Sarraf Saman, Avelar-Pereira Bárbara, Hosseini S M Hadi
Department of Psychiatry and Behavioral Sciences, School of Medicine, Stanford University, Stanford, CA, USA.
Aging Research Center, Karolinska Institutet and Stockholm University, Stockholm, Sweden.
Commun Biol. 2025 Jun 7;8(1):894. doi: 10.1038/s42003-025-08269-4.
We present MINT (Multilayer Integration of Networks Toolbox), a Python package for multimodal data integration and community detection. MINT includes data standardization, Similarity Network Fusion, Generalized Louvain clustering, visualization, cross-validation, and modality selection optimization, capturing complex relationships among disease markers. We applied MINT to two multimodal datasets spanning the Alzheimer's disease (AD) spectrum: a primary cohort of 206 participants and a validation cohort of 143 participants, including structural magnetic resonance imaging (MRI), amyloid positron emission tomography (PET), cerebrospinal fluid (CSF), cognition, and genetics. We hypothesized that modeling intra- and inter-modality associations would improve AD prediction and identify preclinical cases. Across both datasets, MINT identified PET and CSF as optimal modalities and detected two communities: one AD-dominant and one cognitively normal-dominant (CN). Sensitivity and specificity for CN and AD were 84.38% (95% CI: 73.14-92.24) and 92.65% (95% CI: 83.67-97.57). The AD-dominant community exhibited poorer cognition and higher genetic risk and AD pathology (p < 0.001). CN individuals in this group showed elevated amyloid (p=0.009), tau (p=0.004), and ptau (p < 0.001) compared to AD individuals in the CN-dominant group. MINT can identify biologically relevant subgroups, predict disease progression, and serves as a powerful tool for uncovering complex relationships across heterogeneous and multifactorial disorders.
我们展示了MINT(网络多层集成工具箱),这是一个用于多模态数据集成和社区检测的Python包。MINT包括数据标准化、相似性网络融合、广义Louvain聚类、可视化、交叉验证和模态选择优化,捕捉疾病标志物之间的复杂关系。我们将MINT应用于两个跨越阿尔茨海默病(AD)谱系的多模态数据集:一个由206名参与者组成的主要队列和一个由143名参与者组成的验证队列,包括结构磁共振成像(MRI)、淀粉样蛋白正电子发射断层扫描(PET)、脑脊液(CSF)、认知和遗传学。我们假设对模态内和模态间关联进行建模将改善AD预测并识别临床前病例。在两个数据集中,MINT都将PET和CSF识别为最佳模态,并检测到两个社区:一个以AD为主,另一个以认知正常为主(CN)。CN和AD的敏感性和特异性分别为84.38%(95%CI:73.14 - 92.24)和92.65%(95%CI:83.67 - 97.57)。以AD为主的社区表现出较差的认知、更高的遗传风险和AD病理学(p < 0.001)。与以CN为主的组中的AD个体相比,该组中的CN个体显示出更高的淀粉样蛋白(p = 0.009)、tau(p = 0.004)和磷酸化tau(p < 0.001)。MINT可以识别生物学上相关的亚组,预测疾病进展,并作为揭示跨异质性和多因素疾病复杂关系的强大工具。