作者： Sun, Jianguo;Feng, Yanqin*;Zhao, Hui

期刊： Lifetime Data Analysis,2015年21(1):138-155 ISSN：1380-7870

通讯作者： Feng, Yanqin

作者机构： [Sun, Jianguo] Univ Missouri, Dept Stat, Columbia, MO 65211 USA.;[Feng, Yanqin] Wuhan Univ, Sch Math & Stat, Wuhan 430072, Peoples R China.;[Zhao, Hui] Cent China Normal Univ, Sch Math & Stat, Wuhan, Peoples R China.

通讯机构： [Feng, Yanqin] W;Wuhan Univ, Sch Math & Stat, Wuhan 430072, Peoples R China.

关键词： Interval-censored failure time data;Partial likelihood function;Proportional hazards model;Regression analysis

摘要： Interval-censored failure time data occur in many fields including epidemiological and medical studies as well as financial and sociological studies, and many authors have investigated their analysis (Sun, The statistical analysis of interval-censored failure time data, 2006; Zhang, Stat Modeling 9:321-343, 2009). In particular, a number of procedures have been developed for regression analysis of interval-censored data arising from the proportional hazards model (Finkelstein, Biometrics 42:845-854, 1986; Huang, Ann Stat 24:540-568, 1996; Pan, Biometrics 56:199-203, 2000). For most of these procedures, however, one drawback is that they involve estimation of both regression parameters and baseline cumulative hazard function. In this paper, we propose two simple estimation approaches that do not need estimation of the baseline cumulative hazard function. The asymptotic properties of the resulting estimates are given, and an extensive simulation study is conducted and indicates that they work well for practical situations.

语种： 英文

作者： Le Ou-Yang*;Dai, Dao-Qing;Zhang, Xiao-Fei

期刊： IEEE/ACM Transactions on Computational Biology and Bioinformatics,2015年12(6):1333-1344 ISSN：1545-5963

通讯作者： Le Ou-Yang

作者机构： [Dai, Dao-Qing; Le Ou-Yang] Sun Yat Sen Univ, Intelligent Data Ctr, Guangzhou 510275, Guangdong, Peoples R China.;[Dai, Dao-Qing; Le Ou-Yang] Sun Yat Sen Univ, Dept Math, Guangzhou 510275, Guangdong, Peoples R China.;[Zhang, Xiao-Fei] Cent China Normal Univ, Sch Math & Stat, Wuhan 430079, Peoples R China.

通讯机构： [Le Ou-Yang] S;Sun Yat Sen Univ, Intelligent Data Ctr, Guangzhou 510275, Guangdong, Peoples R China.

关键词： Protein-protein interaction;signed network;protein complex;complex-complex interaction;signed graph regularization

摘要： Identification of protein complexes is fundamental for understanding the cellular functional organization. With the accumulation of physical protein-protein interaction (PPI) data, computational detection of protein complexes from available PPI networks has drawn a lot of attentions. While most of the existing protein complex detection algorithms focus on analyzing the physical protein-protein interaction network, none of them take into account the "signs" (i.e., activation-inhibition relationships) of physical interactions. As the "signs" of interactions reflect the way proteins communicate, considering the "signs" of interactions can not only increase the accuracy of protein complex identification, but also deepen our understanding of the mechanisms of cell functions. In this study, we proposed a novel Signed Graph regularized Nonnegative Matrix Factorization (SGNMF) model to identify protein complexes from signed PPI networks. In our experiments, we compared the results collected by our model on signed PPI networks with those predicted by the state-of-the-art complex detection techniques on the original unsigned PPI networks. We observed that considering the "signs" of interactions significantly benefits the detection of protein complexes. Furthermore, based on the predicted complexes, we predicted a set of signed complex-complex interactions for each dataset, which provides a novel insight of the higher level organization of the cell. All the experimental results and codes can be downloaded from http://mail.sysu.edu.cn/home/[email protected]/dai/others/SGNMF.zip. © 2015 IEEE.

语种： 英文

作者： Zhang, Xiao-Fei;Le Ou-Yang;Hu, Xiaohua;Dai, Dao-Qing*

期刊： BMC Genomics,2015年16(1):1-14 ISSN：1471-2164

通讯作者： Dai, Dao-Qing

作者机构： [Zhang, Xiao-Fei] Cent China Normal Univ, Sch Math & Stat, Wuhan 430079, Peoples R China.;[Dai, Dao-Qing; Le Ou-Yang] Sun Yat Sen Univ, Intelligent Data Ctr, Guangzhou 510275, Guangdong, Peoples R China.;[Dai, Dao-Qing; Le Ou-Yang] Sun Yat Sen Univ, Dept Math, Guangzhou 510275, Guangdong, Peoples R China.;[Hu, Xiaohua] Cent China Normal Univ, Sch Comp, Wuhan 430079, Peoples R China.;[Hu, Xiaohua] Drexel Univ, Coll Informat Sci & Technol, Philadelphia, PA 19104 USA.

通讯机构： [Dai, Dao-Qing] S;Sun Yat Sen Univ, Intelligent Data Ctr, Xingang West Rd, Guangzhou 510275, Guangdong, Peoples R China.

