Spatially resolved sequencing technologies have revolutionized our understanding of biological regulatory processes within tissue microenvironments by simultaneously capturing the states of genomic regions, genes, and proteins alongside the spatial organization of cells. However, inherent heterogeneity across modalities and samples poses substantial challenges for the integrative analysis of spatial omics data, underscoring the urgent need for advanced computational methods. In this study, we propose PRESENT, a contrastive learning-based integrative framework for cross-modality representation of spatial multi-omics data. PRESENT employs omics-specific encoders consisting of graph attention networks and Bayesian neural networks coupled with distribution-aware decoders to model distinct modalities, and an inter-omics alignment module for multi-omics integration. By effectively incorporating spatial dependencies with multi-omics information across diverse species and technologies, PRESENT facilitates the accurate identification of spatial domains and the elucidation of underlying regulatory mechanisms. Furthermore, PRESENT can be extended to multi-sample integration via a two-stage training workflow, which incorporates inter-batch alignment loss, intra-batch preserving loss, batch-adversarial learning, and cyclic graph refinement strategies to eliminate batch effects while retaining biological signals. Extensive experiments on tissue samples across different anatomical regions and developmental stages demonstrate that PRESENT enables the characterization of hierarchical tissue structures from a spatiotemporal perspective.

Offering rich contexts to Large Language Models (LLMs) has shown to boost the performance in various tasks, but the resulting longer prompt would increase the computational cost and might exceed the input limit of LLMs. Recently, some prompt compression methods have been suggested to shorten the length of prompts by using language models to generate shorter prompts or by developing computational models to select important parts of original prompt. The generative compression methods would suffer from issues like hallucination, while the selective compression methods have not involved linguistic rules and overlook the global structure of prompt. To this end, we propose a novel selective compression method called PartPrompt. It first obtains a parse tree for each sentence based on linguistic rules, and calculates local information entropy for each node in a parse tree. These local parse trees are then organized into a global tree according to the hierarchical structure such as the dependency of sentences, paragraphs, and sections. After that, the root-ward propagation and leaf-ward propagation are proposed to adjust node values over the global tree. Finally, a recursive algorithm is developed to prune the global tree based on the adjusted node values. The experiments show that PartPrompt receives the state-of-the-art performance across various datasets, metrics, compression ratios, and target LLMs for inference. The in-depth ablation studies confirm the effectiveness of designs in PartPrompt, and other additional experiments also demonstrate its superiority in terms of the coherence of compressed prompts and in the extreme long prompt scenario.

Knowledge Graph Completion (KGC) aims to infer missing triples for a given knowledge graph, which can be adopted to various fields ranging from scientific research to real-world applications. Despite the success of numerous KGC methods, the lack of explainability remains a common drawback. However, the explanation of KGC results is crucial in many cases such as providing medical diagnosis and recommending candidates for costly experiments, which could increase the reliability of these techniques to humans. Although a few explainable KGC methods have been proposed, the explainability module is designed for the specific KGC model and cannot be utilized for state-of-the-art KGC models. In this work, we present a post-hoc generic method, namely KGC-Explainer, that can be applied to any KGC model providing triplet scores. KGC-Explainer not only incorporates the input KGC model itself, but also leverages the structural and textual information in knowledge graphs. To demonstrate KGC-Explainer achieving design goals and the superiority of it over other methods, we conduct extensive experiments on two real-world knowledge graphs with different domains and languages, one coming from medical domain in Chinese and another coming from general domain in English. Additionally, we compare the KGC explanation with human explanation, showcasing the practical significance of KGC-Explainer.

