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Emerging evidence indicates that human cancers are intricately linked to human microbiomes, forming an inseparable connection. However, due to limited sample sizes and significant data loss during collection for various reasons, some machine learning methods have been proposed to address the issue of missing data. These methods have not fully utilized the known clinical information of patients to enhance the accuracy of data imputation. Therefore, we introduce mbVDiT, a novel pre-trained conditional diffusion model for microbiome data imputation and denoising, which uses the unmasked data and patient metadata as conditional guidance for imputating missing values. It is also uses VAE to integrate the the other public microbiome datasets to enhance model performance. The results on the microbiome datasets from three different cancer types demonstrate the performance of our methods in comparison with existing methods.

Single-cell RNA sequencing (scRNA-seq) data analysis is pivotal for understanding cellular heterogeneity. However, the high sparsity and complex noise patterns inherent in scRNA-seq data present significant challenges for traditional clustering methods. To address these issues, we propose a deep clustering method, Attention-Enhanced Structural Deep Embedding Graph Clustering (scASDC), which integrates multiple advanced modules to improve clustering accuracy and robustness.Our approach employs a multi-layer graph convolutional network (GCN) to capture high-order structural relationships between cells, termed as the graph autoencoder module. To mitigate the oversmoothing issue in GCNs, we introduce a ZINB-based autoencoder module that extracts content information from the data and learns latent representations of gene expression. These modules are further integrated through an attention fusion mechanism, ensuring effective combination of gene expression and structural information at each layer of the GCN. Additionally, a self-supervised learning module is incorporated to enhance the robustness of the learned embeddings. Extensive experiments demonstrate that scASDC outperforms existing state-of-the-art methods, providing a robust and effective solution for single-cell clustering tasks. Our method paves the way for more accurate and meaningful analysis of single-cell RNA sequencing data, contributing to better understanding of cellular heterogeneity and biological processes. All code and public datasets used in this paper are available at \url{https://github.com/wenwenmin/scASDC} and \url{https://zenodo.org/records/12814320}.

Accurately determining cell type composition in disease-relevant tissues is crucial for identifying disease targets. Most existing spatial transcriptomics (ST) technologies cannot achieve single-cell resolution, making it challenging to accurately determine cell types. To address this issue, various deconvolution methods have been developed. Most of these methods use single-cell RNA sequencing (scRNA-seq) data from the same tissue as a reference to infer cell types in ST data spots. However, they often overlook the differences between scRNA-seq and ST data. To overcome this limitation, we propose a Masked Adversarial Neural Network (MACD). MACD employs adversarial learning to align real ST data with simulated ST data generated from scRNA-seq data. By mapping them into a unified latent space, it can minimize the differences between the two types of data. Additionally, MACD uses masking techniques to effectively learn the features of real ST data and mitigate noise. We evaluated MACD on 32 simulated datasets and 2 real datasets, demonstrating its accuracy in performing cell type deconvolution. All code and public datasets used in this paper are available at https://github.com/wenwenmin/MACD and https://zenodo.org/records/12804822.

With the rapid development of the latest Spatially Resolved Transcriptomics (SRT) technology, which allows for the mapping of gene expression within tissue sections, the integrative analysis of multiple SRT data has become increasingly important. However, batch effects between multiple slices pose significant challenges in analyzing SRT data. To address these challenges, we have developed a plug-and-play batch correction method called Global Nearest Neighbor (G2N) anchor pairs selection. G2N effectively mitigates batch effects by selecting representative anchor pairs across slices. Building upon G2N, we propose STG3Net, which cleverly combines masked graph convolutional autoencoders as backbone modules. These autoencoders, integrated with generative adversarial learning, enable STG3Net to achieve robust multi-slice spatial domain identification and batch correction. We comprehensively evaluate the feasibility of STG3Net on three multiple SRT datasets from different platforms, considering accuracy, consistency, and the F1LISI metric (a measure of batch effect correction efficiency). Compared to existing methods, STG3Net achieves the best overall performance while preserving the biological variability and connectivity between slices. Source code and all public datasets used in this paper are available at https://github.com/wenwenmin/STG3Net and https://zenodo.org/records/12737170.

