Dataset Information

Reconstructing the transcriptional regulatory network of probiotic L. reuteri is enabled by transcriptomics and machine learning.

ABSTRACT: Limosilactobacillus reuteri, a probiotic microbe instrumental to human health and sustainable food production, adapts to diverse environmental shifts via dynamic gene expression. We applied the independent component analysis (ICA) to 117 RNA-seq data sets to decode its transcriptional regulatory network (TRN), identifying 35 distinct signals that modulate specific gene sets. Our findings indicate that the ICA provides a qualitative advancement and captures nuanced relationships within gene clusters that other methods may miss. This study uncovers the fundamental properties of L. reuteri's TRN and deepens our understanding of its arginine metabolism and the co-regulation of riboflavin metabolism and fatty acid conversion. It also sheds light on conditions that regulate genes within a specific biosynthetic gene cluster and allows for the speculation of the potential role of isoprenoid biosynthesis in L. reuteri's adaptive response to environmental changes. By integrating transcriptomics and machine learning, we provide a system-level understanding of L. reuteri's response mechanism to environmental fluctuations, thus setting the stage for modeling the probiotic transcriptome for applications in microbial food production.

Importance

We have studied Limosilactobacillus reuteri, a beneficial probiotic microbe that plays a significant role in our health and production of sustainable foods, a type of foods that are nutritionally dense and healthier and have low-carbon emissions compared to traditional foods. Similar to how humans adapt their lifestyles to different environments, this microbe adjusts its behavior by modulating the expression of genes. We applied machine learning to analyze large-scale data sets on how these genes behave across diverse conditions. From this, we identified 35 unique patterns demonstrating how L. reuteri adjusts its genes based on 50 unique environmental conditions (such as various sugars, salts, microbial cocultures, human milk, and fruit juice). This research helps us understand better how L. reuteri functions, especially in processes like breaking down certain nutrients and adapting to stressful changes. More importantly, with our findings, we become closer to using this knowledge to improve how we produce more sustainable and healthier foods with the help of microbes.

SUBMITTER: Josephs-Spaulding J

PROVIDER: S-EPMC10949432 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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Publications

Reconstructing the transcriptional regulatory network of probiotic <i>L. reuteri</i> is enabled by transcriptomics and machine learning.

Josephs-Spaulding Jonathan J Rajput Akanksha A Hefner Ying Y Szubin Richard R Balasubramanian Archana A Li Gaoyuan G Zielinski Daniel C DC Jahn Leonie L Sommer Morten M Sommer Morten M Phaneuf Patrick P Palsson Bernhard O BO

mSystems 20240213 3

<i>Limosilactobacillus reuteri</i>, a probiotic microbe instrumental to human health and sustainable food production, adapts to diverse environmental shifts via dynamic gene expression. We applied the independent component analysis (ICA) to 117 RNA-seq data sets to decode its transcriptional regulatory network (TRN), identifying 35 distinct signals that modulate specific gene sets. Our findings indicate that the ICA provides a qualitative advancement and captures nuanced relationships within gen ...[more]

PMID: 38349131

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Project description:Transcriptional regulatory networks (TRNs) program cells to dynamically alter their gene expression in response to changing internal or environmental conditions. In this study, we develop a novel workflow for generating large-scale TRN models that integrates comparative genomics data, global gene expression analyses, and intrinsic properties of transcription factors (TFs). An assessment of this workflow using benchmark datasets for the well-studied γ-proteobacterium Escherichia coli showed that it outperforms expression-based inference approaches, having a significantly larger area under the precision-recall curve. Further analysis indicated that this integrated workflow captures different aspects of the E. coli TRN than expression-based approaches, potentially making them highly complementary. We leveraged this new workflow and observations to build a large-scale TRN model for the α-Proteobacterium Rhodobacter sphaeroides that comprises 120 gene clusters, 1211 genes (including 93 TFs), 1858 predicted protein-DNA interactions and 76 DNA binding motifs. We found that ~67% of the predicted gene clusters in this TRN are enriched for functions ranging from photosynthesis or central carbon metabolism to environmental stress responses. We also found that members of many of the predicted gene clusters were consistent with prior knowledge in R. sphaeroides and/or other bacteria. Experimental validation of predictions from this R. sphaeroides TRN model showed that high precision and recall was also obtained for TFs involved in photosynthesis (PpsR), carbon metabolism (RSP_0489) and iron homeostasis (RSP_3341). In addition, this integrative approach enabled generation of TRNs with increased information content relative to R. sphaeroides TRN models built via other approaches. We also show how this approach can be used to simultaneously produce TRN models for each related organism used in the comparative genomics analysis. Our results highlight the advantages of integrating comparative genomics of closely related organisms with gene expression data to assemble large-scale TRN models with high-quality predictions.