WORLDCOMP'07 Tutorial

The 2006 Nobel Prize for Physiology or Medicine went to the discoverers of RNA interference (RNAi) a mere eight years after the initial publication of their work. Such swift recognition highlights the extreme import of this newly discovered but ubiquitous method of gene regulation, which promises to yield volumes of functional data on the human genome as well as novel medical treatments. The RNAi field, like an increasing number of biological sub-disciplines in the post-genomic era, now faces computational and informatic challenges requiring its practitioners to step out of the chemistry lab and into the computer lab.

This tutorial will begin with a non-specialist?s introduction to the biology of RNAi and a discussion of the wide implications of this exciting, multi-faceted discovery. It will present the current bioinformatic techniques and problems attendant on inducible gene silencing by RNAi, including applications of machine learning, dynamic programming, and data warehousing techniques. Naturally occurring gene regulation by RNAi will also be discussed, with an emphasis on computational genomic modeling methods and prediction of combinatorial effects. Finally, the tutorial will cover future bioinformatics challenges related to genome-wide automated RNAi experiments and RNAi data standards.

• The basic biology underlying RNAi, including general functioning of RNA and proteins and the terminology of siRNAs (small interfering RNAs) and miRNAs (microRNAs)
• The utility of siRNAs as tools for investigating gene function and as possible disease treatments
• The nature of siRNA functionality (ability to silence the intended gene) and the algorithmic techniques used to predict it, as well as their limitations
• The nature of siRNA specificity (ability to avoid silencing unintended gene targets) and the application of existing programming solutions to this new problem
• The nature and sources of the voluminous biological data sets on which siRNAs are based, and the challenges of their collection and maintenance
• The role of naturally occurring miRNAs in cellular regulation
• The computational modeling methods that demonstrate the ubiquitous role of miRNAs in metabolism and the challenges of in silico prediction of combinatorial miRNA interactions
• The future of data standards and RNAi-specific public databases of genome-wide screens

This tutorial is intended for anyone with an understanding of programming techniques and databases who is interested in their application in a rapidly expanding biological discipline. Computer science students considering a specialization in bioinformatics will benefit especially. Only a rudimentary (high-school level) biological background is required.

Amanda Birmingham earned bachelors degrees in Astronomy, Physics, and English from Amherst College in Massachusetts, and promptly left academia for the world of professional programming. A lively scientific interest lured her into the emerging field of bioinformatics, where she has specialized in RNA science. She currently heads the bioinformatics group at Dharmacon (a division of Thermo Fisher Scientific), one of the most highly cited RNAi research labs in the world as well as the leading provider of RNAi reagents. Her widely referenced computational work on siRNA specificity has extended the field of siRNA design and contributed to the understanding of siRNA/miRNA pathway interactions.

Amanda Birmingham
Dharmacon, Thermo Fisher Scientific, Bioinformatics Manager, USA