Identification of the methotrexate resistance-related diagnostic markers in osteosarcoma via adaptive total variation netNMF and multi-omics datasets.

Osteosarcoma is one of the most common malignant bone tumors with high chemoresistance and poor prognosis, exhibiting abnormal gene regulation and epigenetic events. Methotrexate (MTX) is often used as a primary agent in neoadjuvant chemotherapy for osteosarcoma; However, the high dosage of methotrexate and strong drug resistance limit its therapeutic efficacy and application prospects. Studies have shown that abnormal expression and dysfunction of some coding or non-coding RNAs (e.g., DNA methylation and microRNA) affect key features of osteosarcoma progression, such as proliferation, migration, invasion, and drug resistance. Comprehensive multi-omics analysis is critical to understand its chemoresistant and pathogenic mechanisms. Currently, the network analysis-based non-negative matrix factorization (netNMF) method is widely used for multi-omics data fusion analysis. However, the effects of data noise and inflexible settings of regularization parameters affect its performance, while integrating and processing different types of genetic data is also a challenge. In this study, we introduced a novel adaptive total variation netNMF (ATV-netNMF) method to identify feature modules and characteristic genes by integrating methylation and gene expression data, which can adaptively choose an anisotropic smoothing scheme to denoise or preserve feature details based on the gradient information of the data by introducing an adaptive total variation constraint in netNMF. By comparing with other similar methods, the results showed that the proposed method could extract multi-omics fusion features more effectively. Furthermore, by combining the mRNA and miRNA data of methotrexate (MTX) resistance with the extracted feature genes, four genes, Carboxypeptidase E (CPE), LIM, SH3 protein 1 (LASP1), Pyruvate Dehydrogenase Kinase 1 (PDK1) and Serine beta-lactamase-like protein (LACTB) were finally identified. The results showed that the gene signature could reliably predict the prognostic status and immune status of osteosarcoma patients.

Biomimetic hydrogel derived from decellularized dermal matrix facilitates skin wounds healing.

Cutaneous wound healing affecting millions of people worldwide represents an unsolvable clinical issue that is frequently challenged by scar formation with dramatical pain, impaired mobility and disfigurement. Herein, we prepared a kind of light-sensitive decellularized dermal extracellular matrix-derived hydrogel with fast gelling performance, biomimetic porous microstructure and abundant bioactive functions. On account of its excellent cell biocompatibility, this ECM-derived hydrogel could induce a marked cellular infiltration and enhance the tube formation of HUVECs. In vivo experiments based upon excisional wound splinting model showed that the hydrogel prominently imparted skin wound healing, as evidenced by notably increased skin appendages and well-organized collagen expression, coupled with significantly enhanced angiogenesis. Moreover, the skin regeneration mediated by this bioactive hydrogel was promoted by an accelerated M1-to-M2 macrophage phenotype transition. Consequently, the decellularized dermal matrix-derived bioactive hydrogel orchestrates the entire skin healing microenvironment to promote wound healing and will be of high value in treatment of cutaneous wound healing. As such, this biomimetic ddECMMA hydrogel provides a promising versatile opinion for the clinical translation.

An improved immune algorithm with parallel mutation and its application.

The objective of this paper is to design a fast and efficient immune algorithm for solving various optimization problems. The immune algorithm (IA), which simulates the principle of the biological immune system, is one of the nature-inspired algorithms and its many advantages have been revealed. Although IA has shown its superiority over the traditional algorithms in many fields, it still suffers from the drawbacks of slow convergence and local minima trapping problems due to its inherent stochastic search property. Many efforts have been done to improve the search performance of immune algorithms, such as adaptive parameter setting and population diversity maintenance. In this paper, an improved immune algorithm (IIA) which utilizes a parallel mutation mechanism (PM) is proposed to solve the Lennard-Jones potential problem (LJPP). In IIA, three distinct mutation operators involving cauchy mutation (CM), gaussian mutation (GM) and lateral mutation (LM) are conditionally selected to be implemented. It is expected that IIA can effectively balance the exploration and exploitation of the search and thus speed up the convergence. To illustrate its validity, IIA is tested on a two-dimension function and some benchmark functions. Then IIA is applied to solve the LJPP to exhibit its applicability to the real-world problems. Experimental results demonstrate the effectiveness of IIA in terms of the convergence speed and the solution quality.