Gout recurrence is common in real-world settings. While traditional machine learning methods are applicable, their performance is often limited by a lack of diverse data modalities, insufficient understanding of inter-modality interactions, and poor model generalizability. To address these challenges, this work proposes ARL-GRP, a novel framework for forecasting the risk of gout recurrence. This framework is built upon three essential modules: continuous learning utilising real-world multimodel follow-up data, feature representation aggregation employing a pretrained large encoder, and predicting recurrent gout risk using a multilayer perceptron. The experimental comparison demonstrates that our proposed approach generally outperforms conventional machine learning techniques. ARL-GRP can effectively combine structured clinical data and unstructured medical narratives into unified patient representations, significantly outperforming traditional machine learning methods (Accuracy: 0.931, AUC: 0.969). Our method demonstrates strong predictive capability, enabling precise risk assessment and personalised clinical decision-making. Furthermore, the effectiveness of our method is also consolidated through additional analysis using ROC curves and a heatmap.

Node importance estimation (NIE) is the task of inferring the importance scores of the nodes in a graph. Due to the availability of richer data and knowledge, recent research interests of NIE have been dedicated to knowledge graphs (KGs) for predicting future or missing node importance scores. Existing state-of-the-art NIE methods train the model by available labels, and they consider every interested node equally before training. However, the nodes with higher importance often require or receive more attention in real-world scenarios, e.g., people may care more about the movies or webpages with higher importance. To this end, we introduce Label Informed ContrAstive Pretraining (LICAP) to the NIE problem for being better aware of the nodes with high importance scores. Specifically, LICAP is a novel type of contrastive learning (CL) framework that aims to fully utilize continuous labels to generate contrastive samples for pretraining embeddings. Considering the NIE problem, LICAP adopts a novel sampling strategy called top nodes preferred hierarchical sampling to first group all interested nodes into a top bin and a nontop bin based on node importance scores, and then divide the nodes within the top bin into several finer bins also based on the scores. The contrastive samples are generated from those bins and are then used to pretrain node embeddings of KGs via a newly proposed predicate-aware graph attention networks (PreGATs), so as to better separate the top nodes from nontop nodes, and distinguish the top nodes within the top bin by keeping the relative order among finer bins. Extensive experiments demonstrate that the LICAP pretrained embeddings can further boost the performance of existing NIE methods and achieve new state-of-the-art performance regarding both regression and ranking metrics. The source code for reproducibility is available at https://github.com/zhangtia16/LICAP.

Molecular property prediction is a crucial foundation for drug discovery. In recent years, pre-trained deep learning models have been widely applied to this task. Some approaches that incorporate prior biological domain knowledge into the pre-training framework have achieved impressive results. However, these methods heavily rely on biochemical experts, and retrieving and summarizing vast amounts of domain knowledge literature is both time-consuming and expensive. Large Language Models (LLMs) have demonstrated remarkable performance in understanding and efficiently providing general knowledge. Nevertheless, they occasionally exhibit hallucinations and lack precision in generating domain-specific knowledge. Conversely, Domain-specific Small Models (DSMs) possess rich domain knowledge and can accurately calculate molecular domain-related metrics. However, due to their limited model size and singular functionality, they lack the breadth of knowledge necessary for comprehensive representation learning. To leverage the advantages of both approaches in molecular property prediction, we propose a novel Molecular Graph representation learning framework that integrates Large language models and Domain-specific small models (MolGraph-LarDo). Technically, we design a two-stage prompt strategy where DSMs are introduced to calibrate the knowledge provided by LLMs, enhancing the accuracy of domain-specific information and thus enabling LLMs to generate more precise textual descriptions for molecular samples. Subsequently, we employ a multi-modal alignment method to coordinate various modalities, including molecular graphs and their corresponding descriptive texts, to guide the pre-training of molecular representations. Extensive experiments demonstrate the effectiveness of the proposed method.

The increasing adoption of Electric Vehicle (EV) systems necessitates the development of an Energy Market structure that facilitates peer-to-peer energy sharing among multiple EVs and entities while ensuring a self-regulating pricing mechanism. Real-time State of Charge (SoC) estimation is critical to meeting the dynamic energy demands of EV systems. In this study, we propose a blockchain-based automated market maker (AMM) that utilizes constant function products to establish an effective self-regulating pricing system for EV energy market prices. Our unique State of Charge estimation system leverages blockchain-based oracles to efficiently handle requests and monitor EV-oriented energy markets. This enables precise monitoring of battery states and achieves improved SoC values through the interior point method. Experimentation on a blockchain network reveals cost-effective energy regulation within EV systems and enhanced SoC estimation predictability within Energy Markets. All contracts undergo rigorous testing and are deployed at a gas cost of$2.1913742~x 10^{7}$Wei. Our approach demonstrates high efficiency, for all designed protocols, affirming the efficacy of our proposal. By implementing our blockchain-based AMM and State of Charge estimation system, we ensure transparent and self-regulated energy distribution and pricing within EV Markets, fostering the advancement of autonomous EV systems.

