Dataset Information

RNAvigate: Efficient exploration of RNA chemical probing datasets.

ABSTRACT: Chemical probing technologies enable high-throughput examination of diverse structural features of RNA including local nucleotide flexibility, RNA secondary structure, protein- and ligand-binding, through-space interaction networks, and multi-state structural ensembles. Performing these experiments, by themselves, does not directly lead to biological insight. Instead, deep understanding of RNA structure-function relationships typically requires evaluating a system under structure- and function-altering conditions, linking these data with additional information, and visualizing multi-layered relationships. Current platforms lack the broad accessibility, flexibility, and efficiency needed to iterate on integrative analyses of these diverse, complex data. Here, we share the RNA visualization and graphical analysis toolset RNAvigate, a straightforward and flexible Python library. RNAvigate currently automatically parses twenty-one standard file formats (primary sequence annotations, per- and internucleotide data, and secondary and tertiary structures) and outputs eighteen plot types. These features enable efficient exploration of nuanced relationships between chemical probing data, RNA structure, and motif annotations across multiple experimental samples. Compatibility with Jupyter Notebooks enables non-burdensome, reproducible, transparent and organized sharing of multi-step analyses and data visualization strategies. RNAvigate simplifies examination of multi-layered RNA structure information and accelerates discovery and characterization of RNA-centric functions in biology.

SUBMITTER: Irving PS

PROVIDER: S-EPMC10168276 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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RNAvigate: Efficient exploration of RNA chemical probing datasets.

Irving Patrick S PS Weeks Kevin M KM

bioRxiv : the preprint server for biology 20231130

Chemical probing technologies enable high-throughput examination of diverse structural features of RNA including local nucleotide flexibility, RNA secondary structure, protein- and ligand-binding, through-space interaction networks, and multi-state structural ensembles. Performing these experiments, by themselves, does not directly lead to biological insight. Instead, deep understanding of RNA structure-function relationships typically requires evaluating a system under structure- and function-a ...[more]

PMID: 37162917

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Project description:The diversity and importance of the role played by RNAs in the regulation and development of the cell are now well-known and well-documented. This broad range of functions is achieved through specific structures that have been (presumably) optimized through evolution. State-of-the-art methods, such as McCaskill's algorithm, use a statistical mechanics framework based on the computation of the partition function over the canonical ensemble of all possible secondary structures on a given sequence. Although secondary structure predictions from thermodynamics-based algorithms are not as accurate as methods employing comparative genomics, the former methods are the only available tools to investigate novel RNAs, such as the many RNAs of unknown function recently reported by the ENCODE consortium. In this paper, we generalize the McCaskill partition function algorithm to sum over the grand canonical ensemble of all secondary structures of all mutants of the given sequence. Specifically, our new program, RNAmutants, simultaneously computes for each integer k the minimum free energy structure MFE(k) and the partition function Z(k) over all secondary structures of all k-point mutants, even allowing the user to specify certain positions required not to mutate and certain positions required to base-pair or remain unpaired. This technically important extension allows us to study the resilience of an RNA molecule to pointwise mutations. By computing the mutation profile of a sequence, a novel graphical representation of the mutational tendency of nucleotide positions, we analyze the deleterious nature of mutating specific nucleotide positions or groups of positions. We have successfully applied RNAmutants to investigate deleterious mutations (mutations that radically modify the secondary structure) in the Hepatitis C virus cis-acting replication element and to evaluate the evolutionary pressure applied on different regions of the HIV trans-activation response element. In particular, we show qualitative agreement between published Hepatitis C and HIV experimental mutagenesis studies and our analysis of deleterious mutations using RNAmutants. Our work also predicts other deleterious mutations, which could be verified experimentally. Finally, we provide evidence that the 3' UTR of the GB RNA virus C has been optimized to preserve evolutionarily conserved stem regions from a deleterious effect of pointwise mutations. We hope that there will be long-term potential applications of RNAmutants in de novo RNA design and drug design against RNA viruses. This work also suggests potential applications for large-scale exploration of the RNA sequence-structure network. Binary distributions are available at http://RNAmutants.csail.mit.edu/.

Dataset Information

RNAvigate: Efficient exploration of RNA chemical probing datasets.

Publications

RNAvigate: Efficient exploration of RNA chemical probing datasets.

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