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Background: Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer deaths in females worldwide, accounting for 23% of all new cancer cases and 14% of all total cancer deaths in 2008. Five tumor-normal pairs of primary breast epithelial cells were treated for infinite proliferation by

Background: Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer deaths in females worldwide, accounting for 23% of all new cancer cases and 14% of all total cancer deaths in 2008. Five tumor-normal pairs of primary breast epithelial cells were treated for infinite proliferation by using a ROCK inhibitor and mouse feeder cells. Methods: Raw paired-end, 100x coverage RNA-Seq data was aligned to the Human Reference Genome Version 19 using BWA and Tophat. Gene differential expression analysis was completed using Cufflinks and Cuffdiff. Interactive Genome Viewer was used for data visualization. Results: 15 genes were found to be down-regulated by at least one log-fold change in 4/5 of tumor samples. 75 genes were found to be down-regulated in 3/5 of our tumor samples by at least one log-fold change. 11 genes were found to be up-regulated in 4/5 of our tumor samples, and 68 genes were identified to be up-regulated in 3/5 of the tumor samples by at least one-fold change. Conclusion: Expression changes in genes such as AZGP1, AGER, ALG11, and S1007 suggest a disruption in the glycosylation pathway. No correlation was found between Cufflink's Her2 gene-expression and DAKO score classification.
ContributorsHernandez, Fernando (Author) / Anderson, Karen (Thesis director) / Mangone, Marco (Committee member) / Park, Jin (Committee member) / Barrett, The Honors College (Contributor) / Department of Information Systems (Contributor)
Created2013-05
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Extreme events, a type of collective behavior in complex networked dynamical systems, often can have catastrophic consequences. To develop effective strategies to control extreme events is of fundamental importance and practical interest. Utilizing transportation dynamics on complex networks as a prototypical setting, we find that making the network “mobile” can

Extreme events, a type of collective behavior in complex networked dynamical systems, often can have catastrophic consequences. To develop effective strategies to control extreme events is of fundamental importance and practical interest. Utilizing transportation dynamics on complex networks as a prototypical setting, we find that making the network “mobile” can effectively suppress extreme events. A striking, resonance-like phenomenon is uncovered, where an optimal degree of mobility exists for which the probability of extreme events is minimized. We derive an analytic theory to understand the mechanism of control at a detailed and quantitative level, and validate the theory numerically. Implications of our finding to current areas such as cybersecurity are discussed.

ContributorsChen, Yu-Zhong (Author) / Huang, Zi-Gang (Author) / Lai, Ying-Cheng (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2014-08-18
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The relation between flux and fluctuation is fundamental to complex physical systems that support and transport flows. A recently obtained law predicts monotonous enhancement of fluctuation as the average flux is increased, which in principle is valid but only for large systems. For realistic complex systems of small sizes, this

The relation between flux and fluctuation is fundamental to complex physical systems that support and transport flows. A recently obtained law predicts monotonous enhancement of fluctuation as the average flux is increased, which in principle is valid but only for large systems. For realistic complex systems of small sizes, this law breaks down when both the average flux and fluctuation become large. Here we demonstrate the failure of this law in small systems using real data and model complex networked systems, derive analytically a modified flux-fluctuation law, and validate it through computations of a large number of complex networked systems. Our law is more general in that its predictions agree with numerics and it reduces naturally to the previous law in the limit of large system size, leading to new insights into the flow dynamics in small-size complex systems with significant implications for the statistical and scaling behaviors of small systems, a topic of great recent interest.

