Alzheimer’s disease (AD) is a neurodegenerative brain disease, and it is challenging to mine features that distinguish AD and healthy control (HC) from multiple datasets. Brain network modeling technology in AD using single-modal images often lacks supplementary information regarding multi-source resolution and has poor spatiotemporal sensitivity. In this study, we proposed a novel multi-modal LassoNet framework with a neural network for AD-related feature detection and classification. Specifically, data including two modalities of resting-state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging (DTI) were adopted for predicting pathological brain areas related to AD. The results of 10 repeated experiments and validation experiments in three groups prove that our proposed framework outperforms well in classification performance, generalization, and reproducibility. Also, we found discriminative brain regions, such as Hippocampus, Frontal_Inf_Orb_L, Parietal_Sup_L, Putamen_L, Fusiform_R, etc. These discoveries provide a novel method for AD research, and the experimental study demonstrates that the framework will further improve our understanding of the mechanisms underlying the development of AD.

Voxel-based morphometry provides an opportunity to study Alzheimer’s disease (AD) at a subtle level. Therefore, identifying the important brain voxels that can classify AD, early mild cognitive impairment (EMCI) and healthy control (HC) and studying the role of these voxels in AD will be crucial to improve our understanding of the neurobiological mechanism of AD. Combining magnetic resonance imaging (MRI) imaging and gene information, we proposed a novel feature construction method and a novel genetic multi-kernel support vector machine (SVM) method to mine important features for AD detection. Specifically, to amplify the differences among AD, EMCI and HC groups, we used the eigenvalues of the top 24 Single Nucleotide Polymorphisms (SNPs) in a p-value matrix of 24 genes associated with AD for feature construction. Furthermore, a genetic multi-kernel SVM was established with the resulting features. The genetic algorithm was used to detect the optimal weights of 3 kernels and the multi-kernel SVM was used after training to explore the significant features. By analyzing the significance of the features, we identified some brain regions affected by AD, such as the right superior frontal gyrus, right inferior temporal gyrus and right superior temporal gyrus. The findings proved the good performance and generalization of the proposed model. Particularly, significant susceptibility genes associated with AD were identified, such as CSMD1, RBFOX1, PTPRD, CDH13 and WWOX. Some significant pathways were further explored, such as the calcium signaling pathway (corrected p-value = 1.35 × 10⁻⁶) and cell adhesion molecules (corrected p-value = 5.44 × 10⁻⁴). The findings offer new candidate abnormal brain features and demonstrate the contribution of these features to AD.

The cerebrospinal fluid (CSF) levels of total tau (t-tau) and Aβ1–42 are potential early diagnostic markers for probable Alzheimer’s disease (AD). The influence of genetic variation on these CSF biomarkers has been investigated in candidate or genome-wide association studies (GWAS). However, the investigation of statistically modest associations in GWAS in the context of biological networks is still an under-explored topic in AD studies. The main objective of this study is to gain further biological insights via the integration of statistical gene associations in AD with physical protein interaction networks. The CSF and genotyping data of 843 study subjects (199 CN, 85 SMC, 239 EMCI, 207 LMCI, 113 AD) from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) were analyzed. PLINK was used to perform GWAS on the t-tau/Aβ1–42 ratio using quality controlled genotype data, including 563,980 single nucleotide polymorphisms (SNPs), with age, sex and diagnosis as covariates. Gene-level p-values were obtained by VEGAS2. Genes with p-value ≤ 0.05 were mapped on to a protein-protein interaction (PPI) network (9,617 nodes, 39,240 edges, from the HPRD Database). We integrated a consensus model strategy into the iPINBPA network analysis framework, and named it as CM-iPINBPA. Four consensus modules (CMs) were discovered by CM-iPINBPA, and were functionally annotated using the pathway analysis tool Enrichr. The intersection of four CMs forms a common subnetwork of 29 genes, including those related to tau phosphorylation (GSK3B, SUMO1, AKAP5, CALM1 and DLG4), amyloid beta production (CASP8, PIK3R1, PPA1, PARP1, CSNK2A1, NGFR, and RHOA), and AD (BCL3, CFLAR, SMAD1, and HIF1A). This study coupled a consensus module (CM) strategy with the iPINBPA network analysis framework, and applied it to the GWAS of CSF t-tau/Aβ1-42 ratio in an AD study. The genome-wide network analysis yielded 4 enriched CMs that share not only genes related to tau phosphorylation or amyloid beta production but also multiple genes enriching several KEGG pathways such as Alzheimer’s disease, colorectal cancer, gliomas, renal cell carcinoma, Huntington’s disease, and others. This study demonstrated that integration of gene-level associations with CMs could yield statistically significant findings to offer valuable biological insights (e.g., functional interaction among the protein products of these genes) and suggest high confidence candidates for subsequent analyses.