关键词： Protein-protein interactions;Direct physical interactions;Scoring methods;Affinity purification mass spectrometry data

摘要： Background: The identification of protein-protein interactions contributes greatly to the understanding of functional organization within cells. With the development of affinity purification-mass spectrometry (AP-MS) techniques, several computational scoring methods have been proposed to detect protein interactions from AP-MS data. However, most of the current methods focus on the detection of co-complex interactions and do not discriminate between direct physical interactions and indirect interactions. Consequently, less is known about the precise physical wiring diagram within cells. Results: In this paper, we develop a Binary Interaction Network Model (BINM) to computationally identify direct physical interactions from co-complex interactions which can be inferred from purification data using previous scoring methods. This model provides a mathematical framework for capturing topological relationships between direct physical interactions and observed co-complex interactions. It reassigns a confidence score to each observed interaction to indicate its propensity to be a direct physical interaction. Then observed interactions with high confidence scores are predicted as direct physical interactions. We run our model on two yeast co-complex interaction networks which are constructed by two different scoring methods on a same combined AP-MS data. The direct physical interactions identified by various methods are comprehensively benchmarked against different reference sets that provide both direct and indirect evidence for physical contacts. Experiment results show that our model has a competitive performance over the state-of-the-art methods. Conclusions: According to the results obtained in this study, BINM is a powerful scoring method that can solely use network topology to predict direct physical interactions from AP-MS data. This study provides us an alternative approach to explore the information inherent in AP-MS data. The software can be downloaded from https://github.com/Zhangxf-ccnu/BINM. © 2015 Zhang et al.

语种： 英文

作者： Zhu, Liang*;Zhao, Hui;Sun, Jianguo;Leisenring, Wendy;Robison, Leslie L.

期刊： Biometrics,2015年71(1):71-79 ISSN：0006-341X

通讯作者： Zhu, Liang

作者机构： [Zhu, Liang] St Jude Childrens Res Hosp, Dept Biostat, Memphis, TN 38103 USA.;[Zhao, Hui] Cent China Normal Univ, Sch Math & Stat, Wuhan 430079, Peoples R China.;[Sun, Jianguo] Univ Missouri, Dept Stat, Columbia, MO 65211 USA.;[Sun, Jianguo] Jilin Univ, Sch Math, Changchun 130012, Peoples R China.;[Leisenring, Wendy] Fred Hutchinson Canc Res Ctr, Dept Biostat, Seattle, WA 98109 USA.

通讯机构： [Zhu, Liang] S;St Jude Childrens Res Hosp, Dept Biostat, Memphis, TN 38103 USA.

关键词： Additive rate model;Event-history studies;Mixed data;Panel-count data;Recurrent-event data

摘要： Event-history studies of recurrent events are often conducted in fields such as demography, epidemiology, medicine, and social sciences (Cook and Lawless, 2007, The Statistical Analysis of Recurrent Events. New York: Springer-Verlag; Zhao et al., 2011, Test 20, 1-42). For such analysis, two types of data have been extensively investigated: recurrent-event data and panel-count data. However, in practice, one may face a third type of data, mixed recurrent-event and panel-count data or mixed event-history data. Such data occur if some study subjects are monitored or observed continuously and thus provide recurrent-event data, while the others are observed only at discrete times and hence give only panel-count data. A more general situation is that each subject is observed continuously over certain time periods but only at discrete times over other time periods. There exists little literature on the analysis of such mixed data except that published by Zhu et al. (2013, Statistics in Medicine 32, 1954-1963). In this article, we consider the regression analysis of mixed data using the additive rate model and develop some estimating equation-based approaches to estimate the regression parameters of interest. Both finite sample and asymptotic properties of the resulting estimators are established, and the numerical studies suggest that the proposed methodology works well for practical situations. The approach is applied to a Childhood Cancer Survivor Study that motivated this study. © 2014, The International Biometric Society.

语种： 英文

作者： Zhang, Xiao-Fei;Le Ou-Yang;Zhu, Yuan;Wu, Meng-Yun;Dai, Dao-Qing*

期刊： BMC Bioinformatics,2015年16(1):1-13 ISSN：1471-2105

通讯作者： Dai, Dao-Qing

作者机构： [Zhang, Xiao-Fei] Cent China Normal Univ, Sch Math & Stat, Wuhan 430079, Peoples R China.;[Dai, Dao-Qing; Le Ou-Yang] Sun Yat Sen Univ, Intelligent Data Ctr, Guangzhou 510275, Guangdong, Peoples R China.;[Dai, Dao-Qing; Le Ou-Yang] Sun Yat Sen Univ, Dept Math, Guangzhou 510275, Guangdong, Peoples R China.;[Zhu, Yuan] Guangdong Univ Finance & Econ, Sch Math & Stat, Guangzhou 510320, Guangdong, Peoples R China.;[Wu, Meng-Yun] Shanghai Univ Finance & Econ, Sch Stat & Management, Shanghai 200433, Peoples R China.

通讯机构： [Dai, Dao-Qing] S;Sun Yat Sen Univ, Intelligent Data Ctr, Xingang West Rd, Guangzhou 510275, Guangdong, Peoples R China.

