Marcin Magnus

RNAcentral was founded in 2014 to serve as a comprehensive database of non-coding RNA sequences. It began by providing a single unified interface to more specialised resources, and now contains 45 million sequences. It has grown beyond providing a single interface to many specialised resources and now provides several services and analyses. These include secondary structure prediction with R2DT, sequence search, and analysis with Rfam. Since its last publication in 2021, RNAcentral has developed two major features. First, literature integration with the development of LitScan and LitSumm. LitScan automatically identifies and links relevant publications to RNA entries, while LitSumm uses natural language processing to generate functional summaries from the literature. Together, these tools address the critical challenge of connecting sequence data with scattered functional knowledge across thousands of publications. Secondly, RNAcentral has created gene level entries. Gene level entries represent a large structural change to RNAcentral. While RNAcentral previously organized data exclusively at the sequence level, we now group related transcripts into gene-centric views. This allows researchers to explore all isoforms, splice variants, and related sequences for a gene in a unified interface, better reflecting biological organization and facilitating comparative analyses. RNAcentral is freely available at: https://rnacentral.org .

The Critical Assessment of Structure Prediction (CASP) brings together a diverse group of scientists, from deep learning experts to NMR specialists, all aimed at developing accurate prediction algorithms that can effectively characterize the structural aspects of biomolecules relevant to their functions. Engagement within the CASP community has traditionally been limited to the prediction season and the conference, with limited discourse in the 1.5 years between CASP seasons. CASP special interest groups (SIGs) were established in 2023 to encourage continuous dialogue within the community. The online seminar series has drawn global participation from across disciplines and career stages. This has facilitated cross‐disciplinary discussions fostering collaborations. The archives of these seminars have become a vital learning tool for newcomers to the field, lowering the barrier to entry.

The complexity in the generation of RNA multiple sequence alignments and assessment of the accuracy of such alignments contributes to the challenges in the utilization of RNA MSAs in diverse integrative methods. RNAhub is a freely available user-friendly web server for a reliable generation of RNA multiple sequence alignents and the detection of the presence of structural RNA utilizing evolutionary information. This web-based tool, developed by the integration of existing computational approaches, takes an RNA sequence as input and automatically retrieves and aligns sequences homologous to the input (query) RNA sequence through an iterative and structure-agnostic approach. Based on the alignment, this tool statistically assesses whether the query RNA sequence has a conserved RNA structure using covariation analysis. The web server allows the user to efficiently search the sequence of interest against carefully curated, ready-to-use genomic databases to produce an MSA. Using this alignment, our tool either detects the presence of a conserved structural RNA, finds evidence against the presence of a conserved structure, or cannot make any assessment due to a lack of sequence diversity in the alignment. The web server is freely available at https://rnahub.org.

The complexity in the generation of RNA multiple sequence alignments and assessment of the accuracy of such alignments contributes to the challenges in the utilization of RNA alignments in diverse integrative methods. RNAhub is a freely available user-friendly web server for a reliable generation of RNA multiple sequence alignments and the detection of the presence of structural RNA utilizing evolutionary information. This web-based tool, developed by the integration of existing computational approaches, takes an RNA sequence as input and automatically retrieves and aligns sequences homologous to the input (query) RNA sequence through an iterative and structure-agnostic approach. Based on the alignment, this tool statistically assesses whether the query RNA sequence has a conserved RNA structure using covariation analysis. The web server allows the user to efficiently search the sequence of interest against carefully curated, ready-to-use genomic databases to produce a multiple sequence alignment. Using this alignment, our tool either detects the presence of a conserved structural RNA, finds evidence against the presence of a conserved structure, or cannot make any assessment due to a lack of sequence diversity in the alignment. The web server is freely available at https://rnahub.org . Graphical

Today, there are several effective deep learning models for predicting the 3D structure of proteins. Building on their success, models have been developed for predicting the 3D structure of non-coding RNAs. Unfortunately, these models are much less accurate than their protein counterparts. In this paper, we highlight differences between protein and RNA structure, and demonstrate methods for deep learning targeted at addressing those differences, with the aim of prompting discussion on these topics. We present an RNA-specific pipeline for generating structural Multiple Sequence Alignments (MSAs). Derived from the structural alignments, we introduce engineered evolutionary features that strongly inform RNA structure. Further, from the crystal structure, we derive structural features describing RNA base pairing. These evolutionary and structural features can be used in loss functions at different stages of training. Finally, we discuss different cropping strategies informed by RNA structure.

