Journal Articles, BioMed Central and SpringerOpen

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BADGE: A novel Bayesian model for accurate abundance quantification and differential analysis of RNA-Seq data
Gu, Jinghua; Wang, Xiao; Hilakivi-Clarke, Leena; Clarke, Robert; Xuan, Jianhua (2014-09-10)
Background Recent advances in RNA sequencing (RNA-Seq) technology have offered unprecedented scope and resolution for transcriptome analysis. However, precise quantification of mRNA abundance and identification of differentially expressed genes are complicated due to biological and technical variations in RNA-Seq data. Results We systematically study the variation in count data and dissect the sources of variation into between-sample variation and within-sample variation. A novel Bayesian framework is developed for joint estimate of gene level mRNA abundance and differential state, which models the intrinsic variability in RNA-Seq to improve the estimation. Specifically, a Poisson-Lognormal model is incorporated into the Bayesian framework to model within-sample variation; a Gamma-Gamma model is then used to model between-sample variation, which accounts for over-dispersion of read counts among multiple samples. Simulation studies, where sequencing counts are synthesized based on parameters learned from real datasets, have demonstrated the advantage of the proposed method in both quantification of mRNA abundance and identification of differentially expressed genes. Moreover, performance comparison on data from the Sequencing Quality Control (SEQC) Project with ERCC spike-in controls has shown that the proposed method outperforms existing RNA-Seq methods in differential analysis. Application on breast cancer dataset has further illustrated that the proposed Bayesian model can 'blindly' estimate sources of variation caused by sequencing biases. Conclusions We have developed a novel Bayesian hierarchical approach to investigate within-sample and between-sample variations in RNA-Seq data. Simulation and real data applications have validated desirable performance of the proposed method. The software package is available at http://www.cbil.ece.vt.edu/software.htm.
BMRF-MI: integrative identification of protein interaction network by modeling the gene dependency
Shi, Xu; Wang, Xiao; Shajahan, Ayesha; Hilakivi-Clarke, Leena; Clarke, Robert; Xuan, Jianhua (2015-06-11)
Background Identification of protein interaction network is a very important step for understanding the molecular mechanisms in cancer. Several methods have been developed to integrate protein-protein interaction (PPI) data with gene expression data for network identification. However, they often fail to model the dependency between genes in the network, which makes many important genes, especially the upstream genes, unidentified. It is necessary to develop a method to improve the network identification performance by incorporating the dependency between genes. Results We proposed an approach for identifying protein interaction network by incorporating mutual information (MI) into a Markov random field (MRF) based framework to model the dependency between genes. MI is widely used in information theory to measure the uncertainty between random variables. Different from traditional Pearson correlation test, MI is capable of capturing both linear and non-linear relationship between random variables. Among all the existing MI estimators, we choose to use k-nearest neighbor MI (kNN-MI) estimator which is proved to have minimum bias. The estimated MI is integrated with an MRF framework to model the gene dependency in the context of network. The maximum a posterior (MAP) estimation is applied on the MRF-based model to estimate the network score. In order to reduce the computational complexity of finding the optimal network, a probabilistic searching algorithm is implemented. We further increase the robustness and reproducibility of the results by applying a non-parametric bootstrapping method to measure the confidence level of the identified genes. To evaluate the performance of the proposed method, we test the method on simulation data under different conditions. The experimental results show an improved accuracy in terms of subnetwork identification compared to existing methods. Furthermore, we applied our method onto real breast cancer patient data; the identified protein interaction network shows a close association with the recurrence of breast cancer, which is supported by functional annotation. We also show that the identified subnetworks can be used to predict the recurrence status of cancer patients by survival analysis. Conclusions We have developed an integrated approach for protein interaction network identification, which combines Markov random field framework and mutual information to model the gene dependency in PPI network. Improvements in subnetwork identification have been demonstrated with simulation datasets compared to existing methods. We then apply our method onto breast cancer patient data to identify recurrence related subnetworks. The experiment results show that the identified genes are enriched in the pathway and functional categories relevant to progression and recurrence of breast cancer. Finally, the survival analysis based on identified subnetworks achieves a good result of classifying the recurrence status of cancer patients.