关键词： Protein-protein interaction network;Driver proteins;Controllability;Minimum dominating set;Centrality

摘要： Background: Recently, several studies have drawn attention to the determination of a minimum set of driver proteins that are important for the control of the underlying protein-protein interaction (PPI) networks. In general, the minimum dominating set (MDS) model is widely adopted. However, because the MDS model does not generate a unique MDS configuration, multiple different MDSs would be generated when using different optimization algorithms. Therefore, among these MDSs, it is difficult to find out the one that represents the true driver set of proteins. Results: To address this problem, we develop a centrality-corrected minimum dominating set (CC-MDS) model which includes heterogeneity in degree and betweenness centralities of proteins. Both the MDS model and the CC-MDS model are applied on three human PPI networks. Unlike the MDS model, the CC-MDS model generates almost the same sets of driver proteins when we implement it using different optimization algorithms. The CC-MDS model targets more high-degree and high-betweenness proteins than the uncorrected counterpart. The more central position allows CC-MDS proteins to be more important in maintaining the overall network connectivity than MDS proteins. To indicate the functional significance, we find that CC-MDS proteins are involved in, on average, more protein complexes and GO annotations than MDS proteins. We also find that more essential genes, aging genes, disease-associated genes and virus-targeted genes appear in CC-MDS proteins than in MDS proteins. As for the involvement in regulatory functions, the sets of CC-MDS proteins show much stronger enrichment of transcription factors and protein kinases. The results about topological and functional significance demonstrate that the CC-MDS model can capture more driver proteins than the MDS model. Conclusions: Based on the results obtained, the CC-MDS model presents to be a powerful tool for the determination of driver proteins that can control the underlying PPI networks. The software described in this paper and the datasets used are available at https://github.com/Zhangxf-ccnu/CC-MDS. © 2015 Zhang et al.; licensee BioMed Central.

语种： 英文

作者： Zhang, Xinan*;Fang, Yile;Zhao, Yingdong;Zheng, Weiming

期刊： Mathematical Biosciences,2014年253(1):25-29 ISSN：0025-5564

通讯作者： Zhang, Xinan

作者机构： [Zhang, Xinan] Cent China Normal Univ, Sch Math & Stat, Wuhan 430079, Peoples R China.;[Fang, Yile] Huazhong Univ Sci & Technol, Dept Elect & Elect Eduat, Wuchang Branch, Wuhan 430064, Peoples R China.;[Zhao, Yingdong] NCI, Biometr Res Branch, NIH, Bethesda, MD 20892 USA.;[Zheng, Weiming] Tsinghua Univ, Dept Comp Sci & Technol, Beijing 100084, Peoples R China.

通讯机构： [Zhang, Xinan] C;Cent China Normal Univ, Sch Math & Stat, Wuhan 430079, Peoples R China.

关键词： Breast cancer;Mathematical model;Tumorigenesis

摘要： In order to understand the mechanism of human breast cancer we use the growth rates of clonal expansion of intermediate cells and mutation rates as parameters and build two-six stage models to fit the age-specific incidence of breast cancers in the surveillance, epidemiology, and end results (SEER) registry. We propose four types of different mechanisms for the human breast cancer and test those mechanisms by Chi-square test. Our results suggest that loss of functions of instability genes is an early event in the tumorigenesis, which is useful for early diagnosis of breast cancer. The clonal expansion of intermediate cells must depend on the hormone expression level of females, which implies that it may be effective for females to receive hormone blocking therapy for breast cancer before their menopause. (C) 2014 Elsevier Inc. All rights reserved.

语种： 英文

作者： Zhang, Xiao-Fei;Dai, Dao-Qing*;Le Ou-Yang;Yan, Hong

期刊： BMC Bioinformatics,2014年15(1):1-15 ISSN：1471-2105

通讯作者： Dai, Dao-Qing

作者机构： [Zhang, Xiao-Fei] Cent China Normal Univ, Sch Math & Stat, Wuhan 430079, Peoples R China.;[Dai, Dao-Qing; Zhang, Xiao-Fei; Le Ou-Yang] Sun Yat Sen Univ, Intelligent Data Ctr, Guangzhou 510275, Guangdong, Peoples R China.;[Dai, Dao-Qing; Zhang, Xiao-Fei; Le Ou-Yang] Sun Yat Sen Univ, Dept Math, Guangzhou 510275, Guangdong, Peoples R China.;[Zhang, Xiao-Fei; Yan, Hong] City Univ Hong Kong, Dept Elect Engn, Hong Kong, Peoples R China.;[Dai, Dao-Qing] Sun Yat Sen Univ, Intelligent Data Ctr, Xingang Rd West, Guangzhou 510275, Guangdong, Peoples R China.

通讯机构： [Dai, Dao-Qing] S;Sun Yat Sen Univ, Intelligent Data Ctr, Xingang Rd West, Guangzhou 510275, Guangdong, Peoples R China.

