. Deep learning is a data mining algorithm with highly dense inner structure and has achieved many successful applications in the other areas. We propose a hypothesis that rectified-linear-unit-based deep learning algorithm may also be good at the clinical questions, by revising the last layer as a multi-label output. The proof-of-concept experimental data support the hypothesis, and the community may be interested in trying more applications.

CRISPRdigger: detecting CRISPRs with better direct repeat annotations.

Clustered regularly interspaced short palindromic repeats (CRISPRs) are important genetic elements in many bacterial and archaeal genomes, and play a key role in prokaryote immune systems' fight against invasive foreign elements. The CRISPR system has also been engineered to facilitate target gene editing in eukaryotic genomes. Using the common features of mis-annotated CRISPRs in prokaryotic genomes, this study proposed an accurate de novo CRISPR annotation program CRISPRdigger, which can take a partially assembled genome as its input. A comprehensive comparison with the three existing programs demonstrated that CRISPRdigger can recover more Direct Repeats (DRs) for CRISPRs and achieve a higher accuracy for a query genome. The program was implemented by Perl and all the parameters had default values, so that a user could annotate CRISPRs in a query genome by supplying only a genome sequence in the FASTA format. All the supplementary data are available at http://www.healthinformaticslab.org/supp/.