22 research outputs found
Integrative Analysis of Many Weighted Co-Expression Networks Using Tensor Computation
The rapid accumulation of biological networks poses new challenges and calls for powerful integrative analysis tools. Most existing methods capable of simultaneously analyzing a large number of networks were primarily designed for unweighted networks, and cannot easily be extended to weighted networks. However, it is known that transforming weighted into unweighted networks by dichotomizing the edges of weighted networks with a threshold generally leads to information loss. We have developed a novel, tensor-based computational framework for mining recurrent heavy subgraphs in a large set of massive weighted networks. Specifically, we formulate the recurrent heavy subgraph identification problem as a heavy 3D subtensor discovery problem with sparse constraints. We describe an effective approach to solving this problem by designing a multi-stage, convex relaxation protocol, and a non-uniform edge sampling technique. We applied our method to 130 co-expression networks, and identified 11,394 recurrent heavy subgraphs, grouped into 2,810 families. We demonstrated that the identified subgraphs represent meaningful biological modules by validating against a large set of compiled biological knowledge bases. We also showed that the likelihood for a heavy subgraph to be meaningful increases significantly with its recurrence in multiple networks, highlighting the importance of the integrative approach to biological network analysis. Moreover, our approach based on weighted graphs detects many patterns that would be overlooked using unweighted graphs. In addition, we identified a large number of modules that occur predominately under specific phenotypes. This analysis resulted in a genome-wide mapping of gene network modules onto the phenome. Finally, by comparing module activities across many datasets, we discovered high-order dynamic cooperativeness in protein complex networks and transcriptional regulatory networks
A novel context-aware recommendation algorithm with two-level SVD in social networks
With the rapid development of Internet applications and social networks, we have entered an era of big data, and people are hard to effectively find the information they want. Therefore, lots of recommendation algorithms have been proposed to help users select useful and beneficial information, and save their time. Moreover, context-aware recommendation methods are becoming more and more popular since they could provide more accurate or personalized recommendation information, compared with traditional recommendation methods. Singular value decomposition (SVD) has been successfully integrated with some traditional recommendation algorithms. However, the basic SVD can only extra
Shaking table test and numerical analysis of a 1:12 scale model of a special concentrically braced steel frame with pinned connections
Study on the Influence of Lubrication Cooling State on Sliding Shoe and Guiding Plate of Fracturing Pump
Integrated Approach to Identify Heparan Sulfate Ligand Requirements of Robo1
An
integrated methodology is described to establish ligand requirements
for heparan sulfate (HS) binding proteins based on a workflow in which
HS octasaccharides are produced by partial enzymatic degradation of
natural HS followed by size exclusion purification, affinity enrichment
using an immobilized HS-binding protein of interest, putative structure
determination of isolated compounds by a hydrophilic interaction chromatography–high-resolution
mass spectrometry platform, and chemical synthesis of well-defined
HS oligosaccharides for structure–activity relationship studies.
The methodology was used to establish the ligand requirements of human
Roundabout receptor 1 (Robo1), which is involved in a number of developmental
processes. Mass spectrometric analysis of the starting octasaccharide
mixture and the Robo1-bound fraction indicated that Robo1 has a preference
for a specific set of structures. Further analysis was performed by
sequential permethylation, desulfation, and pertrideuteroacetylation
followed by online separation and structural analysis by MS/MS. Sequences
of tetrasaccharides could be deduced from the data, and by combining
the compositional and sequence data, a putative octasaccharide ligand
could be proposed (GlA-GlcNS6S-IdoA-GlcNS-IdoA2S-GlcNS6S-IdoA-GlcNAc6S).
A modular synthetic approach was employed to prepare the target compound,
and binding studies by surface plasmon resonance (SPR) confirmed it
to be a high affinity ligand for Robo1. Further studies with a number
of tetrasaccharides confirmed that sulfate esters at C-6 are critical
for binding, whereas such functionalities at C-2 substantially reduce
binding. High affinity ligands were able to reverse a reduction in
endothelial cell migration induced by Slit2-Robo1 signaling
Gene-by-environment modulation of lifespan and weight gain in the murine BXD family.
How lifespan and body weight vary as a function of diet and genetic differences is not well understood. Here we quantify the impact of differences in diet on lifespan in a genetically diverse family of female mice, split into matched isogenic cohorts fed a low-fat chow diet (CD, n = 663) or a high-fat diet (HFD, n = 685). We further generate key metabolic data in a parallel cohort euthanized at four time points. HFD feeding shortens lifespan by 12%: equivalent to a decade in humans. Initial body weight and early weight gains account for longevity differences of roughly 4-6 days per gram. At 500 days, animals on a HFD typically gain four times as much weight as control, but variation in weight gain does not correlate with lifespan. Classic serum metabolites, often regarded as health biomarkers, are not necessarily strong predictors of longevity. Our data indicate that responses to a HFD are substantially modulated by gene-by-environment interactions, highlighting the importance of genetic variation in making accurate individualized dietary recommendations