Author:
Josephs-Spaulding Jonathan,Rajput Akanksha,Hefner Ying,Szubin Richard,Balasubramanian Archana,Li Gaoyuan,Zielinski Daniel C.,Jahn Leonie,Sommer Morten,Phaneuf Patrick,Palsson Bernhard O.
Abstract
IAbstractLimosilactobacillus reuteri, a probiotic microbe instrumental to human health and sustainable food production, adapts to diverse environmental shifts via dynamic gene expression. We applied independent component analysis to 117 high-quality RNA-seq datasets to decode its transcriptional regulatory network (TRN), identifying 35 distinct signals that modulate specific gene sets. This study uncovers the fundamental properties ofL. reuteri’sTRN, deepens our understanding of its arginine metabolism, and the co-regulation of riboflavin metabolism and fatty acid biosynthesis. It also sheds light on conditions that regulate genes within a specific biosynthetic gene cluster and the role of isoprenoid biosynthesis inL. reuteri’sadaptive response to environmental changes. Through the integration of transcriptomics and machine learning, we provide a systems-level understanding ofL. reuteri’sresponse mechanism to environmental fluctuations, thus setting the stage for modeling the probiotic transcriptome for applications in microbial food production.Graphical AbstractComprehensive iModulon Workflow Overview. Our innovative workflow is grounded in the analysis of the LactoPRECISE compendium, a curated dataset containing 117 internally sequenced RNA-seq samples derived from a diversity of 50 unique conditions, encompassing an extensive range of 13 distinct condition types. We employ the power of Independent Component Analysis (ICA), a cutting-edge machine learning algorithm, to discern the underlying structure of iModulons within this wealth of data. In the subsequent stage of our workflow, the discovered iModulons undergo detailed scrutiny to uncover media-specific regulatory mechanisms governing metabolism, illuminate the context-dependent intricacies of gene expression, and predict pathways leading to the biosynthesis of probiotic secondary metabolites. Our workflow offers an invaluable and innovative lens through which to view probiotic strain design while simultaneously highlighting transformative approaches to data analytics in the field.
Publisher
Cold Spring Harbor Laboratory
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献