With the rapid advancement of Spatial Resolved Transcriptomics (SRT) technology, it is now possible to comprehensively measure gene transcription while preserving the spatial context of tissues. Spatial domain identification and gene denoising are key objectives in SRT data analysis. We propose a Contrastively Augmented Masked Graph Autoencoder (STMGAC) to learn low-dimensional latent representations for domain identification. In the latent space, persistent signals for representations are obtained through self-distillation to guide self-supervised matching. At the same time, positive and negative anchor pairs are constructed using triplet learning to augment the discriminative ability. We evaluated the performance of STMGAC on five datasets, achieving results superior to those of existing baseline methods. All code and public datasets used in this paper are available at https://github.com/wenwenmin/STMGAC and https://zenodo.org/records/13253801.

Spatial transcriptomics (ST) is a groundbreaking genomic technology that enables spatial localization analysis of gene expression within tissue sections. However, it is significantly limited by high costs and sparse spatial resolution. An alternative, more cost-effective strategy is to use deep learning methods to predict high-density gene expression profiles from histological images. However, existing methods struggle to capture rich image features effectively or rely on low-dimensional positional coordinates, making it difficult to accurately predict high-resolution gene expression profiles. To address these limitations, we developed HisToSGE, a method that employs a Pathology Image Large Model (PILM) to extract rich image features from histological images and utilizes a feature learning module to robustly generate high-resolution gene expression profiles. We evaluated HisToSGE on four ST datasets, comparing its performance with five state-of-the-art baseline methods. The results demonstrate that HisToSGE excels in generating high-resolution gene expression profiles and performing downstream tasks such as spatial domain identification. All code and public datasets used in this paper are available at https://github.com/wenwenmin/HisToSGE and https://zenodo.org/records/12792163.

The rapid development of spatial transcriptomics (ST) technologies is revolutionizing our understanding of the spatial organization of biological tissues. Current ST methods, categorized into next-generation sequencing-based (seq-based) and fluorescence in situ hybridization-based (image-based) methods, offer innovative insights into the functional dynamics of biological tissues. However, these methods are limited by their cellular resolution and the quantity of genes they can detect. To address these limitations, we propose SpaDiT, a deep learning method that utilizes a diffusion generative model to integrate scRNA-seq and ST data for the prediction of undetected genes. By employing a Transformer-based diffusion model, SpaDiT not only accurately predicts unknown genes but also effectively generates the spatial structure of ST genes. We have demonstrated the effectiveness of SpaDiT through extensive experiments on both seq-based and image-based ST data. SpaDiT significantly contributes to ST gene prediction methods with its innovative approach. Compared to eight leading baseline methods, SpaDiT achieved state-of-the-art performance across multiple metrics, highlighting its substantial bioinformatics contribution.

The spatial location of cells within tissues and organs is crucial for the manifestation of their specific functions.Spatial transcriptomics technology enables comprehensive measurement of the gene expression patterns in tissues while retaining spatial information. However, current popular spatial transcriptomics techniques either have shallow sequencing depth or low resolution. We present stEnTrans, a deep learning method based on Transformer architecture that provides comprehensive predictions for gene expression in unmeasured areas or unexpectedly lost areas and enhances gene expression in original and inputed spots. Utilizing a self-supervised learning approach, stEnTrans establishes proxy tasks on gene expression profile without requiring additional data, mining intrinsic features of the tissues as supervisory information. We evaluate stEnTrans on six datasets and the results indicate superior performance in enhancing spots resolution and predicting gene expression in unmeasured areas compared to other deep learning and traditional interpolation methods. Additionally, Our method also can help the discovery of spatial patterns in Spatial Transcriptomics and enrich to more biologically significant pathways. Our source code is available at https://github.com/shuailinxue/stEnTrans., Comment: ISBRA2024, Code: https://github.com/shuailinxue/stEnTrans

