An iterative network partition algorithm for accurate identification of dense network modules

A key step in network analysis is to partition a complex network into dense modules. Currently, modularity is one of the most popular benefit functions used to partition network modules. However, recent studies suggested that it has an inherent limitation in detecting dense network modules. In this study, we observed that despite the limitation, modularity has the advantage of preserving the primary network structure of the undetected modules. Thus, we have developed a simple iterative Network Partition (iNP) algorithm to partition a network. The iNP algorithm provides a general framework in which any modularity-based algorithm can be implemented in the network partition step. Here, we tested iNP with three modularity-based algorithms: multi-step greedy (MSG), spectral clustering and Qcut. Compared with the original three methods, iNP achieved a significant improvement in the quality of network partition in a benchmark study with simulated networks, identified more modules with significantly better enrichment of functionally related genes in both yeast protein complex network and breast cancer gene co-expression network, and discovered more cancer-specific modules in the cancer gene co-expression network. As such, iNP should have a broad application as a general method to assist in the analysis of biological networks

Digital-WGS: Automated, highly efficient whole-genome sequencing of single cells by digital microfluidics

单细胞全基因组测序(whole-genome sequencing, WGS)是表征细胞内DNA动态变化的关键手段，可为我们提供全面、深度的生物学信息，是生命科学领域研究的热点。然而，单细胞全基因组测序仍面临着诸如样品制备复杂、成本高、扩增偏置性强、误差大的挑战。杨朝勇教授课题组搭建了基于数字微流控的单细胞操控与纳升级全基因组测序平台Digital-WGS，可用于一体化、全自动的单细胞处理与分析。通过Digital-WGS方法制备的单细胞样本在不同测序深度下均展示出了高均一性、高覆盖率、高准确性的优势，解决了当前单细胞基因组测序操作复杂、成本高、均一性差、准确度低等问题，为单细胞基因组测序的广泛应用提供了新的思路。 本研究工作在化学化工学院杨朝勇教授的指导下完成，2015级iChEM直博生阮庆宇为第一作者。Single-cell whole-genome sequencing (WGS) is critical for characterizing dynamic intercellular changes in DNA. Current sample preparation technologies for single-cell WGS are complex, expensive, and suffer from high amplification bias and errors. Here, we describe Digital-WGS, a sample preparation platform that streamlines high-performance single-cell WGS with automatic processing based on digital microfluidics. Using the method, we provide high single-cell capture efficiency for any amount and types of cells by a wetted hydrodynamic structure. The digital control of droplets in a closed hydrophobic interface enables the complete removal of exogenous DNA, sufficient cell lysis, and lossless amplicon recovery, achieving the low coefficient of variation and high coverage at multiple scales. The single-cell genomic variations profiling performs the excellent detection of copy number variants with the smallest bin of 150 kb and single-nucleotide variants with allele dropout rate of 5.2%, holding great promise for broader applications of single-cell genomics.We thank the National Natural Science Foundation of China (21927806, 21735004, 21521004, and 21325522), the National Key R&D Program of China (2018YFC1602900, 2019YFA0905800), Innovative Research Team of High-Level Local Universities in Shanghai (SSMU-ZLCX20180701), and the Program for Changjiang Scholars and Innovative Research Team in University (IRT13036) for financial support. 研究工作得到了国家自然科学基金(21927806、21735004、21521004、21325522), 国家重点研发项目(2018YFC1602900、2019YFA0905800)和教育部“长江学者和创新团队发展计划” (IRT13036)的资助与支持

Regional differences in HIV prevalence among drug users in China: potential for future spread of HIV?