MOTIVATION: Single-cell technologies play a crucial role in revolutionizing biological research over the past decade, which strengthens our understanding in cell differentiation, development and regulation from a single-cell level perspective. Single-cell RNA sequencing (scRNA-seq) is one of the most common single cell technologies, which enables probing transcriptional states in thousands of cells in one experiment. Identification of cell types from scRNA-seq measurements is a fundamental and crucial question to answer. Most previous studies directly take gene expression as input while ignoring the comprehensive gene-gene interactions. RESULTS: We propose scGraph, an automatic cell identification algorithm leveraging gene interaction relationships to enhance the performance of the cell-type identification. scGraph is based on a graph neural network to aggregate the information of interacting genes. In a series of experiments, we demonstrate that scGraph is accurate and outperforms eight comparison methods in the task of cell-type identification. Moreover, scGraph automatically learns the gene interaction relationships from biological data and the pathway enrichment analysis shows consistent findings with previous analysis, providing insights on the analysis of regulatory mechanism. AVAILABILITY AND IMPLEMENTATION: scGraph is freely available at https://github.com/QijinYin/scGraph and https://figshare.com/articles/software/scGraph/17157743. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Federated learning (FL) is a privacy-preserving paradigm for multi-institutional collaborations, where the aggregation is an essential procedure after training on the local datasets. Conventional aggregation algorithms often apply a weighted averaging of the updates generated from distributed machines to update the global model. However, while the data distributions are non-IID, the large discrepancy between the local updates might lead to a poor averaged result and a lower convergence speed, i.e., more iterations required to achieve a certain performance. To solve this problem, this article proposes a novel method named AggEnhance for enhancing the aggregation, where we synthesize a group of reliable samples from the local models and tune the aggregated result on them. These samples, named class interior points (CIPs) in this work, bound the relevant decision boundaries that ensure the performance of aggregated result. To the best of our knowledge, this is the first work to explicitly design an enhancing method for the aggregation in prevailing FL pipelines. A series of experiments on real data demonstrate that our method has noticeable improvements of the convergence in non-IID scenarios. In particular, our approach reduces the iterations by 31.87% on average for the CIFAR10 dataset and 43.90% for the PASCAL VOC dataset. Since our method does not modify other procedures of FL pipelines, it is easy to apply to most existing FL frameworks. Furthermore, it does not require additional data transmitted from the local clients to the global server, thus holding the same security level as the original FL algorithms.

Training multiple deep neural networks (DNNs) and averaging their outputs is a simple way to improve the predictive performance. Nevertheless, the multiplied training cost prevents this ensemble method to be practical and efficient. Several recent works attempt to save and ensemble the checkpoints of DNNs, which only requires the same computational cost as training a single network. However, these methods suffer from either marginal accuracy improvements due to the low diversity of checkpoints or high risk of divergence due to the cyclical learning rates they adopted. In this paper, we propose a novel method to ensemble the checkpoints, where a boosting scheme is utilized to accelerate model convergence and maximize the checkpoint diversity. We theoretically prove that it converges by reducing exponential loss. The empirical evaluation also indicates our proposed ensemble outperforms single model and existing ensembles in terms of accuracy and efficiency. With the same training budget, our method achieves 4.16% lower error on Cifar-100 and 6.96% on Tiny-ImageNet with ResNet-110 architecture. Moreover, the adaptive sample weights in our method make it an effective solution to address the imbalanced class distribution. In the experiments, it yields up to 5.02% higher accuracy over single EfficientNet-B0 on the imbalanced datasets.

