In all organisms, major biological processes are controlled by complex protein–protein interactions networks (interactomes), yet their structural complexity presents major analytical challenges. Here, we integrate a compendium of over 4300 phenotypes with Arabidopsis interactome (AI-1MAIN). We show that nodes with high connectivity and betweenness are enriched and depleted in conditional and essential phenotypes, respectively. Such nodes are located in the innermost layers of AI-1MAIN and are preferential targets of pathogen effectors. We extend these network-centric analyses to Cell Surface Interactome (CSILRR) and predict its 35 most influential nodes. To determine their biological relevance, we show that these proteins physically interact with pathogen effectors and modulate plant immunity. Overall, our findings contrast with centrality-lethality rule, discover fast information spreading nodes, and highlight the structural properties of pathogen targets in two different interactomes. Finally, this theoretical framework could possibly be applicable to other inter-species interactomes to reveal pathogen contact points.
UPC++ is a C++ library that supports highperformance computation via an asynchronous communication framework. This paper describes a new incarnation that differs substantially from its predecessor, and we discuss the reasons for our design decisions. We present new design features, including future-based asynchrony management, distributed objects, and generalized Remote Procedure Call (RPC).We show microbenchmark performance results demonstrating that one-sided Remote Memory Access (RMA) in UPC++ is competitive with MPI-3 RMA; on a Cray XC40 UPC++ delivers up to a 25% improvement in the latency of blocking RMA put, and up to a 33% bandwidth improvement in an RMA throughput test. We showcase the benefits of UPC++ with irregular applications through a pair of application motifs, a distributed hash table and a sparse solver component. Our distributed hash table in UPC++ delivers near-linear weak scaling up to 34816 cores of a Cray XC40. Our UPC++ implementation of the sparse solver component shows robust strong scaling up to 2048 cores, where it outperforms variants communicating using MPI by up to 3.1x.UPC++ encourages the use of aggressive asynchrony in lowoverhead RMA and RPC, improving programmer productivity and delivering high performance in irregular applications.
BackgroundPlants respond to diverse environmental cues including microbial perturbations by coordinated regulation of thousands of genes. These intricate transcriptional regulatory interactions depend on the recognition of specific promoter sequences by regulatory transcription factors. The combinatorial and cooperative action of multiple transcription factors defines a regulatory network that enables plant cells to respond to distinct biological signals. The identification of immune-related modules in large-scale transcriptional regulatory networks can reveal the mechanisms by which exposure to a pathogen elicits a precise phenotypic immune response.ResultsWe have generated a large-scale immune co-expression network using a comprehensive set of Arabidopsis thaliana (hereafter Arabidopsis) transcriptomic data, which consists of a wide spectrum of immune responses to pathogens or pathogen-mimicking stimuli treatments. We employed both linear and non-linear models to generate Arabidopsis immune co-expression regulatory (AICR) network. We computed network topological properties and ascertained that this newly constructed immune network is densely connected, possesses hubs, exhibits high modularity, and displays hallmarks of a “real” biological network. We partitioned the network and identified 156 novel modules related to immune functions. Gene Ontology (GO) enrichment analyses provided insight into the key biological processes involved in determining finely tuned immune responses. We also developed novel software called OCCEAN (One Click Cis-regulatory Elements ANalysis) to discover statistically enriched promoter elements in the upstream regulatory regions of Arabidopsis at a whole genome level. We demonstrated that OCCEAN exhibits higher precision than the existing promoter element discovery tools. In light of known and newly discovered cis-regulatory elements, we evaluated biological significance of two key immune-related functional modules and proposed mechanism(s) to explain how large sets of diverse GO genes coherently function to mount effective immune responses.ConclusionsWe used a network-based, top-down approach to discover immune-related modules from transcriptomic data in Arabidopsis. Detailed analyses of these functional modules reveal new insight into the topological properties of immune co-expression networks and a comprehensive understanding of multifaceted plant defense responses. We present evidence that our newly developed software, OCCEAN, could become a popular tool for the Arabidopsis research community as well as potentially expand to analyze other eukaryotic genomes.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2164-15-421) contains supplementary material, which is available to authorized users.
The universal nature of networks’ structural and physical properties across diverse systems offers a better prospect to elucidate the interplay between a system and its environment. In the last decade, several large-scale transcriptome and interactome studies were conducted to understand the complex and dynamic nature of interactions between Arabidopsis and its bacterial pathogen, Pseudomonas syringae pv. tomato DC3000. We took advantage of these publicly available datasets and performed “-omics”-based integrative, and network topology analyses to decipher the transcriptional and protein-protein interaction activities of effector targets. We demonstrated that effector targets exhibit shorter distance to differentially expressed genes (DEGs) and possess increased information centrality. Intriguingly, effector targets are differentially expressed in a sequential manner and make for 1% of the total DEGs at any time point of infection with virulent or defense-inducing DC3000 strains. We revealed that DC3000 significantly alters the expression levels of 71% effector targets and their downstream physical interacting proteins in Arabidopsis interactome. Our integrative “-omics”-–based analyses identified dynamic complexes associated with MTI and disease susceptibility. Finally, we discovered five novel plant defense players using a systems biology-fueled top-to-bottom approach and demonstrated immune-related functions for them, further validating the power and resolution of our network analyses.
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