C-Based Design of Heterogeneous Embedded Systems
Grimm, Christoph; Jantsch, Axel; Shukla, Sandeep K.; Villar, Eugenio (2008-07-15)
caBIG VISDA: modeling, visualization, and discovery for cluster analysis of genomic data
Zhu, Yitan; Li, Huai; Miller, David J.; Wang, Zuyi; Xuan, Jianhua; Clarke, Robert; Hoffman, Eric P.; Wang, Yue (2008-09-18)
Background The main limitations of most existing clustering methods used in genomic data analysis include heuristic or random algorithm initialization, the potential of finding poor local optima, the lack of cluster number detection, an inability to incorporate prior/expert knowledge, black-box and non-adaptive designs, in addition to the curse of dimensionality and the discernment of uninformative, uninteresting cluster structure associated with confounding variables. Results In an effort to partially address these limitations, we develop the VIsual Statistical Data Analyzer (VISDA) for cluster modeling, visualization, and discovery in genomic data. VISDA performs progressive, coarse-to-fine (divisive) hierarchical clustering and visualization, supported by hierarchical mixture modeling, supervised/unsupervised informative gene selection, supervised/unsupervised data visualization, and user/prior knowledge guidance, to discover hidden clusters within complex, high-dimensional genomic data. The hierarchical visualization and clustering scheme of VISDA uses multiple local visualization subspaces (one at each node of the hierarchy) and consequent subspace data modeling to reveal both global and local cluster structures in a "divide and conquer" scenario. Multiple projection methods, each sensitive to a distinct type of clustering tendency, are used for data visualization, which increases the likelihood that cluster structures of interest are revealed. Initialization of the full dimensional model is based on first learning models with user/prior knowledge guidance on data projected into the low-dimensional visualization spaces. Model order selection for the high dimensional data is accomplished by Bayesian theoretic criteria and user justification applied via the hierarchy of low-dimensional visualization subspaces. Based on its complementary building blocks and flexible functionality, VISDA is generally applicable for gene clustering, sample clustering, and phenotype clustering (wherein phenotype labels for samples are known), albeit with minor algorithm modifications customized to each of these tasks. Conclusion VISDA achieved robust and superior clustering accuracy, compared with several benchmark clustering schemes. The model order selection scheme in VISDA was shown to be effective for high dimensional genomic data clustering. On muscular dystrophy data and muscle regeneration data, VISDA identified biologically relevant co-expressed gene clusters. VISDA also captured the pathological relationships among different phenotypes revealed at the molecular level, through phenotype clustering on muscular dystrophy data and multi-category cancer data.
ChIP-BIT2: a software tool to detect weak binding events using a Bayesian integration approach
Chen, Xi; Shi, Xu; Neuwald, Andrew F.; Hilakivi-Clarke, Leena; Clarke, Robert; Xuan, Jianhua (2021-04-15)
Background ChIP-seq combines chromatin immunoprecipitation assays with sequencing and identifies genome-wide binding sites for DNA binding proteins. While many binding sites have strong ChIP-seq ‘peak’ observations and are well captured, there are still regions bound by proteins weakly, with a relatively low ChIP-seq signal enrichment. These weak binding sites, especially those at promoters and enhancers, are functionally important because they also regulate nearby gene expression. Yet, it remains a challenge to accurately identify weak binding sites in ChIP-seq data due to the ambiguity in differentiating these weak binding sites from the amplified background DNAs. Results ChIP-BIT2 ( http://sourceforge.net/projects/chipbitc/) is a software package for ChIP-seq peak detection. ChIP-BIT2 employs a mixture model integrating protein and control ChIP-seq data and predicts strong or weak protein binding sites at promoters, enhancers, or other genomic locations. For binding sites at gene promoters, ChIP-BIT2 simultaneously predicts their target genes. ChIP-BIT2 has been validated on benchmark regions and tested using large-scale ENCODE ChIP-seq data, demonstrating its high accuracy and wide applicability. Conclusion ChIP-BIT2 is an efficient ChIP-seq peak caller. It provides a better lens to examine weak binding sites and can refine or extend the existing binding site collection, providing additional regulatory regions for decoding the mechanism of gene expression regulation.