In the studies of Alzheimer’s disease (AD), jointly analyzing imaging data and genetic data provides an effective method to explore the potential biomarkers of AD. AD can be separated into healthy controls (HC), early mild cognitive impairment (EMCI), late mild cognitive impairment (LMCI) and AD. In the meantime, identifying the important biomarkers of AD progression, and analyzing these biomarkers in AD provide valuable insights into understanding the mechanism of AD. In this paper, we present a novel data fusion method and a genetic weighted random forest method to mine important features. Specifically, we amplify the difference among AD, LMCI, EMCI and HC by introducing eigenvalues calculated from the gene p-value matrix for feature fusion. Furthermore, we construct the genetic weighted random forest using the resulting fused features. Genetic evolution is used to increase the diversity among decision trees and the decision trees generated are weighted by weights. After training, the genetic weighted random forest is analyzed further to detect the significant fused features. The validation experiments highlight the performance and generalization of our proposed model. We analyze the biological significance of the results and identify some significant genes (CSMD1, CDH13, PTPRD, MACROD2 and WWOX). Furthermore, the calcium signaling pathway, arrhythmogenic right ventricular cardiomyopathy and the glutamatergic synapse pathway were identified. The investigational findings demonstrate that our proposed model presents an accurate and efficient approach to identifying significant biomarkers in AD.

Alzheimer’s disease (AD) is a significant neurological disorder characterized by progressive cognitive decline and memory loss. One essential task is understanding the molecular mechanisms underlying brain disorders of AD. Detecting biomarkers that contribute significantly to the classification of AD is an effective means to accomplish this essential task. However, most machine learning methods used to detect AD biomarkers require lengthy training and are unable to rapidly and effectively detect AD biomarkers. To detect biomarkers for AD accurately and efficiently, we proposed a novel approach using the Multi-Kernel Support Vector Machine (SVM) with Apriori algorithm to mine strongly associated feature sets from functional magnetic resonance imaging (fMRI) and gene expression profiles. Firstly, we downloaded the imaging data and genetic data of 121 participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and transformed gene sequences into labeled sequences by encoding the four types of bases (A, T, C, and G) into distinct labels. Subsequently, we extracted the first 130 temporal sequences of brain regions and employed Pearson correlation analysis to construct “brain region gene pairs”. The integration of these data allowed us to explore the correlations between genes and brain regions. To improve classification accuracy and feature selection, we applied the Apriori algorithm to the multi-kernel SVM, dynamically building feature combinations and continuously validating classification results. By iteratively generating frequent itemsets, we obtained important brain region gene pairs. Experimental results show the effectiveness of our proposed approach. The Multi-Kernel SVM with Apriori model achieves an accuracy of 92.9%, precision of 95%, and an F1 score of 95% in classifying brain region-gene pairs within the AD–Late mild cognitive impairment (AD-LMCI) group. The amygdala, BIN1, RPN2, and IL15 associated with AD have been identified and demonstrate potential in identifying potential pathogenic factors of AD. The selected brain regions and associated genes may serve as valuable biomarkers for early AD diagnosis and better understanding of the disease’s molecular mechanisms. The integration of fMRI and gene data using the Multi-Kernel SVM–Apriori model holds great potential for advancing our knowledge of brain function and the genetic basis of neurological disorders. This approach provides a valuable tool for neuroscientists and researchers in the field of genomics and brain imaging studies.

Read separating from write is a strategy that NewSQL adopts to incorporate the advantages of traditional relation database and NoSQL database. Under this architecture, baseline data is split into multiple partitions stored at distributed physical nodes, while delta data is stored at single transaction node. For reducing the pressure of transaction node and improving the query performance, delta data needs to be synchronized into storage nodes. The current strategies trigger the procedure of data synchronization per partition, meaning that unchanged partitions will also participate in data synchronization, which consumes extra network cost, local IO and space resources. For improving the efficiency of data synchronization meanwhile mitigating space utilization, the fine-grained data synchronization strategy is proposed, whose main idea includes that fine-grained logical partitions upon original coarse-grained partitions is established, providing more correct synchronized unit; the delta data sensing strategy is introduced, which records the mapping between changed partitions and its delta data; instead of partition driven, the data synchronization through the delta-broadcasting mechanism is driven, constraining that only changed partitions can participate in data synchronization. The fine-grained data synchronization strategy on Oceanbase is implemented, which is a distributed database with read separating from write, and the results show that our strategy is better than other strategies in efficiency of data synchronizing and space utilization.