Applications of high throughput gene expression profiling in early drug discovery

Speaker
  • Senior Scientist at Biogazelle and Associate professor, Faculty of Medicine and Health Sciences, Ghent University, Belgium
    BIOGRAPHY

Abstract
Early stages of drug discovery often depend on relatively simple reporter assays or phenotypic readouts, providing little or no information on the drug’s mechanism of action (MOA). Gene expression profiling technologies like RNA-sequencing enable a more comprehensive characterization of compounds by measuring the activity of molecular pathways. This information can complement phenotypic readouts and can be used to prioritize candidate compounds for further testing. RNA expression profiling also serves as a generic test that can be applied to any drug development pipeline without the need for target-dependent customization.
 
In this webinar, Pieter Mestdagh will present a workflow that processes 384 cell lysates with RNA seq to generate expression data analyzed at the pathway level. Reliable pathway insights can be obtained at high throughput and relatively low cost while not being limited to a predefined set of genes or pathways. In cell perturbation screenings (small molecules, RNAi, antisense or CRISPR), the application can provide in depth information on the mode of action underlying the induced cellular phenotypes as well as molecular similarity scores to identify those perturbations acting similar to a reference condition or via shared molecular mechanisms.
 
Learning objectives:
  • Review a workflow showing that shallow sequencing of crude cell lysates reproducibly detects over 5000 genes with at least 10 reads.
  • Demonstrate how subsampling of deep sequencing datasets shows that differential pathway analysis is largely unaffected when reducing the number of genes to this level.
  • Discuss cell perturbation screenings and the ways this methodology can be applied to repurpose off-target siRNA hits from library screens to reveal novel candidate therapeutic targets for drug development.
  • Demonstrate how coupling the data generated from the workflow with a tailored visualization platform can facilitate data interpretation.

Show Resources
You May Also Like
FEB 24, 2021 10:00 AM PST
C.E. CREDITS
FEB 24, 2021 10:00 AM PST
DATE: February 24, 2021 TIME: 10am PST Automated lab instruments such as liquid handlers and cell sorters are increasingly common in all types of laboratories, driving fast results for labor...
SEP 14, 2021 7:00 AM PDT
Add to Calendar Select one of the following: iCal Google Calendar Outlook Calendar Yahoo Calendar
C.E. CREDITS
SEP 14, 2021 7:00 AM PDT
Add to Calendar Select one of the following: iCal Google Calendar Outlook Calendar Yahoo Calendar
Date: September 14, 2021 Time: 7am PDT, 10am EDT, 4pm CEST A conventional thermal cycler has long been a commodity product in the lab and end-point PCR techniques can be completed almost wit...
MAR 30, 2021 8:00 AM PDT
MAR 30, 2021 8:00 AM PDT
DATE: March 30, 2021 TIME: 08:00am PST In this talk, we will discuss the value of moving towards modular and automated, closed-system technologies designed to enable scalable and cost-effect...
APR 21, 2021 10:00 AM PDT
C.E. CREDITS
APR 21, 2021 10:00 AM PDT
Date: April 21, 2021 Time: 10:00am (PDT), 1:00pm (EDT) Serological testing for SARS-CoV-2 has been steadily adopted into clinical practice over the course of this pandemic. In this webinar,...
APR 07, 2021 9:00 AM PDT
C.E. CREDITS
APR 07, 2021 9:00 AM PDT
One challenge pharmaceutical companies face, is moving promising biotherapeutic products into the clinic as fast as safely possible. Devoting the correct amount of time and resources to earl...
C.E. CREDITS
Parkinson’s disease (PD) is the second most common neurodegenerative disorder with multiple motor and non-motor symptoms. PD is characterized by the presence on proteinaceous neuronal...
Loading Comments...
Show Resources