In recent years, the advent of spatial transcriptomics (ST) technology has unlocked unprecedented opportunities for delving into the complexities of gene expression patterns within intricate biological systems. Despite its transformative potential, the prohibitive cost of ST technology remains a significant barrier to its widespread adoption in large-scale studies. An alternative, more cost-effective strategy involves employing artificial intelligence to predict gene expression levels using readily accessible whole-slide images (WSIs) stained with Hematoxylin and Eosin (H\&E). However, existing methods have yet to fully capitalize on multimodal information provided by H&E images and ST data with spatial location. In this paper, we propose \textbf{mclSTExp}, a multimodal contrastive learning with Transformer and Densenet-121 encoder for Spatial Transcriptomics Expression prediction. We conceptualize each spot as a "word", integrating its intrinsic features with spatial context through the self-attention mechanism of a Transformer encoder. This integration is further enriched by incorporating image features via contrastive learning, thereby enhancing the predictive capability of our model. Our extensive evaluation of \textbf{mclSTExp} on two breast cancer datasets and a skin squamous cell carcinoma dataset demonstrates its superior performance in predicting spatial gene expression. Moreover, mclSTExp has shown promise in interpreting cancer-specific overexpressed genes, elucidating immune-related genes, and identifying specialized spatial domains annotated by pathologists. Our source code is available at https://github.com/shizhiceng/mclSTExp., Comment: BIB, Code: https://github.com/shizhiceng/mclSTExp

Nonnegative Matrix Factorization (NMF) is a widely applied technique in the fields of machine learning and data mining. Graph Regularized Non-negative Matrix Factorization (GNMF) is an extension of NMF that incorporates graph regularization constraints. GNMF has demonstrated exceptional performance in clustering and dimensionality reduction, effectively discovering inherent low-dimensional structures embedded within high-dimensional spaces. However, the sensitivity of GNMF to noise limits its stability and robustness in practical applications. In order to enhance feature sparsity and mitigate the impact of noise while mining row sparsity patterns in the data for effective feature selection, we introduce the $\ell_{2,0}$-norm constraint as the sparsity constraints for GNMF. We propose an unsupervised feature learning framework based on GNMF\_$\ell_{20}$ and devise an algorithm based on PALM and its accelerated version to address this problem. Additionally, we establish the convergence of the proposed algorithms and validate the efficacy and superiority of our approach through experiments conducted on both simulated and real image data., Comment: Submitted to IEEE Trans journal

Spatially resolved transcriptomics represents a significant advancement in single-cell analysis by offering both gene expression data and their corresponding physical locations. However, this high degree of spatial resolution entails a drawback, as the resulting spatial transcriptomic data at the cellular level is notably plagued by a high incidence of missing values. Furthermore, most existing imputation methods either overlook the spatial information between spots or compromise the overall gene expression data distribution. To address these challenges, our primary focus is on effectively utilizing the spatial location information within spatial transcriptomic data to impute missing values, while preserving the overall data distribution. We introduce \textbf{stMCDI}, a novel conditional diffusion model for spatial transcriptomics data imputation, which employs a denoising network trained using randomly masked data portions as guidance, with the unmasked data serving as conditions. Additionally, it utilizes a GNN encoder to integrate the spatial position information, thereby enhancing model performance. The results obtained from spatial transcriptomics datasets elucidate the performance of our methods relative to existing approaches., Comment: Submitted to IJCAI2024