ContributorsHuang, Zi-Gang (Author) / Dong, Jia-Qi (Author) / Huang, Liang (Author) / Lai, Ying-Cheng (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2014-10-27
Description

Throughout the long history of virus-host co-evolution, viruses have developed delicate strategies to facilitate their invasion and replication of their genome, while silencing the host immune responses through various mechanisms. The systematic characterization of viral protein-host interactions would yield invaluable information in the understanding of viral invasion/evasion, diagnosis and therapeutic

Throughout the long history of virus-host co-evolution, viruses have developed delicate strategies to facilitate their invasion and replication of their genome, while silencing the host immune responses through various mechanisms. The systematic characterization of viral protein-host interactions would yield invaluable information in the understanding of viral invasion/evasion, diagnosis and therapeutic treatment of a viral infection, and mechanisms of host biology. With more than 2,000 viral genomes sequenced, only a small percent of them are well investigated. The access of these viral open reading frames (ORFs) in a flexible cloning format would greatly facilitate both in vitro and in vivo virus-host interaction studies. However, the overall progress of viral ORF cloning has been slow. To facilitate viral studies, we are releasing the initiation of our panviral proteome collection of 2,035 ORF clones from 830 viral genes in the Gateway® recombinational cloning system. Here, we demonstrate several uses of our viral collection including highly efficient production of viral proteins using human cell-free expression system in vitro, global identification of host targets for rubella virus using Nucleic Acid Programmable Protein Arrays (NAPPA) containing 10,000 unique human proteins, and detection of host serological responses using micro-fluidic multiplexed immunoassays. The studies presented here begin to elucidate host-viral protein interactions with our systemic utilization of viral ORFs, high-throughput cloning, and proteomic technologies. These valuable plasmid resources will be available to the research community to enable continued viral functional studies.

ContributorsYu, Xiaobo (Author) / Bian, Xiaofang (Author) / Throop, Andrea (Author) / Song, Lusheng (Author) / del Moral, Lerys (Author) / Park, Jin (Author) / Seiler, Catherine (Author) / Fiacco, Michael (Author) / Steel, Jason (Author) / Hunter, Preston (Author) / Saul, Justin (Author) / Wang, Jie (Author) / Qiu, Ji (Author) / Pipas, James M. (Author) / LaBaer, Joshua (Author) / Biodesign Institute (Contributor)
Created2013-11-30
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Description

Evolutionary dynamical models for cyclic competitions of three species (e.g., rock, paper, and scissors, or RPS) provide a paradigm, at the microscopic level of individual interactions, to address many issues in coexistence and biodiversity. Real ecosystems often involve competitions among more than three species. By extending the RPS game model

Evolutionary dynamical models for cyclic competitions of three species (e.g., rock, paper, and scissors, or RPS) provide a paradigm, at the microscopic level of individual interactions, to address many issues in coexistence and biodiversity. Real ecosystems often involve competitions among more than three species. By extending the RPS game model to five (rock-paper-scissors-lizard-Spock, or RPSLS) mobile species, we uncover a fundamental type of mesoscopic interactions among subgroups of species. In particular, competitions at the microscopic level lead to the emergence of various local groups in different regions of the space, each involving three species. It is the interactions among the groups that fundamentally determine how many species can coexist. In fact, as the mobility is increased from zero, two transitions can occur: one from a five- to a three-species coexistence state and another from the latter to a uniform, single-species state. We develop a mean-field theory to show that, in order to understand the first transition, group interactions at the mesoscopic scale must be taken into account. Our findings suggest, more broadly, the importance of mesoscopic interactions in coexistence of great many species.

ContributorsCheng, Hongyan (Author) / Yao, Nan (Author) / Huang, Zi-Gang (Author) / Park, Junpyo (Author) / Do, Younghae (Author) / Lai, Ying-Cheng (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2014-12-15
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Description

Dynamical systems based on the minority game (MG) have been a paradigm for gaining significant insights into a variety of social and biological behaviors. Recently, a grouping phenomenon has been unveiled in MG systems of multiple resources (strategies) in which the strategies spontaneously break into an even number of groups,