关键词： Protein complex detection;Protein-protein interaction network;Functional profile;Generative model

摘要： Background: Identification of protein complexes can help us get a better understanding of cellular mechanism. With the increasing availability of large-scale protein-protein interaction (PPI) data, numerous computational approaches have been proposed to detect complexes from the PPI networks. However, most of the current approaches do not consider overlaps among complexes or functional annotation information of individual proteins. Therefore, they might not be able to reflect the biological reality faithfully or make full use of the available domain-specific knowledge.Results: In this paper, we develop a Generative Model with Functional and Topological Properties (GMFTP) to describe the generative processes of the PPI network and the functional profile. The model provides a working mechanism for capturing the interaction structures and the functional patterns of proteins. By combining the functional and topological properties, we formulate the problem of identifying protein complexes as that of detecting a group of proteins which frequently interact with each other in the PPI network and have similar annotation patterns in the functional profile. Using the idea of link communities, our method naturally deals with overlaps among complexes. The benefits brought by the functional properties are demonstrated by real data analysis. The results evaluated using four criteria with respect to two gold standards show that GMFTP has a competitive performance over the state-of-the-art approaches. The effectiveness of detecting overlapping complexes is also demonstrated by analyzing the topological and functional features of multi- and mono-group proteins.Conclusions: Based on the results obtained in this study, GMFTP presents to be a powerful approach for the identification of overlapping protein complexes using both the PPI network and the functional profile. The software can be downloaded from http://mail.sysu.edu.cn/home/stsddq@mail.sysu.edu.cn/dai/others/GMFTP.zip. © 2014 Zhang et al.; licensee BioMed Central Ltd.

语种： 英文

作者： Ou-Yang, Le;Dai, Dao-Qing*;Li, Xiao-Li;Wu, Min;Zhang, Xiao-Fei;...

期刊： BMC Bioinformatics,2014年15(1):1-14 ISSN：1471-2105

通讯作者： Dai, Dao-Qing

作者机构： [Ou-Yang, Le; Dai, Dao-Qing] Sun Yat Sen Univ, Intelligent Data Ctr, Guangzhou 510275, Guangdong, Peoples R China.;[Ou-Yang, Le; Dai, Dao-Qing] Sun Yat Sen Univ, Dept Math, Guangzhou 510275, Guangdong, Peoples R China.;[Wu, Min; Li, Xiao-Li; Yang, Peng] ASTAR, Inst Infocomm Res I2R, Singapore 138632, Singapore.;[Zhang, Xiao-Fei] Cent China Normal Univ, Sch Math & Stat, Wuhan 430079, Peoples R China.

通讯机构： [Dai, Dao-Qing] S;Sun Yat Sen Univ, Intelligent Data Ctr, Guangzhou 510275, Guangdong, Peoples R China.

关键词： Dynamic protein-protein interaction;Gene expression;Stable interaction;Transient interaction;Protein complex

摘要： Background: Proteins dynamically interact with each other to perform their biological functions. The dynamic operations of protein interaction networks (PPI) are also reflected in the dynamic formations of protein complexes. Existing protein complex detection algorithms usually overlook the inherent temporal nature of protein interactions within PPI networks. Systematically analyzing the temporal protein complexes can not only improve the accuracy of protein complex detection, but also strengthen our biological knowledge on the dynamic protein assembly processes for cellular organization. Results: In this study, we propose a novel computational method to predict temporal protein complexes. Particularly, we first construct a series of dynamic PPI networks by joint analysis of time-course gene expression data and protein interaction data. Then a Time Smooth Overlapping Complex Detection model (TS-OCD) has been proposed to detect temporal protein complexes from these dynamic PPI networks. TS-OCD can naturally capture the smoothness of networks between consecutive time points and detect overlapping protein complexes at each time point. Finally, a nonnegative matrix factorization based algorithm is introduced to merge those very similar temporal complexes across different time points. Conclusions: Extensive experimental results demonstrate the proposed method is very effective in detecting temporal protein complexes than the state-of-the-art complex detection techniques. © 2014 Ou-Yang et al.

语种： 英文

作者： Bi, Ping;Ruan, Shigui*;Zhang, Xinan

期刊： CHAOS,2014年24(2):023101 ISSN：1054-1500

通讯作者： Ruan, Shigui

作者机构： [Bi, Ping] E China Normal Univ, Shanghai Key Lab PMMP, Dept Math, Shanghai 200241, Peoples R China.;[Bi, Ping] E China Normal Univ, Ctr Partial Differential Equat, Shanghai 200241, Peoples R China.;[Ruan, Shigui] Univ Miami, Dept Math, Coral Gables, FL 33124 USA.;[Zhang, Xinan] Cent China Normal Univ, Sch Math & Stat, Wuhan 430079, Peoples R China.

通讯机构： [Ruan, Shigui] U;Univ Miami, Dept Math, Coral Gables, FL 33124 USA.

关键词： asymptotic stability;bifurcation;cellular biophysics;chaos;delays;differential equations;nonlinear dynamical systems;oscillations;physiological models;polynomials;system theory;time-varying systems;tumours

摘要： In this paper, a tumor and immune system interaction model consisted of two differential equations with three time delays is considered in which the delays describe the proliferation of tumor cells, the process of effector cells growth stimulated by tumor cells, and the differentiation of immune effector cells, respectively. Conditions for the asymptotic stability of equilibria and existence of Hopf bifurcations are obtained by analyzing the roots of a second degree exponential polynomial characteristic equation with delay dependent coefficients. It is shown that the positive equilibrium is asymptotically stable if all three delays are less than their corresponding critical values and Hopf bifurcations occur if any one of these delays passes through its critical value. Numerical simulations are carried out to illustrate the rich dynamical behavior of the model with different delay values including the existence of regular and irregular long periodic oscillations.

