RNA World (beta)

RNA World (beta)
RNA World logo
Project
Status	Inactive
Category	Bioinformatics, Molecular biology, RNA research
Compute	CPU
Requires	BOINC, VirtualBox (for some applications)
Development
Developer	Rechenkraft.net e.V.
Sponsor	Rechenkraft.net e.V.
Maintainer	Dr. Michael H. W. Weber and the RNA World team
Initial release	January 1, 2010  (16 years ago)
Repository	https://www.rnaworld.de/rnaworld/
Software
Written in	C, C++, Python
Operating system	Windows, Linux, macOS
Size	Variable depending on work unit and VirtualBox image
Metadata
Website	https://www.rnaworld.de/rnaworld/
License	Open source components and scientific software

RNA World (beta) is a volunteer distributed computing project based on the BOINC platform. The project is operated by the German non profit organization Rechenkraft.net e.V. and focuses on large scale computational analysis of ribonucleic acid (RNA) molecules and RNA related biological processes.

RNA World distributes scientific calculations to Internet connected volunteer computers around the world. Participants donate unused CPU processing time to help researchers identify, analyze, classify, and model biologically important RNA structures and sequences. The project collaborates with academic institutions including the Philipps University of Marburg and the Indian Institute of Science in Bangalore.

Overview

RNA molecules perform a wide range of biological functions beyond their traditional role as intermediaries between DNA and proteins. Modern molecular biology has shown that RNA molecules can act as enzymes, regulators, structural elements, and signaling molecules. One of the most notable examples is the ribosome, a complex ribonucleoprotein assembly responsible for protein synthesis. The catalytic core of the ribosome is itself composed primarily of RNA, making it a natural ribozyme.

The project takes its name from the RNA world hypothesis, a scientific theory proposing that early life on Earth may have relied primarily on RNA molecules before the evolution of DNA and proteins. In this model, RNA would have served both as genetic material and as a catalytic molecule capable of supporting primitive biochemical reactions.

Many RNA molecules fold into complex secondary and tertiary structures governed by base pairing interactions. RNA folding predictions frequently involve thermodynamic calculations that minimize free energy. Typical RNA folding algorithms attempt to minimize:

<math>\Delta G = \Delta H - T\Delta S</math>

where <math>\Delta G</math> is the Gibbs free energy of folding, <math>\Delta H</math> is enthalpy, <math>T</math> is temperature, and <math>\Delta S</math> is entropy.

Scientific background

Every protein in a living cell is synthesized from a messenger RNA molecule, commonly abbreviated as mRNA. During translation, ribosomes decode the nucleotide sequence of mRNA into a corresponding amino acid sequence. RNA molecules are therefore central to nearly all known biological systems.

The sequencing of the human genome revealed that only a relatively small portion of human DNA directly encodes proteins. Subsequent research demonstrated that large regions of the genome produce non coding RNAs involved in regulation, cellular differentiation, and gene expression. Among the most important classes are microRNAs (miRNAs), short RNA molecules that regulate messenger RNA stability and translation.

MicroRNAs are now known to play important roles in development, cancer biology, viral infection, and cellular differentiation. Misregulation of miRNA expression has been associated with many diseases including leukemia, breast cancer, and neurological disorders.

Goals

RNA World was designed as a distributed bioinformatics platform capable of performing large scale RNA analysis using volunteer computing resources contributed by the public. Unlike conventional centralized supercomputers, the project operates as a heterogeneous distributed cluster composed of thousands of independently managed computers across multiple operating systems and hardware configurations.

The project aims to:

• identify novel non coding RNA molecules
• analyze RNA sequence conservation across species
• predict RNA secondary structures
• support comparative genomics studies
• contribute results to established RNA databases such as Rfam
• provide computational resources for RNA related scientific investigations

One major RNA World application uses the Infernal software suite, originally developed in the laboratory of Sean Eddy. Infernal uses covariance models to identify homologous RNA sequences and conserved secondary structures in genomic datasets.

