Graph Neural Networks (GNNs) excel at modeling graph data but often amplify biases tied to sensitive attributes like gender and race. Existing causality-based methods use isolated interventions on graph topology or features but struggle to produce representations that balance predictive power with fairness. This leads to two issues: (1) weak predictive power, where representations miss critical task-relevant features, and (2) bias amplification, where representations encode sensitive attributes, causing unfair outcomes. To address these issues, we introduce the Probability of Necessity and Sufficiency (PNS), where necessity ensures representations capture only essential features for predictions, and sufficiency guarantees these features are adequate without relying on sensitive attributes. We propose FairSNR, a fairness-aware graph representation learning framework that introduces constraints based on the PNS. This leverages PNS to guide the learning of fair representations from graph data. In particular, FairSNR employs an encoder to learn node representations with high PNS for downstream tasks. To compute and optimize PNS, FairSNR introduces an intervenor to generate the most challenging counterfactual interventions on the representations, thereby enhancing the model’s causal stability even under worst-case scenarios. Further, a discriminator is trained to detect and mitigate sensitive information leakage in the learned representations, effectively disentangling sensitive biases from task-relevant features. Experiments on real-world graph datasets demonstrate that FairSNR outperforms existing state-of-the-art (SOTA) methods in both fairness and utility.

By generating massive gene transcriptome data and analyzing transcriptomic variations at the cell level, single-cell RNA-sequencing (scRNA-seq) technology has provided new way to explore cellular heterogeneity and functionality. Clustering scRNA-seq data could discover the hidden diversity and complexity of cell populations, which can aid to the identification of the disease mechanisms and biomarkers. In this paper, a novel method (DSINMF) is presented for clustering single cell RNA sequencing data by using deep matrix factorization. Our proposed method comprises four steps: first, the feature selection is utilized to remove irrelevant features. Then, the dropout imputation is used to handle missing value problem. Further, the dimension reduction is employed to preserve data characteristics and reduce noise effects. Finally, the deep matrix factorization with bi-stochastic graph regularization is used to obtain cluster results from scRNA-seq data. We compare DSINMF with other state-of-the-art algorithms on nine datasets and the results show our method outperformances than other methods. The code can be downloaded from https://github.com/lanbiolab/DSINMF.

Few-shot medical image semantic segmentation aims to predict masks for unseen classes with only a few of pixel-level samples. Although prior methods have significantly improved segmentation performance, obtaining richer semantic information from both support and query images remains an open problem. To address this issue, we propose Interactive Adaptation Prototypes for Few-shot Medical Image semantic Segmentation (IAPNet), which mainly consists of two components: interactiveguided prototype generation and an adaptive prototype fusion module. Specifically, the Interactive-Guided Prototype Generation involves two directions of interaction: (1) guiding the query image segmentation by extracting semantic features from the support images to obtain query mask. (2) using the predicted query mask to guide the segmentation of the support images. This bidirectional interaction not only enhances the semantic richness of the generated prototypes but also reinforces the shared meta-information critical for few-shot generalization. Furthermore, the adaptive prototype fusion module is designed to learn optimal fusion weights during training, allowing the final prototype to better capture class-relevant semantic features and improve the model's class discrimination capability. Extensive experiments conducted on the Abdominal-CMR, AbdominalCT, and Cardiac-MRI datasets demonstrate that the proposed method achieves competitive performance compared to state-of-the-art approaches, showing strong advantages for clinical application.

Recommender systems are crucial for providing personalised experiences, but their effectiveness is often undermined by confounding bias, particularly in the presence of latent confounders. Existing debiasing methods typically address only one type of latent confounding bias, often ignoring the complex interactions caused by latent confounders, such as those between items and user feedback, and between item exposure and user feedback. To tackle these challenges, we propose a novel Deep Instrumental Variables (IV) approach for debiased representation learning in Recommendation Systems, referred to as DIVERS. Specifically, DIVERS leverages user feature embeddings as IVs to mitigate the confounding bias between items and user feedback caused by latent confounders, and combines the debiased item embeddings with an item exposure vector to generate a reconstructed item exposure vector. Moreover, DIVERS employs an identifiable Variational Auto-Encoder (iVAE) to infer identifiable representations by utilising information from both the original and reconstructed item exposure vectors, effectively addressing the confounding bias introduced by latent confounders between item exposure and user feedback. Additionally, we provide theoretical analyses to demonstrate the soundness of using IV and the identifiability of the representation learned by DIVERS. Extensive experiments on both synthetic and real-world datasets confirm that DIVERS outperforms state-of-the-art models in reducing bias and providing reliable recommendations. Our source code is available at: https://github.com/djf-web/DIVERS.

