Boundary-Aware Gradient Operator Network for Medical Image Segmentation.

Medical image segmentation is a crucial task in computer-aided diagnosis. Although convolutional neural networks (CNNs) have made significant progress in the field of medical image segmentation, the convolution kernels of CNNs are optimized from random initialization without explicitly encoding gradient information, leading to a lack of specificity for certain features, such as blurred boundary features. Furthermore, the frequently applied down-sampling operation also loses the fine structural features in shallow layers. Therefore, we propose a boundary-aware gradient operator network (BG-Net) for medical image segmentation, in which the gradient convolution (GConv) and the boundary-aware mechanism (BAM) modules are developed to simulate image boundary features and the remote dependencies between channels. The GConv module transforms the gradient operator into a convolutional operation that can extract gradient features; it attempts to extract more features such as images boundaries and textures, thereby fully utilizing limited input to capture more features representing boundaries. In addition, the BAM can increase the amount of global contextual information while suppressing invalid information by focusing on feature dependencies and the weight ratios between channels. Thus, the boundary perception ability of BG-Net is improved. Finally, we use a multi-modal fusion mechanism to effectively fuse lightweight gradient convolution and U-shaped branch features into a multilevel feature, enabling global dependencies and low-level spatial details to be effectively captured in a shallower manner. We conduct extensive experiments on eight datasets that broadly cover medical images to evaluate the effectiveness of the proposed BG-Net. The experimental results demonstrate that BG-Net outperforms the state-of-the-art methods, particularly those focused on boundary segmentation. The codes are available at https://github.com/LiYu51/BG-Net.

Identification of important gene signatures in schizophrenia through feature fusion and genetic algorithm.

Schizophrenia is a debilitating psychiatric disorder that can significantly affect a patient's quality of life and lead to permanent brain damage. Although medical research has identified certain genetic risk factors, the specific pathogenesis of the disorder remains unclear. Despite the prevalence of research employing magnetic resonance imaging, few studies have focused on the gene level and gene expression profile involving a large number of screened genes. However, the high dimensionality of genetic data presents a great challenge to accurately modeling the data. To tackle the current challenges, this study presents a novel feature selection strategy that utilizes heuristic feature fusion and a multi-objective optimization genetic algorithm. The goal is to improve classification performance and identify the key gene subset for schizophrenia diagnostics. Traditional gene screening techniques are inadequate for accurately determining the precise number of key genes associated with schizophrenia. Our innovative approach integrates a filter-based feature selection method to reduce data dimensionality and a multi-objective optimization genetic algorithm for improved classification tasks. By combining the filtering and wrapper methods, our strategy leverages their respective strengths in a deliberate manner, leading to superior classification accuracy and a more efficient selection of relevant genes. This approach has demonstrated significant improvements in classification results across 11 out of 14 relevant datasets. The performance on the remaining three datasets is comparable to the existing methods. Furthermore, visual and enrichment analyses have confirmed the practicality of our proposed method as a promising tool for the early detection of schizophrenia.

TsImpute: an accurate two-step imputation method for single-cell RNA-seq data.

MOTIVATION: Single-cell RNA sequencing (scRNA-seq) technology has enabled discovering gene expression patterns at single cell resolution. However, due to technical limitations, there are usually excessive zeros, called "dropouts," in scRNA-seq data, which may mislead the downstream analysis. Therefore, it is crucial to impute these dropouts to recover the biological information. RESULTS: We propose a two-step imputation method called tsImpute to impute scRNA-seq data. At the first step, tsImpute adopts zero-inflated negative binomial distribution to discriminate dropouts from true zeros and performs initial imputation by calculating the expected expression level. At the second step, it conducts clustering with this modified expression matrix, based on which the final distance weighted imputation is performed. Numerical results based on both simulated and real data show that tsImpute achieves favorable performance in terms of gene expression recovery, cell clustering, and differential expression analysis. AVAILABILITY AND IMPLEMENTATION: The R package of tsImpute is available at https://github.com/ZhengWeihuaYNU/tsImpute.

Precise Facial Landmark Detection by Reference Heatmap Transformer.

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.

Characteristics of groundwater microbial communities and the correlation with the environmental factors in a decommissioned acid in-situ uranium mine.

Microorganisms play an important role in the bioremediation process for the decommissioned acid in-situ leaching uranium mine. It is crucial to understand the original microbial community characteristics before the in-situ bioremediation. However, there are limited studies on the groundwater microbial characteristics in the decommissioned acid in-situ uranium mine. To this end, we collected groundwater samples, including the groundwater that originally residual in the borehole (RW) and the aquifer water (AW), from a decommissioned acid in-situ uranium mine in the southern margin of Ili Basin in Xinjiang, China. The occurrence characteristics of the groundwater microbial communities and their correlation with environmental factors were systematically studied based on the high throughput 16S rRNA gene sequencing data and geochemical data. Results found that the AW samples had higher alpha- and beta- diversity than the RW samples. The relative abundance of Sporosarcina, Sulfobacillus, Pedobacter and Pseudomonas were significantly different in the AW and RW samples, which had significant correlation with pH, metals, and sulfate, etc. A series of reducing microorganisms were discovered, such as sulfate reduction (e.g., Desulfosporosinus) and metal reduction (e.g., Arthrobacter, Bacillus, Clostridium, Pseudomonas, and Rhodanobacter), which have the potential to attenuate sulfate and uranium in groundwater. In addition, we found that pH and redox potential (Eh) were the dominant environmental factors affecting the microbial composition. This study extends our knowledge of microbial community structure changes in the decommissioned acid in-situ uranium mine and has positive implications for assessing the potential of natural attenuation and bioremediation strategies.