Kretzschmar M, Zhang W, Mikolajczyk RT, et al. Regional differences in HIV prevalence among drug users in China: potential for future spread of HIV? BMC Infectious Diseases. 2008;8(1):108.Background: Drug use and in particular injecting drug use has been at the forefront of the explosive spread of HIV in general populations in many countries in Asia. There is concern that also in China increased HIV incidence in drug users might spark off a generalized epidemic in the wider population. Close monitoring of HIV incidence and risk factors in drug users is therefore important to be able to target interventions effectively. Second generation surveillance was launched to assess HIV prevalence and risk behaviours jointly with the purpose of describing trends and predicting future developments. To assess whether these goals were fulfilled among drug users in China we provide an analysis of risk factors for HIV infection and of regional differences in HIV prevalence. Methods: We analysed data collected in 2005 in 21 drug user second generation surveillance sentinel sites from 14 provinces in China. We used random effects logistic regression to test for risk factors for HIV infection and regional differences. Results: The overall HIV-1 antibody prevalence was 5.4% (279/5128); 4.9% among injecting drug users (IDU) not sharing needles and 3.7% among non-injecting drug users. We found substantial heterogeneity among the surveillance sites with prevalence rates ranging between 0% and 54%. HIV status was strongly affected by the regional prevalence of HIV. Risk behaviours were highly prevalent in regions where HIV prevalence is still low. The distribution of duration of drug use in different sites indicated different stages of the drug use epidemics. Conclusion: ]Regional differences in HIV prevalence in China reflect different stages of the drug use and HIV epidemics rather than differences in risk behaviours. Therefore, outbreaks of HIV among drug users in regions where prevalence is still low can be expected in the future. However, methodological limitations of surveillance embedded into routine systems limit the usability of existing data. More standardized approaches to data collection in secondary generation HIV surveillance are necessary to better understand regional differences in risk behaviour and prevalence and to design targeted intervention for those regions at risk of experiencing outbreaks

Neutrino Physics with JUNO

The Jiangmen Underground Neutrino Observatory (JUNO), a 20 kton multi-purposeunderground liquid scintillator detector, was proposed with the determinationof the neutrino mass hierarchy as a primary physics goal. It is also capable ofobserving neutrinos from terrestrial and extra-terrestrial sources, includingsupernova burst neutrinos, diffuse supernova neutrino background, geoneutrinos,atmospheric neutrinos, solar neutrinos, as well as exotic searches such asnucleon decays, dark matter, sterile neutrinos, etc. We present the physicsmotivations and the anticipated performance of the JUNO detector for variousproposed measurements. By detecting reactor antineutrinos from two power plantsat 53-km distance, JUNO will determine the neutrino mass hierarchy at a 3-4sigma significance with six years of running. The measurement of antineutrinospectrum will also lead to the precise determination of three out of the sixoscillation parameters to an accuracy of better than 1\%. Neutrino burst from atypical core-collapse supernova at 10 kpc would lead to ~5000inverse-beta-decay events and ~2000 all-flavor neutrino-proton elasticscattering events in JUNO. Detection of DSNB would provide valuable informationon the cosmic star-formation rate and the average core-collapsed neutrinoenergy spectrum. Geo-neutrinos can be detected in JUNO with a rate of ~400events per year, significantly improving the statistics of existing geoneutrinosamples. The JUNO detector is sensitive to several exotic searches, e.g. protondecay via the $p\to K^++\bar\nu$ decay channel. The JUNO detector will providea unique facility to address many outstanding crucial questions in particle andastrophysics. It holds the great potential for further advancing our quest tounderstanding the fundamental properties of neutrinos, one of the buildingblocks of our Universe

Potential of Core-Collapse Supernova Neutrino Detection at JUNO

JUNO is an underground neutrino observatory under construction in Jiangmen, China. It uses 20kton liquid scintillator as target, which enables it to detect supernova burst neutrinos of a large statistics for the next galactic core-collapse supernova (CCSN) and also pre-supernova neutrinos from the nearby CCSN progenitors. All flavors of supernova burst neutrinos can be detected by JUNO via several interaction channels, including inverse beta decay, elastic scattering on electron and proton, interactions on C12 nuclei, etc. This retains the possibility for JUNO to reconstruct the energy spectra of supernova burst neutrinos of all flavors. The real time monitoring systems based on FPGA and DAQ are under development in JUNO, which allow prompt alert and trigger-less data acquisition of CCSN events. The alert performances of both monitoring systems have been thoroughly studied using simulations. Moreover, once a CCSN is tagged, the system can give fast characterizations, such as directionality and light curve