Dynamical systems based on the minority game (MG) have been a paradigm for gaining significant insights into a variety of social and biological behaviors. Recently, a grouping phenomenon has been unveiled in MG systems of multiple resources (strategies) in which the strategies spontaneously break into an even number of groups, each exhibiting an identical oscillation pattern in the attendance of game players. Here we report our finding of spontaneous breakup of resources into three groups, each exhibiting period-three oscillations. An analysis is developed to understand the emergence of the striking phenomenon of triple grouping and period-three oscillations. In the presence of random disturbances, the triple-group/period-three state becomes transient, and we obtain explicit formula for the average transient lifetime using two methods of approximation. Our finding indicates that, period-three oscillation, regarded as one of the most fundamental behaviors in smooth nonlinear dynamical systems, can also occur in much more complex, evolutionary-game dynamical systems. Our result also provides a plausible insight for the occurrence of triple grouping observed, for example, in the U.S. housing market.

ContributorsDong, Jia-Qi (Author) / Huang, Zi-Gang (Author) / Huang, Liang (Author) / Lai, Ying-Cheng (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2014-12-23
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Description

Understanding the dynamics of human movements is key to issues of significant current interest such as behavioral prediction, recommendation, and control of epidemic spreading. We collect and analyze big data sets of human movements in both cyberspace (through browsing of websites) and physical space (through mobile towers) and find a

Understanding the dynamics of human movements is key to issues of significant current interest such as behavioral prediction, recommendation, and control of epidemic spreading. We collect and analyze big data sets of human movements in both cyberspace (through browsing of websites) and physical space (through mobile towers) and find a superlinear scaling relation between the mean frequency of visit〈f〉and its fluctuation σ : σ ∼〈f⟩β with β ≈ 1.2. The probability distribution of the visiting frequency is found to be a stretched exponential function. We develop a model incorporating two essential ingredients, preferential return and exploration, and show that these are necessary for generating the scaling relation extracted from real data. A striking finding is that human movements in cyberspace and physical space are strongly correlated, indicating a distinctive behavioral identifying characteristic and implying that the behaviors in one space can be used to predict those in the other.

ContributorsZhao, Zhidan (Author) / Huang, Zi-Gang (Author) / Huang, Liang (Author) / Liu, Huan (Author) / Lai, Ying-Cheng (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2014-11-12
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Description

Sera from patients with ovarian cancer contain autoantibodies (AAb) to tumor-derived proteins that are potential biomarkers for early detection. To detect AAb, we probed high-density programmable protein microarrays (NAPPA) expressing 5177 candidate tumor antigens with sera from patients with serous ovarian cancer (n = 34 cases/30 controls) and measured bound

Sera from patients with ovarian cancer contain autoantibodies (AAb) to tumor-derived proteins that are potential biomarkers for early detection. To detect AAb, we probed high-density programmable protein microarrays (NAPPA) expressing 5177 candidate tumor antigens with sera from patients with serous ovarian cancer (n = 34 cases/30 controls) and measured bound IgG. Of these, 741 antigens were selected and probed with an independent set of ovarian cancer sera (n = 60 cases/60 controls). Twelve potential autoantigens were identified with sensitivities ranging from 13 to 22% at >93% specificity. These were retested using a Luminex bead array using 60 cases and 60 controls, with sensitivities ranging from 0 to 31.7% at 95% specificity. Three AAb (p53, PTPRA, and PTGFR) had area under the curve (AUC) levels >60% (p < 0.01), with the partial AUC (SPAUC) over 5 times greater than for a nondiscriminating test (p < 0.01). Using a panel of the top three AAb (p53, PTPRA, and PTGFR), if at least two AAb were positive, then the sensitivity was 23.3% at 98.3% specificity. AAb to at least one of these top three antigens were also detected in 7/20 sera (35%) of patients with low CA 125 levels and 0/15 controls. AAb to p53, PTPRA, and PTGFR are potential biomarkers for the early detection of ovarian cancer.