A Novel Sparse Graph-Regularized Singular Value Decomposition Model and Its Application to Genomic Data Analysis.

Learning the gene coexpression pattern is a central challenge for high-dimensional gene expression analysis. Recently, sparse singular value decomposition (SVD) has been used to achieve this goal. However, this model ignores the structural information between variables (e.g., a gene network). The typical graph-regularized penalty can be used to incorporate such prior graph information to achieve more accurate discovery and better interpretability. However, the existing approach fails to consider the opposite effect of variables with negative correlations. In this article, we propose a novel sparse graph-regularized SVD model with absolute operator (AGSVD) for high-dimensional gene expression pattern discovery. The key of AGSVD is to impose a novel graph-regularized penalty ( | u|T L| u| ). However, such a penalty is a nonconvex and nonsmooth function, so it brings new challenges to model solving. We show that the nonconvex problem can be efficiently handled in a convex fashion by adopting an alternating optimization strategy. The simulation results on synthetic data show that our method is more effective than the existing SVD-based ones. In addition, the results on several real gene expression data sets show that the proposed methods can discover more biologically interpretable expression patterns by incorporating the prior gene network.

Network-based cancer genomic data integration for pattern discovery.

BACKGROUND: Since genes involved in the same biological modules usually present correlated expression profiles, lots of computational methods have been proposed to identify gene functional modules based on the expression profiles data. Recently, Sparse Singular Value Decomposition (SSVD) method has been proposed to bicluster gene expression data to identify gene modules. However, this model can only handle the gene expression data where no gene interaction information is integrated. Ignoring the prior gene interaction information may produce the identified gene modules hard to be biologically interpreted. RESULTS: In this paper, we develop a Sparse Network-regularized SVD (SNSVD) method that integrates a prior gene interaction network from a protein protein interaction network and gene expression data to identify underlying gene functional modules. The results on a set of simulated data show that SNSVD is more effective than the traditional SVD-based methods. The further experiment results on real cancer genomic data show that most co-expressed modules are not only significantly enriched on GO/KEGG pathways, but also correspond to dense sub-networks in the prior gene interaction network. Besides, we also use our method to identify ten differentially co-expressed miRNA-gene modules by integrating matched miRNA and mRNA expression data of breast cancer from The Cancer Genome Atlas (TCGA). Several important breast cancer related miRNA-gene modules are discovered. CONCLUSIONS: All the results demonstrate that SNSVD can overcome the drawbacks of SSVD and capture more biologically relevant functional modules by incorporating a prior gene interaction network. These identified functional modules may provide a new perspective to understand the diagnostics, occurrence and progression of cancer.

TSCCA: A tensor sparse CCA method for detecting microRNA-gene patterns from multiple cancers.

Existing studies have demonstrated that dysregulation of microRNAs (miRNAs or miRs) is involved in the initiation and progression of cancer. Many efforts have been devoted to identify microRNAs as potential biomarkers for cancer diagnosis, prognosis and therapeutic targets. With the rapid development of miRNA sequencing technology, a vast amount of miRNA expression data for multiple cancers has been collected. These invaluable data repositories provide new paradigms to explore the relationship between miRNAs and cancer. Thus, there is an urgent need to explore the complex cancer-related miRNA-gene patterns by integrating multi-omics data in a pan-cancer paradigm. In this study, we present a tensor sparse canonical correlation analysis (TSCCA) method for identifying cancer-related miRNA-gene modules across multiple cancers. TSCCA is able to overcome the drawbacks of existing solutions and capture both the cancer-shared and specific miRNA-gene co-expressed modules with better biological interpretations. We comprehensively evaluate the performance of TSCCA using a set of simulated data and matched miRNA/gene expression data across 33 cancer types from the TCGA database. We uncover several dysfunctional miRNA-gene modules with important biological functions and statistical significance. These modules can advance our understanding of miRNA regulatory mechanisms of cancer and provide insights into miRNA-based treatments for cancer.

Edge-group sparse PCA for network-guided high dimensional data analysis.

Motivation: Principal component analysis (PCA) has been widely used to deal with high-dimensional gene expression data. In this study, we proposed an Edge-group Sparse PCA (ESPCA) model by incorporating the group structure from a prior gene network into the PCA framework for dimension reduction and feature interpretation. ESPCA enforces sparsity of principal component (PC) loadings through considering the connectivity of gene variables in the prior network. We developed an alternating iterative algorithm to solve ESPCA. The key of this algorithm is to solve a new k-edge sparse projection problem and a greedy strategy has been adapted to address it. Here we adopted ESPCA for analyzing multiple gene expression matrices simultaneously. By incorporating prior knowledge, our method can overcome the drawbacks of sparse PCA and capture some gene modules with better biological interpretations. Results: We evaluated the performance of ESPCA using a set of artificial datasets and two real biological datasets (including TCGA pan-cancer expression data and ENCODE expression data), and compared their performance with PCA and sparse PCA. The results showed that ESPCA could identify more biologically relevant genes, improve their biological interpretations and reveal distinct sample characteristics. Availability and implementation: An R package of ESPCA is available at http://page.amss.ac.cn/shihua.zhang/. Supplementary information: Supplementary data are available at Bioinformatics online.

Network-Regularized Sparse Logistic Regression Models for Clinical Risk Prediction and Biomarker Discovery.

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 , which can reduce to different penalties, including Lasso, elastic net, and network-regularized terms with different . 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 and 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 to consider the difference between the absolute values of the coefficients. 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.