The "RNA world" represents a novel frontier for the study of fundamental biological processes and human diseases and is paving the way for the development of new drugs tailored to each patient's biomolecular characteristics. Although scientific data about coding and non-coding RNA molecules are constantly produced and available from public repositories, they are scattered across different databases and a centralized, uniform, and semantically consistent representation of the "RNA world" is still lacking. We propose RNA-KG, a knowledge graph (KG) encompassing biological knowledge about RNAs gathered from more than 60 public databases, integrating functional relationships with genes, proteins, and chemicals and ontologically grounded biomedical concepts. To develop RNA-KG, we first identified, pre-processed, and characterized each data source; next, we built a meta-graph that provides an ontological description of the KG by representing all the bio-molecular entities and medical concepts of interest in this domain, as well as the types of interactions connecting them. Finally, we leveraged an instance-based semantically abstracted knowledge model to specify the ontological alignment according to which RNA-KG was generated. RNA-KG can be downloaded in different formats and also queried by a SPARQL endpoint. A thorough topological analysis of the resulting heterogeneous graph provides further insights into the characteristics of the "RNA world". RNA-KG can be both directly explored and visualized, and/or analyzed by applying computational methods to infer bio-medical knowledge from its heterogeneous nodes and edges. The resource can be easily updated with new experimental data, and specific views of the overall KG can be extracted according to the bio-medical problem to be studied.
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http://dx.doi.org/10.1038/s41597-024-03673-7 | DOI Listing |
Entropy (Basel)
November 2024
Institute of Computing Science, Poznan University of Technology, 60-965 Poznan, Poland.
During the evolution of the RNA World, compartments, which were fragments of space surrounded by a primitive lipid membrane, had to have emerged. These led eventually to the formation of modern cellular membranes. Inside these compartments, another process had to take place-switching from RNA to DNA as a primary storage of genetic information.
View Article and Find Full Text PDFNat Chem
January 2025
Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, Los Angeles, CA, USA.
Understanding the emergence of complex biochemical systems, such as protein translation, is a great challenge. Although synthetic approaches can provide insight into the potential early stages of life, they do not address the equally important question of why the complex systems of life would have evolved. In particular, the intricacies of the mechanisms governing the transfer of information from nucleic acid sequences to proteins make it difficult to imagine how coded protein synthesis could have emerged from a prebiotic soup.
View Article and Find Full Text PDFActa Biochim Biophys Sin (Shanghai)
January 2025
Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study, Hangzhou 310024; University of Chinese Academy of Sciences, Beijing 100049, China.
Chembiochem
December 2024
University of Minnesota, Department of Genetics, Cell Biology, and Development, MCB 5-130, 420 Washington Avenue SE, 55455, Minneapolis, UNITED STATES OF AMERICA.
RNA exhibits remarkable capacity as a functional polymer, with broader catalytic and ligand-binding capability than previously thought. Despite this, the low side chain diversity present in nucleic acids (two purines and two pyrimidines) relative to proteins (20+ side chains of varied charge, polarity, and chemical functionality) limits the capacity of functional RNAs to act as environmentally responsive polymers, as is possible for peptide-based receptors and catalysts. Here we show that incorporation of the modified nucleobase 2-thiouridine (2sU) into functional (aptamer and ribozyme) RNAs produces functionally inactivated polymers that can be activated by oxidative treatment.
View Article and Find Full Text PDFNucleic Acids Res
December 2024
Computational Biology Branch, Division of Intramural Research, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA.
Viroids, the agents of several plant diseases, are the smallest and simplest known replicators that consist of covalently closed circular (ccc) RNA molecules between 200 and 400 nucleotides in size. Viroids encode no proteins and rely on host RNA polymerases for replication, but some contain ribozymes involved in replication intermediate processing. Although other viroid-like agents with cccRNAs genomes, such as satellite RNAs, ribozyviruses and retrozymes, have been discovered, until recently, the spread of these agents in the biosphere appeared narrow, and their actual diversity and evolution remained poorly understood.
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