Graph Anomaly Detection (GAD) aims to identify nodes that deviate from the majority within a graph, playing a crucial role in applications such as social networks and e-commerce. Despite the current advancements in deep learning-based GAD, existing approaches often suffer from high deployment costs and poor scalability due to their complex and resource-intensive training processes. Surprisingly, our empirical findings suggest that the training phase of deep GAD methods, commonly perceived as crucial, may actually contribute less to anomaly detection performance than expected. Inspired by this, we propose FreeGAD, a novel training-free yet effective GAD method. Specifically, it leverages an affinity-gated residual encoder to generate anomaly-aware representations. Meanwhile, FreeGAD identifies anchor nodes as pseudo-normal and anomalous guides, followed by calculating anomaly scores through anchor-guided statistical deviations. Extensive experiments demonstrate that FreeGAD achieves superior anomaly detection performance, efficiency, and scalability on multiple benchmark datasets from diverse domains, without any training or iterative optimization.

Large language models (LLMs) have gained increasing attention in recommender systems, but their inherent hallucination issues significantly compromise the accuracy and reliability of recommendation results.Existing LLM-based recommender systems predominantly rely on standard fine-tuning methodologies, often ignoring hallucination issues during the fine-tuning process.To address this challenge, we propose Logit Space Constraints Fine-Tuning (LCFT), a novel fine-tuning framework designed to mitigate hallucination in LLM-based recommenders.Specifically, LCFT takes as input semantically positive and negative instruction pairs and incorporates Kullback-Leibler (KL) divergence into the training objective to explicitly maximise their distributional disparity in the logit space.By conducting such logit space-constrained fine-tuning, LCFT encourages more distinguishable and semantically grounded representations, thereby reducing the model's susceptibility to hallucination.Extensive experiments on two recommendation models with distinct LLM backbones and four realworld datasets demonstrate that LCFT consistently reduces hallucination and enhances recommendation performance.Our source

With the rapid development of Large Language Model (LLM) technology, it has become an indispensable force in biomedical data analysis research. However, biomedical researchers currently have limited knowledge about LLM. Therefore, there is an urgent need for a summary of LLM applications in biomedical data analysis. Herein, we propose this review by summarizing the latest research work on LLM in biomedicine. In this review, LLM techniques are first outlined. We then discuss biomedical datasets and frameworks for biomedical data analysis, followed by a detailed analysis of LLM applications in genomics, proteomics, transcriptomics, radiomics, single-cell analysis, medical texts and drug discovery. Finally, the challenges of LLM in biomedical data analysis are discussed. In summary, this review is intended for researchers interested in LLM technology and aims to help them understand and apply LLM in biomedical data analysis research.

Graph neural networks (GNNs) excel in graph representation learning by integrating graph structure and node features. Existing GNNs, unfortunately, fail to account for the uncertainty of class probabilities that vary with the depth of the model, leading to unreliable and risky predictions in real-world scenarios. To bridge the gap, in this article, we propose a novel evidence-fusing graph neural network (EFGNN) to achieve trustworthy prediction, enhance node classification accuracy, and make explicit the risk of wrong predictions. In particular, we integrate the evidence theory with multihop propagation-based GNN architecture to quantify the prediction uncertainty of each node with the consideration of multiple receptive fields. Moreover, a parameter-free cumulative belief fusion (CBF) mechanism is developed to leverage the changes in prediction uncertainty and fuse the evidence to improve the trustworthiness of the final prediction. To effectively optimize the EFGNN model, we carefully design a joint learning objective composed of evidence cross-entropy, dissonance coefficient, and false confident penalty. The experimental results on various datasets and theoretical analyses demonstrate the effectiveness of the proposed model in terms of accuracy and trustworthiness, as well as its robustness to potential attacks.

