Gauging the systemic effects of non-synonymous single nucleotide polymorphisms (nsSNPs) is an important topic in the pursuit of personalized medicine. However, it is a non-trivial task to understand how a change at the protein structure level eventually affects a cell's behavior. This is because complex information at both the protein and pathway level has to be integrated. Given that the idea of integrating both protein and pathway dynamics to estimate the systemic impact of missense mutations in proteins remains predominantly unexplored, we investigate the practicality of such an approach by formulating mathematical models and comparing them with experimental data to study missense mutations. We present two case studies: (1) interpreting systemic perturbation for mutations within the cell cycle control mechanisms (G2 to mitosis transition) for yeast; (2) phenotypic classification of neuron-related human diseases associated with mutations within the mitogen-activated protein kinase (MAPK) pathway. We show that the application of simplified mathematical models is feasible for understanding the effects of small sequence changes on cellular behavior. Furthermore, we show that the systemic impact of missense mutations can be effectively quantified as a combination of protein stability change and pathway perturbation.

Random projection (RP) is a common technique for dimensionality reduction under L2 norm for which many significant space embedding results have been demonstrated. However, many similarity search applications often require very low dimension embeddings in order to reduce overhead and boost performance. Inspired by the use of symmetric probability distributions in previous work, we propose a novel RP algorithm, Beta Random Projection, and give its probabilistic analyses based on Beta and Gaussian approximations. We evaluate the algorithm in terms of standard similarity metrics with other RP algorithms as well as the singular value decomposition (SVD). Our experimental results show that BRP preserves both similarity metrics well and, under various dataset types including random point sets, text (TREC5) and images, provides sharper and consistent performance.

Recent analyses of human genome sequences have given rise to impressive advances in identifying non-synonymous single nucleotide polymorphisms (nsSNPs). By contrast, the annotation of nsSNPs and their links to diseases are progressing at a much slower pace. Many of the current approaches to analysing disease-associated nsSNPs use primarily sequence and evolutionary information, while structural information is relatively less exploited. In order to explore the potential of such information, we developed a structure-based approach, Bongo (Bonds ON Graph), to predict structural effects of nsSNPs. Bongo considers protein structures as residue-residue interaction networks and applies graph theoretical measures to identify the residues that are critical for maintaining structural stability by assessing the consequences on the interaction network of single point mutations. Our results show that Bongo is able to identify mutations that cause both local and global structural effects, with a remarkably low false positive rate. Application of the Bongo method to the prediction of 506 disease-associated nsSNPs resulted in a performance (positive predictive value, PPV, 78.5%) similar to that of PolyPhen (PPV, 77.2%) and PANTHER (PPV, 72.2%). As the Bongo method is solely structure-based, our results indicate that the structural changes resulting from nsSNPs are closely associated to their pathological consequences.

In this paper we propose Daedalus, a monitoring overlay network designed to compute approximate aggregate functions over multi-million of nodes, dynamic networks. Our design combines techniques from DBs and P2P systems. A small subset of related work is briefly described throughout the paper. Daedalus further extends these ideas to networks of much larger sizes, which we believe is a unique challenge.

The authors presented a novel approach for keyword searching for file sharing applications based on a simple hash function and extension to current distributed hash tables (DHT) topology. Depart from standard hash methods on DHT systems, this approach is to develop a locality preserving hash function so that objects containing the same keyword tend to have similar hash values under Hamming metric. It is shown that this hash function is locality preserving and proposes the embedding of keyword edges to facilitate query processing. As such, several class of problems in keyword search were reduced into a network multicast problem.