ACLNDA: an asymmetric graph contrastive learning framework for predicting noncoding RNA-disease associations in heterogeneous graphs.

Noncoding RNAs (ncRNAs), including long noncoding RNAs (lncRNAs) and microRNAs (miRNAs), play crucial roles in gene expression regulation and are significant in disease associations and medical research. Accurate ncRNA-disease association prediction is essential for understanding disease mechanisms and developing treatments. Existing methods often focus on single tasks like lncRNA-disease associations (LDAs), miRNA-disease associations (MDAs), or lncRNA-miRNA interactions (LMIs), and fail to exploit heterogeneous graph characteristics. We propose ACLNDA, an asymmetric graph contrastive learning framework for analyzing heterophilic ncRNA-disease associations. It constructs inter-layer adjacency matrices from the original lncRNA, miRNA, and disease associations, and uses a Top-K intra-layer similarity edges construction approach to form a triple-layer heterogeneous graph. Unlike traditional works, to account for both node attribute features (ncRNA/disease) and node preference features (association), ACLNDA employs an asymmetric yet simple graph contrastive learning framework to maximize one-hop neighborhood context and two-hop similarity, extracting ncRNA-disease features without relying on graph augmentations or homophily assumptions, reducing computational cost while preserving data integrity. Our framework is capable of being applied to a universal range of potential LDA, MDA, and LMI association predictions. Further experimental results demonstrate superior performance to other existing state-of-the-art baseline methods, which shows its potential for providing insights into disease diagnosis and therapeutic target identification. The source code and data of ACLNDA is publicly available at https://github.com/AI4Bread/ACLNDA.

Identifying TAD-like domains on single-cell Hi-C data by graph embedding and changepoint detection.

MOTIVATION: Topologically associating domains (TADs) are fundamental building blocks of 3D genome. TAD-like domains in single cells are regarded as the underlying genesis of TADs discovered in bulk cells. Understanding the organization of TAD-like domains helps to get deeper insights into their regulatory functions. Unfortunately, it remains a challenge to identify TAD-like domains on single-cell Hi-C data due to its ultra-sparsity. RESULTS: We propose scKTLD, an in silico tool for the identification of TAD-like domains on single-cell Hi-C data. It takes Hi-C contact matrix as the adjacency matrix for a graph, embeds the graph structures into a low-dimensional space with the help of sparse matrix factorization followed by spectral propagation, and the TAD-like domains can be identified using a kernel-based changepoint detection in the embedding space. The results tell that our scKTLD is superior to the other methods on the sparse contact matrices, including downsampled bulk Hi-C data as well as simulated and experimental single-cell Hi-C data. Besides, we demonstrated the conservation of TAD-like domain boundaries at single-cell level apart from heterogeneity within and across cell types, and found that the boundaries with higher frequency across single cells are more enriched for architectural proteins and chromatin marks, and they preferentially occur at TAD boundaries in bulk cells, especially at those with higher hierarchical levels. AVAILABILITY AND IMPLEMENTATION: scKTLD is freely available at https://github.com/lhqxinghun/scKTLD.

scHiCPTR: unsupervised pseudotime inference through dual graph refinement for single-cell Hi-C data.

MOTIVATION: The emerging single-cell Hi-C technology provides opportunities to study dynamics of chromosomal organization. How to construct a pseudotime path using single-cell Hi-C contact matrices to order cells along developmental trajectory is a challenging topic, since these matrices produced by the technology are inherently high dimensional and sparse, they suffer from noises and biases, and the topology of trajectory underlying them may be diverse. RESULTS: We present scHiCPTR, an unsupervised graph-based pipeline to infer pseudotime from single-cell Hi-C contact matrices. It provides a workflow consisting of imputation and embedding, graph construction, dual graph refinement, pseudotime calculation and result visualization. Beyond the few existing methods, scHiCPTR ties to optimize graph structure by two parallel procedures of graph pruning, which help reduce the spurious cell links resulted from noises and determine a global developmental directionality. Besides, it has an ability to handle developmental trajectories with multiple topologies, including linear, bifurcated and circular ones, and is competitive with methods developed for single-cell RNA-seq data. The comparative results tell that our scHiCPTR can achieve higher performance in pseudotime inference, and the inferred developmental trajectory exhibit a reasonable biological significance. AVAILABILITY AND IMPLEMENTATION: scHiCPTR is freely available at https://github.com/lhqxinghun/scHiCPTR. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

A Bevel Gear Quality Inspection System Based on Multi-Camera Vision Technology.

Surface defect detection and dimension measurement of automotive bevel gears by manual inspection are costly, inefficient, low speed and low accuracy. In order to solve these problems, a synthetic bevel gear quality inspection system based on multi-camera vision technology is developed. The system can detect surface defects and measure gear dimensions simultaneously. Three efficient algorithms named Neighborhood Average Difference (NAD), Circle Approximation Method (CAM) and Fast Rotation-Position (FRP) are proposed. The system can detect knock damage, cracks, scratches, dents, gibbosity or repeated cutting of the spline, etc. The smallest detectable defect is 0.4 mm × 0.4 mm and the precision of dimension measurement is about 40-50 µm. One inspection process takes no more than 1.3 s. Both precision and speed meet the requirements of real-time online inspection in bevel gear production.

KGRACDA: A Model Based on Knowledge Graph from Recursion and Attention Aggregation for CircRNA-disease Association Prediction.