Increasing multiple behavior recommendation models have achieved great successes. However, many models do not consider commonalities and differences between behaviors and data sparsity of the target behavior. This article proposes a novel multi-behavior recommendation model based on contrastive clustering learning (MBRCC). Specifically, the graph convolutional network (GCN) is employed to obtain the embeddings of users and items, respectively. Then, three kinds of tasks (including behavior-level embedding, instance-level embedding, and cluster-level embedding) are designed to optimize the embeddings of users and items. In behavior-level embedding, we design an adaptive parameter learning strategy to analyze the impact of auxiliary behaviors on the target behavior. Then, the embeddings of users for each behavior are weighted to obtain the final embeddings of users. In instance-level embedding, we employ contrastive learning to analyze the instances of user and item for mitigating the issue of data sparsity. In cluster-level embedding, we design a new cluster contrastive learning method to capture the similarity between groups of user and item. Finally, we combine these three tasks to improve the quality of the embeddings of users and items. We conduct extensive experiments on three real-world datasets and experimental results indicate that the MBRCC remarkably outperforms numerous existing recommendation models.

Unsupervised graph representation learning (UGRL) based on graph neural networks (GNNs), has received increasing attention owing to its efficacy in handling graph-structured data. However, existing UGRL methods ideally assume that the node features are noise-free, which makes them fail to distinguish between useful information and noise when applied to real data with noisy features, thus affecting the quality of learned representations. This urges us to take node noisy features into account in real-world UGRL. With empirical analysis, we reveal that feature propagation, the essential operation in GNNs, acts as a "double-edged sword" in handling noisy features - it can both denoise and diffuse noise, leading to varying feature quality across nodes, even within the same node at different hops. Building on this insight, we propose a novel UGRL method based on Multi-hop feature Quality Estimation (MQE for short). Unlike most UGRL models that directly utilize propagation-based GNNs to generate representations, our approach aims to learn representations through estimating the quality of propagated features at different hops. Specifically, we introduce a Gaussian model that utilizes a learnable "meta-representation" as a condition to estimate the expectation and variance of multi-hop propagated features via neural networks. In this way, the ''meta representation'' captures the semantic and structural information underlying multiple propagated features but is naturally less susceptible to interference by noise, thereby serving as high-quality node representations beneficial for downstream tasks. Extensive experiments on multiple real-world datasets demonstrate that MQE in learning reliable node representations in scenarios with diverse types of feature noise.

Recommender systems rely on observational data to predict user ratings for unseen items. Since the observational data is typically missing not at random (MNAR), they contain biases, predominantly selection bias, thus models trained on such data are inherently biased. If a shadow variable, which is a variable used instead of user's latent variables that influence both the treatment and the outcome, can be identified, it is possible to build unbiased models for recommender systems. To overcome the challenge of manually identifying valid shadow variables in the data, we propose a Shadow Variable Catcher (SVC), a model designed to learn the latent representation of shadow variables from observational data. By using the learned representation of shadow variables by SVC, we develop the Shadow Debiased Recommender (SDR) method to build an unbiased collaborative filtering model for addressing selection bias in recommender systems. Comprehensive experiments on both synthetic and real-world datasets, have verified the performance of SDR and demonstrated its effectiveness and robustness, and offer new insights into the mitigation of bias in recommender systems.

Graph anomaly detection (GAD), which aims to identify abnormal nodes that differ from the majority within a graph, has garnered significant attention. However, current GAD methods necessitate training specific to each dataset, resulting in high training costs, substantial data requirements, and limited generalizability when being applied to new datasets and domains. To address these limitations, this paper proposes ARC, a generalist GAD approach that enables a ``one-for-all'' GAD model to detect anomalies across various graph datasets on-the-fly. Equipped with in-context learning, ARC can directly extract dataset-specific patterns from the target dataset using few-shot normal samples at the inference stage, without the need for retraining or fine-tuning on the target dataset. ARC comprises three components that are well-crafted for capturing universal graph anomaly patterns: 1) smoothness-based feature **A**lignment module that unifies the features of different datasets into a common and anomaly-sensitive space; 2) ego-neighbor **R**esidual graph encoder that learns abnormality-related node embeddings; and 3) cross-attentive in-**C**ontext anomaly scoring module that predicts node abnormality by leveraging few-shot normal samples. Extensive experiments on multiple benchmark datasets from various domains demonstrate the superior anomaly detection performance, efficiency, and generalizability of ARC.