Coexistence of filamentary and homogeneous resistive switching with memristive and meminductive memory effects in Al/MnO2/SS thin film metal–insulator–metal device
Kamble, Girish U.; Shetake, Nitin P.; Yadav, Suhas D.; Teli, Aviraj M.; Patil, Dipali S.; Pawar, Sachin A.; Karanjkar, Milind M.; Patil, Pramod S.; Shin, Jae C.; Orlowski, Marius K.; Kamat, Rajanish K.; Dongale, Tukaram D. (2018-09-19)
In the present investigation, we have experimentally demonstrated the coexistence of filamentary and homogeneous resistive switching mechanisms in single Al/MnO2/SS thin film metal–insulator–metal device. The voltage-induced resistive switching leads to clockwise and counter-clockwise resistive switching effects. The present investigations confirm that the coexistence of both RS mechanisms is dependent on input voltage, charge-flux and time. Furthermore, the non-zero I–V crossing locations and crossovers hysteresis loops suggested that the developed device has memristive and meminductive properties. The memristive and meminductive memory effects are further confirmed by electrochemical impedance spectroscopy. The results suggested that the mem-device dynamics and electrochemical kinetics during different voltage sweeps and sweep rates are responsible for the coexistence of filamentary and homogeneous resistive switching mechanisms as well as memristive and meminductive memory effect in single Al/MnO2/SS metal–insulator–metal device. The coexistence of both RS effects is useful for the development of high-performance resistive memory and electronic synapse devices. Furthermore, the coexistence of memristive and meminductive memory effects is important for the development of adaptive and self-resonating devices and circuits.
Cognitive radio engine parametric optimization utilizing Taguchi analysis
Amanna, Ashwin E.; Ali, Daniel; Gadhiok, Manik; Price, Matthew; Reed, Jeffrey H. (2012-01-09)
Cognitive radio (CR) engines often contain multiple system parameters that require careful tuning to obtain favorable overall performance. This aspect is a crucial element in the design cycle yet is often addressed with ad hoc methods. Efficient methodologies are required in order to make the best use of limited manpower, resources, and time. Statistical methods for approaching parameter tuning exist that provide formalized processes to avoid inefficient ad hoc methods. These methods also apply toward overall system performance testing. This article explores the use of the Taguchi method and orthogonal testing arrays as a tool for identifying favorable genetic algorithm (GA) parameter settings utilized within a hybrid case base reasoning/genetic algorithm CR engine realized in simulation. This method utilizes a small number of test cases compared to traditional design of experiments that rely on full factorial combinations of system parameters. Background on the Taguchi method, its drawbacks and limitations, past efforts in GA parameter tuning, and the use of GA within CR are overviewed. Multiple CR metrics are aggregated into a single figure-of-merit for quantification of performance. Desirability functions are utilized as a tool for identifying ideal settings from multiple responses. Kiviat graphs visualize overall CR performance. The Taguchi method analysis yields a predicted best combination of GA parameters from nine test cases. A confirmation experiment utilizing the predicted best settings is compared against the predicted mean, and desirability. Results show that the predicted performance falls within 1.5% of the confirmation experiment based on 9 test cases as opposed to the 81 test cases required for a full factorial design of experiments analysis.
