 Hi, I'm Jishnu Das. I'm a graduate student in Dr. Haiwan News Lab and we are here in the Weil Institute for Cell and Molecular Biology at Cornell University. Our lab studies human disease and evolution using protein networks. Today I'm going to talk about how we examine these disease mutations in the context of a protein network, but it's not just any network that we are talking about here. It's an atomic resolution network, meaning it's as if we are taking a magnifying glass and zooming in on where these mutations are on the proteins. A typical protein network is like a connectivity map. It tells you how all these complex proteins bind to each other within a cell and carry out their functions. But what's missing from these maps is structural information. Proteins have complex three dimensional structures. So what we do in an atomic resolution network is we not just have the connectivity. We can also tell you where the proteins bind to each other. So we partition the protein into three parts, the interface residues of the key amino acids mediating where they bind to each other, the entire interacting domain, and then the rest of the protein. And people have typically believed that it is really the interface residues that are most important for the interaction. But we find here that disease mutations are not just enriched at these hotspot interface residues, but in the entire interacting domain, meaning that any kind of disruption within the whole domain, not just the hotspot residues, can break the interaction. So why is this finding important? It's crucial because it gives us a mechanistic understanding of how human disease progresses. So what happens in these complex diseases is that protein function is lost or altered, and that happens by disruption of specific interactions. So the mutations both at the hotspots and in the rest of the interacting domain have a tremendous amount of power to disrupt specific interactions, and that causes some functions to be lost, and that's how disease happens. To understand more about these mutations, how they were common structural properties of these mutations, I invite you to read our study in detail.