Covariance models combine sequence conservation and structural conservation into probabilistic scoring systems. The probability of a sequence alignment may be represented by:

<math>P(S,M) = \prod_i P(s_i \mid m_i)</math>

where <math>S</math> represents the observed sequence and <math>M</math> represents the covariance model state path.

Volunteer computing

BOINC Manager software used to connect to RNA World

RNA World uses the BOINC middleware platform developed at the University of California, Berkeley. BOINC enables scientific projects to distribute computational workloads to volunteer computers connected through the Internet.

Participants install the BOINC client software and attach their computers to RNA World. Work units are downloaded automatically, processed locally, and returned to the project servers upon completion.

The project has historically supported Linux, Microsoft Windows, and macOS systems. Some applications additionally require VirtualBox virtualization support.

VirtualBox applications

Several RNA World applications operate within virtualized environments using VirtualBox. These applications allow researchers to deploy complex Linux based bioinformatics pipelines independent of the volunteer's host operating system.

Users participating in VirtualBox based applications must ensure that hardware virtualization extensions such as AMD V or Intel VT x are enabled in the system BIOS or UEFI firmware. Older RNA World applications also depended on specific VirtualBox versions for compatibility.

Some cmsearch virtual machine tasks are known for extremely long runtimes exceeding 1000 hours. Deadlines may be automatically extended by the project server.

Project organization

RNA World was created within the Rechenkraft.net e.V. volunteer computing community and is operated entirely by volunteers. The project infrastructure, software maintenance, and scientific administration are maintained collaboratively.

Active development team

Role	Staff
Project manager	Dr. Michael H. W. Weber
Server administration	Christian Beer and Uwe Beckert
Software development	Christian Beer, Tilman Giese, Volker Hatzenberger, Nico Mittenzwey, Stephan Ude
Graphics and design	Lasse J. Kolb, Rebirther, Dr. Michael H. W. Weber

Former contributors

Contributor	Contribution
Martin Bertheau	Linux checkpointing and BOINC progress bar improvements
Jacques Kühl	General checkpointing mechanisms
Maximilian Palm	Development of the user job submission interface
Andre Schmitz	ARM software development

Scientific publications

Research associated with RNA World has contributed to multiple peer reviewed publications in molecular biology, RNA biochemistry, and ribosome research.

1. Hoch, Philipp G. et al. "Phenotypic characterization and complementation analysis of Bacillus subtilis 6S RNA single and double deletion mutants." Biochimie (2015). DOI: 10.1016/j.biochi.2014.12.019.
2. Sinha, Akesh et al. "Biochemical Characterization of Pathogenic Mutations in Human Mitochondrial Methionyl tRNA Formyltransferase." Journal of Biological Chemistry (2014). DOI: 10.1074/jbc.M114.610626.
3. Arora, Smriti et al. "Role of the Ribosomal P Site Elements of m2G966, m5C967, and the S9 C Terminal Tail in Maintenance of the Reading Frame during Translational Elongation in Escherichia coli." Journal of Bacteriology (2013). DOI: 10.1128/JB.00455-13.
4. Arora, Smriti et al. "Distinctive contributions of the ribosomal P site elements m2G966, m5C967 and the C terminal tail of the S9 protein in the fidelity of initiation of translation in Escherichia coli." Nucleic Acids Research (2013). DOI: 10.1093/nar/gkt175.
5. Seshadri, Anuradha et al. "Impact of rRNA methylations on ribosome recycling and fidelity of initiation in Escherichia coli." Molecular Microbiology (2009). DOI: 10.1111/j.1365-2958.2009.06685.x.

See also

• BOINC
• RNA world hypothesis
• Bioinformatics
• Rfam
• Infernal
• Volunteer computing

External links

• Official RNA World website
• RNA World project description
• Rechenkraft.net e.V.
• BOINC