Dataset Information

NetMUG: a novel network-guided multi-view clustering workflow for dissecting genetic and facial heterogeneity.

ABSTRACT: Introduction: Multi-view data offer advantages over single-view data for characterizing individuals, which is crucial in precision medicine toward personalized prevention, diagnosis, or treatment follow-up. Methods: Here, we develop a network-guided multi-view clustering framework named netMUG to identify actionable subgroups of individuals. This pipeline first adopts sparse multiple canonical correlation analysis to select multi-view features possibly informed by extraneous data, which are then used to construct individual-specific networks (ISNs). Finally, the individual subtypes are automatically derived by hierarchical clustering on these network representations. Results: We applied netMUG to a dataset containing genomic data and facial images to obtain BMI-informed multi-view strata and showed how it could be used for a refined obesity characterization. Benchmark analysis of netMUG on synthetic data with known strata of individuals indicated its superior performance compared with both baseline and benchmark methods for multi-view clustering. The clustering derived from netMUG achieved an adjusted Rand index of 1 with respect to the synthesized true labels. In addition, the real-data analysis revealed subgroups strongly linked to BMI and genetic and facial determinants of these subgroups. Discussion: netMUG provides a powerful strategy, exploiting individual-specific networks to identify meaningful and actionable strata. Moreover, the implementation is easy to generalize to accommodate heterogeneous data sources or highlight data structures.

SUBMITTER: Li Z

PROVIDER: S-EPMC10731261 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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netMUG: a novel network-guided multi-view clustering workflow for dissecting genetic and facial heterogeneity.

Li Zuqi Z Melograna Federico F Hoskens Hanne H Duroux Diane D Marazita Mary L ML Walsh Susan S Weinberg Seth M SM Shriver Mark D MD Müller-Myhsok Bertram B Claes Peter P Van Steen Kristel K

Frontiers in genetics 20231206

<b>Introduction:</b> Multi-view data offer advantages over single-view data for characterizing individuals, which is crucial in precision medicine toward personalized prevention, diagnosis, or treatment follow-up. <b>Methods:</b> Here, we develop a network-guided multi-view clustering framework named netMUG to identify actionable subgroups of individuals. This pipeline first adopts sparse multiple canonical correlation analysis to select multi-view features possibly informed by extraneous data, ...[more]

PMID: 38125750

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Project description:BackgroundResting-state brain networks represent the interconnectivity of different brain regions during rest. Utilizing brain network analysis methods to model these networks can enhance our understanding of how different brain regions collaborate and communicate without explicit external stimuli. However, analyzing resting-state brain networks faces challenges due to high heterogeneity and noise correlation between subjects. This study proposes a brain structure learning-guided multi-view graph representation learning method to address the limitations of current brain network analysis and improve the diagnostic accuracy (ACC) of mental disorders.MethodsWe first used multiple thresholds to generate different sparse levels of brain networks. Subsequently, we introduced graph pooling to optimize the brain network representation by reducing noise edges and data inconsistency, thereby providing more reliable input for subsequent graph convolutional networks (GCNs). Following this, we designed a multi-view GCN to comprehensively capture the complexity and variability of brain structure. Finally, we employed an attention-based adaptive module to adjust the contributions of different views, facilitating their fusion. Considering that the Smith atlas offers superior characterization of resting-state brain networks, we utilized the Smith atlas to construct the graph network.ResultsExperiments on two mental disorder datasets, the Autism Brain Imaging Data Exchange (ABIDE) dataset and the Mexican Cocaine Use Disorders (SUDMEX CONN) dataset, show that our model outperforms the state-of-the-art methods, achieving nearly 75% ACC and 70% area under the receiver operating characteristic curve (AUC) on both datasets.ConclusionsThese findings demonstrate that our method of combining multi-view graph learning and brain structure learning can effectively capture crucial structural information in brain networks while facilitating the acquisition of feature information from diverse perspectives, thereby improving the performance of brain network analysis.

Project description:BackgroundGastric cancer (GC) is clinically heterogenous according to location (cardia/non-cardia) and histopathology (diffuse/intestinal). We aimed to characterize the genetic risk architecture of GC according to its subtypes. Another aim was to examine whether cardia GC and oesophageal adenocarcinoma (OAC) and its precursor lesion Barrett's oesophagus (BO), which are all located at the gastro-oesophageal junction (GOJ), share polygenic risk architecture.MethodsWe did a meta-analysis of ten European genome-wide association studies (GWAS) of GC and its subtypes. All patients had a histopathologically confirmed diagnosis of gastric adenocarcinoma. For the identification of risk genes among GWAS loci we did a transcriptome-wide association study (TWAS) and expression quantitative trait locus (eQTL) study from gastric corpus and antrum mucosa. To test whether cardia GC and OAC/BO share genetic aetiology we also used a European GWAS sample with OAC/BO.FindingsOur GWAS consisting of 5816 patients and 10,999 controls highlights the genetic heterogeneity of GC according to its subtypes. We newly identified two and replicated five GC risk loci, all of them with subtype-specific association. The gastric transcriptome data consisting of 361 corpus and 342 antrum mucosa samples revealed that an upregulated expression of MUC1, ANKRD50, PTGER4, and PSCA are plausible GC-pathomechanisms at four GWAS loci. At another risk locus, we found that the blood-group 0 exerts protective effects for non-cardia and diffuse GC, while blood-group A increases risk for both GC subtypes. Furthermore, our GWAS on cardia GC and OAC/BO (10,279 patients, 16,527 controls) showed that both cancer entities share genetic aetiology at the polygenic level and identified two new risk loci on the single-marker level.InterpretationOur findings show that the pathophysiology of GC is genetically heterogenous according to location and histopathology. Moreover, our findings point to common molecular mechanisms underlying cardia GC and OAC/BO.FundingGerman Research Foundation (DFG).

Dataset Information

NetMUG: a novel network-guided multi-view clustering workflow for dissecting genetic and facial heterogeneity.

Publications

netMUG: a novel network-guided multi-view clustering workflow for dissecting genetic and facial heterogeneity.

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