Deep learning-based multi-omics data integration methods have the capability to reveal the mechanisms of cancer development, discover cancer biomarkers and identify pathogenic targets. However, current methods ignore the potential correlations between samples in integrating multi-omics data. In addition, providing accurate biological explanations still poses significant challenges due to the complexity of deep learning models. Therefore, there is an urgent need for a deep learning-based multi-omics integration method to explore the potential correlations between samples and provide model interpretability. Herein, we propose a novel interpretable multi-omics data integration method (DeepKEGG) for cancer recurrence prediction and biomarker discovery. In DeepKEGG, a biological hierarchical module is designed for local connections of neuron nodes and model interpretability based on the biological relationship between genes/miRNAs and pathways. In addition, a pathway self-attention module is constructed to explore the correlation between different samples and generate the potential pathway feature representation for enhancing the prediction performance of the model. Lastly, an attribution-based feature importance calculation method is utilized to discover biomarkers related to cancer recurrence and provide a biological interpretation of the model. Experimental results demonstrate that DeepKEGG outperforms other state-of-the-art methods in 5-fold cross validation. Furthermore, case studies also indicate that DeepKEGG serves as an effective tool for biomarker discovery. The code is available at https://github.com/lanbiolab/DeepKEGG.

Lung adenocarcinoma (LUAD) is the most common histologic subtype of lung cancer. Early-stage patients have a 30-50% probability of metastatic recurrence after surgical treatment. Here, we propose a new computational framework, Interpretable Biological Pathway Graph Neural Networks (IBPGNET), based on pathway hierarchy relationships to predict LUAD recurrence and explore the internal regulatory mechanisms of LUAD. IBPGNET can integrate different omics data efficiently and provide global interpretability. In addition, our experimental results show that IBPGNET outperforms other classification methods in 5-fold cross-validation. IBPGNET identified PSMC1 and PSMD11 as genes associated with LUAD recurrence, and their expression levels were significantly higher in LUAD cells than in normal cells. The knockdown of PSMC1 and PSMD11 in LUAD cells increased their sensitivity to afatinib and decreased cell migration, invasion and proliferation. In addition, the cells showed significantly lower EGFR expression, indicating that PSMC1 and PSMD11 may mediate therapeutic sensitivity through EGFR expression.

With the rapidly development of biotechnology, it is now possible to obtain single-cell multi-omics data in the same cell. However, how to integrate and analyze these single-cell multi-omics data remains a great challenge. Herein, we introduce an interpretable multitask framework (scMoMtF) for comprehensively analyzing single-cell multi-omics data. The scMoMtF can simultaneously solve multiple key tasks of single-cell multi-omics data including dimension reduction, cell classification and data simulation. The experimental results shows that scMoMtF outperforms current state-of-the-art algorithms on these tasks. In addition, scMoMtF has interpretability which allowing researchers to gain a reliable understanding of potential biological features and mechanisms in single-cell multi-omics data.

CircRNA has been shown to be involved in the occurrence of many diseases. Several computational frameworks have been proposed to identify circRNA-disease associations. Despite the existing computational methods have obtained considerable successes, these methods still require to be improved as their performance may degrade due to the sparsity of the data and the problem of memory overflow. We develop a novel computational framework called LGCDA to predict circRNA-disease associations by fusing local and global features to solve the above mentioned problems. First, we construct closed local subgraphs by using k-hop closed subgraph and label the subgraphs to obtain rich graph pattern information. Then, the local features are extracted by using graph neural network (GNN). In addition, we fuse Gaussian interaction profile (GIP) kernel and cosine similarity to obtain global features. Finally, the score of circRNA-disease associations is predicted by using the multilayer perceptron (MLP) based on local and global features. We perform five-fold cross validation on five datasets for model evaluation and our model surpasses other advanced methods.

Multiview subspace clustering (MVSC) has been used to explore the internal structure of multiview datasets by revealing unique information from different views. Most existing methods ignore the consistent information and angular information of different views. In this article, we propose a novel MVSC via low-rank symmetric affinity graph (LSGMC) to tackle these problems. Specifically, considering the consistent information, we pursue a consistent low-rank structure across views by decomposing the coefficient matrix into three factors. Then, the symmetry constraint is utilized to guarantee weight consistency for each pair of data samples. In addition, considering the angular information, we utilize the fusion mechanism to capture the inherent structure of data. Furthermore, to alleviate the effect brought by the noise and the high redundant data, the Schatten p-norm is employed to obtain a low-rank coefficient matrix. Finally, an adaptive information reduction strategy is designed to generate a high-quality similarity matrix for spectral clustering. Experimental results on 11 datasets demonstrate the superiority of LSGMC in clustering performance compared with ten state-of-the-art multiview clustering methods.