Application of orthogonal sparse joint non-negative matrix factorization based on connectivity in Alzheimer's disease research.

Based on the mining of micro- and macro-relationships of genetic variation and brain imaging data, imaging genetics has been widely applied in the early diagnosis of Alzheimer's disease (AD). However, effective integration of prior knowledge remains a barrier to determining the biological mechanism of AD. This paper proposes a new connectivity-based orthogonal sparse joint non-negative matrix factorization (OSJNMF-C) method based on integrating the structural magnetic resonance image, single nucleotide polymorphism and gene expression data of AD patients; the correlation information, sparseness, orthogonal constraint and brain connectivity information between the brain image data and genetic data are designed as constraints in the proposed algorithm, which efficiently improved the accuracy and convergence through multiple iterative experiments. Compared with the competitive algorithm, OSJNMF-C has significantly smaller related errors and objective function values than the competitive algorithm, showing its good anti-noise performance. From the biological point of view, we have identified some biomarkers and statistically significant relationship pairs of AD/mild cognitive impairment (MCI), such as rs75277622 and BCL7A, which may affect the function and structure of multiple brain regions. These findings will promote the prediction of AD/MCI.

A Novel Longitudinal Phenotype-Genotype Association Study Based on Deep Feature Extraction and Hypergraph Models for Alzheimer's Disease.

Traditional image genetics primarily uses linear models to investigate the relationship between brain image data and genetic data for Alzheimer's disease (AD) and does not take into account the dynamic changes in brain phenotype and connectivity data across time between different brain areas. In this work, we proposed a novel method that combined Deep Subspace reconstruction with Hypergraph-Based Temporally-constrained Group Sparse Canonical Correlation Analysis (DS-HBTGSCCA) to discover the deep association between longitudinal phenotypes and genotypes. The proposed method made full use of dynamic high-order correlation between brain regions. In this method, the deep subspace reconstruction technique was applied to retrieve the nonlinear properties of the original data, and hypergraphs were used to mine the high-order correlation between two types of rebuilt data. The molecular biological analysis of the experimental findings demonstrated that our algorithm was capable of extracting more valuable time series correlation from the real data obtained by the AD neuroimaging program and finding AD biomarkers across multiple time points. Additionally, we used regression analysis to verify the close relationship between the extracted top brain areas and top genes and found the deep subspace reconstruction approach with a multi-layer neural network was helpful in enhancing clustering performance.

An improved MOPSO approach with adaptive strategy for identifying biomarkers from gene expression dataset.

Biomarkers plays an important role in the prediction and diagnosis of cancers. Therefore, it is urgent to design effective methods to extract biomarkers. The corresponding pathway information of the microarray gene expression data can be obtained from public database, which makes possible to identify biomarkers based on pathway information and has been attracted extensive attention. In the most existing methods, all the member genes in the same pathway are regarded as equally important for inferring pathway activity. However, the contribution of each gene should be different in the process of inferring pathway activity. In this research, an improved multi-objective particle swarm optimization algorithm with penalty boundary intersection decomposition mechanism (IMOPSO-PBI) has been proposed to quantify the relevance of each gene in pathway activity inference. In the proposed algorithm, two optimization objectives namely t-score and z-score respectively has been introduced. In addition, in order to solve the problem that optimal set with poor diversity in the most multi-objective optimization algorithms, an adaptive mechanism for adjusting penalty parameters based on PBI decomposition has been introduced. The performance of the proposed IMOPSO-PBI approach compared with some existing methods on six gene expression datasets has been given. To verify the effectiveness of the proposed IMOPSO-PBI algorithm, experiments were carried out on six gene datasets and the results has been compared with the existing methods. The comparative experiment results show that the proposed IMOPSO-PBI method has a higher classification accuracy and the extracted feature genes are verified possess biological significance.

Multimodal data fusion based on IGERNNC algorithm for detecting pathogenic brain regions and genes in Alzheimer's disease.

