Liquid-liquid phase separation (LLPS) is a key mechanism driving the assembly of membrane-less organelles and is increasingly recognized for its involvement in essential cellular functions and various diseases. However, existing computational approaches largely rely on sequence-level descriptors and often fail to explicitly incorporate structural topology information, limiting their ability to capture the complex determinants of LLPS behavior. Accurate identification of LLPS-capable proteins remains challenging due to their sequence diversity and complex structural determinants. Here, we present MuFGPS (Multi-level Feature Graph-based Predictor for Phase-Separating proteins), a predictive framework integrating sequence-derived physicochemical features, Define Secondary Structure of Proteins-annotated secondary structures, and graph-based structural embeddings from AlphaFold residue contact maps via a multi-head Graph Attention Network. Class imbalance is addressed using Synthetic Minority Oversampling Technique (SMOTE), and classification is performed through a stacking ensemble of Random Forest, XGBoost, and LightGBM. Benchmarks against six representative methods demonstrate that MuFGPS achieves superior performance across all metrics, with notable gains in F1-score and matthews correlation coefficient (MCC). Ablation analyses confirm the synergistic contributions of structural features and ensemble learning to accuracy and robustness. MuFGPS offers a scalable and high-accuracy framework for proteome-wide LLPS protein prediction.

Pseudouridine is a type of abundant RNA modification that is seen in many different animals and is crucial for a variety of biological functions. Accurately identifying pseudouridine sites within the RNA sequence is vital for the subsequent study of various biological mechanisms of pseudouridine. However, the use of traditional experimental methods faces certain challenges. The development of fast and convenient computational methods is necessary to accurately identify pseudouridine sites from RNA sequence information. To address this, we introduce a novel pseudouridine site prediction model called PseU-KeMRF, which can identify pseudouridine sites in three species, H. sapiens, S. cerevisiae, and M. musculus. Through comprehensive analysis, we selected four RNA coding schemes, including binary feature, position-specific trinucleotide propensity based on single strand (PSTNPss), nucleotide chemical property (NCP) and pseudo k-tuple composition (PseKNC). Then the support vector machine-recursive feature elimination (SVM-RFE) method was used for feature selection and the feature subset was optimized. Finally, the best feature subsets are input into the kernel based on multinomial random forests (KeMRF) classifier for cross-validation and independent testing. As a new classification method, compared with the traditional random forest, KeMRF not only improves the node splitting process of decision tree construction based on multinomial distribution, but also combines the easy to interpret kernel method for prediction, which makes the classification performance better. Our results indicate superior predictive performance of PseU-KeMRF over other existing models, which can prove that PseU-KeMRF is a highly competitive predictive model that can successfully identify pseudouridine sites in RNA sequences.

Advances in single-cell RNA sequencing (scRNA-seq) technologies allow researchers to analyze the genome-wide transcription profile and to solve biological problems at the individual-cell resolution. However, existing clustering methods on scRNA-seq suffer from high dropout rate and curse of dimensionality in the data. Here, we propose a novel pipeline, scBKAP, the cornerstone of which is a single-cell bisecting K-means clustering method based on an autoencoder network and a dimensionality reduction model MPDR. Specially, scBKAP utilizes an autoencoder network to reconstruct gene expression values from scRNA-seq data to alleviate the dropout issue, and the MPDR model composed of the M3Drop feature selection algorithm and the PHATE dimensionality reduction algorithm to reduce the dimensions of reconstructed data. The dimensionality-reduced data are then fed into the bisecting K-means clustering algorithm to identify the clusters of cells. Comprehensive experiments demonstrate scBKAP's superior performance over nine state-of-the-art single-cell clustering methods on 21 public scRNA-seq datasets and simulated datasets. The source codes and datasets are available at https://github.com/YuBinLab-QUST/scBKAP/ and https://doi.org/10.24433/CO.4592131.v1.

Single-cell RNA-sequencing (scRNA-seq) data widely exist in bioinformatics. It is crucial to devise a distance metric for scRNA-seq data. Almost all existing clustering methods based on spectral clustering algorithms work in three separate steps: similarity graph construction; continuous labels learning; discretization of the learned labels by k-means clustering. However, this common practice has potential flaws that may lead to severe information loss and degradation of performance. Furthermore, the performance of a kernel method is largely determined by the selected kernel; a self-weighted multiple kernel learning model can help choose the most suitable kernel for scRNA-seq data. To this end, we propose to automatically learn similarity information from data. We present a new clustering method in the form of a multiple kernel combination that can directly discover groupings in scRNA-seq data. The main proposition is that automatically learned similarity information from scRNA-seq data is used to transform the candidate solution into a new solution that better approximates the discrete one. The proposed model can be efficiently solved by the standard support vector machine (SVM) solvers. Experiments on benchmark scRNA-Seq data validate the superior performance of the proposed model. Spectral clustering with multiple kernels is implemented in Matlab, licensed under Massachusetts Institute of Technology (MIT) and freely available from the Github website, https://github.com/Cuteu/SMSC/.

The rapid development of single-cell RNA sequencing (scRNA-Seq) technology provides strong technical support for accurate and efficient analyzing single-cell gene expression data. However, the analysis of scRNA-Seq is accompanied by many obstacles, including dropout events and the curse of dimensionality. Here, we propose the scGMAI, which is a new single-cell Gaussian mixture clustering method based on autoencoder networks and the fast independent component analysis (FastICA). Specifically, scGMAI utilizes autoencoder networks to reconstruct gene expression values from scRNA-Seq data and FastICA is used to reduce the dimensions of reconstructed data. The integration of these computational techniques in scGMAI leads to outperforming results compared to existing tools, including Seurat, in clustering cells from 17 public scRNA-Seq datasets. In summary, scGMAI is an effective tool for accurately clustering and identifying cell types from scRNA-Seq data and shows the great potential of its applicative power in scRNA-Seq data analysis. The source code is available at https://github.com/QUST-AIBBDRC/scGMAI/.

Appropriate ways to measure the similarity between single-cell RNA-sequencing (scRNA-seq) data are ubiquitous in bioinformatics, but using single clustering or classification methods to process scRNA-seq data is generally difficult. This has led to the emergence of integrated methods and tools that aim to automatically process specific problems associated with scRNA-seq data. These approaches have attracted a lot of interest in bioinformatics and related fields. In this paper, we systematically review the integrated methods and tools, highlighting the pros and cons of each approach. We not only pay particular attention to clustering and classification methods but also discuss methods that have emerged recently as powerful alternatives, including nonlinear and linear methods and descending dimension methods. Finally, we focus on clustering and classification methods for scRNA-seq data, in particular, integrated methods, and provide a comprehensive description of scRNA-seq data and download URLs.

Most existing metric learning methods focus on learning a similarity or distance measure relying on similar and dissimilar relations between sample pairs. However, pairs of samples cannot be simply identified as similar or dissimilar in many real-world applications, e.g., multi-label learning, label distribution learning or tasks with continuous decision values. To this end, in this paper we propose a novel relation alignment metric learning (RAML) formulation to handle the metric learning problem in those scenarios. Since the relation of two samples can be measured by the difference degree of the decision values, motivated by the consistency of the sample relations in the feature space and decision space, our proposed RAML utilizes the sample relations in the decision space to guide the metric learning in the feature space. Specifically, our RAML method formulates metric learning as a kernel regression problem, which can be efficiently optimized by the standard regression solvers. We carry out several experiments on the single-label classification, multi-label classification, and label distribution learning tasks, to demonstrate that our method achieves favorable performance against the state-of-the-art methods.