语种： 英文

作者： Li, Yong;Zhang, Jinhui;Zhang, Xinan*

期刊： International Journal of Environmental Research and Public Health,2014年11(3):3108-3117 ISSN：1661-7827

通讯作者： Zhang, Xinan

作者机构： [Zhang, Xinan; Li, Yong; Zhang, Jinhui] Huazhong Normal Univ, Sch Math & Stat, Wuhan 430079, Peoples R China.;[Zhang, Xinan] Huazhong Normal Univ, Sch Math & Stat, 152 Luo Yu Rd, Wuhan 430079, Peoples R China.

通讯机构： [Zhang, Xinan] H;Huazhong Normal Univ, Sch Math & Stat, 152 Luo Yu Rd, Wuhan 430079, Peoples R China.

关键词： HFMD;the basic reproductive number;Chi-square test;goodness of fit

摘要： This paper concentrates on the HFMD data of China from March 2009 to December 2012. We set up a mathematical model to fit those data with the goodness of fit and obtain the optimal parameter values of the model. By the Chi-square test of statistical inference, the optimal parameter values of the model are reasonable. We obtained the basic reproductive number of the disease for each year, and it is larger than 1. Thus, we conclude that HFMD will persist in China under the current conditions, so we investigate the preventive measures to control the HFMD. If the preventive measures proposed in our paper were implemented, HFMD would be controlled quickly and the number of infections would decline rapidly over a period of time.

语种： 英文

作者： Mao, Xizeng;Ma, Qin;Zhou, Chuan;Chen, Xin;Zhang, Hanyuan;...

期刊： Nucleic Acids Research,2014年42(D1):D654-D659 ISSN：0305-1048

通讯作者： Xu, Ying

作者机构： [Chen, Xin; Zhang, Hanyuan; Zhou, Chuan; Mao, Fenglou; Xu, Ying; Mao, Xizeng; Lai, Wei; Ma, Qin] Univ Georgia, Dept Biochem & Mol Biol, Computat Syst Biol Lab, Athens, GA 30602 USA.;[Chen, Xin; Zhang, Hanyuan; Zhou, Chuan; Mao, Fenglou; Xu, Ying; Mao, Xizeng; Lai, Wei; Ma, Qin] Univ Georgia, Inst Bioinformat, Athens, GA 30602 USA.;[Xu, Ying; Mao, Xizeng; Ma, Qin] Oak Ridge Natl Lab, BioEnergy Sci Ctr BESC, Oak Ridge, TN 37831 USA.;[Zhou, Chuan] Shandong Univ, Sch Math, Jinan 250100, Shandong, Peoples R China.;[Chen, Xin; Zhang, Hanyuan; Xu, Ying] Jilin Univ, Coll Comp Sci & Technol, Changchun 130012, Jilin, Peoples R China.

通讯机构： [Xu, Ying] U;Univ Georgia, Dept Biochem & Mol Biol, Computat Syst Biol Lab, Athens, GA 30602 USA.

关键词： genome;operon;rna

摘要： We have recently developed a new version of the DOOR operon database, DOOR 2.0, which is available online at http://csbl.bmb.uga.edu/DOOR/ and will be updated on a regular basis. DOOR 2.0 contains genome-scale operons for 2072 prokaryotes with complete genomes, three times the number of genomes covered in the previous version published in 2009. DOOR 2.0 has a number of new features, compared with its previous version, including (i) more than 250 000 transcription units, experimentally validated or computationally predicted based on RNA-seq data, providing a dynamic functional view of the underlying operons; (ii) an integrated operon-centric data resource that provides not only operons for each covered genome but also their functional and regulatory information such as their cis-regulatory binding sites for transcription initiation and termination, gene expression levels estimated based on RNA-seq data and conservation information across multiple genomes; (iii) a high-performance web service for online operon prediction on user-provided genomic sequences; (iv) an intuitive genome browser to support visualization of user-selected data; and (v) a keyword-based Google-like search engine for finding the needed information intuitively and rapidly in this database.

语种： 英文

作者： Fang, Kai-Tai;Li, Gang*;Lu, Xuyang;Qin, Hong

期刊： Computational and Mathematical Methods in Medicine,2013年2013(2):469373:1-469373:9 ISSN：1748-6718

通讯作者： Li, Gang

作者机构： [Fang, Kai-Tai] Hong Kong Baptist Univ, Beijing Normal Univ, United Int Coll, Zhuhai 519085, Peoples R China.;[Li, Gang; Lu, Xuyang] Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90095 USA.;[Qin, Hong] Cent China Normal Univ, Dept Stat, Wuhan 430079, Peoples R China.

通讯机构： [Li, Gang] U;Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90095 USA.

摘要： This paper develops a new empirical likelihood method for semiparametric linear regression with a completely unknown error distribution and right censored survival data. The method is based on the Buckley-James (1979) estimating equation. It inherits some appealing properties of the complete data empirical likelihood method. For example, it does not require variance estimation which is problematic for the Buckley-James estimator. We also extend our method to incorporate auxiliary information. We compare our method with the synthetic data empirical likelihood of Li and Wang (2003) using simulations. We also illustrate our method using Stanford heart transplantation data. © 2013 Kai-Tai Fang et al.