At present, the study on the pathogenesis of Alzheimer's disease (AD) by multimodal data fusion analysis has been attracted wide attention. It often has the problems of small sample size and high dimension with the multimodal medical data. In view of the characteristics of multimodal medical data, the existing genetic evolution random neural network cluster (GERNNC) model combine genetic evolution algorithm and neural network for the classification of AD patients and the extraction of pathogenic factors. However, the model does not take into account the non-linear relationship between brain regions and genes and the problem that the genetic evolution algorithm can fall into local optimal solutions, which leads to the overall performance of the model is not satisfactory. In order to solve the above two problems, this paper made some improvements on the construction of fusion features and genetic evolution algorithm in GERNNC model, and proposed an improved genetic evolution random neural network cluster (IGERNNC) model. The IGERNNC model uses mutual information correlation analysis method to combine resting-state functional magnetic resonance imaging data with single nucleotide polymorphism data for the construction of fusion features. Based on the traditional genetic evolution algorithm, elite retention strategy and large variation genetic algorithm are added to avoid the model falling into the local optimal solution. Through multiple independent experimental comparisons, the IGERNNC model can more effectively identify AD patients and extract relevant pathogenic factors, which is expected to become an effective tool in the field of AD research.

Predicting the prognosis of hepatocellular carcinoma based on the interaction between pyroptosis, apoptosis, and necroptosis.

Multiple programmed cell death pathways (pyroptosis, apoptosis, and necroptosis) are closely related to the progression of hepatocellular carcinoma (HCC). Furthermore, molecular interactions among pyroptotic, apoptotic, and necroptotic components may be new targets for cancer therapy. However, the signature of the genes involved in the interaction between pyroptosis, apoptosis, and necroptosis (PANRGs), and their prognostic value, is still unclear in HCC. In this study, we used HCC clinical and expression data from TCGA and GEO to explore the relationship between PANRGs and HCC. First, we determined the copy number variation incidence of 41 PANRGs genes and explored the prognostic correlation of these genes in HCC. Based on PANRGs, two molecular subgroups of HCC associated with prognosis were identified. We also found significant differences in the overall survival time and the immune infiltration of HCC patients between the two subgroups. Finally, based on the nine PANRGs (CDC25B, EZH2, HMOX1, PLK1, SQSTM1, WEE1, TREM2, MYCN, and FLT3), we constructed a prognostic model using LASSO-Cox regression analysis. The prognostic model could predict OS of HCC patients in TCGA and GEO cohorts with high accuracy. Significant correlations were found between prognosis-related PANRGs and the tumor immune microenvironment (TIME), tumor mutational burden (TMB), and drug sensitivity. In conclusion, we explored the role of PANRGs in HCC and the association of these genes with TIME, TMB, and drug sensitivity.

Biomarker Genes Discovery of Alzheimer's Disease by Multi-Omics-Based Gene Regulatory Network Construction of Microglia.

Microglia, the major immune cells in the brain, mediate neuroinflammation, increased oxidative stress, and impaired neurotransmission in Alzheimer's disease (AD), in which most AD risk genes are highly expressed. In microglia, due to the limitations of current single-omics data analysis, risk genes, the regulatory mechanisms, the mechanisms of action of immune responses and the exploration of drug targets for AD immunotherapy are still unclear. Therefore, we proposed a method to integrate multi-omics data based on the construction of gene regulatory networks (GRN), by combining weighted gene co-expression network analysis (WGCNA) with single-cell regulatory network inference and clustering (SCENIC). This enables snRNA-seq data and bulkRNA-seq data to obtain data on the deeper intermolecular regulatory relationships, related genes, and the molecular mechanisms of immune-cell action. In our approach, not only were central transcription factors (TF) STAT3, CEBPB, SPI1, and regulatory mechanisms identified more accurately than with single-omics but also immunotherapy targeting central TFs to drugs was found to be significantly different between patients. Thus, in addition to providing new insights into the potential regulatory mechanisms and pathogenic genes of AD microglia, this approach can assist clinicians in making the most rational treatment plans for patients with different risks; it also has significant implications for identifying AD immunotherapy targets and targeting microglia-associated immune drugs.

Identify Biomarkers of Alzheimer's Disease Based on Multi-task Canonical Correlation Analysis and Regression Model.