Detecting cancer signals in cell-free DNA (cfDNA) high-throughput sequencing data is emerging as a novel noninvasive cancer detection method. Due to the high cost of sequencing, it is crucial to make robust and precise predictions with low-depth cfDNA sequencing data. Here we propose a novel approach named DISMIR, which can provide ultrasensitive and robust cancer detection by integrating DNA sequence and methylation information in plasma cfDNA whole-genome bisulfite sequencing (WGBS) data. DISMIR introduces a new feature termed as 'switching region' to define cancer-specific differentially methylated regions, which can enrich the cancer-related signal at read-resolution. DISMIR applies a deep learning model to predict the source of every single read based on its DNA sequence and methylation state and then predicts the risk that the plasma donor is suffering from cancer. DISMIR exhibited high accuracy and robustness on hepatocellular carcinoma detection by plasma cfDNA WGBS data even at ultralow sequencing depths. Further analysis showed that DISMIR tends to be insensitive to alterations of single CpG sites' methylation states, which suggests DISMIR could resist to technical noise of WGBS. All these results showed DISMIR with the potential to be a precise and robust method for low-cost early cancer detection.

MOTIVATION: Cell-free DNA (cfDNA) is gaining substantial attention from both biological and clinical fields as a promising marker for liquid biopsy. Many aspects of disease-related features have been discovered from cfDNA high-throughput sequencing (HTS) data. However, there is still a lack of integrative and systematic tools for cfDNA HTS data analysis and quality control (QC). RESULTS: Here, we propose cfDNApipe, an easy-to-use and systematic python package for cfDNA whole-genome sequencing (WGS) and whole-genome bisulfite sequencing (WGBS) data analysis. It covers the entire analysis pipeline for the cfDNA data, including raw sequencing data processing, QC and sophisticated statistical analysis such as detecting copy number variations (CNVs), differentially methylated regions and DNA fragment size alterations. cfDNApipe provides one-command-line-execution pipelines and flexible application programming interfaces for customized analysis. AVAILABILITY AND IMPLEMENTATION: https://xwanglabthu.github.io/cfDNApipe/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Histopathological image retrieval aims to search histopathological images sharing similar content with the query image, which could provide pathologists with an approach to easily obtain similar diagnostic cases for reference. Recent histopathological image retrieval methods are usually based on CNN feature extractors, which require a large amount of annotated data for training. Besides, most of existing methods could not define a reasonable similarity metric for histopathological images. In this paper, we apply deep metric learning to liver histopathological image retrieval. We construct a model based on mixed attention mechanism and train the model with a modified version of multi-similarity loss, which enables embedding vectors of similar images in the given metric space to be closer and dissimilar ones to be far from each other. Additionally, our model can be well fitted with limited data. Finally, we evaluate the proposed method with our own established liver histopathological image dataset. Compared with several published methods, our model shows higher performance.

Available and objective clinical documents are important for research of assistant diagnosis, development of algorithms, and education. To facilitate the readability and variability of clinical documents, this paper presents a rule-based approach to develop a question-answer dataset for chest X-rays from a public collection of radiology examinations, including both images and radiologist narrative reports. Our method simplified the complicated reports via hand-selected keywords, generated more than 63 thousand question-answer pairs via hand-written patterns, and augmented the question-answer dataset to more than 130 thousand pairs via rule-based question answering. To the best of our knowledge, this is the first generated question-answer dataset for chest X-rays by rule-based method. The dataset is promising for future researches and applications such as visual question answering, computer-aided diagnosis and so on.

