Eigenvector localization as a tool to study small communities in online social networks

We present and discuss a mathematical procedure for identification of small "communities" or segments within large bipartite networks. The procedure is based on spectral analysis of the matrix encoding network structure. The principal tool here is localization of eigenvectors of the matrix, by means of which the relevant network segments become visible. We exemplified our approach by analyzing the data related to product reviewing on Amazon.com. We found several segments, a kind of hybrid communities of densely interlinked reviewers and products, which we were able to meaningfully interpret in terms of the type and thematic categorization of reviewed items. The method provides a complementary approach to other ways of community detection, typically aiming at identification of large network modules

FixMiner: Mining Relevant Fix Patterns for Automated Program Repair

Patching is a common activity in software development. It is generally performed on a source code base to address bugs or add new functionalities. In this context, given the recurrence of bugs across projects, the associated similar patches can be leveraged to extract generic fix actions. While the literature includes various approaches leveraging similarity among patches to guide program repair, these approaches often do not yield fix patterns that are tractable and reusable as actionable input to APR systems. In this paper, we propose a systematic and automated approach to mining relevant and actionable fix patterns based on an iterative clustering strategy applied to atomic changes within patches. The goal of FixMiner is thus to infer separate and reusable fix patterns that can be leveraged in other patch generation systems. Our technique, FixMiner, leverages Rich Edit Script which is a specialized tree structure of the edit scripts that captures the AST-level context of the code changes. FixMiner uses different tree representations of Rich Edit Scripts for each round of clustering to identify similar changes. These are abstract syntax trees, edit actions trees, and code context trees. We have evaluated FixMiner on thousands of software patches collected from open source projects. Preliminary results show that we are able to mine accurate patterns, efficiently exploiting change information in Rich Edit Scripts. We further integrated the mined patterns to an automated program repair prototype, PARFixMiner, with which we are able to correctly fix 26 bugs of the Defects4J benchmark. Beyond this quantitative performance, we show that the mined fix patterns are sufficiently relevant to produce patches with a high probability of correctness: 81% of PARFixMiner's generated plausible patches are correct.Comment: 31 pages, 11 figure

Monoaminergic modulation of photoreception in ascidian:evidence for a proto-hypothalamo-retinal territory

Background : The retina of craniates/vertebrates has been proposed to derive from a photoreceptor prosencephalic territory in ancestral chordates, but the evolutionary origin of the different cell types making the retina is disputed. Except for photoreceptors, the existence of homologs of retinal cells remains uncertain outside vertebrates. Methods : The expression of genes expressed in the sensory vesicle of the ascidian Ciona intestinalis including those encoding components of the monoaminergic neurotransmission systems, was analyzed by in situ hybridization or in vivo transfection of the corresponding regulatory elements driving fluorescent reporters. Modulation of photic responses by monoamines was studied by electrophysiology combined with pharmacological treatments. Results : We show that many molecular characteristics of dopamine-synthesizing cells located in the vicinity of photoreceptors in the sensory vesicle of the ascidian Ciona intestinalis are similar to those of amacrine dopamine cells of the vertebrate retina. The ascidian dopamine cells share with vertebrate amacrine cells the expression of the key-transcription factor Ptf1a, as well as that of dopamine-synthesizing enzymes. Surprisingly, the ascidian dopamine cells accumulate serotonin via a functional serotonin transporter, as some amacrine cells also do. Moreover, dopamine cells located in the vicinity of the photoreceptors modulate the light-off induced swimming behavior of ascidian larvae by acting on alpha2-like receptors, instead of dopamine receptors, supporting a role in the modulation of the photic response. These cells are located in a territory of the ascidian sensory vesicle expressing genes found both in the retina and the hypothalamus of vertebrates (six3/6, Rx, meis, pax6, visual cycle proteins). Conclusion : We propose that the dopamine cells of the ascidian larva derive from an ancestral multifunctional cell population located in the periventricular, photoreceptive field of the anterior neural tube of chordates, which also gives rise to both anterior hypothalamus and the retina in craniates/vertebrates. It also shows that the existence of multiple cell types associated with photic responses predates the formation of the vertebrate retina

Proteomic analysis of the Plasmodium male gamete reveals the key role for glycolysis in flagellar motility.

BACKGROUND: Gametogenesis and fertilization play crucial roles in malaria transmission. While male gametes are thought to be amongst the simplest eukaryotic cells and are proven targets of transmission blocking immunity, little is known about their molecular organization. For example, the pathway of energy metabolism that power motility, a feature that facilitates gamete encounter and fertilization, is unknown. METHODS: Plasmodium berghei microgametes were purified and analysed by whole-cell proteomic analysis for the first time. Data are available via ProteomeXchange with identifier PXD001163. RESULTS: 615 proteins were recovered, they included all male gamete proteins described thus far. Amongst them were the 11 enzymes of the glycolytic pathway. The hexose transporter was localized to the gamete plasma membrane and it was shown that microgamete motility can be suppressed effectively by inhibitors of this transporter and of the glycolytic pathway. CONCLUSIONS: This study describes the first whole-cell proteomic analysis of the malaria male gamete. It identifies glycolysis as the likely exclusive source of energy for flagellar beat, and provides new insights in original features of Plasmodium flagellar organization

Examination of the relationship between essential genes in PPI network and hub proteins in reverse nearest neighbor topology