Comparative analysis of methods for detecting interacting loci
Chen, Li; Yu, Guoqiang; Langefeld, Carl D.; Miller, David J.; Guy, Richard T.; Raghuram, Jayaram; Yuan, Xiguo; Herrington, David M.; Wang, Yue (Biomed Central, 2011-07-05)
Background: Interactions among genetic loci are believed to play an important role in disease risk. While many methods have been proposed for detecting such interactions, their relative performance remains largely unclear, mainly because different data sources, detection performance criteria, and experimental protocols were used in the papers introducing these methods and in subsequent studies. Moreover, there have been very few studies strictly focused on comparison of existing methods. Given the importance of detecting gene-gene and gene-environment interactions, a rigorous, comprehensive comparison of performance and limitations of available interaction detection methods is warranted. Results: We report a comparison of eight representative methods, of which seven were specifically designed to detect interactions among single nucleotide polymorphisms (SNPs), with the last a popular main-effect testing method used as a baseline for performance evaluation. The selected methods, multifactor dimensionality reduction (MDR), full interaction model (FIM), information gain (IG), Bayesian epistasis association mapping (BEAM), SNP harvester (SH), maximum entropy conditional probability modeling (MECPM), logistic regression with an interaction term (LRIT), and logistic regression (LR) were compared on a large number of simulated data sets, each, consistent with complex disease models, embedding multiple sets of interacting SNPs, under different interaction models. The assessment criteria included several relevant detection power measures, family-wise type I error rate, and computational complexity. There are several important results from this study. First, while some SNPs in interactions with strong effects are successfully detected, most of the methods miss many interacting SNPs at an acceptable rate of false positives. In this study, the best-performing method was MECPM. Second, the statistical significance assessment criteria, used by some of the methods to control the type I error rate, are quite conservative, thereby limiting their power and making it difficult to fairly compare them. Third, as expected, power varies for different models and as a function of penetrance, minor allele frequency, linkage disequilibrium and marginal effects. Fourth, the analytical relationships between power and these factors are derived, aiding in the interpretation of the study results. Fifth, for these methods the magnitude of the main effect influences the power of the tests. Sixth, most methods can detect some ground-truth SNPs but have modest power to detect the whole set of interacting SNPs. Conclusion: This comparison study provides new insights into the strengths and limitations of current methods for detecting interacting loci. This study, along with freely available simulation tools we provide, should help support development of improved methods. The simulation tools are available at: http://code.google.com/p/simulationtool-bmc-ms9169818735220977/downloads/list.
DBS: a fast and informative segmentation algorithm for DNA copy number analysis
Ruan, Jun; Liu, Zhen; Sun, Ming; Wang, Yue; Yue, Junqiu; Yu, Guoqiang (2019-01-03)
Background Genome-wide DNA copy number changes are the hallmark events in the initiation and progression of cancers. Quantitative analysis of somatic copy number alterations (CNAs) has broad applications in cancer research. With the increasing capacity of high-throughput sequencing technologies, fast and efficient segmentation algorithms are required when characterizing high density CNAs data. Results A fast and informative segmentation algorithm, DBS (Deviation Binary Segmentation), is developed and discussed. The DBS method is based on the least absolute error principles and is inspired by the segmentation method rooted in the circular binary segmentation procedure. DBS uses point-by-point model calculation to ensure the accuracy of segmentation and combines a binary search algorithm with heuristics derived from the Central Limit Theorem. The DBS algorithm is very efficient requiring a computational complexity of O(n*log n), and is faster than its predecessors. Moreover, DBS measures the change-point amplitude of mean values of two adjacent segments at a breakpoint, where the significant degree of change-point amplitude is determined by the weighted average deviation at breakpoints. Accordingly, using the constructed binary tree of significant degree, DBS informs whether the results of segmentation are over- or under-segmented. Conclusion DBS is implemented in a platform-independent and open-source Java application (ToolSeg), including a graphical user interface and simulation data generation, as well as various segmentation methods in the native Java language.
Dynamic Bandwidth Allocation Based on Online Traffic Prediction for Real-Time MPEG-4 Video Streams
Liang, Yao; Han, Mei (2006-09-13)
The distinct characteristics of variable bit rate (VBR) video traffic and its quality of service (QoS) constraints have posed a unique challenge on network resource allocation and management for future integrated networks. Dynamic bandwidth allocation attempts to adaptively allocate resources to capture the burstiness of VBR video traffic, and therefore could potentially increase network utilization substantially while still satisfying the desired QoS requirements. We focus on prediction-based dynamic bandwidth allocation. In this context, the multiresolution learning neural-network-based traffic predictor is rigorously examined. A well-known-heuristic based approach RED-VBR scheme is used as a baseline for performance evaluation. Simulations using real-world MPEG-4 VBR video traces are conducted, and a comprehensive performance metrics is presented. In addition, a new concept of renegotiation control is introduced and a novel renegotiation control algorithm based on binary exponential backoff (BEB) is proposed to efficiently reduce renegotiation frequency.