Accumulating evidences demonstrate that circular RNA (circRNA) plays an important role in human diseases. Identification of circRNA-disease associations can help for the diagnosis of human diseases, while the traditional method based on biological experiments is time-consuming. In order to address the limitation, a series of computational methods have been proposed in recent years. However, few works have summarized these methods or compared the performance of them. In this paper, we divided the existing methods into three categories: information propagation, traditional machine learning and deep learning. Then, the baseline methods in each category are introduced in detail. Further, 5 different datasets are collected, and 14 representative methods of each category are selected and compared in the 5-fold, 10-fold cross-validation and the de novo experiment. In order to further evaluate the effectiveness of these methods, six common cancers are selected to compare the number of correctly identified circRNA-disease associations in the top-10, top-20, top-50, top-100 and top-200. In addition, according to the results, the observation about the robustness and the character of these methods are concluded. Finally, the future directions and challenges are discussed.

Detecting anomalies for dynamic graphs has drawn increasing attention due to their wide applications in social networks, e-commerce, and cybersecurity. Recent deep learning-based approaches have shown promising results over shallow methods. However, they fail to address two core challenges of anomaly detection in dynamic graphs: the lack of informative encoding for unattributed nodes and the difficulty of learning discriminate knowledge from coupled spatial-temporal dynamic graphs. To overcome these challenges, in this paper, we present a novelTransformer-basedAnomalyDetection framework forDYnamic graphs (TADDY). Our framework constructs a comprehensive node encoding strategy to better represent each node’s structural and temporal roles in an evolving graphs stream. Meanwhile, TADDY captures informative representation from dynamic graphs with coupled spatial-temporal patterns via a dynamic graph transformer model. The extensive experimental results demonstrate that our proposed TADDY framework outperforms the state-of-the-art methods by a large margin on six real-world datasets.

Assay of single cell transposase-accessible chromatin with high-throughput sequencing (scATAC-seq) have enabled massively profiling of the chromatin accessibility landscape at the single-cell level. The essential step in analyzing scATAC-seq data is to cluster the cells into different clusters and utilize the clustering information in the subsequent downstream analysis. However, there are some challenges in the clustering analysis of scATAC-seq data. For example, scATAC-seq data are often high-dimensional and extremely sparse, as well as featuring high loss rate or noise. In this study, we proposed the scIAC to address these challenges of scATACseq data. In particular, scIAC combines the Student’s t-distribution similarity imputation and the denoising autoencoder based on the Zero-inflated Negative Binomial (ZINB) distribution. The Student’s t-distribution similarity imputation is used to solve the problem of high sparsity and high loss rate. The denoising autoencoder is employ to extract features which are useful for clustering and to reduce data noises. In addition, the self-training soft K-means and pairwise constraints are utilized in the clustering phase to enhance clustering performance. The experimental validation on several datasets shows that the proposed method performed better than other state-of-the-art methods. In conclusion, scIAC is an effective method to accurately cluster and identify cell types in scATAC-seq data.

Increasing evidences have proved that circRNA plays a significant role in the development of many diseases. In addition, many researches have shown that circRNA can be considered as the potential biomarker for clinical diagnosis and treatment of disease. Some computational methods have been proposed to predict circRNA-disease associations. However, the performance of these methods is limited as the sparsity of low-order interaction information. In this paper, we propose a new computational method (KGANCDA) to predict circRNA-disease associations based on knowledge graph attention network. The circRNA-disease knowledge graphs are constructed by collecting multiple relationship data among circRNA, disease, miRNA and lncRNA. Then, the knowledge graph attention network is designed to obtain embeddings of each entity by distinguishing the importance of information from neighbors. Besides the low-order neighbor information, it can also capture high-order neighbor information from multisource associations, which alleviates the problem of data sparsity. Finally, the multilayer perceptron is applied to predict the affinity score of circRNA-disease associations based on the embeddings of circRNA and disease. The experiment results show that KGANCDA outperforms than other state-of-the-art methods in 5-fold cross validation. Furthermore, the case study demonstrates that KGANCDA is an effective tool to predict potential circRNA-disease associations.

