Matching Items (191)
Description
Premise of the study: Land-plant plastid genomes have only rarely undergone significant changes in gene content and order. Thus, discovery of additional examples adds power to tests for causes of such genome-scale structural changes.
Methods: Using next-generation sequence data, we assembled the plastid genome of saguaro cactus and probed the nuclear genome for transferred plastid genes and functionally related nuclear genes. We combined these results with available data across Cactaceae and seed plants more broadly to infer the history of gene loss and to assess the strength of phylogenetic association between gene loss and loss of the inverted repeat (IR).
Key results: The saguaro plastid genome is the smallest known for an obligately photosynthetic angiosperm (∼113 kb), having lost the IR and plastid ndh genes. This loss supports a statistically strong association across seed plants between the loss of ndh genes and the loss of the IR. Many nonplastid copies of plastid ndh genes were found in the nuclear genome, but none had intact reading frames; nor did three related nuclear-encoded subunits. However, nuclear pgr5, which functions in a partially redundant pathway, was intact.
Conclusions: The existence of an alternative pathway redundant with the function of the plastid NADH dehydrogenase-like complex (NDH) complex may permit loss of the plastid ndh gene suite in photoautotrophs like saguaro. Loss of these genes may be a recurring mechanism for overall plastid genome size reduction, especially in combination with loss of the IR.
Methods: Using next-generation sequence data, we assembled the plastid genome of saguaro cactus and probed the nuclear genome for transferred plastid genes and functionally related nuclear genes. We combined these results with available data across Cactaceae and seed plants more broadly to infer the history of gene loss and to assess the strength of phylogenetic association between gene loss and loss of the inverted repeat (IR).
Key results: The saguaro plastid genome is the smallest known for an obligately photosynthetic angiosperm (∼113 kb), having lost the IR and plastid ndh genes. This loss supports a statistically strong association across seed plants between the loss of ndh genes and the loss of the IR. Many nonplastid copies of plastid ndh genes were found in the nuclear genome, but none had intact reading frames; nor did three related nuclear-encoded subunits. However, nuclear pgr5, which functions in a partially redundant pathway, was intact.
Conclusions: The existence of an alternative pathway redundant with the function of the plastid NADH dehydrogenase-like complex (NDH) complex may permit loss of the plastid ndh gene suite in photoautotrophs like saguaro. Loss of these genes may be a recurring mechanism for overall plastid genome size reduction, especially in combination with loss of the IR.
ContributorsSanderson, Michael J. (Author) / Copetti, Dario (Author) / Burquez, Alberto (Author) / Bustamante, Enriquena (Author) / Charboneau, Joseph L. M. (Author) / Eguiarte, Luis E. (Author) / Kumar, Sudhir (Author) / Lee, Hyun Oh (Author) / Lee, Junki (Author) / McMahon, Michelle (Author) / Steele, Kelly (Author) / Wing, Rod (Author) / Yang, Tae-Jin (Author) / Zwickl, Derrick (Author) / Wojciechowski, Martin (Author) / College of Integrative Sciences and Arts (Contributor) / College of Liberal Arts and Sciences (Contributor) / School of Life Sciences (Contributor)
Created2015-07-01
Description
Background:
Many pharmaceutical drugs are known to be ineffective or have negative side effects in a substantial proportion of patients. Genomic advances are revealing that some non-synonymous single nucleotide variants (nsSNVs) may cause differences in drug efficacy and side effects. Therefore, it is desirable to evaluate nsSNVs of interest in their ability to modulate the drug response.
Results:
We found that the available data on the link between drug response and nsSNV is rather modest. There were only 31 distinct drug response-altering (DR-altering) and 43 distinct drug response-neutral (DR-neutral) nsSNVs in the whole Pharmacogenomics Knowledge Base (PharmGKB). However, even with this modest dataset, it was clear that existing bioinformatics tools have difficulties in correctly predicting the known DR-altering and DR-neutral nsSNVs. They exhibited an overall accuracy of less than 50%, which was not better than random diagnosis. We found that the underlying problem is the markedly different evolutionary properties between positions harboring nsSNVs linked to drug responses and those observed for inherited diseases. To solve this problem, we developed a new diagnosis method, Drug-EvoD, which was trained on the evolutionary properties of nsSNVs associated with drug responses in a sparse learning framework. Drug-EvoD achieves a TPR of 84% and a TNR of 53%, with a balanced accuracy of 69%, which improves upon other methods significantly.
