Sean P. Mason

Bio: Sean P. Mason is an academic researcher from Northwestern University. The author has contributed to research in topics: Proteome & Saccharomyces cerevisiae. The author has an hindex of 1, co-authored 1 publications receiving 4800 citations.

Lethality and centrality in protein networks

Abstract: The most highly connected proteins in the cell are the most important for its survival. Proteins are traditionally identified on the basis of their individual actions as catalysts, signalling molecules, or building blocks in cells and microorganisms. But our post-genomic view is expanding the protein's role into an element in a network of protein–protein interactions as well, in which it has a contextual or cellular function within functional modules1,2. Here we provide quantitative support for this idea by demonstrating that the phenotypic consequence of a single gene deletion in the yeast Saccharomyces cerevisiae is affected to a large extent by the topological position of its protein product in the complex hierarchical web of molecular interactions.

Statistical mechanics of complex networks

Abstract: The emergence of order in natural systems is a constant source of inspiration for both physical and biological sciences. While the spatial order characterizing for example the crystals has been the basis of many advances in contemporary physics, most complex systems in nature do not offer such high degree of order. Many of these systems form complex networks whose nodes are the elements of the system and edges represent the interactions between them. Traditionally complex networks have been described by the random graph theory founded in 1959 by Paul Erdohs and Alfred Renyi. One of the defining features of random graphs is that they are statistically homogeneous, and their degree distribution (characterizing the spread in the number of edges starting from a node) is a Poisson distribution. In contrast, recent empirical studies, including the work of our group, indicate that the topology of real networks is much richer than that of random graphs. In particular, the degree distribution of real networks is a power-law, indicating a heterogeneous topology in which the majority of the nodes have a small degree, but there is a significant fraction of highly connected nodes that play an important role in the connectivity of the network. The scale-free topology of real networks has very important consequences on their functioning. For example, we have discovered that scale-free networks are extremely resilient to the random disruption of their nodes. On the other hand, the selective removal of the nodes with highest degree induces a rapid breakdown of the network to isolated subparts that cannot communicate with each other. The non-trivial scaling of the degree distribution of real networks is also an indication of their assembly and evolution. Indeed, our modeling studies have shown us that there are general principles governing the evolution of networks. Most networks start from a small seed and grow by the addition of new nodes which attach to the nodes already in the system. This process obeys preferential attachment: the new nodes are more likely to connect to nodes with already high degree. We have proposed a simple model based on these two principles wich was able to reproduce the power-law degree distribution of real networks. Perhaps even more importantly, this model paved the way to a new paradigm of network modeling, trying to capture the evolution of networks, not just their static topology.

The Structure and Function of Complex Networks

Abstract: Inspired by empirical studies of networked systems such as the Internet, social networks, and biological networks, researchers have in recent years developed a variety of techniques and models to help us understand or predict the behavior of these systems. Here we review developments in this field, including such concepts as the small-world effect, degree distributions, clustering, network correlations, random graph models, models of network growth and preferential attachment, and dynamical processes taking place on networks.

Analysis of protein-coding genetic variation in 60,706 humans

Abstract: Large-scale reference data sets of human genetic variation are critical for the medical and functional interpretation of DNA sequence changes. Here we describe the aggregation and analysis of high-quality exome (protein-coding region) DNA sequence data for 60,706 individuals of diverse ancestries generated as part of the Exome Aggregation Consortium (ExAC). This catalogue of human genetic diversity contains an average of one variant every eight bases of the exome, and provides direct evidence for the presence of widespread mutational recurrence. We have used this catalogue to calculate objective metrics of pathogenicity for sequence variants, and to identify genes subject to strong selection against various classes of mutation; identifying 3,230 genes with near-complete depletion of predicted protein-truncating variants, with 72% of these genes having no currently established human disease phenotype. Finally, we demonstrate that these data can be used for the efficient filtering of candidate disease-causing variants, and for the discovery of human 'knockout' variants in protein-coding genes.

Network biology: understanding the cell's functional organization

Abstract: A key aim of postgenomic biomedical research is to systematically catalogue all molecules and their interactions within a living cell. There is a clear need to understand how these molecules and the interactions between them determine the function of this enormously complex machinery, both in isolation and when surrounded by other cells. Rapid advances in network biology indicate that cellular networks are governed by universal laws and offer a new conceptual framework that could potentially revolutionize our view of biology and disease pathologies in the twenty-first century.