Accumulating evidences have shown that circRNA plays an important role in human diseases. It can be used as potential biomarker for diagnose and treatment of disease. Although some computational methods have been proposed to predict circRNA-disease associations, the performance still need to be improved. In this paper, we propose a new computational model based on Improved Graph convolutional network and Negative Sampling to predict CircRNA-Disease Associations. In our method, it constructs the heterogeneous network based on known circRNA-disease associations. Then, an improved graph convolutional network is designed to obtain the feature vectors of circRNA and disease. Further, the multi-layer perceptron is employed to predict circRNA-disease associations based on the feature vectors of circRNA and disease. In addition, the negative sampling method is employed to reduce the effect of the noise samples, which selects negative samples based on circRNA's expression profile similarity and Gaussian Interaction Profile kernel similarity. The 5-fold cross validation is utilized to evaluate the performance of the method. The results show that IGNSCDA outperforms than other state-of-the-art methods in the prediction performance. Moreover, the case study shows that IGNSCDA is an effective tool for predicting potential circRNA-disease associations.

It has been proved that long noncoding RNA (lncRNA) plays critical roles in many human diseases. Therefore, inferring associations between lncRNAs and diseases can contribute to disease diagnosis, prognosis and treatment. To overcome the limitation of traditional experimental methods such as expensive and time-consuming, several computational methods have been proposed to predict lncRNA-disease associations by fusing different biological data. However, the prediction performance of lncRNA-disease associations identification needs to be improved. In this study, we propose a computational model (named LDICDL) to identify lncRNA-disease associations based on collaborative deep learning. It uses an automatic encoder to denoise multiple lncRNA feature information and multiple disease feature information, respectively. Then, the matrix decomposition algorithm is employed to predict the potential lncRNA-disease associations. In addition, to overcome the limitation of matrix decomposition, the hybrid model is developed to predict associations between new lncRNA (or disease) and diseases (or lncRNA). The ten-fold cross validation and de novo test are applied to evaluate the performance of method. The experimental results show LDICDL outperforms than other state-of-the-art methods in prediction performance.

The rapid spread and huge impact of the COVID-19 pandemic caused by the emerging SARS-CoV-2 have driven large efforts for sequencing and analyzing the viral genomes. Mutation analyses have revealed that the virus keeps mutating and shows a certain degree of genetic diversity, which could result in the alteration of its infectivity and pathogenicity. Therefore, appropriate delineation of SARS-CoV-2 genetic variants enables us to understand its evolution and transmission patterns. By focusing on the nucleotides that co-substituted, we first identified 42 co-mutation modules that consist of at least two co-substituted nucleotides during the SARS-CoV-2 evolution. Then based on these co-mutation modules, we classified the SARS-CoV-2 population into 43 groups and further identified the phylogenetic relationships among groups based on the number of inconsistent co-mutation modules, which were validated with phylogenetic trees. Intuitively, we tracked tempo-spatial patterns of the 43 groups, of which 11 groups were geographic-specific. Different epidemic periods showed specific co-circulating groups, where the dominant groups existed and had multiple sub-groups of parallel evolution. Our work enables us to capture the evolution and transmission patterns of SARS-CoV-2, which can contribute to guiding the prevention and control of the COVID-19 pandemic. An interactive website for grouping SARS-CoV-2 genomes and visualizing the spatio-temporal distribution of groups is available at https://www.jianglab.tech/cmm-grouping/.

The dysregulation and mutation of long non-coding RNAs (lncRNAs) have been proved to result in a variety of human diseases. Identifying potential disease-related lncRNAs may benefit disease diagnosis, treatment and prognosis. A number of methods have been proposed to predict the potential lncRNA-disease relationships. However, most of them may give rise to incorrect results due to relying on single similarity measure. This article proposes a novel framework (ILDMSF) by fusing the lncRNA similarities and disease similarities, which are measured by lncRNA-related gene and known lncRNA-disease interaction and disease semantic interaction, and known lncRNA-disease interaction, respectively. Further, the support vector machine is employed to identify the potential lncRNA-disease associations based on the integrated similarity. The leave-one-out cross validation is performed to compare ILDMSF with other state of the art methods. The experimental results demonstrate our method is prospective in exploring potential correlations between lncRNA and disease.