RNA-Puzzles is a collective endeavor dedicated to the advancement and improvement of RNA three-dimensional structure prediction. With agreement from structural biologists, RNA structures are predicted by modeling groups before publication of the experimental structures. We report a large-scale set of predictions by 18 groups for 23 RNA-Puzzles: 4 RNA elements, 2 Aptamers, 4 Viral elements, 5 Ribozymes and 8 Riboswitches. We describe automatic assessment protocols for comparisons between prediction and experiment. Our analyses reveal some critical steps to be overcome to achieve good accuracy in modeling RNA structures: identification of helix-forming pairs and of non-Watson–Crick modules, correct coaxial stacking between helices and avoidance of entanglements. Three of the top four modeling groups in this round also ranked among the top four in the CASP15 contest.

Research on ribonucleic acid (RNA) structures and functions benefits from easy-to-use tools for computational prediction and analyses of RNA three-dimensional (3D) structure. The SimRNAweb server version 2.0 offers an enhanced, user-friendly platform for RNA 3D structure prediction and analysis of RNA folding trajectories based on the SimRNA method. SimRNA employs a coarse-grained model, Monte Carlo sampling and statistical potentials to explore RNA conformational space, optionally guided by spatial restraints. Recognized for its accuracy in RNA 3D structure prediction in RNA-Puzzles and CASP competitions, SimRNA is particularly useful for incorporating restraints based on experimental data. The new server version introduces performance optimizations and extends user control over simulations and the processing of results. It allows the application of various hard and soft restraints, accommodating alternative structures involving canonical and noncanonical base pairs and unpaired residues, while also integrating data from chemical probing methods. Enhanced features include an improved analysis of folding trajectories, offering advanced clustering options and multiple analyses of the generated trajectories. These updates provide comprehensive tools for detailed RNA structure analysis. SimRNAweb v2.0 significantly broadens the scope of RNA modeling, emphasizing flexibility and user-defined parameter control. The web server is available at https://genesilico.pl/SimRNAweb.

Summary: Structure determination is a key step in the functional characterization of many non-coding RNA molecules. High-resolution RNA 3D structure determination efforts, however, are not keeping up with the pace of discovery of new non-coding RNA sequences. This increases the importance of computational approaches and low-resolution experimental data, such as from the small-angle X-ray scattering experiments. We present RNA Masonry, a computer program and a web service for a fully automated modeling of RNA 3D structures. It assemblies RNA fragments into geometrically plausible models that meet user-provided secondary structure constraints, restraints on tertiary contacts, and small-angle X-ray scattering data. We illustrate the method description with detailed benchmarks and its application to structural studies of viral RNAs with SAXS restraints. Availability and implementation: The program web server is available at http://iimcb.genesilico.pl/rnamasonry. The source code is available at https://gitlab.com/gchojnowski/rnamasonry.

Significant improvements have been made in the efficiency and accuracy of RNA 3D structure prediction methods in recent years; however, many tools developed in the field stay exclusive to only a few bioinformatic groups. To perform a complete RNA 3D structure modeling analysis as proposed by the RNA-Puzzles community, researchers must familiarize themselves with a quite complex set of tools. In order to facilitate the processing of RNA sequences and structures, we previously developed the rna-tools package. However, using rna-tools requires the installation of a mixture of libraries and tools, basic knowledge of the command line and the Python programming language. To provide an opportunity for the broader community of biologists to take advantage of the new developments in RNA structural biology, we developed rna-tools.online. The web server provides a user-friendly platform to perform many standard analyses required for the typical modeling workflow: 3D structure manipulation and editing, structure minimization, structure analysis, quality assessment, and comparison. rna-tools.online supports biologists to start benefiting from the maturing field of RNA 3D structural bioinformatics and can be used for educational purposes. The web server is available at https://rna-tools.online.

We present RNA Masonry, a computer program and a web service for a fully automated assembly of RNA fragments into geometrically plausible models fulfilling user-provided secondary structure constraints and restraints on tertiary contacts and Small Angle X-ray Scattering (SAXS) data. We illustrate the method description with its recent application to structural studies of viral RNAs with SAXS restraints. The program web server is available at http://iimcb.genesilico.pl/rnamasonry. Contact gchojnowski{at}embl-hamburg.de