Chest X-rays (CXRs) are commonly utilized as a low-dose modality for lung screening. Nonetheless, the efficacy of CXRs is somewhat impeded, given that approximately 75% of the lung area overlaps with bone, which in turn hampers the detection and diagnosis of diseases. As a remedial measure, bone suppression techniques have been introduced. The current dual-energy subtraction imaging technique in the clinic requires costly equipment and subjects being exposed to high radiation. To circumvent these issues, deep learning-based image generation algorithms have been proposed. However, existing methods fall short in terms of producing high-quality images and capturing texture details, particularly with pulmonary vessels. To address these issues, this paper proposes a new bone suppression framework, termed BS-Diff, that comprises a conditional diffusion model equipped with a U-Net architecture and a simple enhancement module to incorporate an autoencoder. Our proposed network cannot only generate soft tissue images with a high bone suppression rate but also possesses the capability to capture fine image details. Additionally, we compiled the largest dataset since 2010, including data from 120 patients with high-definition, high-resolution paired CXRs and soft tissue images collected by our affiliated hospital. Extensive experiments, comparative analyses, ablation studies, and clinical evaluations indicate that the proposed BS-Diff outperforms several bone-suppression models across multiple metrics. Our code can be accessed at https://github.com/Benny0323/BS-Diff., Comment: 5 pages, 2 figures, accepted by IEEE ISBI 2024

Tensor data represents a multidimensional array. Regression methods based on low-rank tensor decomposition leverage structural information to reduce the parameter count. Multilinear logistic regression serves as a powerful tool for the analysis of multidimensional data. To improve its efficacy and interpretability, we present a Multilinear Sparse Logistic Regression model with $\ell_0$-constraints ($\ell_0$-MLSR). In contrast to the $\ell_1$-norm and $\ell_2$-norm, the $\ell_0$-norm constraint is better suited for feature selection. However, due to its nonconvex and nonsmooth properties, solving it is challenging and convergence guarantees are lacking. Additionally, the multilinear operation in $\ell_0$-MLSR also brings non-convexity. To tackle these challenges, we propose an Accelerated Proximal Alternating Linearized Minimization with Adaptive Momentum (APALM$^+$) method to solve the $\ell_0$-MLSR model. We provide a proof that APALM$^+$ can ensure the convergence of the objective function of $\ell_0$-MLSR. We also demonstrate that APALM$^+$ is globally convergent to a first-order critical point as well as establish convergence rate by using the Kurdyka-Lojasiewicz property. Empirical results obtained from synthetic and real-world datasets validate the superior performance of our algorithm in terms of both accuracy and speed compared to other state-of-the-art methods., Comment: arXiv admin note: text overlap with arXiv:2308.12126

We propose an accelerated block proximal linear framework with adaptive momentum (ABPL$^+$) for nonconvex and nonsmooth optimization. We analyze the potential causes of the extrapolation step failing in some algorithms, and resolve this issue by enhancing the comparison process that evaluates the trade-off between the proximal gradient step and the linear extrapolation step in our algorithm. Furthermore, we extends our algorithm to any scenario involving updating block variables with positive integers, allowing each cycle to randomly shuffle the update order of the variable blocks. Additionally, under mild assumptions, we prove that ABPL$^+$ can monotonically decrease the function value without strictly restricting the extrapolation parameters and step size, demonstrates the viability and effectiveness of updating these blocks in a random order, and we also more obviously and intuitively demonstrate that the derivative set of the sequence generated by our algorithm is a critical point set. Moreover, we demonstrate the global convergence as well as the linear and sublinear convergence rates of our algorithm by utilizing the Kurdyka-Lojasiewicz (K{\L}) condition. To enhance the effectiveness and flexibility of our algorithm, we also expand the study to the imprecise version of our algorithm and construct an adaptive extrapolation parameter strategy, which improving its overall performance. We apply our algorithm to multiple non-negative matrix factorization with the $\ell_0$ norm, nonnegative tensor decomposition with the $\ell_0$ norm, and perform extensive numerical experiments to validate its effectiveness and efficiency.