Imaging genetics using imaging technology is regarded as a neuroanatomical phenotype to evaluate gene single nucleotide polymorphisms and their effects on the structure and function of different brain regions. It plays a vital role in bridging the initial understanding of the genetic basis of brain structure and dysfunction. Sparse canonical correlation analysis (SCCA) has become a widespread technique in this field because of its powerful ability to identify bivariate relationships and feature selection. Since most traditional SCCA algorithms assume that the input features are independent, this method obviously cannot be used to analyze genetic image data. The MT-SCCA model is unsupervised and cannot identify the genotype-phenotype associations for diagnostic guidance. Meanwhile, a single biological clinical index cannot fully reflect the physiological process of a comprehensive disease. Therefore, it is necessary to find biomarkers that can reflect Alzheimer's disease and physiological functions that can more comprehensively reflect the development of the disease. This article uses a multi-task sparse canonical correlation analysis and regression (MT-SCCAR) model to combine the annual depression level total score (GDSCALE), clinical dementia assessment scale (GLOBAL CDR), functional activity questionnaire (FAQ), and neuropsychiatric Symptom Questionnaire (NPI-Q) in this paper. These four clinical data are used as compensation information and embedded in the algorithm in a linear regression manner. It also reflects its superiority and robustness compared to traditional correlation analysis methods on actual and simulated data. Meanwhile, compared with MT-SCCA, the model utilized in this paper obtains a higher gene-ROI weight and identifies clearer biomarkers, which provides a practical basis for the study of complex human disease pathology.

Exploring autophagy-related prognostic genes of Alzheimer's disease based on pathway crosstalk analysis.

Recent studies have shown that different signaling pathways are involved in the pathogenesis of Alzheimer's disease (AD), with complex molecular connections existing between these pathways. Autophagy is crucial for the degradation and production of pathogenic proteins in AD, and it shows link with other AD-related pathways. However, current methods for identifying potential therapeutic targets for AD are primarily based on single-gene analysis or a single signal pathway, both of which are somewhat limited. Finding other methods is necessary for providing novel underlying AD therapeutic targets. Therefore, given the central role of autophagy in AD and its interplay with its pathways, we aimed to identify prognostic genes related to autophagy within and between these pathways based on pathway crosstalk analysis. The method of pathway analysis based on global influence (PAGI) was applied to find the feature mRNAs involved in the crosstalk between autophagy and other AD-related pathways. Subsequently, the weighted gene co-expression network analysis (WGCNA) was used to construct a co-expression module of feature mRNAs and differential lncRNAs. Finally, based on 2 autophagy-related crosstalk genes (CD40 and SMAD7), we constructed a prognosis model by multivariate Cox regression, which could predict the overall survival of AD patients with medium-to-high accuracy. In conclusion, we provided an effective method for extracting autophagy-related significant genes based on pathway crosstalk in AD. We found the biomarkers valuable to the AD prognosis, which may also play an essential role in the development and treatment of AD.

Detecting Biomarkers of Alzheimer's Disease Based on Multi-constrained Uncertainty-Aware Adaptive Sparse Multi-view Canonical Correlation Analysis.

Image genetics mainly explores the pathogenesis of Alzheimer's disease (AD) by studying the relationship between genetic data (such as SNP, gene expression data, and DNA methylation) and imaging data (such as structural MRI (sMRI), fMRI, and PET). Most of the existing research on brain imaging genomics uses two-way or three-way bi-multivariate methods to explore the correlation analysis between genes and brain imaging. However, many of these methods are still affected by the gradient domination or cannot take into account the effect of feature redundancy on the results, so that the typical correlation coefficient and program running speed are not significantly improved. In order to solve the above problems, this paper proposes a multi-constrained uncertainty-aware adaptive sparse multi-view canonical correlation analysis method (MC-unAdaSMCCA) to explore associations among SNPs, gene expression data, and sMRI; that is, based on traditional unAdaSMCCA, orthogonal constraints are imposed on the weights of the three data features through linear programming, which can reduce the redundancy of feature weights to improve the correlation between the data and reduce the complexity of the algorithm to significantly speed up the running speed of the program. Three adaptive sparse multi-view canonical correlation analysis methods are used as benchmarks to evaluate the difference between real neuroimaging data and synthetic data. Compared with the other three methods, our proposed method has obtained better or comparable typical correlation coefficients and typical weights. Moreover, the following experimental results show that the MC-unAdaSMCCA method cannot only identify biomarkers related to AD and mild cognitive impairment (MCI), but also has a strong ability to resist noise and process high-dimensional data. Therefore, our proposed method provides a reliable approach to multi-modal imaging genetic researches.

