As computer networks increase in size, become more heterogeneous and span greater geographic distances, applications must be designed to cope with the very large scale, poor reliability, and often, with the extreme dynamism of the underlying network. Aggregation is a key functional building block for such applications: it refers to a set of functions that provide components of a distributed system access to global information including network size, average load, average uptime, location and description of hotspots, etc. Local access to global information is often very useful, if not indispensable for building applications that are robust and adaptive. For example, in an industrial control application, some aggregate value reaching a threshold may trigger the execution of certain actions; a distributed storage system will want to know the total available free space; load balancing protocols may benefit from knowing the target average load so as to minimize the load they transfer. We propose a gossip-based protocol for computing aggregate values over network components in a fully decentralized fashion. The class of aggregate functions we can compute is very broad and includes many useful special cases such as counting, averages, sums, products and extremal values. The protocol is suitable for extremely large and highly dynamic systems due to its proactive structure-all nodes receive the aggregate value continuously, thus being able to track any changes in the system. The protocol is also extremely lightweight making it suitable for many distributed applications including peer-to-peer and grid computing systems. We demonstrate the efficiency and robustness of our gossip-based protocol both theoretically and experimentally under a variety of scenarios including node and communication failures.

Gossip-based communication protocols are appealing in large-scale distributed applications such as information dissemination, aggregation, and overlay topology management. This paper factors out a fundamental mechanism at the heart of all these protocols: the peer-sampling service. In short, this service provides every node with peers to gossip with. We promote this service to the level of a first-class abstraction of a large-scale distributed system, similar to a name service being a first-class abstraction of a local-area system. We present a generic framework to implement a peer-sampling service in a decentralized manner by constructing and maintaining dynamic unstructured overlays through gossiping membership information itself. Our framework generalizes existing approaches and makes it easy to discover new ones. We use this framework to empirically explore and compare several implementations of the peer-sampling service. Through extensive simulation experiments we show that-although all protocols provide a good quality uniform random stream of peers to each node locally-traditional theoretical assumptions about the randomness of the unstructured overlays as a whole do not hold in any of the instances. We also show that different design decisions result in severe differences from the point of view of two crucial aspects: load balancing and fault tolerance. Our simulations are validated by means of a wide-area implementation.

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Intense experimental and theoretical efforts have been made to globally map genetic interactions, yet we still do not understand how gene-gene interactions arise from the operation of biomolecular networks. To bridge the gap between empirical and computational studies, we: i) quantitatively measure genetic interactions between ~185,000 metabolic gene pairs in Saccharomyces cerevisiae, ii) superpose the data on a detailed systems biology model of metabolism, and iii) introduce a machine-learning method to reconcile empirical interaction data with model predictions. We systematically investigate the relative impacts of functional modularity and metabolic flux coupling on the distribution of negative and positive genetic interactions. We also provide a mechanistic explanation for the link between the degree of genetic interaction, pleiotropy, and gene dispensability. Last, we demonstrate the feasibility of automated metabolic model refinement by correcting misannotations in NAD biosynthesis and confirming them by in vivo experiments.