Sparse Partial Least Squares (sPLS) is a common dimensionality reduction technique for data fusion, which projects data samples from two views by seeking linear combinations with a small number of variables with the maximum variance. However, sPLS extracts the combinations between two data sets with all data samples so that it cannot detect latent subsets of samples. To extend the application of sPLS by identifying a specific subset of samples and remove outliers, we propose an $\ell_\infty/\ell_0$-norm constrained weighted sparse PLS ($\ell_\infty/\ell_0$-wsPLS) method for joint sample and feature selection, where the $\ell_\infty/\ell_0$-norm constrains are used to select a subset of samples. We prove that the $\ell_\infty/\ell_0$-norm constrains have the Kurdyka-\L{ojasiewicz}~property so that a globally convergent algorithm is developed to solve it. Moreover, multi-view data with a same set of samples can be available in various real problems. To this end, we extend the $\ell_\infty/\ell_0$-wsPLS model and propose two multi-view wsPLS models for multi-view data fusion. We develop an efficient iterative algorithm for each multi-view wsPLS model and show its convergence property. As well as numerical and biomedical data experiments demonstrate the efficiency of the proposed methods.

Most facial landmark detection methods predict landmarks by mapping the input facial appearance features to landmark heatmaps and have achieved promising results. However, when the face image is suffering from large poses, heavy occlusions and complicated illuminations, they cannot learn discriminative feature representations and effective facial shape constraints, nor can they accurately predict the value of each element in the landmark heatmap, limiting their detection accuracy. To address this problem, we propose a novel Reference Heatmap Transformer (RHT) by introducing reference heatmap information for more precise facial landmark detection. The proposed RHT consists of a Soft Transformation Module (STM) and a Hard Transformation Module (HTM), which can cooperate with each other to encourage the accurate transformation of the reference heatmap information and facial shape constraints. Then, a Multi-Scale Feature Fusion Module (MSFFM) is proposed to fuse the transformed heatmap features and the semantic features learned from the original face images to enhance feature representations for producing more accurate target heatmaps. To the best of our knowledge, this is the first study to explore how to enhance facial landmark detection by transforming the reference heatmap information. The experimental results from challenging benchmark datasets demonstrate that our proposed method outperforms the state-of-the-art methods in the literature., Comment: Accepted by IEEE Transactions on Image Processing, March 2023

Non-negative matrix factorization (NMF) is a powerful tool for dimensionality reduction and clustering. Unfortunately, the interpretation of the clustering results from NMF is difficult, especially for the high-dimensional biological data without effective feature selection. In this paper, we first introduce a row-sparse NMF with $\ell_{2,0}$-norm constraint (NMF_$\ell_{20}$), where the basis matrix $W$ is constrained by the $\ell_{2,0}$-norm, such that $W$ has a row-sparsity pattern with feature selection. It is a challenge to solve the model, because the $\ell_{2,0}$-norm is non-convex and non-smooth. Fortunately, we prove that the $\ell_{2,0}$-norm satisfies the Kurdyka-\L{ojasiewicz} property. Based on the finding, we present a proximal alternating linearized minimization algorithm and its monotone accelerated version to solve the NMF_$\ell_{20}$ model. In addition, we also present a orthogonal NMF with $\ell_{2,0}$-norm constraint (ONMF_$\ell_{20}$) to enhance the clustering performance by using a non-negative orthogonal constraint. We propose an efficient algorithm to solve ONMF_$\ell_{20}$ by transforming it into a series of constrained and penalized matrix factorization problems. The results on numerical and scRNA-seq datasets demonstrate the efficiency of our methods in comparison with existing methods.

Sparse Singular Value Decomposition (SVD) models have been proposed for biclustering high dimensional gene expression data to identify block patterns with similar expressions. However, these models do not take into account prior group effects upon variable selection. To this end, we first propose group-sparse SVD models with group Lasso (GL1-SVD) and group L0-norm penalty (GL0-SVD) for non-overlapping group structure of variables. However, such group-sparse SVD models limit their applicability in some problems with overlapping structure. Thus, we also propose two group-sparse SVD models with overlapping group Lasso (OGL1-SVD) and overlapping group L0-norm penalty (OGL0-SVD). We first adopt an alternating iterative strategy to solve GL1-SVD based on a block coordinate descent method, and GL0-SVD based on a projection method. The key of solving OGL1-SVD is a proximal operator with overlapping group Lasso penalty. We employ an alternating direction method of multipliers (ADMM) to solve the proximal operator. Similarly, we develop an approximate method to solve OGL0-SVD. Applications of these methods and comparison with competing ones using simulated data demonstrate their effectiveness. Extensive applications of them onto several real gene expression data with gene prior group knowledge identify some biologically interpretable gene modules., Comment: 14 pages, 4 figures