MOTIVATION: Hi-C is a genome-wide technology for investigating 3D chromatin conformation by measuring physical contacts between pairs of genomic regions. The resolution of Hi-C data directly impacts the effectiveness and accuracy of downstream analysis such as identifying topologically associating domains (TADs) and meaningful chromatin loops. High resolution Hi-C data are valuable resources which implicate the relationship between 3D genome conformation and function, especially linking distal regulatory elements to their target genes. However, high resolution Hi-C data across various tissues and cell types are not always available due to the high sequencing cost. It is therefore indispensable to develop computational approaches for enhancing the resolution of Hi-C data. RESULTS: We proposed hicGAN, an open-sourced framework, for inferring high resolution Hi-C data from low resolution Hi-C data with generative adversarial networks (GANs). To the best of our knowledge, this is the first study to apply GANs to 3D genome analysis. We demonstrate that hicGAN effectively enhances the resolution of low resolution Hi-C data by generating matrices that are highly consistent with the original high resolution Hi-C matrices. A typical scenario of usage for our approach is to enhance low resolution Hi-C data in new cell types, especially where the high resolution Hi-C data are not available. Our study not only presents a novel approach for enhancing Hi-C data resolution, but also provides fascinating insights into disclosing complex mechanism underlying the formation of chromatin contacts. AVAILABILITY AND IMPLEMENTATION: We release hicGAN as an open-sourced software at https://github.com/kimmo1019/hicGAN. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

BACKGROUND: Cryo-electron tomography (cryo-ET) enables the 3D visualization of cellular organization in near-native state which plays important roles in the field of structural cell biology. However, due to the low signal-to-noise ratio (SNR), large volume and high content complexity within cells, it remains difficult and time-consuming to localize and identify different components in cellular cryo-ET. To automatically localize and recognize in situ cellular structures of interest captured by cryo-ET, we proposed a simple yet effective automatic image analysis approach based on Faster-RCNN. RESULTS: Our experimental results were validated using in situ cyro-ET-imaged mitochondria data. Our experimental results show that our algorithm can accurately localize and identify important cellular structures on both the 2D tilt images and the reconstructed 2D slices of cryo-ET. When ran on the mitochondria cryo-ET dataset, our algorithm achieved Average Precision >0.95. Moreover, our study demonstrated that our customized pre-processing steps can further improve the robustness of our model performance. CONCLUSIONS: In this paper, we proposed an automatic Cryo-ET image analysis algorithm for localization and identification of different structure of interest in cells, which is the first Faster-RCNN based method for localizing an cellular organelle in Cryo-ET images and demonstrated the high accuracy and robustness of detection and classification tasks of intracellular mitochondria. Furthermore, our approach can be easily applied to detection tasks of other cellular structures as well.

In this paper, we propose a novel probabilistic graphical model to address the off-line signature verification problem. Different from previous work, our approach introduces the concept of feature roles according to their distribution in genuine and forgery signatures, with all these features represented by a unique graphical model. And we propose several new techniques to improve the performance of the new signature verification system. Results based on 200 persons' signatures (16000 signature samples) indicate that the proposed method outperforms other popular techniques for off-line signature verification with a great improvement.

A Hidden Markov Model (HMM) approach to off-line signature verification is presented. First, each of the signature images is represented as a landmark point set, which includes turning points, isolated points, trifurcate points, intersection points and termination points on signature skeleton. Then we propose a novel deformable grid partition technique. Based on landmark point matching, we build the matching relations between planar regions to get the deformable grids, and then extract grid features from them. By using HMM in signature modeling, the deformable grid partition method shows remarkable improvements over traditional grid partition methods in discriminative ability.

This paper describes a new approach to emotion recognition based on pressure sensor keyboards. The pressure sensor keyboard is a new product that occurs in the market recently, which produces a pressure sequence when keystroke occurs. The analysis of the pressure sequence should be a novel research area. It has been used for identity verification in our previous research. In this paper, we use the pressure sequence for emotion recognition. Three methods (global features of pressure sequences, dynamic time warping and traditional keystroke dynamics) are proposed for the emotion recognition task; then we combined the three methods together using a classifier fusion technique. Several experiments were performed on a database containing 3000 samples (from 50 individuals, including six emotions: neutral, anger, fear, happiness, sadness and surprise) and the best result were achieved utilizing all the method, obtaining an overall accuracy of 93.4%. Our technique of emotion recognition has been used for intelligent game controlling and several other applications.