“Harnessing protein structure and network to unravel the contribution of genes and genetic variants to human disorders: challenges and opportunities”

“One the greatest challenges in human genetics is to prioritize and characterize the overwhelming number of genetic variants identified by large sequencing projects, in order to determine which ones cause, or increase the risk of developing disease and should be tested further e.g. with in vitro studies. In silico prioritization algorithms are invaluable allies in this selection process. However, current in silico methods rely mainly on sequence conservation and suffer from high false positive rate, thus making the development of novel in silico approaches highly desirable. Exploring the effect of a genetic variant on protein structure, function and, ultimately, on the protein’s ability to interact with other proteins and small molecules within the cell protein network, can provide powerful information, complementary to existing sequence-based approaches.  In this talk, I will discuss how harnessing protein structure and interactome can provide new insight into gene function and association to disease, as well as aid in the prioritization and characterization of genetic variants identified through exome sequencing. I will also discuss how protein network data can be used to develop novel algorithms aimed at investigating the genetic background of human disorders, such as dyslipidaemia.“

 

Alessia David

Imperial College London (Centre for Integrative System Biology & Bioinformatics)