Torque: topology-free querying of protein interaction networks

Torque is a tool for cross-species querying of protein–protein interaction networks. It aims to answer the following question: given a set of proteins constituting a known complex or a pathway in one species, can a similar complex or pathway be found in the protein network of another species? To this end, Torque seeks a matching set of proteins that are sequence similar to the query proteins and span a connected region of the target network, while allowing for both insertions and deletions. Unlike existing approaches, Torque does not require knowledge of the interconnections among the query proteins. It can handle large queries of up to 25 proteins. The Torque web server is freely available for use at http://www.cs.tau.ac.il/∼bnet/torque.html

Effects of Exposure to Community Violence and Family Violence on School Functioning Problems among Urban Youth: The Potential Mediating Role of Posttraumatic Stress Symptoms

Adolescents who are exposed to violence during childhood are at an increased risk for developing posttraumatic stress (PTS) symptoms. The literature suggests that violence exposure might also have negative effects on school functioning, and that PTS might serve as a potential mediator in this association. The purpose of the current study was to replicate and extend prior research by examining PTS symptoms as a mediator of the relationship between two types of violence exposure and school functioning problems among ado- lescent youth from an urban setting. Participants included a sample of 121 junior high and high school students (M = 15 years; range = 13–16 years; 60 males, 61 females) within high-crime neighborhoods. Consistent with our hypotheses, community violence and fam- ily violence were associated with PTS symptoms and school functioning problems. Our data suggest that community and family violence were indirectly related to school func- tioning problems through PTS symptoms. Findings from this study demonstrate that PTS symptoms potentially mediate the relationship between violence exposure and school functioning problems across two settings (community and home). Future research should further examine protective factors that can prevent youth violence exposure as well as negative outcomes related to violence

Lymphatic filariasis epidemiology in Samoa in 2018: geographic clustering and higher antigen prevalence in older age groups

Background: Samoa conducted eight nationwide rounds of mass drug administration (MDA) for lymphatic filariasis (LF) between 1999 and 2011, and two targeted rounds in 2015 and 2017 in North West Upolu (NWU), one of three evaluation units (EUs). Transmission Assessment Surveys (TAS) were conducted in 2013 (failed in NWU) and 2017 (all three EUs failed). In 2018, Samoa was the first in the world to distribute nationwide triple-drug MDA using ivermectin, diethylcarbamazine, and albendazole. Surveillance and Monitoring to Eliminate LF and Scabies from Samoa (SaMELFS Samoa) is an operational research program designed to evaluate the effectiveness of triple-drug MDA on LF transmission and scabies prevalence in Samoa, and to compare the usefulness of different indicators of LF transmission. This paper reports results from the 2018 baseline survey and aims to i) investigate antigen (Ag) prevalence and spatial epidemiology, including geographic clustering; ii) compare Ag prevalence between two different age groups (5–9 years versus ≥10 years) as indicators of areas of ongoing transmission; and iii) assess the prevalence of limb lymphedema in those aged ≥15 years. Methods: A community-based cluster survey was conducted in 30 randomly selected and five purposively selected clusters (primary sampling units, PSUs), each comprising one or two villages. Participants were recruited through household surveys (age ≥5 years) and convenience surveys (age 5–9 years). Alere Filariasis Test Strips (FTS) were used to detect Ag, and prevalence was adjusted for survey design and standardized for age and gender. Adjusted Ag prevalence was estimated for each age group (5–9, ≥10, and all ages ≥5 years) for random and purposive PSUs, and by region. Intraclass correlation (ICC) was used to quantify clustering at regions, PSUs, and households. Results: A total of 3940 persons were included (1942 children aged 5–9 years, 1998 persons aged ≥10 years). Adjusted Ag prevalence in all ages ≥5 years in randomly and purposively selected PSUs were 4.0% (95% CI 2.8–5.6%) and 10.0% (95% CI 7.4–13.4%), respectively. In random PSUs, Ag prevalence was lower in those aged 5–9 years (1.3%, 95% CI 0.8–2.1%) than ≥10 years (4.7%, 95% CI 3.1–7.0%), and poorly correlated at the PSU level (R-square = 0.1459). Adjusted Ag prevalence in PSUs ranged from 0% to 10.3% (95% CI 5.9–17.6%) in randomly selected and 3.8% (95% CI 1.3–10.8%) to 20.0% (95% CI 15.3–25.8%) in purposively selected PSUs. ICC for Ag-positive individuals was higher at households (0.46) compared to PSUs (0.18) and regions (0.01). Conclusions: Our study confirmed ongoing transmission of LF in Samoa, in accordance with the 2017 TAS results. Ag prevalence varied significantly between PSUs, and there was poor correlation between prevalence in 5–9 year-olds and older ages, who had threefold higher prevalence. Sampling older age groups would provide more accurate estimates of overall prevalence, and be more sensitive for identifying residual hotspots. Higher prevalence in purposively selected PSUs shows local knowledge can help identify at least some hotspots