Editorial
Bourlard, Hervé; Pitas, Ioannis; Lam, Kenneth Kin-Man; Wang, Yue (2004-04-21)
Examining the Viability of FPGA Supercomputing
Craven, Stephen; Athanas, Peter M. (2007-01-10)
For certain applications, custom computational hardware created using field programmable gate arrays (FPGAs) can produce significant performance improvements over processors, leading some in academia and industry to call for the inclusion of FPGAs in supercomputing clusters. This paper presents a comparative analysis of FPGAs and traditional processors, focusing on floating-point performance and procurement costs, revealing economic hurdles in the adoption of FPGAs for general high-performance computing (HPC).
Gene Selection for Multiclass Prediction by Weighted Fisher Criterion
Xuan, Jianhua; Wang, Yue; Dong, Yibin; Feng, Yuanjian; Wang, Bin; Khan, Javed; Bakay, Maria; Wang, Zuyi; Pachman, Lauren; Winokur, Sara; Chen, Yi-Wen; Clarke, Robert; Hoffman, Eric P. (2007-07-10)
Gene expression profiling has been widely used to study molecular signatures of many diseases and to develop molecular diagnostics for disease prediction. Gene selection, as an important step for improved diagnostics, screens tens of thousands of genes and identifies a small subset that discriminates between disease types. A two-step gene selection method is proposed to identify informative gene subsets for accurate classification of multiclass phenotypes. In the first step, individually discriminatory genes (IDGs) are identified by using one-dimensional weighted Fisher criterion (wFC). In the second step, jointly discriminatory genes (JDGs) are selected by sequential search methods, based on their joint class separability measured by multidimensional weighted Fisher criterion (wFC). The performance of the selected gene subsets for multiclass prediction is evaluated by artificial neural networks (ANNs) and/or support vector machines (SVMs). By applying the proposed IDG/JDG approach to two microarray studies, that is, small round blue cell tumors (SRBCTs) and muscular dystrophies (MDs), we successfully identified a much smaller yet efficient set of JDGs for diagnosing SRBCTs and MDs with high prediction accuracies (96.9% for SRBCTs and 92.3% for MDs, resp.). These experimental results demonstrated that the two-step gene selection method is able to identify a subset of highly discriminative genes for improved multiclass prediction.
Genome-wide identification of significant aberrations in cancer genome
Yuan, Xiguo; Yu, Guoqiang; Hou, Xuchu; Shih, Ie-Ming; Clarke, Robert; Zhang, Junying; Hoffman, Eric P.; Wang, Roger R.; Zhang, Zhen; Wang, Yue (2012-07-27)
Background Somatic Copy Number Alterations (CNAs) in human genomes are present in almost all human cancers. Systematic efforts to characterize such structural variants must effectively distinguish significant consensus events from random background aberrations. Here we introduce Significant Aberration in Cancer (SAIC), a new method for characterizing and assessing the statistical significance of recurrent CNA units. Three main features of SAIC include: (1) exploiting the intrinsic correlation among consecutive probes to assign a score to each CNA unit instead of single probes; (2) performing permutations on CNA units that preserve correlations inherent in the copy number data; and (3) iteratively detecting Significant Copy Number Aberrations (SCAs) and estimating an unbiased null distribution by applying an SCA-exclusive permutation scheme. Results We test and compare the performance of SAIC against four peer methods (GISTIC, STAC, KC-SMART, CMDS) on a large number of simulation datasets. Experimental results show that SAIC outperforms peer methods in terms of larger area under the Receiver Operating Characteristics curve and increased detection power. We then apply SAIC to analyze structural genomic aberrations acquired in four real cancer genome-wide copy number data sets (ovarian cancer, metastatic prostate cancer, lung adenocarcinoma, glioblastoma). When compared with previously reported results, SAIC successfully identifies most SCAs known to be of biological significance and associated with oncogenes (e.g., KRAS, CCNE1, and MYC) or tumor suppressor genes (e.g., CDKN2A/B). Furthermore, SAIC identifies a number of novel SCAs in these copy number data that encompass tumor related genes and may warrant further studies. Conclusions Supported by a well-grounded theoretical framework, SAIC has been developed and used to identify SCAs in various cancer copy number data sets, providing useful information to study the landscape of cancer genomes. Open-source and platform-independent SAIC software is implemented using C++, together with R scripts for data formatting and Perl scripts for user interfacing, and it is easy to install and efficient to use. The source code and documentation are freely available at http://www.cbil.ece.vt.edu/software.htm.