语种： 英文

作者： Zhu, Liang;Zhao, Hui*;Sun, Jianguo;Pounds, Stanley;Zhang, Hui

期刊： BIOMETRICAL JOURNAL,2013年55(1):5-16 ISSN：0323-3847

通讯作者： Zhao, Hui

作者机构： [Zhang, Hui; Zhu, Liang; Pounds, Stanley] St Jude Childrens Res Hosp, Dept Biostat, Memphis, TN 38103 USA.;[Zhao, Hui] Cent China Normal Univ, Sch Math & Stat, Wuhan 430079, Hubei Province, Peoples R China.;[Sun, Jianguo] Univ Missouri, Dept Stat, Columbia, MO 65211 USA.;[Sun, Jianguo] Jilin Univ, Sch Math, Changchun 130012, Peoples R China.

通讯机构： [Zhao, Hui] C;Cent China Normal Univ, Sch Math & Stat, Wuhan 430079, Hubei Province, Peoples R China.

关键词： Joint model;Longitudinal data analysis;Random effect;Recurrent episode process

摘要： This paper discusses regression analysis of longitudinal data in which the observation process may be related to the longitudinal process of interest. Such data have recently attracted a great deal of attention and some methods have been developed. However, most of those methods treat the observation process as a recurrent event process, which assumes that one observation can immediately follow another. Sometimes, this is not the case, as there may be some delay or observation duration. Such a process is often referred to as a recurrent episode process. One example is the medical cost related to hospitalization, where each hospitalization serves as a single observation. For the problem, we present a joint analysis approach for regression analysis of both longitudinal and observation processes and a simulation study is conducted that assesses the finite sample performance of the approach. The asymptotic properties of the proposed estimates are also given and the method is applied to the medical cost data that motivated this study. © 2013.

语种： 英文

作者： Li, Ni;Zhao, Hui;Sun, Jianguo*

期刊： Statistics in Medicine,2013年32(17):3039-3054 ISSN：0277-6715

通讯作者： Sun, Jianguo

作者机构： [Li, Ni] Hainan Normal Univ, Sch Math & Stat, Haikou 571158, Peoples R China.;[Zhao, Hui] Cent China Normal Univ, Dept Stat, Wuhan 430079, Peoples R China.;[Sun, Jianguo] Univ Missouri, Dept Stat, Columbia, MO 65211 USA.;[Sun, Jianguo] Univ Missouri, Dept Stat, 146 Middlebush Hall, Columbia, MO 65211 USA.

通讯机构： [Sun, Jianguo] U;Univ Missouri, Dept Stat, 146 Middlebush Hall, Columbia, MO 65211 USA.

关键词： estimating equation;informative follow-up process;informative observation process;transformation models

摘要： The statistical analysis of panel count data has recently attracted a great deal of attention, and a number of approaches have been developed. However, most of these approaches are for situations where the observation and follow-up processes are independent of the underlying recurrent event process unconditional or conditional on covariates. In this paper, we discuss a more general situation where both the observation and the follow-up processes may be related with the recurrent event process of interest. For regression analysis, we present a class of semiparametric transformation models and develop some estimating equations for estimation of regression parameters. Numerical studies under different settings conducted for assessing the proposed methodology suggest that it works well for practical situations, and the approach is applied to a skin cancer study that motivated the study. Copyright © 2013 John Wiley & Sons, Ltd.

语种： 英文

作者： Zhu, Liang*;Tong, Xingwei;Zhao, Hui;Sun, Jianguo;Srivastava, Deo Kumar;...

期刊： Statistics in Medicine,2013年32(11):1954-1963 ISSN：0277-6715

通讯作者： Zhu, Liang

作者机构： [Robison, Leslie L.; Srivastava, Deo Kumar; Zhu, Liang] St Jude Childrens Res Hosp, Memphis, TN 38103 USA.;[Tong, Xingwei] Beijing Normal Univ, Beijing 100875, Peoples R China.;[Zhao, Hui] Cent China Normal Univ, Sch Math & Stat, Wuhan, Peoples R China.;[Sun, Jianguo] Univ Missouri, Columbia, MO USA.;[Leisenring, Wendy] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA USA.

通讯机构： [Zhu, Liang] S;St Jude Childrens Res Hosp, Dept Biostat, Memphis, TN 38103 USA.

关键词： Childhood Cancer Survivor Study;Estimating equation-based approach;Regression analysis

摘要： Event history studies occur in many fields including economics, medical studies, and social science. In such studies concerning some recurrent events, two types of data have been extensively discussed in the literature. One is recurrent event data that arise if study subjects are monitored or observed continuously. In this case, the observed information provides the times of all occurrences of the recurrent events of interest. The other is panel count data, which occur if the subjects are monitored or observed only periodically. This can happen if the continuous observation is too expensive or not practical, and in this case, only the numbers of occurrences of the events between subsequent observation times are available. In this paper, we discuss a third type of data, which is a mixture of recurrent event and panel count data and for which there exists little literature. For regression analysis of such data, we present a marginal mean model and propose an estimating equation-based approach for estimation of regression parameters. We conduct a simulation study to assess the finite sample performance of the proposed methodology, and the results indicate that it works well for practical situations. Finally, we apply it to a motivating study on childhood cancer survivors. Copyright © 2012 John Wiley & Sons, Ltd.

