Multi-omic network inference from time-series data

Abstract Biological phenotypes emerge from complex interactions across molecular layers. Yet, data-driven approaches to infer these regulatory networks have primarily focused on single-omic studies, overlooking inter-layer regulatory relationships. To address these limitations, we developed MINIE, a...

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Published in:npj Systems Biology and Applications
Main Authors: María Moscardó García, Atte Aalto, Arthur N. Montanari, Alexander Skupin, Jorge Gonçalves
Format: Article
Language:English
Published: Nature Portfolio 2025-10-01
Online Access:https://doi.org/10.1038/s41540-025-00591-1
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author María Moscardó García
Atte Aalto
Arthur N. Montanari
Alexander Skupin
Jorge Gonçalves
author_facet María Moscardó García
Atte Aalto
Arthur N. Montanari
Alexander Skupin
Jorge Gonçalves
author_sort María Moscardó García
collection DOAJ
container_title npj Systems Biology and Applications
description Abstract Biological phenotypes emerge from complex interactions across molecular layers. Yet, data-driven approaches to infer these regulatory networks have primarily focused on single-omic studies, overlooking inter-layer regulatory relationships. To address these limitations, we developed MINIE, a computational method that integrates multi-omic data from bulk metabolomics and single-cell transcriptomics through a Bayesian regression approach that explicitly models the timescale separation between molecular layers. We validate the method on both simulated datasets and experimental Parkinson’s disease data. MINIE exhibits accurate and robust predictive performance across and within omic layers, including curated multi-omic networks and the lac operon. Benchmarking demonstrated significant improvements over state-of-the-art methods while ranking among the top performers in comprehensive single-cell network inference analysis. The integration of regulatory dynamics across molecular layers and temporal scales provides a powerful tool for comprehensive multi-omic network inference.
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spelling doaj-art-22b7e8b1ea984fd6b37ba85b4e2d39012025-10-19T11:30:57ZengNature Portfolionpj Systems Biology and Applications2056-71892025-10-0111111310.1038/s41540-025-00591-1Multi-omic network inference from time-series dataMaría Moscardó García0Atte Aalto1Arthur N. Montanari2Alexander Skupin3Jorge Gonçalves4Luxembourg Centre for Systems Biomedicine, University of LuxembourgLuxembourg Centre for Systems Biomedicine, University of LuxembourgLuxembourg Centre for Systems Biomedicine, University of LuxembourgLuxembourg Centre for Systems Biomedicine, University of LuxembourgLuxembourg Centre for Systems Biomedicine, University of LuxembourgAbstract Biological phenotypes emerge from complex interactions across molecular layers. Yet, data-driven approaches to infer these regulatory networks have primarily focused on single-omic studies, overlooking inter-layer regulatory relationships. To address these limitations, we developed MINIE, a computational method that integrates multi-omic data from bulk metabolomics and single-cell transcriptomics through a Bayesian regression approach that explicitly models the timescale separation between molecular layers. We validate the method on both simulated datasets and experimental Parkinson’s disease data. MINIE exhibits accurate and robust predictive performance across and within omic layers, including curated multi-omic networks and the lac operon. Benchmarking demonstrated significant improvements over state-of-the-art methods while ranking among the top performers in comprehensive single-cell network inference analysis. The integration of regulatory dynamics across molecular layers and temporal scales provides a powerful tool for comprehensive multi-omic network inference.https://doi.org/10.1038/s41540-025-00591-1
spellingShingle María Moscardó García
Atte Aalto
Arthur N. Montanari
Alexander Skupin
Jorge Gonçalves
Multi-omic network inference from time-series data
title Multi-omic network inference from time-series data
title_full Multi-omic network inference from time-series data
title_fullStr Multi-omic network inference from time-series data
title_full_unstemmed Multi-omic network inference from time-series data
title_short Multi-omic network inference from time-series data
title_sort multi omic network inference from time series data
url https://doi.org/10.1038/s41540-025-00591-1
work_keys_str_mv AT mariamoscardogarcia multiomicnetworkinferencefromtimeseriesdata
AT atteaalto multiomicnetworkinferencefromtimeseriesdata
AT arthurnmontanari multiomicnetworkinferencefromtimeseriesdata
AT alexanderskupin multiomicnetworkinferencefromtimeseriesdata
AT jorgegoncalves multiomicnetworkinferencefromtimeseriesdata