Feasibility of Implementing a School Nutrition Intervention That Addresses Policies, Systems, and Environment

We conducted a process evaluation of the Shaping Healthy Choices Program, a multicomponent school-based nutrition program, when implemented in partnership with University of California (UC) CalFresh and UC Cooperative Extension (UCCE). There were positive impacts on participating students, but results varied across counties, possibly due to variation in fidelity to the curriculum and implementation of program components. Our evaluation identified the strength of UCCE in delivering nutrition education and a need for additional support and training for building capacity to effect change in school policies, systems, and environment. Because educators throughout Extension are working to integrate programs addressing policies, systems, and environment, our results may have applicability in other Extension programs

Topological reversibility and causality in feed-forward networks

Systems whose organization displays causal asymmetry constraints, from evolutionary trees to river basins or transport networks, can be often described in terms of directed paths (causal flows) on a discrete state space. Such a set of paths defines a feed-forward, acyclic network. A key problem associated with these systems involves characterizing their intrinsic degree of path reversibility: given an end node in the graph, what is the uncertainty of recovering the process backwards until the origin? Here we propose a novel concept, \textit{topological reversibility}, which rigorously weigths such uncertainty in path dependency quantified as the minimum amount of information required to successfully revert a causal path. Within the proposed framework we also analytically characterize limit cases for both topologically reversible and maximally entropic structures. The relevance of these measures within the context of evolutionary dynamics is highlighted.Comment: 9 pages, 3 figure

Longitudinal Bioluminescence Imaging of Primary Versus Abdominal Metastatic Tumor Growth in Orthotopic Pancreatic Tumor Models in NSG Mice

Objectives: The purpose of the present study was to develop and validate noninvasive bioluminescence imaging methods for differentially monitoring primary and abdominal metastatic tumor growth in mouse orthotopic models of pancreatic cancer. Methods: A semiautomated maximum entropy segmentation method was implemented for the primary tumor region of interest, and a rule-based method for manually drawing a region of interest for the abdominal metastatic region was developed for monitoring tumor growth in orthotopic models of pancreatic cancer. The 2 region-of-interest methods were validated by having 2 observers independently segment Panc-1 tumors, and the results were compared with the number of mesenteric lymph node nodules and histopathologic assessment of liver metastases. The findings were extended to orthotopic tumors of the more metastatic MIA PaCa-2 and AsPC-1 cells where separate groups of animals were implanted with different numbers of cells. Results: The results demonstrated that the segmentation methods were highly reliable, reproducible, and robust and allowed statistically significant discrimination in the growth rates of primary and abdominal metastatic tumors of different cell lines implanted with different numbers of cells. Conclusions: The present results demonstrate that primary tumors and abdominal metastatic foci in orthotopic pancreatic cancer models can be reliably quantified separately and noninvasively over time with bioluminescence imaging

Mapping Genetically Compensatory Pathways from Synthetic Lethal Interactions in Yeast

Background: Synthetic lethal genetic interaction analysis has been successfully applied to predicting the functions of genes and their pathway identities. In the context of synthetic lethal interaction data alone, the global similarity of synthetic lethal interaction patterns between two genes is used to predict gene function. With physical interaction data, such as proteinprotein interactions, the enrichment of physical interactions within subsets of genes and the enrichment of synthetic lethal interactions between those subsets of genes are used as an indication of compensatory pathways. Result: In this paper, we propose a method of mapping genetically compensatory pathways from synthetic lethal interactions. Our method is designed to discover pairs of gene-sets in which synthetic lethal interactions are depleted among the genes in an individual set and where such gene-set pairs are connected by many synthetic lethal interactions. By its nature, our method could select compensatory pathway pairs that buffer the deleterious effect of the failure of either one, without the need of physical interaction data. By focusing on compensatory pathway pairs where genes in each individual pathway have a highly homogenous cellular function, we show that many cellular functions have genetically compensatory properties. Conclusion: We conclude that synthetic lethal interaction data are a powerful source to map genetically compensatory pathways, especially in systems lacking physical interaction information, and that the cellular function network contain