Ground-based instruments of the PWING project to investigate dynamics of the inner magnetosphere at subauroral latitudes as a part of the ERG-ground coordinated observation network
Shiokawa, Kazuo; Katoh, Yasuo; Hamaguchi, Yoshiyuki; Yamamoto, Yuka; Adachi, Takumi; Ozaki, Mitsunori; Oyama, Shin-Ichiro; Nosé, Masahito; Nagatsuma, Tsutomu; Tanaka, Yoshimasa; Otsuka, Yuichi; Miyoshi, Yoshizumi; Kataoka, Ryuho; Takagi, Yuki; Takeshita, Yuhei; Shinbori, Atsuki; Kurita, Satoshi; Hori, Tomoaki; Nishitani, Nozomu; Shinohara, Iku; Tsuchiya, Fuminori; Obana, Yuki; Suzuki, Shin; Takahashi, Naoko; Seki, Kanako; Kadokura, Akira; Hosokawa, Keisuke; Ogawa, Yasunobu; Connors, Martin; Ruohoniemi, J. Michael; Engebretson, Mark J.; Turunen, Esa; Ulich, Thomas; Manninen, Jyrki; Raita, Tero; Kero, Antti; Oksanen, Arto; Back, Marko; Kauristie, Kirsti; Mattanen, Jyrki; Baishev, Dmitry; Kurkin, Vladimir; Oinats, Alexey; Pashinin, Alexander; Vasilyev, Roman; Rakhmatulin, Ravil; Bristow, William A.; Karjala, Marty (2017-11-28)
The plasmas (electrons and ions) in the inner magnetosphere have wide energy ranges from electron volts to mega-electron volts (MeV). These plasmas rotate around the Earth longitudinally due to the gradient and curvature of the geomagnetic field and by the co-rotation motion with timescales from several tens of hours to less than 10 min. They interact with plasma waves at frequencies of mHz to kHz mainly in the equatorial plane of the magnetosphere, obtain energies up to MeV, and are lost into the ionosphere. In order to provide the global distribution and quantitative evaluation of the dynamical variation of these plasmas and waves in the inner magnetosphere, the PWING project (study of dynamical variation of particles and waves in the inner magnetosphere using ground-based network observations, (http://www.isee.nagoya-u.ac.jp/dimr/PWING/) has been carried out since April 2016. This paper describes the stations and instrumentation of the PWING project. We operate all-sky airglow/aurora imagers, 64-Hz sampling induction magnetometers, 40-kHz sampling loop antennas, and 64-Hz sampling riometers at eight stations at subauroral latitudes (~ 60° geomagnetic latitude) in the northern hemisphere, as well as 100-Hz sampling EMCCD cameras at three stations. These stations are distributed longitudinally in Canada, Iceland, Finland, Russia, and Alaska to obtain the longitudinal distribution of plasmas and waves in the inner magnetosphere. This PWING longitudinal network has been developed as a part of the ERG (Arase)-ground coordinated observation network. The ERG (Arase) satellite was launched on December 20, 2016, and has been in full operation since March 2017. We will combine these ground network observations with the ERG (Arase) satellite and global modeling studies. These comprehensive datasets will contribute to the investigation of dynamical variation of particles and waves in the inner magnetosphere, which is one of the most important research topics in recent space physics, and the outcome of our research will improve safe and secure use of geospace around the Earth.