Conclusions:
The new tool will enable researchers to computationally identify nsSNVs that may affect drug responses. However, much larger training and testing datasets are needed to develop more reliable and accurate tools.
ContributorsGerek, Nevin Z. (Author) / Liu, Li (Author) / Gerold, Kristyn (Author) / Biparva, Pegah (Author) / Thomas, Eric D. (Author) / Kumar, Sudhir (Author) / Biodesign Institute (Contributor) / Center for Evolution and Medicine (Contributor)
Created2015-01-15
Description
The evolution of resistance in Staphylococcus aureus occurs rapidly, and in response to all known antimicrobial treatments. Numerous studies of model species describe compensatory roles of mutations in mediating competitive fitness, and there is growing evidence that these mutation types also drive adaptation of S. aureus strains. However, few studies have tracked amino acid changes during the complete evolutionary trajectory of antibiotic adaptation or been able to predict their functional relevance. Here, we have assessed the efficacy of computational methods to predict biological resistance of a collection of clinically known Resistance Associated Mutations (RAMs). We have found that >90% of known RAMs are incorrectly predicted to be functionally neutral by at least one of the prediction methods used. By tracing the evolutionary histories of all of the false negative RAMs, we have discovered that a significant number are reversion mutations to ancestral alleles also carried in the MSSA476 methicillin-sensitive isolate. These genetic reversions are most prevalent in strains following daptomycin treatment and show a tendency to accumulate in biological pathway reactions that are distinct from those accumulating non-reversion mutations. Our studies therefore show that in addition to non-reversion mutations, reversion mutations arise in isolates exposed to new antibiotic treatments. It is possible that acquisition of reversion mutations in the genome may prevent substantial fitness costs during the progression of resistance. Our findings pose an interesting question to be addressed by further clinical studies regarding whether or not these reversion mutations lead to a renewed vulnerability of a vancomycin or daptomycin resistant strain to antibiotics administered at an earlier stage of infection.
ContributorsChampion, Mia (Author) / Gray, Vanessa (Author) / Eberhard, Carl (Author) / Kumar, Sudhir (Author) / Biodesign Institute (Contributor) / Center for Evolution and Medicine (Contributor)
Created2013-02-12
Description
Background
Multicellular organisms consist of cells of many different types that are established during development. Each type of cell is characterized by the unique combination of expressed gene products as a result of spatiotemporal gene regulation. Currently, a fundamental challenge in regulatory biology is to elucidate the gene expression controls that generate the complex body plans during development. Recent advances in high-throughput biotechnologies have generated spatiotemporal expression patterns for thousands of genes in the model organism fruit fly Drosophila melanogaster. Existing qualitative methods enhanced by a quantitative analysis based on computational tools we present in this paper would provide promising ways for addressing key scientific questions.
Results
We develop a set of computational methods and open source tools for identifying co-expressed embryonic domains and the associated genes simultaneously. To map the expression patterns of many genes into the same coordinate space and account for the embryonic shape variations, we develop a mesh generation method to deform a meshed generic ellipse to each individual embryo. We then develop a co-clustering formulation to cluster the genes and the mesh elements, thereby identifying co-expressed embryonic domains and the associated genes simultaneously. Experimental results indicate that the gene and mesh co-clusters can be correlated to key developmental events during the stages of embryogenesis we study. The open source software tool has been made available at http://compbio.cs.odu.edu/fly/.
Conclusions
Our mesh generation and machine learning methods and tools improve upon the flexibility, ease-of-use and accuracy of existing methods.