The interaction between gene loci, namely epistasis, is a widespread biological genetic phenomenon. In genome-wide association studies(GWAS), epistasis detection of complex diseases is a major challenge. Although many approaches using statistics, machine learning, and information entropy were proposed for epistasis detection, the privacy preserving for single nucleotide polymorphism(SNP) data has been largely ignored. Thus, this paper proposes a novel two-stage approach. A fusion strategy assists in combining and sorting the SNPs importance scores obtained by the relief and mutual information, thereby obtaining a candidate set of SNPs. This avoids missing some SNPs with strong interaction. Furthermore, differentially private decision tree is applied to search for SNPs. This achieves the efficient epistasis detection of complex diseases on the basis of privacy preserving compared with heuristic methods. The recognition rate on simulation data set is more than 90%. Also, several susceptible loci including rs380390 and rs1329428 are found in the real data set for Age-related Macular Degeneration (AMD). This demonstrates that our method is promising in epistasis detection.

MOTIVATION: Next-generation sequencing platforms have produced huge amounts of sequence data. This is revolutionizing every aspect of genetic and genomic research. However, these sequence datasets contain quite a number of machine-induced errors-e.g. errors due to substitution can be as high as 2.5%. Existing error-correction methods are still far from perfect. In fact, more errors are sometimes introduced than correct corrections, especially by the prevalent k-mer based methods. The existing methods have also made limited exploitation of on-demand cloud computing. RESULTS: We introduce an error-correction method named MEC, which uses a two-layered MapReduce technique to achieve high correction performance. In the first layer, all the input sequences are mapped to groups to identify candidate erroneous bases in parallel. In the second layer, the erroneous bases at the same position are linked together from all the groups for making statistically reliable corrections. Experiments on real and simulated datasets show that our method outperforms existing methods remarkably. Its per-position error rate is consistently the lowest, and the correction gain is always the highest. AVAILABILITY AND IMPLEMENTATION: The source code is available at bioinformatics.gxu.edu.cn/ngs/mec. CONTACTS: [email protected] or [email protected]. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Frequently recurring RNA structural motifs play important roles in RNA folding process and interaction with other molecules. Traditional index-based and shape-based schemas are useful in modeling RNA secondary structures but ignore the structural discrepancy of individual RNA family member. Further, the in-depth analysis of underlying substructure pattern is insufficient due to varied and unnormalized substructure data. This prevents us from understanding RNAs functions and their inherent synergistic regulation networks. This article thus proposes a novel labeled graph-based algorithm RnaGraph to uncover frequently RNA substructure patterns. Attribute data and graph data are combined to characterize diverse substructures and their correlations, respectively. Further, a top-k graph pattern mining algorithm is developed to extract interesting substructure motifs by integrating frequency and similarity. The experimental results show that our methods assist in not only modelling complex RNA secondary structures but also identifying hidden but interesting RNA substructure patterns.

BACKGROUND: Regulation mechanisms between miRNAs and genes are complicated. To accomplish a biological function, a miRNA may regulate multiple target genes, and similarly a target gene may be regulated by multiple miRNAs. Wet-lab knowledge of co-regulating miRNAs is limited. This work introduces a computational method to group miRNAs of similar functions to identify co-regulating miRNAsfrom a similarity matrix of miRNAs. RESULTS: We define a novel information content of gene ontology (GO) to measure similarity between two sets of GO graphs corresponding to the two sets of target genes of two miRNAs. This between-graph similarity is then transferred as a functional similarity between the two miRNAs. Our definition of the information content is based on the size of a GO term's descendants, but adjusted by a weight derived from its depth level and the GO relationships at its path to the root node or to the most informative common ancestor (MICA). Further, a self-tuning technique and the eigenvalues of the normalized Laplacian matrix are applied to determine the optimal parameters for the spectral clustering of the similarity matrix of the miRNAs. CONCLUSIONS: Experimental results demonstrate that our method has better clustering performance than the existing edge-based, node-based or hybrid methods. Our method has also demonstrated a novel usefulness for the function annotation of new miRNAs, as reported in the detailed case studies.