ContributorsAnderson, Karen (Author) / Cramer, Daniel W. (Author) / Sibani, Sahar (Author) / Wallstrom, Garrick (Author) / Wong, Jessica (Author) / Park, Jin (Author) / Qiu, Ji (Author) / Vitonis, Allison (Author) / LaBaer, Joshua (Author) / Biodesign Institute (Contributor)
Created2015-01-01
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Description

Resource allocation takes place in various types of real-world complex systems such as urban traffic, social services institutions, economical and ecosystems. Mathematically, the dynamical process of resource allocation can be modeled as minority games. Spontaneous evolution of the resource allocation dynamics, however, often leads to a harmful herding behavior accompanied

Resource allocation takes place in various types of real-world complex systems such as urban traffic, social services institutions, economical and ecosystems. Mathematically, the dynamical process of resource allocation can be modeled as minority games. Spontaneous evolution of the resource allocation dynamics, however, often leads to a harmful herding behavior accompanied by strong fluctuations in which a large majority of agents crowd temporarily for a few resources, leaving many others unused. Developing effective control methods to suppress and eliminate herding is an important but open problem. Here we develop a pinning control method, that the fluctuations of the system consist of intrinsic and systematic components allows us to design a control scheme with separated control variables. A striking finding is the universal existence of an optimal pinning fraction to minimize the variance of the system, regardless of the pinning patterns and the network topology. We carry out a generally applicable theory to explain the emergence of optimal pinning and to predict the dependence of the optimal pinning fraction on the network topology. Our work represents a general framework to deal with the broader problem of controlling collective dynamics in complex systems with potential applications in social, economical and political systems.

ContributorsZhang, Ji-Qiang (Author) / Huang, Zi-Gang (Author) / Wu, Zhi-Xi (Author) / Su, Riqi (Author) / Lai, Ying-Cheng (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2016-02-17
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Description

Background: Tissue-specific RNA plasticity broadly impacts the development, tissue identity and adaptability of all organisms, but changes in composition, expression levels and its impact on gene regulation in different somatic tissues are largely unknown. Here we developed a new method, polyA-tagging and sequencing (PAT-Seq) to isolate high-quality tissue-specific mRNA from Caenorhabditis

Background: Tissue-specific RNA plasticity broadly impacts the development, tissue identity and adaptability of all organisms, but changes in composition, expression levels and its impact on gene regulation in different somatic tissues are largely unknown. Here we developed a new method, polyA-tagging and sequencing (PAT-Seq) to isolate high-quality tissue-specific mRNA from Caenorhabditis elegans intestine, pharynx and body muscle tissues and study changes in their tissue-specific transcriptomes and 3’UTRomes.

Results: We have identified thousands of novel genes and isoforms differentially expressed between these three tissues. The intestine transcriptome is expansive, expressing over 30% of C. elegans mRNAs, while muscle transcriptomes are smaller but contain characteristic unique gene signatures. Active promoter regions in all three tissues reveal both known and novel enriched tissue-specific elements, along with putative transcription factors, suggesting novel tissue-specific modes of transcription initiation. We have precisely mapped approximately 20,000 tissue-specific polyadenylation sites and discovered that about 30% of transcripts in somatic cells use alternative polyadenylation in a tissue-specific manner, with their 3’UTR isoforms significantly enriched with microRNA targets.

Conclusions: For the first time, PAT-Seq allowed us to directly study tissue specific gene expression changes in an in vivo setting and compare these changes between three somatic tissues from the same organism at single-base resolution within the same experiment. We pinpoint precise tissue-specific transcriptome rearrangements and for the first time link tissue-specific alternative polyadenylation to miRNA regulation, suggesting novel and unexplored tissue-specific post-transcriptional regulatory networks in somatic cells.

ContributorsBlazie, Stephen (Author) / Babb, Cody (Author) / Wilky, Henry (Author) / Rawls, Alan (Author) / Park, Jin (Author) / Mangone, Marco (Author) / College of Liberal Arts and Sciences (Contributor)
Created2015-01-20