Integration of Imaging Genomics Data for the Study of Alzheimer's Disease Using Joint-Connectivity-Based Sparse Nonnegative Matrix Factorization.

Imaging genetics reveals the connection between microscopic genetics and macroscopic imaging, enabling the identification of disease biomarkers. In this work, we make full use of prior knowledge that has significant reference value for investigating the correlation between the brain and genetics to explore more biologically substantial biomarkers. In this paper, we propose joint-connectivity-based sparse nonnegative matrix factorization (JCB-SNMF). The algorithm simultaneously projects structural magnetic resonance imaging (sMRI), single-nucleotide polymorphism sites (SNPs), and gene expression data onto a common feature space, where heterogeneous variables with large coefficients in the same projection direction form a common module. In addition, the connectivity information for each region of the brain and genetic data are added as prior knowledge to identify regions of interest (ROIs), SNPs, and gene-related risks related to Alzheimer's disease (AD) patients. GraphNet regularization increases the anti-noise performance of the algorithm and the biological interpretability of the results. The simulation results show that compared with other NMF-based algorithms (JNMF, JSNMNMF), JCB-SNMF has better anti-noise performance and can identify and predict biomarkers closely related to AD from significant modules. By constructing a protein-protein interaction (PPI) network, we identified SF3B1, RPS20, and RBM14 as potential biomarkers of AD. We also found some significant SNP-ROI and gene-ROI pairs. Among them, two SNPs rs4472239 and rs11918049 and three genes KLHL8, ZC3H11A, and OSGEPL1 may have effects on the gray matter volume of multiple brain regions. This model provides a new way to further integrate multimodal impact genetic data to identify complex disease association patterns.

Identifying Biomarkers of Alzheimer's Disease via a Novel Structured Sparse Canonical Correlation Analysis Approach.

Using correlation analysis to study the potential connection between brain genetics and imaging has become an effective method to understand neurodegenerative diseases. Sparse canonical correlation analysis (SCCA) makes it possible to study high-dimensional genetic information. The traditional SCCA methods can only process single-modal genetic and image data, which to some extent weaken the close connection of the brain's biological network. In some recently proposed multimodal SCCA methods, due to the limitations of penalty items, the pre-processed data needs to be further filtered to make the dimensions uniform, which may destroy the potential association of data in the same modal. In this research, in order to combine data between different modalities and to ensure that the chain relationship or graph network relationship within the same modality will not be destroyed, the original generalized fused lasso penalty was replaced with the fused pairwise group lasso (FGL) and the graph-guided pairwise group lasso (GGL) based on the method of joint sparse canonical correlation analysis (JSCCA). We used prior knowledge to construct a supervised bivariate learning model and use linear regression to select quantitative traits (QTs) of images that are strongly correlated with the Mini-mental State Examination (MMSE) scores. Compared with FGL-SCCA, the model we constructed obtained a higher gene-ROI correlation coefficient and identified more significant biomarkers, providing a theoretical basis for further understanding the complex pathology of neurodegenerative diseases.

Associating brain imaging phenotypes and genetic in Alzheimer's disease via JSCCA approach with autocorrelation constraints.