High-frequency irreversible electroporation (H-FIRE) for non-thermal ablation without muscle contraction
Arena, Christopher B.; Sano, Michael B.; Rossmeisl, John H. Jr.; Caldwell, John L.; Garcia, Paulo A.; Rylander, M. Nichole; Davalos, Rafael V. (2011-11-21)
Background Therapeutic irreversible electroporation (IRE) is an emerging technology for the non-thermal ablation of tumors. The technique involves delivering a series of unipolar electric pulses to permanently destabilize the plasma membrane of cancer cells through an increase in transmembrane potential, which leads to the development of a tissue lesion. Clinically, IRE requires the administration of paralytic agents to prevent muscle contractions during treatment that are associated with the delivery of electric pulses. This study shows that by applying high-frequency, bipolar bursts, muscle contractions can be eliminated during IRE without compromising the non-thermal mechanism of cell death. Methods A combination of analytical, numerical, and experimental techniques were performed to investigate high-frequency irreversible electroporation (H-FIRE). A theoretical model for determining transmembrane potential in response to arbitrary electric fields was used to identify optimal burst frequencies and amplitudes for in vivo treatments. A finite element model for predicting thermal damage based on the electric field distribution was used to design non-thermal protocols for in vivo experiments. H-FIRE was applied to the brain of rats, and muscle contractions were quantified via accelerometers placed at the cervicothoracic junction. MRI and histological evaluation was performed post-operatively to assess ablation. Results No visual or tactile evidence of muscle contraction was seen during H-FIRE at 250 kHz or 500 kHz, while all IRE protocols resulted in detectable muscle contractions at the cervicothoracic junction. H-FIRE produced ablative lesions in brain tissue that were characteristic in cellular morphology of non-thermal IRE treatments. Specifically, there was complete uniformity of tissue death within targeted areas, and a sharp transition zone was present between lesioned and normal brain. Conclusions H-FIRE is a feasible technique for non-thermal tissue ablation that eliminates muscle contractions seen in IRE treatments performed with unipolar electric pulses. Therefore, it has the potential to be performed clinically without the administration of paralytic agents.
High-performance biocomputing for simulating the spread of contagion over large contact networks
Bisset, Keith R.; Aji, Ashwin M.; Marathe, Madhav V.; Feng, Wu-chun (BMC, 2012-04-12)
Background Many important biological problems can be modeled as contagion diffusion processes over interaction networks. This article shows how the EpiSimdemics interaction-based simulation system can be applied to the general contagion diffusion problem. Two specific problems, computational epidemiology and human immune system modeling, are given as examples. We then show how the graphics processing unit (GPU) within each compute node of a cluster can effectively be used to speed-up the execution of these types of problems. Results We show that a single GPU can accelerate the EpiSimdemics computation kernel by a factor of 6 and the entire application by a factor of 3.3, compared to the execution time on a single core. When 8 CPU cores and 2 GPU devices are utilized, the speed-up of the computational kernel increases to 9.5. When combined with effective techniques for inter-node communication, excellent scalability can be achieved without significant loss of accuracy in the results. Conclusions We show that interaction-based simulation systems can be used to model disparate and highly relevant problems in biology. We also show that offloading some of the work to GPUs in distributed interaction-based simulations can be an effective way to achieve increased intra-node efficiency.
Identifying cancer biomarkers by network-constrained support vector machines
Chen, Li; Xuan, Jianhua; Riggins, Rebecca B.; Clarke, Robert; Wang, Yue (2011-10-12)
Background One of the major goals in gene and protein expression profiling of cancer is to identify biomarkers and build classification models for prediction of disease prognosis or treatment response. Many traditional statistical methods, based on microarray gene expression data alone and individual genes' discriminatory power, often fail to identify biologically meaningful biomarkers thus resulting in poor prediction performance across data sets. Nonetheless, the variables in multivariable classifiers should synergistically interact to produce more effective classifiers than individual biomarkers. Results We developed an integrated approach, namely network-constrained support vector machine (netSVM), for cancer biomarker identification with an improved prediction performance. The netSVM approach is specifically designed for network biomarker identification by integrating gene expression data and protein-protein interaction data. We first evaluated the effectiveness of netSVM using simulation studies, demonstrating its improved performance over state-of-the-art network-based methods and gene-based methods for network biomarker identification. We then applied the netSVM approach to two breast cancer data sets to identify prognostic signatures for prediction of breast cancer metastasis. The experimental results show that: (1) network biomarkers identified by netSVM are highly enriched in biological pathways associated with cancer progression; (2) prediction performance is much improved when tested across different data sets. Specifically, many genes related to apoptosis, cell cycle, and cell proliferation, which are hallmark signatures of breast cancer metastasis, were identified by the netSVM approach. More importantly, several novel hub genes, biologically important with many interactions in PPI network but often showing little change in expression as compared with their downstream genes, were also identified as network biomarkers; the genes were enriched in signaling pathways such as TGF-beta signaling pathway, MAPK signaling pathway, and JAK-STAT signaling pathway. These signaling pathways may provide new insight to the underlying mechanism of breast cancer metastasis. Conclusions We have developed a network-based approach for cancer biomarker identification, netSVM, resulting in an improved prediction performance with network biomarkers. We have applied the netSVM approach to breast cancer gene expression data to predict metastasis in patients. Network biomarkers identified by netSVM reveal potential signaling pathways associated with breast cancer metastasis, and help improve the prediction performance across independent data sets.