Real-time Monitoring for the Next Core-Collapse Supernova in JUNO

Core-collapse supernova (CCSN) is one of the most energetic astrophysical events in the Universe. The early and prompt detection of neutrinos before (pre-SN) and during the SN burst is a unique opportunity to realize the multi-messenger observation of the CCSN events. In this work, we describe the monitoring concept and present the sensitivity of the system to the pre-SN and SN neutrinos at the Jiangmen Underground Neutrino Observatory (JUNO), which is a 20 kton liquid scintillator detector under construction in South China. The real-time monitoring system is designed with both the prompt monitors on the electronic board and online monitors at the data acquisition stage, in order to ensure both the alert speed and alert coverage of progenitor stars. By assuming a false alert rate of 1 per year, this monitoring system can be sensitive to the pre-SN neutrinos up to the distance of about 1.6 (0.9) kpc and SN neutrinos up to about 370 (360) kpc for a progenitor mass of 30$M_{\odot}$ for the case of normal (inverted) mass ordering. The pointing ability of the CCSN is evaluated by using the accumulated event anisotropy of the inverse beta decay interactions from pre-SN or SN neutrinos, which, along with the early alert, can play important roles for the followup multi-messenger observations of the next Galactic or nearby extragalactic CCSN.Comment: 24 pages, 9 figure

Detection of the Diffuse Supernova Neutrino Background with JUNO

As an underground multi-purpose neutrino detector with 20 kton liquid scintillator, Jiangmen Underground Neutrino Observatory (JUNO) is competitive with and complementary to the water-Cherenkov detectors on the search for the diffuse supernova neutrino background (DSNB). Typical supernova models predict 2-4 events per year within the optimal observation window in the JUNO detector. The dominant background is from the neutral-current (NC) interaction of atmospheric neutrinos with 12C nuclei, which surpasses the DSNB by more than one order of magnitude. We evaluated the systematic uncertainty of NC background from the spread of a variety of data-driven models and further developed a method to determine NC background within 15\% with {\it{in}} {\it{situ}} measurements after ten years of running. Besides, the NC-like backgrounds can be effectively suppressed by the intrinsic pulse-shape discrimination (PSD) capabilities of liquid scintillators. In this talk, I will present in detail the improvements on NC background uncertainty evaluation, PSD discriminator development, and finally, the potential of DSNB sensitivity in JUNO

Non-linear Static Analysis of Offshore Steep Wave Riser

A new solution combining finite difference method and shooting method is developed to analyze the behavior of steep wave riser suffering from current loading. Based on the large deformation beam theory and mechanics equilibrium principle, a set of non-linear ordinary differential equations describing the motion of the steep wave riser are obtained. Then, finite difference method and shooting method are adopted and combined to solve the ordinary differential equations with zero moment boundary conditions at both the seabed end and surface end of the steep wave riser. The resulting non-linear finite difference formulations can be solved effectively by Newton-Raphson method. To improve iterative efficiency, shooting method is also employed to obtain the initial value for Newton-Raphson method. Results are compared with that of FEM by OrcaFlex, to verify the accuracy and reliability of the numerical method

Non-linear Static Analysis of Offshore Steep Wave Riser

A new solution combining finite difference method and shooting method is developed to analyze the behavior of steep wave riser suffering from current loading. Based on the large deformation beam theory and mechanics equilibrium principle, a set of non-linear ordinary differential equations describing the motion of the steep wave riser are obtained. Then, finite difference method and shooting method are adopted and combined to solve the ordinary differential equations with zero moment boundary conditions at both the seabed end and surface end of the steep wave riser. The resulting non-linear finite difference formulations can be solved effectively by Newton-Raphson method. To improve iterative efficiency, shooting method is also employed to obtain the initial value for Newton-Raphson method. Results are compared with that of FEM by OrcaFlex, to verify the accuracy and reliability of the numerical method