Abstract Background In many protein-protein interaction (PPI) networks, densely connected hub proteins are more likely to be essential proteins. This is referred to as the "centrality-lethality rule", which indicates that the topological placement of a protein in PPI network is connected with its biological essentiality. Though such connections are observed in many PPI networks, the underlying topological properties for these connections are not yet clearly understood. Some suggested putative connections are the involvement of essential proteins in the maintenance of overall network connections, or that they play a role in essential protein clusters. In this work, we have attempted to examine the placement of essential proteins and the network topology from a different perspective by determining the correlation of protein essentiality and reverse nearest neighbor topology (RNN). Results The RNN topology is a weighted directed graph derived from PPI network, and it is a natural representation of the topological dependences between proteins within the PPI network. Similar to the original PPI network, we have observed that essential proteins tend to be hub proteins in RNN topology. Additionally, essential genes are enriched in clusters containing many hub proteins in RNN topology (RNN protein clusters). Based on these two properties of essential genes in RNN topology, we have proposed a new measure; the RNN cluster centrality. Results from a variety of PPI networks demonstrate that RNN cluster centrality outperforms other centrality measures with regard to the proportion of selected proteins that are essential proteins. We also investigated the biological importance of RNN clusters. Conclusions This study reveals that RNN cluster centrality provides the best correlation of protein essentiality and placement of proteins in PPI network. Additionally, merged RNN clusters were found to be topologically important in that essential proteins are significantly enriched in RNN clusters, and biologically important because they play an important role in many Gene Ontology (GO) processes.http://deepblue.lib.umich.edu/bitstream/2027.42/78257/1/1471-2105-11-505.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78257/2/1471-2105-11-505-S1.DOChttp://deepblue.lib.umich.edu/bitstream/2027.42/78257/3/1471-2105-11-505.pdfPeer Reviewe

Functional modules in the Arabidopsis core cell cycle binary protein-protein interaction network

As in other eukaryotes, cell division in plants is highly conserved and regulated by cyclin-dependent kinases (CDKs) that are themselves predominantly regulated at the posttranscriptional level by their association with proteins such as cyclins. Although over the last years the knowledge of the plant cell cycle has considerably increased, little is known on the assembly and regulation of the different CDK complexes. To map protein-protein interactions between core cell cycle proteins of Arabidopsis thaliana, a binary protein-protein interactome network was generated using two complementary high-throughput interaction assays, yeast two-hybrid and bimolecular fluorescence complementation. Pairwise interactions among 58 core cell cycle proteins were tested, resulting in 357 interactions, of which 293 have not been reported before. Integration of the binary interaction results with cell cycle phase-dependent expression information and localization data allowed the construction of a dynamic interaction network. The obtained interaction map constitutes a framework for further in-depth analysis of the cell cycle machinery

Damage localization using experimental modal parameters and topology optimization

This work focuses on the developement of a damage detection and localization tool using the Topology Optimization feature of MSC.Nastran. This approach is based on the correlation of a local stiness loss and the change in modal parameters due to damages in structures. The loss in stiness is accounted by the Topology Optimization approach for updating undamaged numerical models towards similar models with embedded damages. Hereby, only a mass penalization and the changes in experimentally obtained modal parameters are used as objectives. The theoretical background for the implementation of this method is derived and programmed in a Nastran input file and the general feasibility of the approach is validated numerically, as well as experimentally by updating a model of an experimentally tested composite laminate specimen. The damages have been introduced to the specimen by controlled low energy impacts and high quality vibration tests have been conducted on the specimen for dierent levels of damage. These supervised experiments allow to test the numerical diagnosis tool by comparing the result with both NDT technics and results of previous works (concerning shifts in modal parameters due to damage). Good results have finally been archieved for the localization of the damages by the Topology Optimization

Novel components of the Toxoplasma inner membrane complex revealed by BioID.

UNLABELLED:The inner membrane complex (IMC) of Toxoplasma gondii is a peripheral membrane system that is composed of flattened alveolar sacs that underlie the plasma membrane, coupled to a supporting cytoskeletal network. The IMC plays important roles in parasite replication, motility, and host cell invasion. Despite these central roles in the biology of the parasite, the proteins that constitute the IMC are largely unknown. In this study, we have adapted a technique named proximity-dependent biotin identification (BioID) for use in T. gondii to identify novel components of the IMC. Using IMC proteins in both the alveoli and the cytoskeletal network as bait, we have uncovered a total of 19 new IMC proteins in both of these suborganellar compartments, two of which we functionally evaluate by gene knockout. Importantly, labeling of IMC proteins using this approach has revealed a group of proteins that localize to the sutures of the alveolar sacs that have been seen in their entirety in Toxoplasma species only by freeze fracture electron microscopy. Collectively, our study greatly expands the repertoire of known proteins in the IMC and experimentally validates BioID as a strategy for discovering novel constituents of specific cellular compartments of T. gondii. IMPORTANCE:The identification of binding partners is critical for determining protein function within cellular compartments. However, discovery of protein-protein interactions within membrane or cytoskeletal compartments is challenging, particularly for transient or unstable interactions that are often disrupted by experimental manipulation of these compartments. To circumvent these problems, we adapted an in vivo biotinylation technique called BioID for Toxoplasma species to identify binding partners and proximal proteins within native cellular environments. We used BioID to identify 19 novel proteins in the parasite IMC, an organelle consisting of fused membrane sacs and an underlying cytoskeleton, whose protein composition is largely unknown. We also demonstrate the power of BioID for targeted discovery of proteins within specific compartments, such as the IMC cytoskeleton. In addition, we uncovered a new group of proteins localizing to the alveolar sutures of the IMC. BioID promises to reveal new insights on protein constituents and interactions within cellular compartments of Toxoplasma