2025 Hyper Recent •CC0 1.0 Universal

This work is dedicated to the public domain. No rights reserved.

Access Preprint From Server
July 17th, 2025
Version: 2
Washington University in St. Louis
systems biology
biorxiv

Gene-Embedded Multi-Modal Networks for Population-Scale Multi-Omics Discovery

Akbary Moghaddam, V.Open in Google Scholar•Acharya, S.Open in Google Scholar•Schwaiger-Haber, M.Open in Google Scholar•Liao, S.Open in Google Scholar•Jung, W. J.Open in Google Scholar•Thyagarajan, B.Open in Google Scholar•Shriver, L. P.Open in Google Scholar•Daw, E. W.Open in Google Scholar•Saccone, N. L.Open in Google Scholar•An, P.Open in Google Scholaret al.

We present Gene-Embedded Multi-modal Networks (GEM-Net), a semi-supervised framework for constructing multi-modal networks centered on genes. GEM-Net uses gene-level modules and selectively incorporates heterogeneous omics profiles using a correlated meta-analysis strategy that accounts for scale imbalance, missingness, and intra-modular correlation. Prior to network inference, we developed a harmonized data processing protocol that adjusts each omic layer independently through a shared mathematical workflow involving transformation, dimensionality reduction, and regression-based covariate adjustment. GEM-Net modules were inferred and benchmarked against unsupervised methods using transcriptomic, metabolomic, and lipidomic data from the Long Life Family Study (LLFS), a unique cohort enriched for exceptional familial longevity and health. GEM-Net modules were more diverse and biologically interpretable, with stronger support from protein-protein interactions, transcriptional regulation, and metabolic annotations. Applying GEM-Net to metabolic health in LLFS revealed an axis between the microbiome-derived metabolite N-acetylglycine and immune genes (FCER1A, HDC, CPA3, MS4A2) associated with improved insulin sensitivity and reduced inflammation in healthy older individuals. GEM-Nets offer a reusable reference from a long-lived population and a generalizable framework for multi-omics discovery. https://doi.org/10.5281/zenodo.15003731.

Similar Papers

biorxiv
Thu Jul 17 2025
Cell type-specific master metabolic regulators of Alzheimer's disease
Alzheimer\'s disease (AD) exhibits metabolic heterogeneity; yet, the consequences on metabolic dynamics in a cell-type-specific manner and the underlying metabolite-sensor network basis remain unclear. Here, we show that neurons exhibit a striking decrease in energy and lipid-related metabolic activity, contrasted by an increase in microglial metabolism associated with neuroinflammation. To identi...
Qiu, Y.
•
Hou, Y.
•
Wetzel, L.
•
Caldwell, J. Z. K.
...•
Cheng, F.
biorxiv
Thu Jul 17 2025
Lifetime exposure to known and emerging groundwater contaminants significantly alters poultry microbiome and metabolome
The exposome encompasses all lifetime environmental exposures affecting health. Its complexity and high data dimensionality make it challenging to link specific exposure combinations to adverse health outcomes. Establishing relevant exposome criteria is key to addressing current knowledge gaps. This study evaluated contaminant levels in Wisconsin groundwater and their effects on host health. We fo...
Chatman, C. C.
•
Olson, E. G.
•
Ricke, S. C.
•
Majumder, E. L.- W.
biorxiv
Thu Jul 17 2025
Inferring fungal cis-regulatory networks from genome sequences via unsupervised and interpretable representation learning.
Gene expression patterns are determined to a large extent by transcription factor binding to non-coding regulatory regions in the genome. However, gene expression cannot yet be systematically predicted from genome sequences, in part because non-functional matches to the sequence patterns (motifs) recognized by transcription factors (TFs) occur frequently throughout the genome. Large-scale function...
Moses, A. M.
•
Stajich, J. E.
•
Gasch, A. P.
•
Knowles, D. A.
biorxiv
Thu Jul 17 2025
Cahn-Hilliard dynamical models for condensed biomolecular systems
Biomolecular condensates create dynamic subcellular compartments that alter systems-level properties of the networks surrounding them. One model combining soluble and condensed states is the Cahn-Hilliard equation, which specifies a diffuse interface between the two phases. Customized approaches required to solve this equation are largely inaccessible. Using two complementary numerical strategies,...
Groves, S. M.
•
Lu, M.-J.
•
Alvarez-Yela, A. C.
•
Gerardo-Ramirez, M.
...•
Janes, K. A.
biorxiv
Wed Jul 16 2025
Metabolomic fingerprints of PAH exposure - identifying toxicological biomarkers in dynamically cultured 3D cell spheroids
Environmental exposure to polycyclic aromatic hydrocarbons (PAHs) causes metabolic dysfunction, but reliable biomarkers are still needed to assess human health effects. This study used 21-day matured human HepG2 spheroids, a metabolically competent three-dimensional (3D) liver model, to assess metabolic responses to graded, non-cytotoxic concentrations of benzo[a]pyrene (BaP) and benzo[b]fluoranth...
Bosnjakovic, A.
•
Eichmann, T.
•
Stern, A.
•
Rasmussen, M. A.
...•
Zegura, B.
biorxiv
Wed Jul 16 2025
Tracking of in vivo O-GlcNAcylation in an Alzheimer's Disease and Aging C. elegans Model
We investigated O-linked {beta}-N-acetylglucosamine (O-GlcNAc), a post-translational modification (PTM), in an in vivo Caenorhabditis elegans model of Alzheimer\'s Disease (AD) and aging. Employing a chemoenzymatic labeling strategy combined with an automated image processing, we analyzed both post-hatching and adult stages of wild-type (WT, N2) and transgenic strain expressing human tau V337M und...
Garcia, F. C.
biorxiv
Wed Jul 16 2025
OpenDVP: An experimental and computational framework for community-empowered deep visual proteomics
Deep visual proteomics (DVP) is an emerging approach for cell type-specific and spatially resolved proteomics. However, its broad adoption has been constrained by the lack of open-source end-to-end workflows in a community-driven ecosystem. Here, we introduce openDVP, an experimental and computational framework for simplifying and democratizing DVP. OpenDVP integrates open-source software for imag...
Nimo, J.
•
Fritzsche, S.
•
Valdes, D. S.
•
Trinh, M. T.
...•
Coscia, F.
biorxiv
Tue Jul 15 2025
The role of Platelet-derived growth factor (PDGF) in uremic vascular calcification.
Vascular calcification is common in chronic kidney disease (CKD), contributing to increased cardiovascular morbidity and mortality. One of the proposed mechanisms of driving vascular calcification is a phenotypic switch of vascular smooth muscle cells (VSMCs). The platelet-derived growth factors (PDGFs) and their receptors (PDGFRs), particularly PDGFR-{beta}, were shown to modulate the VSMC phenot...
Yesilyurt Ozturk, B.
•
Zhang, L.
•
von Stillfried, S.
•
Klinkhammer, B. M.
...•
Boor, P.
biorxiv
Tue Jul 15 2025
Which evolutionary game-theoretic model best captures non-small cell lung cancer dynamics?
Understanding and predicting the eco-evolutionary dynamics of cancer requires identifying mathematical models that best capture tumor growth and treatment response. In this study, we fit a family of two-population models to in-vitro data from non-small cell lung cancer (NSCLC), tracking drug-sensitive and drug-resistant cells under varying environmental conditions. The dataset, originally presente...
Garjani, H.
•
Dubbeldam, J.
•
Stankova, K.
•
Brown, J.