Imaging genetics research can explore the potential correlation between imaging and genomics. Most association analysis methods cannot effectively use the prior knowledge of the original data. In this respect, we add the prior knowledge of each original data to mine more effective biomarkers. The study of imaging genetics based on the sparse canonical correlation analysis (SCCA) is helpful to mine the potential biomarkers of neurological diseases. To improve the performance and interpretability of SCCA, we proposed a penalty method based on the autocorrelation matrix for discovering the possible biological mechanism between single nucleotide polymorphisms (SNP) variations and brain regions changes of Alzheimer's disease (AD). The addition of the penalty allows the proposed algorithm to analyze the correlation between different modal features. The proposed algorithm obtains more biologically interpretable ROIs and SNPs that are significantly related to AD, which has better anti-noise performance. Compared with other SCCA-based algorithms (JCB-SCCA, JSNMNMF), the proposed algorithm can still maintain a stronger correlation with ground truth even when the noise is larger. Then, we put the regions of interest (ROI) selected by the three algorithms into the SVM classifier. The proposed algorithm has higher classification accuracy. Also, we use ridge regression with SNPs selected by three algorithms and four AD risk ROIs. The proposed algorithm has a smaller root mean square error (RMSE). It shows that proposed algorithm has a good ability in association recognition and feature selection. Furthermore, it selects important features more stably, improving the clinical diagnosis of new potential biomarkers.

Identifying Imaging Genetics Biomarkers of Alzheimer's Disease by Multi-Task Sparse Canonical Correlation Analysis and Regression.

Imaging genetics combines neuroimaging and genetics to assess the relationships between genetic variants and changes in brain structure and metabolism. Sparse canonical correlation analysis (SCCA) models are well-known tools for identifying meaningful biomarkers in imaging genetics. However, most SCCA models incorporate only diagnostic status information, which poses challenges for finding disease-specific biomarkers. In this study, we proposed a multi-task sparse canonical correlation analysis and regression (MT-SCCAR) model to reveal disease-specific associations between single nucleotide polymorphisms and quantitative traits derived from multi-modal neuroimaging data in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. MT-SCCAR uses complementary information carried by multiple-perspective cognitive scores and encourages group sparsity on genetic variants. In contrast with two other multi-modal SCCA models, MT-SCCAR embedded more accurate neuropsychological assessment information through linear regression and enhanced the correlation coefficients, leading to increased identification of high-risk brain regions. Furthermore, MT-SCCAR identified primary genetic risk factors for Alzheimer's disease (AD), including rs429358, and found some association patterns between genetic variants and brain regions. Thus, MT-SCCAR contributes to deciphering genetic risk factors of brain structural and metabolic changes by identifying potential risk biomarkers.

Detecting genetic associations with brain imaging phenotypes in Alzheimer's disease via a novel structured KCCA approach.

Neuroimaging genetics has become an important research topic since it can reveal complex associations between genetic variants (i.e. single nucleotide polymorphisms (SNPs) and the structures or functions of the human brain. However, existing kernel mapping is difficult to directly use the sparse representation method in the kernel feature space, which makes it difficult for most existing sparse canonical correlation analysis (SCCA) methods to be directly promoted in the kernel feature space. To bridge this gap, we adopt a novel alternating projected gradient approach, gradient KCCA (gradKCCA) model to develop a powerful model for exploring the intrinsic associations among genetic markers, imaging quantitative traits (QTs) of interest. Specifically, this model solves kernel canonical correlation (KCCA) with an additional constraint that projection directions have pre-images in the original data space, a sparsity-inducing variant of the model is achieved through controlling the [Formula: see text]-norm of the preimages of the projection directions. We evaluate this model using Alzheimer's disease Neuroimaging Initiative (ADNI) cohort to discover the relationships among SNPs from Alzheimer's disease (AD) risk gene APOE, imaging QTs extracted from structural magnetic resonance imaging (MRI) scans. Our results show that the algorithm not only outperforms the traditional KCCA method in terms of Root Mean Square Error (RMSE) and Correlation Coefficient (CC) but also identify the meaningful and relevant biomarkers of SNPs (e.g. rs157594 and rs405697), which are positively related to right Postcentral and right SupraMarginal brain regions in this study. Empirical results indicate its promising capability in revealing biologically meaningful neuroimaging genetics associations and improving the disease-related mechanistic understanding of AD.

Prediction of Overall Survival Rate in Patients With Hepatocellular Carcinoma Using an Integrated Model Based on Autophagy Gene Marker.