Multicellular organisms consist of cells of many different types that are established during development. Each type of cell is characterized by the unique combination of expressed gene products as a result of spatiotemporal gene regulation. Currently, a fundamental challenge in regulatory biology is to elucidate the gene expression controls that generate the complex body plans during development. Recent advances in high-throughput biotechnologies have generated spatiotemporal expression patterns for thousands of genes in the model organism fruit fly Drosophila melanogaster. Existing qualitative methods enhanced by a quantitative analysis based on computational tools we present in this paper would provide promising ways for addressing key scientific questions.
Results
We develop a set of computational methods and open source tools for identifying co-expressed embryonic domains and the associated genes simultaneously. To map the expression patterns of many genes into the same coordinate space and account for the embryonic shape variations, we develop a mesh generation method to deform a meshed generic ellipse to each individual embryo. We then develop a co-clustering formulation to cluster the genes and the mesh elements, thereby identifying co-expressed embryonic domains and the associated genes simultaneously. Experimental results indicate that the gene and mesh co-clusters can be correlated to key developmental events during the stages of embryogenesis we study. The open source software tool has been made available at http://compbio.cs.odu.edu/fly/.
Conclusions
Our mesh generation and machine learning methods and tools improve upon the flexibility, ease-of-use and accuracy of existing methods.
ContributorsZhang, Wenlu (Author) / Feng, Daming (Author) / Li, Rongjian (Author) / Chernikov, Andrey (Author) / Chrisochoides, Nikos (Author) / Osgood, Christopher (Author) / Konikoff, Charlotte (Author) / Newfeld, Stuart (Author) / Kumar, Sudhir (Author) / Ji, Shuiwang (Author) / Biodesign Institute (Contributor) / Center for Evolution and Medicine (Contributor) / College of Liberal Arts and Sciences (Contributor) / School of Life Sciences (Contributor)
Created2013-12-28
Learning Sparse Representations for Fruit-Fly Gene Expression Pattern Image Annotation and Retrieval
Description
Background
Fruit fly embryogenesis is one of the best understood animal development systems, and the spatiotemporal gene expression dynamics in this process are captured by digital images. Analysis of these high-throughput images will provide novel insights into the functions, interactions, and networks of animal genes governing development. To facilitate comparative analysis, web-based interfaces have been developed to conduct image retrieval based on body part keywords and images. Currently, the keyword annotation of spatiotemporal gene expression patterns is conducted manually. However, this manual practice does not scale with the continuously expanding collection of images. In addition, existing image retrieval systems based on the expression patterns may be made more accurate using keywords.
Results
In this article, we adapt advanced data mining and computer vision techniques to address the key challenges in annotating and retrieving fruit fly gene expression pattern images. To boost the performance of image annotation and retrieval, we propose representations integrating spatial information and sparse features, overcoming the limitations of prior schemes.
Conclusions
We perform systematic experimental studies to evaluate the proposed schemes in comparison with current methods. Experimental results indicate that the integration of spatial information and sparse features lead to consistent performance improvement in image annotation, while for the task of retrieval, sparse features alone yields better results.
Fruit fly embryogenesis is one of the best understood animal development systems, and the spatiotemporal gene expression dynamics in this process are captured by digital images. Analysis of these high-throughput images will provide novel insights into the functions, interactions, and networks of animal genes governing development. To facilitate comparative analysis, web-based interfaces have been developed to conduct image retrieval based on body part keywords and images. Currently, the keyword annotation of spatiotemporal gene expression patterns is conducted manually. However, this manual practice does not scale with the continuously expanding collection of images. In addition, existing image retrieval systems based on the expression patterns may be made more accurate using keywords.
Results
In this article, we adapt advanced data mining and computer vision techniques to address the key challenges in annotating and retrieving fruit fly gene expression pattern images. To boost the performance of image annotation and retrieval, we propose representations integrating spatial information and sparse features, overcoming the limitations of prior schemes.
Conclusions
We perform systematic experimental studies to evaluate the proposed schemes in comparison with current methods. Experimental results indicate that the integration of spatial information and sparse features lead to consistent performance improvement in image annotation, while for the task of retrieval, sparse features alone yields better results.
