Biochemistry Seminar - Dr. Robert Nadon

Dr. Robert Nadon
McGill University
Associate Professor, Department of Human Genetics
Principal Investigator, McGill University and Genome Quebec Innovation Centre

“Detection of Rare Biological Events in High-Throughput Screens”

Primary high-throughput screens (HTS) are used to identify rare biological events among a large number of inactive features.  This needle-in-the-haystack problem is made even more difficult when attempting to discover weak effects in contexts such as fragment-based screens, which examine low potency low-molecular-weight ligands that bind to biologically significant macromolecules, RNAi screens in which weak but genuine phenotypes can be caused either by partial knockdown of a gene with a strong effect or a strong knockdown of a gene with a weak effect, and in pharmaceutical screens for maximizing discovery of new chemical series or scaffolds for drug development.  Current standard HTS practice unfortunately performs poorly in these circumstances due to measurement uncertainty.  Inherent random variability of the assays places limits on hit discovery and reproducibility; systematic errors (bias) introduced by procedures, equipment, and materials, can both mask biological activity and give the appearance of activity when there is none.  I will present recent work from my lab which shows how study design, diagnostic graphical methods, normalization, and statistical inference tests can substantially improve detection of weak effects in primary HTS screens.  An Excel add-in software package implementing the methods is available.

Mandatory for Graduate Students