The autophagy cell, which can inhibit the formation of tumor in the early stage and can promote the development of tumor in the late stage, plays an important role in the development of tumor. Therefore, it has potential significance to explore the influence of autophagy-related genes (AAGs) on the prognosis of hepatocellular carcinoma (HCC). The differentially expressed AAGs are selected from HCC gene expression profile data and clinical data downloaded from the TCGA database, and human autophagy database (HADB). The role of AAGs in HCC is elucidated by GO functional annotation and KEGG pathway enrichment analysis. Combining with clinical data, we selected age, gender, grade, stage, T state, M state, and N state as Cox model indexes to construct the multivariate Cox model and survival curve of Kaplan Meier (KM) was drawn to estimate patients' survival between high- and low-risk groups. Through an ROC curve drawn by univariate and multivariate Cox regression analysis, we found that seven genes with high expression levels, including HSP90AB1, SQSTM1, RHEB, HDAC1, ATIC, HSPB8, and BIRC5 were associated with poor prognosis of HCC patients. Then the ICGC database is used to verify the reliability and robustness of the model. Therefore, the prognosis model of HCC constructed by autophagy genes might effectively predict the overall survival rate and help to find the best personalized targeted therapy of patients with HCC, which can provide better prognosis for patients.

Exploring the changes of brain immune microenvironment in Alzheimer's disease based on PANDA algorithm combined with blood brain barrier injury-related genes.

Studies have shown that the specific entry of peripheral cells into the brain parenchyma caused by BBB injury and the imbalance of the immune microenvironment in the brain are closely related to the pathogenesis of Alzheimer's disease (AD). Because of the difficulty of obtaining data inside the brain, it is urgent to find out the relationship between the peripheral and intracerebral data and their influence on the development of AD by machine learning methods. However, in the actual algorithm design, it is still a challenge to extract relevant information from a variety of data to establish a complete and accurate regulatory network. In order to overcome the above difficulties, we presented a method based on a message passing model (Passing Attributes between Networks for Data Assimilation, PANDA) to discover the correlation between internal and external brain by the BBB injury-related genes, and further explore their regulatory mechanism of the brain immune environment for AD pathology. The Biological analysis of the results showed that pathways such as immune response pathway, inflammatory response pathway and chemokine signaling pathway are closely related to the pathogenesis of AD. Especially, some significant genes such as RELA, LAMA4, PPBP were found play certain roles in the injury of BBB and the change of permeability in AD patients, thus leading to the change of immune microenvironment in AD brain.

Peripheral Blood Biomarkers CXCL12 and TNFRSF13C Associate with Cerebrospinal Fluid Biomarkers and Infiltrating Immune Cells in Alzheimer Disease.

Neuroinflammation-induced neurodegeneration and immune cell infiltration are two features of Alzheimer disease (AD). This study aimed to identify potential peripheral biomarkers that interact with cerebrospinal fluid (CSF) and infiltrating immune cells in AD. Blood and CSF data were downloaded from the Alzheimer's disease Neuroimaging Initiative database. We identified differentially expressed genes (DEGs) in AD and assessed infiltrating immune cells using the Immune Cell Abundance Identifier (ImmuCellAI) algorithm. Blood-brain barrier (BBB) and immune-related genes were identified from medical databases, and common genes were used to construct a protein-protein interaction network (PPI). Potential biomarkers reflecting the clinical features of AD were screened using Pearson correlations and logistic regression analysis. We identified 210 DEGs in the AD group. ImmuCellAI indicated that blood samples from patients with AD had a higher abundance of exhausted T (Tex; 0.196 vs. 0.132) and induced regulatory T (iTreg; 0.180 vs. 0.137) cells than controls. Thirty-two genes overlapped between the BBB and immune-related genes, and 27 genes in the PPI network were associated with eight pathways, including the cytokine-cytokine receptor interaction pathway (hsa04060) and the chemokine signaling pathway (hsa04062). Pearson correlations showed that five genes were associated with the CSF biomarkers, Aß, total, and phosphorylated tau. Logistics analysis showed that the B cell-associated genes, CXCL12 and TNFRSF13C, were independent risk factors for AD diagnosis. Peripheral CXCL12 and TNFRSF13C genes that correlated with immune cell infiltration in AD might serve as easily accessible biomarkers for the early diagnosis of AD.