ContributorsYuan, Lei (Author) / Woodard, Alexander (Author) / Ji, Shuiwang (Author) / Jiang, Yuan (Author) / Zhou, Zhi-Hua (Author) / Kumar, Sudhir (Author) / Ye, Jieping (Author) / Biodesign Institute (Contributor) / Center for Evolution and Medicine (Contributor) / Ira A. Fulton Schools of Engineering (Contributor) / College of Liberal Arts and Sciences (Contributor) / School of Life Sciences (Contributor)
Created2012-05-23
Description
Concrete stands at the forefront of the construction industry as one of the most useful building materials. Economic and efficient improvements in concrete strengthening and manufacturing are widely sought to continuously improve the performance of the material. Fiber reinforcement is a significant technique in strengthening precast concrete, but manufacturing limitations are common which has led to reliance on steel reinforcement. Two-dimensional textile reinforcement has emerged as a strong and efficient alternative to both fiber and steel reinforced concrete with pultrusion manufacturing shown as one of the most effective methods of precasting concrete. The intention of this thesis project is to detail the components, functions, and outcomes shown in the development of an automated pultrusion system for manufacturing textile reinforced concrete (TRC). Using a preexisting, manual pultrusion system and current-day manufacturing techniques as a basis, the automated pultrusion system was designed as a series of five stations that centered on textile impregnation, system driving, and final pressing. The system was then constructed in the Arizona State University Structures Lab over the course of the spring and summer of 2015. After fabricating each station, a computer VI was coded in LabVIEW software to automatically drive the system. Upon completing construction of the system, plate and angled structural sections were then manufactured to verify the adequacy of the technique. Pultruded TRC plates were tested in tension and flexure while full-scale structural sections were tested in tension and compression. Ultimately, the automated pultrusion system was successful in establishing an efficient and consistent manufacturing process for continuous TRC sections.
ContributorsBauchmoyer, Jacob Macgregor (Author) / Mobasher, Barzin (Thesis director) / Neithalath, Narayanan (Committee member) / Civil, Environmental and Sustainable Engineering Programs (Contributor) / The Design School (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Many forms of programmable matter have been proposed for various tasks. We use an abstract model of self-organizing particle systems for programmable matter which could be used for a variety of applications, including smart paint and coating materials for engineering or programmable cells for medical uses. Previous research using this model has focused on shape formation and other spatial configuration problems, including line formation, compression, and coating. In this work we study foundational computational tasks that exceed the capabilities of the individual constant memory particles described by the model. These tasks represent new ways to use these self-organizing systems, which, in conjunction with previous shape and configuration work, make the systems useful for a wider variety of tasks. We present an implementation of a counter using a line of particles, which makes it possible for the line of particles to count to and store values much larger than their individual capacities. We then present an algorithm that takes a matrix and a vector as input and then sets up and uses a rectangular block of particles to compute the matrix-vector multiplication. This setup also utilizes the counter implementation to store the resulting vector from the matrix-vector multiplication. Operations such as counting and matrix multiplication can leverage the distributed and dynamic nature of the self-organizing system to be more efficient and adaptable than on traditional linear computing hardware. Such computational tools also give the systems more power to make complex decisions when adapting to new situations or to analyze the data they collect, reducing reliance on a central controller for setup and output processing. Finally, we demonstrate an application of similar types of computations with self-organizing systems to image processing, with an implementation of an image edge detection algorithm.