Given two data matrices $X$ and $Y$, sparse canonical correlation analysis (SCCA) is to seek two sparse canonical vectors $u$ and $v$ to maximize the correlation between $Xu$ and $Yv$. However, classical and sparse CCA models consider the contribution of all the samples of data matrices and thus cannot identify an underlying specific subset of samples. To this end, we propose a novel sparse weighted canonical correlation analysis (SWCCA), where weights are used for regularizing different samples. We solve the $L_0$-regularized SWCCA ($L_0$-SWCCA) using an alternating iterative algorithm. We apply $L_0$-SWCCA to synthetic data and real-world data to demonstrate its effectiveness and superiority compared to related methods. Lastly, we consider also SWCCA with different penalties like LASSO (Least absolute shrinkage and selection operator) and Group LASSO, and extend it for integrating more than three data matrices., Comment: 8 pages, 5 figures

Molecular profiling data (e.g., gene expression) has been used for clinical risk prediction and biomarker discovery. However, it is necessary to integrate other prior knowledge like biological pathways or gene interaction networks to improve the predictive ability and biological interpretability of biomarkers. Here, we first introduce a general regularized Logistic Regression (LR) framework with regularized term $\lambda \|\bm{w}\|_1 + \eta\bm{w}^T\bm{M}\bm{w}$, which can reduce to different penalties, including Lasso, elastic net, and network-regularized terms with different $\bm{M}$. This framework can be easily solved in a unified manner by a cyclic coordinate descent algorithm which can avoid inverse matrix operation and accelerate the computing speed. However, if those estimated $\bm{w}_i$ and $\bm{w}_j$ have opposite signs, then the traditional network-regularized penalty may not perform well. To address it, we introduce a novel network-regularized sparse LR model with a new penalty $\lambda \|\bm{w}\|_1 + \eta|\bm{w}|^T\bm{M}|\bm{w}|$ to consider the difference between the absolute values of the coefficients. And we develop two efficient algorithms to solve it. Finally, we test our methods and compare them with the related ones using simulated and real data to show their efficiency., Comment: 10 pages, 3 figures

Learning the "blocking" structure is a central challenge for high dimensional data (e.g., gene expression data). Recently, a sparse singular value decomposition (SVD) has been used as a biclustering tool to achieve this goal. However, this model ignores the structural information between variables (e.g., gene interaction graph). Although typical graph-regularized norm can incorporate such prior graph information to get accurate discovery and better interpretability, it fails to consider the opposite effect of variables with different signs. Motivated by the development of sparse coding and graph-regularized norm, we propose a novel sparse graph-regularized SVD as a powerful biclustering tool for analyzing high-dimensional data. The key of this method is to impose two penalties including a novel graph-regularized norm ($|\pmb{u}|\pmb{L}|\pmb{u}|$) and $L_0$-norm ($\|\pmb{u}\|_0$) on singular vectors to induce structural sparsity and enhance interpretability. We design an efficient Alternating Iterative Sparse Projection (AISP) algorithm to solve it. Finally, we apply our method and related ones to simulated and real data to show its efficiency in capturing natural blocking structures., Comment: 8 pages, 2 figures

To understand the structure and organization of a large-scale social, biological or technological network, it can be helpful to describe and extract local communities or modules of the network. In this article, we develop a neurodynamic framework to describe the local communities which correspond to the stable states of a neuro-system built based on the network. The quantitative criteria to describe the neurodynamic system can cover a large range of objective functions. The resolution limit of these functions enable us to propose a generic criterion to explore multi-resolution local communities. We explain the advantages of this framework and illustrate them by testing on a number of model and real-world networks., Comment: 4 figures