In situ accurate control of 2D-3D transition parameters for growth of low-density InAs/GaAs self-assembled quantum dots
Li, Mi-Feng; Yu, Ying; He, Ji-Fang; Wang, Li-Juan; Zhu, Yan; Shang, Xiang-jun; Ni, Hai-Qiao; Niu, Zhi-Chuan (2013-02-18)
A method to improve the growth repeatability of low-density InAs/GaAs self-assembled quantum dots by molecular beam epitaxy is reported. A sacrificed InAs layer was deposited firstly to determine in situ the accurate parameters of two- to three-dimensional transitions by observation of reflection high-energy electron diffraction patterns, and then the InAs layer annealed immediately before the growth of the low-density InAs quantum dots (QDs). It is confirmed by micro-photoluminescence that control repeatability of low-density QD growth is improved averagely to about 80% which is much higher than that of the QD samples without using a sacrificed InAs layer.
Incorporating prior biological knowledge for network-based differential gene expression analysis using differentially weighted graphical LASSO
Zuo, Yiming; Cui, Yi; Yu, Guoqiang; Li, Ruijiang; Ressom, Habtom W. (2017-02-10)
Background Conventional differential gene expression analysis by methods such as student’s t-test, SAM, and Empirical Bayes often searches for statistically significant genes without considering the interactions among them. Network-based approaches provide a natural way to study these interactions and to investigate the rewiring interactions in disease versus control groups. In this paper, we apply weighted graphical LASSO (wgLASSO) algorithm to integrate a data-driven network model with prior biological knowledge (i.e., protein-protein interactions) for biological network inference. We propose a novel differentially weighted graphical LASSO (dwgLASSO) algorithm that builds group-specific networks and perform network-based differential gene expression analysis to select biomarker candidates by considering their topological differences between the groups. Results Through simulation, we showed that wgLASSO can achieve better performance in building biologically relevant networks than purely data-driven models (e.g., neighbor selection, graphical LASSO), even when only a moderate level of information is available as prior biological knowledge. We evaluated the performance of dwgLASSO for survival time prediction using two microarray breast cancer datasets previously reported by Bild et al. and van de Vijver et al. Compared with the top 10 significant genes selected by conventional differential gene expression analysis method, the top 10 significant genes selected by dwgLASSO in the dataset from Bild et al. led to a significantly improved survival time prediction in the independent dataset from van de Vijver et al. Among the 10 genes selected by dwgLASSO, UBE2S, SALL2, XBP1 and KIAA0922 have been confirmed by literature survey to be highly relevant in breast cancer biomarker discovery study. Additionally, we tested dwgLASSO on TCGA RNA-seq data acquired from patients with hepatocellular carcinoma (HCC) on tumors samples and their corresponding non-tumorous liver tissues. Improved sensitivity, specificity and area under curve (AUC) were observed when comparing dwgLASSO with conventional differential gene expression analysis method. Conclusions The proposed network-based differential gene expression analysis algorithm dwgLASSO can achieve better performance than conventional differential gene expression analysis methods by integrating information at both gene expression and network topology levels. The incorporation of prior biological knowledge can lead to the identification of biologically meaningful genes in cancer biomarker studies.

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