ContributorsPorter, Alexandra Marie (Author) / Richa, Andrea (Thesis director) / Xue, Guoliang (Committee member) / School of Music (Contributor) / Computer Science and Engineering Program (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
Manufacture of building materials requires significant energy, and as demand for these materials continues to increase, the energy requirement will as well. Offsetting this energy use will require increased focus on sustainable building materials. Further, the energy used in building, particularly in heating and air conditioning, accounts for 40 percent of a buildings energy use. Increasing the efficiency of building materials will reduce energy usage over the life time of the building. Current methods for maintaining the interior environment can be highly inefficient depending on the building materials selected. Materials such as concrete have low thermal efficiency and have a low heat capacity meaning it provides little insulation. Use of phase change materials (PCM) provides the opportunity to increase environmental efficiency of buildings by using the inherent latent heat storage as well as the increased heat capacity. Incorporating PCM into concrete via lightweight aggregates (LWA) by direct addition is seen as a viable option for increasing the thermal storage capabilities of concrete, thereby increasing building energy efficiency. As PCM change phase from solid to liquid, heat is absorbed from the surroundings, decreasing the demand on the air conditioning systems on a hot day or vice versa on a cold day. Further these materials provide an additional insulating capacity above the value of plain concrete. When the temperature drops outside the PCM turns back into a solid and releases the energy stored from the day. PCM is a hydrophobic material and causes reductions in compressive strength when incorporated directly into concrete, as shown in previous studies. A proposed method for mitigating this detrimental effect, while still incorporating PCM into concrete is to encapsulate the PCM in aggregate. This technique would, in theory, allow for the use of phase change materials directly in concrete, increasing the thermal efficiency of buildings, while negating the negative effect on compressive strength of the material.
ContributorsSharma, Breeann (Author) / Neithalath, Narayanan (Thesis advisor) / Mobasher, Barzin (Committee member) / Rajan, Subramaniam D. (Committee member) / Arizona State University (Publisher)
Created2013
Description
This dissertation considers the question of how convenient access to copious networked observational data impacts our ability to learn causal knowledge. It investigates in what ways learning causality from such data is different from -- or the same as -- the traditional causal inference which often deals with small scale i.i.d. data collected from randomized controlled trials? For example, how can we exploit network information for a series of tasks in the area of learning causality? To answer this question, the dissertation is written toward developing a suite of novel causal learning algorithms that offer actionable insights for a series of causal inference tasks with networked observational data. The work aims to benefit real-world decision-making across a variety of highly influential applications. In the first part of this dissertation, it investigates the task of inferring individual-level causal effects from networked observational data. First, it presents a representation balancing-based framework for handling the influence of hidden confounders to achieve accurate estimates of causal effects. Second, it extends the framework with an adversarial learning approach to properly combine two types of existing heuristics: representation balancing and treatment prediction. The second part of the dissertation describes a framework for counterfactual evaluation of treatment assignment policies with networked observational data. A novel framework that captures patterns of hidden confounders is developed to provide more informative input for downstream counterfactual evaluation methods. The third part presents a framework for debiasing two-dimensional grid-based e-commerce search with observational search log data where there is an implicit network connecting neighboring products in a search result page. A novel inverse propensity scoring framework that models user behavior patterns for two-dimensional display in e-commerce websites is developed, which aims to optimize online performance of ranking algorithms with offline log data.
ContributorsGuo, Ruocheng (Author) / Liu, Huan (Thesis advisor) / Candan, K. Selcuk (Committee member) / Xue, Guoliang (Committee member) / Kiciman, Emre (Committee member) / Arizona State University (Publisher)
Created2021
Description
Recent advances in cyber-physical systems, artificial intelligence, and cloud computing have driven the widespread deployment of Internet-of-Things (IoT) devices in smart homes. However, the spate of cyber attacks exploiting the vulnerabilities and weak security management of smart home IoT devices have highlighted the urgency and challenges of designing efficient mechanisms for detecting, analyzing, and mitigating security threats towards them. In this dissertation, I seek to address the security and privacy issues of smart home IoT devices from the perspectives of traffic measurement, pattern recognition, and security applications. I first propose an efficient multidimensional smart home network traffic measurement framework, which enables me to deeply understand the smart home IoT ecosystem and detect various vulnerabilities and flaws. I further design intelligent schemes to efficiently extract security-related IoT device event and user activity patterns from the encrypted smart home network traffic. Based on the knowledge of how smart home operates, different systems for securing smart home networks are proposed and implemented, including abnormal network traffic detection across multiple IoT networking protocol layers, smart home safety monitoring with extracted spatial information about IoT device events, and system-level IoT vulnerability analysis and network hardening.
ContributorsWan, Yinxin (Author) / Xue, Guoliang (Thesis advisor) / Xu, Kuai (Thesis advisor) / Yang, Yezhou (Committee member) / Zhang, Yanchao (Committee member) / Arizona State University (Publisher)
Created2023