语种： 英文

作者： Zhang, Xinan*;Jaramillo, Maria;Singh, Satish;Kumta, Prashant;Banerjee, Ipsita

期刊： PLOS ONE,2012年7(4):e35700 ISSN：1932-6203

通讯作者： Zhang, Xinan

作者机构： [Zhang, Xinan] Cent China Normal Univ, Sch Math & Stat, Wuhan, Peoples R China.;[Zhang, Xinan; Singh, Satish; Kumta, Prashant; Banerjee, Ipsita] Univ Pittsburgh, Dept Chem Engn, Pittsburgh, PA 15261 USA.;[Kumta, Prashant; Jaramillo, Maria; Banerjee, Ipsita] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA USA.;[Kumta, Prashant] Univ Pittsburgh, Dept Mech Engn & Mat Sci, Pittsburgh, PA USA.;[Kumta, Prashant] Univ Pittsburgh, Ctr Complex Engn Multifunct Mat, Pittsburgh, PA USA.

通讯机构： [Zhang, Xinan] C;Cent China Normal Univ, Sch Math & Stat, Wuhan, Peoples R China.

关键词： Cell differentiation;Endoderm;Fibrin;Stiffness;Embryonic stem cells;Fibrinogen;Transcription factors;Gene expression

摘要： Embryonic stem cells are conventionally differentiated by modulating specific growth factors in the cell culture media. Recently the effect of cellular mechanical microenvironment in inducing phenotype specific differentiation has attracted considerable attention. We have shown the possibility of inducing endoderm differentiation by culturing the stem cells on fibrin substrates of specific stiffness [1]. Here, we analyze the regulatory network involved in such mechanically induced endoderm differentiation under two different experimental configurations of 2-dimensional and 3-dimensional culture, respectively. Mouse embryonic stem cells are differentiated on an array of substrates of varying mechanical properties and analyzed for relevant endoderm markers. The experimental data set is further analyzed for identification of co-regulated transcription factors across different substrate conditions using the technique of bi-clustering. Overlapped bi-clusters are identified following an optimization formulation, which is solved using an evolutionary algorithm. While typically such analysis is performed at the mean value of expression data across experimental repeats, the variability of stem cell systems reduces the confidence on such analysis of mean data. Bootstrapping technique is thus integrated with the bi-clustering algorithm to determine sets of robust bi-clusters, which is found to differ significantly from corresponding bi-clusters at the mean data value. Analysis of robust bi-clusters reveals an overall similar network interaction as has been reported for chemically induced endoderm or endodermal organs but with differences in patterning between 2-dimensional and 3-dimensional culture. Such analysis sheds light on the pathway of stem cell differentiation indicating the prospect of the two culture configurations for further maturation.

语种： 英文

作者： Mathew, Shibin;Jaramillo, Maria;Zhang, Xinan;Zhang, Li Ang;Soto-Gutierrez, Alejandro;...

期刊： BMC Systems Biology,2012年6(1):1-13 ISSN：1752-0509

通讯作者： Banerjee, Ipsita

作者机构： [Mathew, Shibin; Zhang, Li Ang; Banerjee, Ipsita] Univ Pittsburgh, Dept Chem & Petr Engn, Pittsburgh, PA 15261 USA.;[Jaramillo, Maria; Banerjee, Ipsita] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA 15219 USA.;[Zhang, Xinan] Cent China Normal Univ, Sch Math & Stat, Wuhan, Peoples R China.;[Soto-Gutierrez, Alejandro] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA 15261 USA.;[Soto-Gutierrez, Alejandro] Univ Pittsburgh, McGowan Inst Regenerat Med, Pittsburgh, PA 15261 USA.

通讯机构： [Banerjee, Ipsita] U;Univ Pittsburgh, Dept Chem & Petr Engn, 1249 Benedum Hall,3700 OHara St, Pittsburgh, PA 15261 USA.

关键词： Human embryonic stem cells;Endoderm;Hierarchical clustering;Biclustering;Bootstrap

摘要： Background: Lineage specific differentiation of human embryonic stem cells (hESCs) is largely mediated by specific growth factors and extracellular matrix molecules. Growth factors initiate a cascade of signals which control gene transcription and cell fate specification. There is a lot of interest in inducing hESCs to an endoderm fate which serves as a pathway towards more functional cell types like the pancreatic cells. Research over the past decade has established several robust pathways for deriving endoderm from hESCs, with the capability of further maturation. However, in our experience, the functional maturity of these endoderm derivatives, specifically to pancreatic lineage, largely depends on specific pathway of endoderm induction. Hence it will be of interest to understand the underlying mechanism mediating such induction and how it is translated to further maturation. In this work we analyze the regulatory interactions mediating different pathways of endoderm induction by identifying co-regulated transcription factors.Results: hESCs were induced towards endoderm using activin A and 4 different growth factors (FGF2 (F), BMP4 (B), PI3KI (P), and WNT3A (W)) and their combinations thereof, resulting in 15 total experimental conditions. At the end of differentiation each condition was analyzed by qRT-PCR for 12 relevant endoderm related transcription factors (TFs). As a first approach, we used hierarchical clustering to identify which growth factor combinations favor up-regulation of different genes. In the next step we identified sets of co-regulated transcription factors using a biclustering algorithm. The high variability of experimental data was addressed by integrating the biclustering formulation with bootstrap re-sampling to identify robust networks of co-regulated transcription factors. Our results show that the transition from early to late endoderm is favored by FGF2 as well as WNT3A treatments under high activin. However, induction of late endoderm markers is relatively favored by WNT3A under high activin.Conclusions: Use of FGF2, WNT3A or PI3K inhibition with high activin A may serve well in definitive endoderm induction followed by WNT3A specific signaling to direct the definitive endoderm into late endodermal lineages. Other combinations, though still feasible for endoderm induction, appear less promising for pancreatic endoderm specification in our experiments. © 2012 Mathew et al.; licensee BioMed Central Ltd.

