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Reverse engineering directed gene regulatory networks from transcriptomics and proteomics data of biomining bacterial communities with approximate Bayesian computation and steady-state signalling simulations
Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Università della Svizzera italiana, Switzerland;Swiss Institute of Bioinformatics, Switzerland. (Linnaeus Ctr Biomat Chem, BMC;Ctr Ecol & Evolut Microbial Model Syst EEMiS)ORCID iD: 0000-0002-6469-0296
University of Luxembourg, Luxembourg.
Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science. (Ctr Ecol & Evolut Microbial Model Syst EEMiS)ORCID iD: 0000-0003-0021-2452
QNLM, China.
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2020 (English)In: BMC Bioinformatics, E-ISSN 1471-2105, Vol. 21, no 1, p. 1-15, article id 23Article in journal (Refereed) Published
Abstract [en]

Background: Network inference is an important aim of systems biology. It enables the transformation of OMICs datasets into biological knowledge. It consists of reverse engineering gene regulatory networks from OMICs data, such as RNAseq or mass spectrometry-based proteomics data, through computational methods. This approach allows to identify signalling pathways involved in specific biological functions. The ability to infer causality in gene regulatory networks, in addition to correlation, is crucial for several modelling approaches and allows targeted control in biotechnology applications. Methods: We performed simulations according to the approximate Bayesian computation method, where the core model consisted of a steady-state simulation algorithm used to study gene regulatory networks in systems for which a limited level of details is available. The simulations outcome was compared to experimentally measured transcriptomics and proteomics data through approximate Bayesian computation. Results: The structure of small gene regulatory networks responsible for the regulation of biological functions involved in biomining were inferred from multi OMICs data of mixed bacterial cultures. Several causal inter- and intraspecies interactions were inferred between genes coding for proteins involved in the biomining process, such as heavy metal transport, DNA damage, replication and repair, and membrane biogenesis. The method also provided indications for the role of several uncharacterized proteins by the inferred connection in their network context. Conclusions: The combination of fast algorithms with high-performance computing allowed the simulation of a multitude of gene regulatory networks and their comparison to experimentally measured OMICs data through approximate Bayesian computation, enabling the probabilistic inference of causality in gene regulatory networks of a multispecies bacterial system involved in biomining without need of single-cell or multiple perturbation experiments. This information can be used to influence biological functions and control specific processes in biotechnology applications.

Place, publisher, year, edition, pages
BioMed Central (BMC), 2020. Vol. 21, no 1, p. 1-15, article id 23
National Category
Microbiology Bioinformatics and Computational Biology
Research subject
Ecology, Microbiology
Identifiers
URN: urn:nbn:se:lnu:diva-92609DOI: 10.1186/s12859-019-3337-9ISI: 000513604400001PubMedID: 31964336Scopus ID: 2-s2.0-85078093666OAI: oai:DiVA.org:lnu-92609DiVA, id: diva2:1411940
Funder
Swedish Research Council, 2014-6545Available from: 2020-03-04 Created: 2020-03-04 Last updated: 2025-02-05Bibliographically approved

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Buetti-Dinh, AntoineChristel, StephanBellenberg, SörenFriedman, RanDopson, Mark

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