MicroRNA (miRNA) is an endogenous small noncoding RNA that plays an important role in gene expression through the post-transcriptional gene regulation pathways. There are many literature works focusing on predicting miRNA targets and exploring gene regulatory networks of miRNA families. We suggest, however, the study to identify the interaction between miRNAs is insufficient. This paper presents a framework to identify relationships between miRNAs using joint entropy, to investigate the regulatory features of miRNAs. Both the sequence and secondary structure are taken into consideration to make our method more relevant from the biological viewpoint. Further, joint entropy is applied to identify correlated miRNAs, which are more desirable from the perspective of the gene regulatory network. A data set including Drosophila melanogaster and Anopheles gambiae is used in the experiment. The results demonstrate that our approach is able to identify known miRNA interaction and uncover novel patterns of miRNA regulatory network.

Many raw biological sequence data have been generated by the human genome project and related efforts. The understanding of structural information encoded by biological sequences is important to acquire knowledge of their biochemical functions but remains a fundamental challenge. Recent interest in RNA regulation has resulted in a rapid growth of deposited RNA secondary structures in varied databases. However, a functional classification and characterization of the RNA structure have only been partially addressed. This article aims to introduce a novel interval-based distance metric for structure-based RNA function assignment. The characterization of RNA structures relies on distance vectors learned from a collection of predicted structures. The distance measure considers the intersected, disjoint, and inclusion between intervals. A set of RNA pseudoknotted structures with known function are applied and the function of the query structure is determined by measuring structure similarity. This not only offers sequence distance criteria to measure the similarity of secondary structures but also aids the functional classification of RNA structures with pesudoknots.

The identification of RNA secondary structures has been among the most exciting recent developments in biology and medical science. It has been recognized that there is an abundance of functional structures with frameshifting, regulation of translation, and splicing functions. However, the inherent signal for secondary structures is weak and generally not straightforward due to complex interleaving substrings. This makes it difficult to explore their potential functions from various structure data. Our approach, based on a collection of predicted RNA secondary structures, allows us to efficiently capture interesting characteristic relations in RNA and bring out the top-ranked rules for specified association groups. Our results not only point to a number of interesting associations and include a brief biological interpretation to them. It assists biologists in sorting out the most significant characteristic structure patterns and predicting structure-function relationships in RNA.

An RNA pseudoknot consists of nonnested double-stranded stems connected by single-stranded loops. There is increasing recognition that RNA pseudoknots are one of the most prevalent RNA structures and fulfill a diverse set of biological roles within cells, and there is an expanding rate of studies into RNA pseudoknotted structures as well as increasing allocation of function. These not only produce valuable structural data but also facilitate an understanding of structural and functional characteristics in RNA molecules. PseudoBase is a database providing structural, functional, and sequence data related to RNA pseudoknots. To capture the features of RNA pseudoknots, we present a novel framework using quantitative association rule mining to analyze the pseudoknot data. The derived rules are classified into specified association groups regarding structure, function, and category of RNA pseudoknots. The discovered association rules assist biologists in filtering out significant knowledge of structure-function and structure-category relationships. A brief biological interpretation to the relationships is presented, and their potential correlations with each other are highlighted.

BACKGROUND: AMP-activated protein kinase (AMPK) has emerged as a significant signaling intermediary that regulates metabolisms in response to energy demand and supply. An investigation into the degree of activation and deactivation of AMPK subunits under exercise can provide valuable data for understanding AMPK. In particular, the effect of AMPK on muscle cellular energy status makes this protein a promising pharmacological target for disease treatment. As more AMPK regulation data are accumulated, data mining techniques can play an important role in identifying frequent patterns in the data. Association rule mining, which is commonly used in market basket analysis, can be applied to AMPK regulation. RESULTS: This paper proposes a framework that can identify the potential correlation, either between the state of isoforms of alpha, beta and gamma subunits of AMPK, or between stimulus factors and the state of isoforms. Our approach is to apply item constraints in the closed interpretation to the itemset generation so that a threshold is specified in terms of the amount of results, rather than a fixed threshold value for all itemsets of all sizes. The derived rules from experiments are roughly analyzed. It is found that most of the extracted association rules have biological meaning and some of them were previously unknown. They indicate direction for further research. CONCLUSION: Our findings indicate that AMPK has a great impact on most metabolic actions that are related to energy demand and supply. Those actions are adjusted via its subunit isoforms under specific physical training. Thus, there are strong co-relationships between AMPK subunit isoforms and exercises. Furthermore, the subunit isoforms are correlated with each other in some cases. The methods developed here could be used when predicting these essential relationships and enable an understanding of the functions and metabolic pathways regarding AMPK.