语种： 英文

作者： Zhang, Xinan*;Zhao, Yingdong;Neumann, Avidan U.

期刊： JOURNAL OF COMPUTATIONAL BIOLOGY,2010年17(12):1689-1696 ISSN：1066-5277

通讯作者： Zhang, Xinan

作者机构： [Zhang, Xinan] Cent China Normal Univ, Sch Math & Stat, Wuhan 430079, Peoples R China.;[Zhao, Yingdong] NCI, Biometr Res Branch, Bethesda, MD 20892 USA.;[Neumann, Avidan U.] Bar Ilan Univ, Fac Life Sci, Ramat Gan, Israel.

通讯机构： [Zhang, Xinan] C;Cent China Normal Univ, Sch Math & Stat, Wuhan 430079, Peoples R China.

关键词： chi-square test of goodness of fit;influenza type A;mathematical modeling

摘要： In this article, we estimated the basic reproductive numbers by mathematical modeling and computer simulation using the hospitalization data of influenza type A (H3N2) from the United States as provided by the Centers for Disease Control and Prevention (CDC) from the 2001 to 2006 influenza seasons, respectively. The mean value of basic reproductive number from the 2001-2002 to 2005-2006 influenza seasons is 1.2440, with a 95% confidence interval of 1.1170-1.3710. Our model predicts that the proportion of vaccination of susceptible is 20% and 60 million doses of vaccines should be prepared for each influenza season in the United States. The chi-square test of goodness of fit indicates that our model fits the data reasonably well. © Mary Ann Liebert, Inc.

语种： 英文

作者： Gu, MG*;Sun, LQ;Zuo, GX

期刊： Lifetime Data Analysis,2005年11(4):473-488 ISSN：1380-7870

通讯作者： Gu, MG

作者机构： [Gu, MG] Univ Hong Kong, Dept Stat, Hong Kong, Hong Kong, Peoples R China.;Chinese Acad Sci, Inst Appl Math, Acad Math & Syst Sci, Beijing 100080, Peoples R China.;Cent China Normal Univ, Dept Stat, Wuhan 430079, Peoples R China.

通讯机构： [Gu, MG] U;Univ Hong Kong, Dept Stat, Hong Kong, Hong Kong, Peoples R China.

关键词： interval censored data;marginal likelihood;Markov chain Monte Carlo methods;semiparametric models;stochastic approximation;transformation models

摘要： An important property of Cox regression model is that the estimation of regression parameters using the partial likelihood procedure does not depend on its baseline survival function. We call such a procedure baseline-free. Using marginal likelihood, we show that an baseline-free procedure can be derived for a class of general transformation models under interval censoring framework. The baseline-free procedure results a simplified and stable computation algorithm for some complicated and important semiparametric models, such as frailty models and heteroscedastic hazard/rank regression models, where the estimation procedures so far available involve estimation of the infinite dimensional baseline function. A detailed computational algorithm using Markov Chain Monte Carlo stochastic approximation is presented. The proposed procedure is demonstrated through extensive simulation studies, showing the validity of asymptotic consistency and normality. We also illustrate the procedure with a real data set from a study of breast cancer. A heuristic argument showing that the score function is a mean zero martingale is provided.

语种： 英文

作者： Huang, JH*;Lu, G;Ruan, SG

期刊： Journal of Mathematical Biology,2003年46(2):132-152 ISSN：0303-6812

通讯作者： Huang, JH

作者机构： [Huang, JH] Cent China Normal Univ, Dept Math, Wuhan 430079, Hubei, Peoples R China.;Univ Miami, Dept Math, Coral Gables, FL 33124 USA.

通讯机构： [Huang, JH] C;Cent China Normal Univ, Dept Math, Wuhan 430079, Hubei, Peoples R China.

关键词： Periodic Orbit;Wave Solution;Small Amplitude;Hopf Bifurcation;Functional Response

摘要：  We establish the existence of traveling front solutions and small amplitude traveling wave train solutions for a reaction-diffusion system based on a predator-prey model with Holling type-II functional response. The traveling front solutions are equivalent to heteroclinic orbits in R 4 and the small amplitude traveling wave train solutions are equivalent to small amplitude periodic orbits in R 4 . The methods used to prove the results are the shooting argument and the Hopf bifurcation theorem.

语种： 英文