Network Archaeology: Uncovering Ancient Networks from Present-day Interactions

Often questions arise about old or extinct networks. What proteins interacted in a long-extinct ancestor species of yeast? Who were the central players in the Last.fm social network 3 years ago? Our ability to answer such questions has been limited by the unavailability of past versions of networks. To overcome these limitations, we propose several algorithms for reconstructing a network's history of growth given only the network as it exists today and a generative model by which the network is believed to have evolved. Our likelihood-based method finds a probable previous state of the network by reversing the forward growth model. This approach retains node identities so that the history of individual nodes can be tracked. We apply these algorithms to uncover older, non-extant biological and social networks believed to have grown via several models, including duplication-mutation with complementarity, forest fire, and preferential attachment. Through experiments on both synthetic and real-world data, we find that our algorithms can estimate node arrival times, identify anchor nodes from which new nodes copy links, and can reveal significant features of networks that have long since disappeared.Comment: 16 pages, 10 figure

Geochemistry of abyssal peridotites (Mid-Atlantic Ridge, 15°20′N, ODP Leg 209) : implications for fluid/rock interaction in slow spreading environments

Author Posting. © Elsevier B.V., 2006. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Chemical Geology 234 (2006): 179-210, doi:10.1016/j.chemgeo.2006.04.011.Abyssal peridotite from the 15°20’N area of the Mid-Atlantic Ridge show complex geochemical variations among the different sites drilled during ODP Leg 209. Major element compositions indicate variable degrees of melt depletion and refertilization as well as local hydrothermal metasomatism. Strongest evidence for melt-rock interactions are correlated Light Rare Earth Element (LREE) and High Field Strength Element (HFSE) additions at sites 1270 and 1271. In contrast, hydrothermal alteration at Sites 1274, 1272, and 1268 causes LREE mobility associated with minor HFSE variability, reflecting the low solubility of HFSE in aqueous solutions. Site 1274 contains the least-altered, highly refractory, peridotite with strong depletion in LREE and shows a gradual increase in the intensity of isochemical serpentinization; except for the addition of H2O which causes a mass gain of up to 20 g/100 g. The formation of magnetite is reflected in decreasing Fe2+/Fe3+ ratios. This style of alteration is referred to as rock-dominated serpentinization. In contrast, fluid-dominated serpentinization at Site 1268 is characterized by gains in sulfur and development of U-shaped REE pattern with strong positive Eu anomalies which are also characteristic for hot (350 to 400°C) vent-type fluids discharging from black smoker fields. Serpentinites at Site 1268 were overprinted by talc alteration under static conditions due to interaction with high aSiO2 fluids causing the development of smooth, LREE-enriched patterns with pronounced negative Eu anomalies. These results show that hydrothermal fluid-peridotite and fluid-serpentinite interaction processes are an important factor regarding the budget of exchange processes between the lithosphere and the hydrosphere in slow spreading environments.ODP is sponsored by the U.S. National Science Foundation (NSF) and participating countries under management of Joint Oceanographic Institutions (JOI), Inc

Chromosomal-level assembly of the Asian Seabass genome using long sequence reads and multi-layered scaffolding

We report here the ~670 Mb genome assembly of the Asian seabass (Lates calcarifer), a tropical marine teleost. We used long-read sequencing augmented by transcriptomics, optical and genetic mapping along with shared synteny from closely related fish species to derive a chromosome-level assembly with a contig N50 size over 1 Mb and scaffold N50 size over 25 Mb that span ~90% of the genome. The population structure of L. calcarifer species complex was analyzed by re-sequencing 61 individuals representing various regions across the species' native range. SNP analyses identified high levels of genetic diversity and confirmed earlier indications of a population stratification comprising three clades with signs of admixture apparent in the South-East Asian population. The quality of the Asian seabass genome assembly far exceeds that of any other fish species, and will serve as a new standard for fish genomics