During atherogenesis and vascular inflammation quiescent platelets are activated to increase the surface expression and ligand affinity of the integrin αIIbβ3 via inside-out signaling. Diverse signals such as thrombin, ADP and epinephrine transduce signals through their respective GPCRs to activate protein kinases that ultimately lead to the phosphorylation of the cytoplasmic tail of the integrin αIIbβ3 and augment its function. The signaling pathways that transmit signals from the GPCR to the cytosolic domain of the integrin are not well defined. In an effort to better understand these pathways, we employed a combination of proteomic profiling and computational analyses of isolated human platelets. We analyzed ten independent human samples and identified a total of 1507 unique proteins in platelets. This is the most comprehensive platelet proteome assembled to date and includes 190 membrane-associated and 262 phosphorylated proteins, which were identified via independent proteomic and phospho-proteomic profiling. We used this proteomic dataset to create a platelet protein-protein interaction (PPI) network and applied novel contextual information about the phosphorylation step to introduce limited directionality in the PPI graph. This newly developed contextual PPI network computationally recapitulated an integrin signaling pathway. Most importantly, our approach not only provided insights into the mechanism of integrin αIIbβ3 activation in resting platelets but also provides an improved model for analysis and discovery of PPI dynamics and signaling pathways in the future.

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Given a large directed graph, rapidly answering reachability queries between source and target nodes is an important problem. Existing methods for reachability tradeoff indexing time and space versus query time performance. However, the biggest limitation of existing methods is that they do not scale to very large real-world graphs. We present a simple yet scalable reachability index, called GRAIL, that is based on the idea of randomized interval labeling and that can effectively handle very large graphs. Based on an extensive set of experiments, we show that while more sophisticated methods work better on small graphs, GRAIL is the only index that can scale to millions of nodes and edges. GRAIL has linear indexing time and space, and the query time ranges from constant time to being linear in the graph order and size. Our reference C++ implementations are open source and available for download at

Abstract:In this paper, we introduce the concept of α-orthogonal patterns to mine a representative set of graph patterns. Intuitively, two graph patterns are α-orthogonal if their similarity is bounded above by α. Each α-orthogonal pattern is also a representative for those patterns that are at least β similar to it. Given user defined α, β ∈ [0, 1], the goal is to mine an α-orthogonal, β-representative set that minimizes the set of unrepresented patterns.We present ORIGAMI, an effective algorithm for mining the set of representative orthogonal patterns. ORIGAMI first uses a randomized algorithm to randomly traverse the pattern space, seeking previously unexplored regions, to return a set of maximal patterns. ORIGAMI then extracts an α-orthogonal, β-representative set from the mined maximal patterns. We show the effectiveness of our algorithm on a number of real and synthetic datasets. In particular, we show that our method is able to extract high-quality patterns even in cases where existing enumerative graph mining methods fail to do so. 

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