RNAi Global Projects and Activities for 2006

For the Genome-Wide RNAi Global Initiative, 2006 marks a year full of activities and projects born of productive interactions amongst the members of this growing partnership. The membership represents a globally distributed alliance of research institutions that have increased steadily in number. The most recent additions to the Initiative include the Institut Pasteur Korea in Seoul, Korea and Trinity College in Dublin, Ireland illustrating the worldwide representation and underscoring the mission to foster “international scientific exchange and the collaboration of leading research institutions”. Together, these research groups from Europe, North America and Asia bring a broad range of expertise to RNAi-based screening strategies. Their collective efforts promise to speed progress towards understanding medically relevant biological processes including developmental biology, cancer biologyand host-pathogen interactions through high throughput and high content RNAi screens.

Facilitating Discussion and Collaboration

A critical aspect to the RNAi Global Initiative is regular communication amongst the partner institutions via monthly teleconferences, biannual meetings and an electronic forum hosted by Dharmacon (now part of ThermoFisher Scientific). Among the fruits of these regularly scheduled interactions is the formation of several work group initiatives focused on addressing issues relevant to RNAi-based strategies. These include the development of quality metrics and guidelines for data reporting, the assembly of general protocols, controls, data analysis, and more. The ultimate goal of these efforts is to improve the utility of, and confidence in, RNAi as a tool in basic research and drug discovery programs. In 2006, the most active of these initiatives was the Informatics Work Group which has followed the example of the microarray community by formulating a set of guidelines for Minimum Information About an RNAi Experiments (MIARE). Other initiatives have been proposed for focused discussions around assay selection, high content platforms, information portals for the annotation of the human transcriptome, and collaborative endeavors to build data sets and resources for the scientific community at large. To-date, typically 80% of the member institutions are represented at the monthly teleconferences and biannual meetings where round-table discussions and presentations provide members an opportunity to share data or to solicit feedback about experimental practices, issues and strategies. To facilitate extended discussions outside the monthly teleconferences, Dharmacon also hosts www.rnaiglobla.org, a site where members are encouraged to post public-facing information about their research programs. A moderated discussion board for threaded and extended discussions is also available to members to post information about instruments, assays, protocols, and data sets. In this way, a dynamic forum is provided for threaded discussions around key considerations related to high throughput and high content strategies and workflow, infrastructure, reagents and controls, assay selection, general observations, etc.

MIARE: Minimum Information About an RNAi Experiment

As mentioned above, one of the most productive RNAi Global interactions is the Informatics Work Group (IWG). Select representatives from each RNAi Global institution have tackled the inevitable challenge of managing large data sets associated with whole genome screens. By taking a lead from the microarray community and MGED (Microarray Gene Expression Data) Society and the IWG recognized the necessity to engage the research community in developing guidelines that would permit cross-comparisons and evaluation of data derived from different sources and platforms. To aid in the development process of MIARE, the founding members of the RNAi Global Initiative conducted a multi-center benchmark screen for the purpose of illustrating the practicality and identifying the challenges of cross-comparisons. Using the simplest model whereby all groups performed the same assay, the founding members of RNAi Global each separately performed a highly controlled kinome and cell cycle screen to define a baseline of understanding of the degree of inter and intra-variability in the data sets. This is intended as the first phase in a concerted effort to incorporate lessons learned from practical exercises of actual screens and comparing data outcomes to help better define methods for reporting minimal but sufficiently useful information. The effort to derive a working set of MIARE guidelines is clearly open for discussion and in very early stages of development. The basic concept has been presented at several meetings including the HUPO PSI Spring Workshop 2006 and as a poster at Discovery on Target in Boston October 23-26. MIARE has also been cited in recent publications focused on similar efforts among other scientific disciplines [1-3]. The Informatics Work Group, lead by RNAi Global members at the Scottish Centre for Genomic Technology and Informatics (GTI) has set up a website hosted by sourceforge to provide a resource of information about the development of MIARE and other standards and more importantly to solicit feedback. The IWG and the RNAi Global Initiative broadly represent the RNAi community at large and look forward to input and feedback from colleagues as the field of RNAi-based strategies develop.

References

1. Echeverri, C.J. and N. Perrimon, High-throughput RNAi screening in cultured cells: a user's guide. Nat Rev Genet, 2006. 7(5): p. 373-84.
2. Echeverri, C.J., et al., Minimizing the risk of reporting false positives in large-scale RNAi screens. Nat Methods, 2006. 3(10): p. 777-9.
3. Brazma, A., M. Krestyaninova, and U. Sarkans, Standards for systems biology. Nat Rev Genet, 2006. 7(8): p. 593-605.