CircRNA is closely related to human disease, so it is important to predict circRNA-disease association (CDA). However, the traditional biological detection methods have high difficulty and low accuracy, and computational methods represented by deep learning ignore the ability of the model to explicitly extract local depth information of the CDA. We propose a model based on knowledge graph from recursion and attention aggregation for circRNA-disease association prediction (KGRACDA). This model combines explicit structural features and implicit embedding information of graphs, optimizing graph embedding vectors. First, we built large-scale, multi-source heterogeneous datasets and construct a knowledge graph of multiple RNAs and diseases. After that, we use a recursive method to build multi-hop subgraphs and optimize graph attention mechanism by gating mechanism, mining local depth information. At the same time, the model uses multi-head attention mechanism to balance global and local depth features of graphs, and generate CDA prediction scores. KGRACDA surpasses other methods by capturing local and global depth information related to CDA. We update an interactive web platform HNRBase v2.0, which visualizes circRNA data, and allows users to download data and predict CDA using model.

TADfit is a multivariate linear regression model for profiling hierarchical chromatin domains on replicate Hi-C data.

Topologically associating domains (TADs) are fundamental building blocks of three dimensional genome, and organized into complex hierarchies. Identifying hierarchical TADs on Hi-C data helps to understand the relationship between genome architectures and gene regulation. Herein we propose TADfit, a multivariate linear regression model for profiling hierarchical chromatin domains, which tries to fit the interaction frequencies in Hi-C contact matrix with and without replicates using all-possible hierarchical TADs, and the significant ones can be determined by the regression coefficients obtained with the help of an online learning solver called Follow-The-Regularized-Leader (FTRL). Beyond the existing methods, TADfit has an ability to handle multiple contact matrix replicates and find partially overlapping TADs on them, which helps to find the comprehensive underlying TADs across replicates from different experiments. The comparative results tell that TADfit has better accuracy and reproducibility, and the hierarchical TADs called by it exhibit a reasonable biological relevance.

Comparison of normalization methods for Hi-C data.

Hi-C has been predominately used to study the genome-wide interactions of genomes. In Hi-C experiments, it is believed that biases originating from different systematic deviations lead to extraneous variability among raw samples, and affect the reliability of downstream interpretations. As an important pipeline in Hi-C analysis, normalization seeks to remove the unwanted systematic biases; thus, a comparison between Hi-C normalization methods benefits their choice and the downstream analysis. In this article, a comprehensive comparison is proposed to investigate six Hi-C normalization methods in terms of multiple considerations. In light of comparison results, it has been shown that a cross-sample approach significantly outperforms individual sample methods in most considerations. The differences between these methods are analyzed, some practical recommendations are given, and the results are summarized in a table to facilitate the choice of the six normalization methods. The source code for the implementation of these methods is available at https://github.com/lhqxinghun/bioinformatics/tree/master/Hi-C/NormCompare.

TADBD: a sensitive and fast method for detection of typologically associated domain boundaries.

A topologically associated domain (TAD) is a self-interacting genomic block. Detection of TAD boundaries on Hi-C contact matrix is one of the most important issues in the analysis of 3D genome architecture at TAD level. Here, we present TAD boundary detection (TADBD), a sensitive and fast computational method for detection of TAD boundaries on Hi-C contact matrix. This method implements a Haar-based algorithm by considering Haar diagonal template, acceleration via a compact integrogram, multi-scale aggregation at template size and statistical filtering. In most cases, comparison results from simulated and experimental data show that TADBD outperforms the other five methods. In addition, a new R package for TADBD is freely available online.

A filter feature selection method based on the Maximal Information Coefficient and Gram-Schmidt Orthogonalization for biomedical data mining.

A filter feature selection technique has been widely used to mine biomedical data. Recently, in the classical filter method minimal-Redundancy-Maximal-Relevance (mRMR), a risk has been revealed that a specific part of the redundancy, called irrelevant redundancy, may be involved in the minimal-redundancy component of this method. Thus, a few attempts to eliminate the irrelevant redundancy by attaching additional procedures to mRMR, such as Kernel Canonical Correlation Analysis based mRMR (KCCAmRMR), have been made. In the present study, a novel filter feature selection method based on the Maximal Information Coefficient (MIC) and Gram-Schmidt Orthogonalization (GSO), named Orthogonal MIC Feature Selection (OMICFS), was proposed to solve this problem. Different from other improved approaches under the max-relevance and min-redundancy criterion, in the proposed method, the MIC is used to quantify the degree of relevance between feature variables and target variable, the GSO is devoted to calculating the orthogonalized variable of a candidate feature with respect to previously selected features, and the max-relevance and min-redundancy can be indirectly optimized by maximizing the MIC relevance between the GSO orthogonalized variable and target. This orthogonalization strategy allows OMICFS to exclude the irrelevant redundancy without any additional procedures. To verify the performance, OMICFS was compared with other filter feature selection methods in terms of both classification accuracy and computational efficiency by conducting classification experiments on two types of biomedical datasets. The results showed that OMICFS outperforms the other methods in most cases. In addition, differences between these methods were analyzed, and the application of OMICFS in the mining of high-dimensional biomedical data was discussed. The Matlab code for the proposed method is available at https://github.com/lhqxinghun/bioinformatics/tree/master/OMICFS/.