Matching Items (62)
Description
The Kilombero Valley lies at the intersection of a network of protected areas that cross Tanzania. The wetlands and woodlands of the Valley, as well as the forest of surrounding mountains are abundant in biodiversity and are considered to be critical areas for conservation. This area, however, is also the home to more than a half million people, primarily poor smallholder farmers. In an effort to support the livelihoods and food security of these farmers and the larger Tanzanian population, the country has recently targeted a series of programs to increase agricultural production in the Kilombero Valley and elsewhere in the country. Bridging concepts and methods from land change science, political ecology, and sustainable livelihoods, I present an integrated assessment of the linkages between development and conservation efforts in the Kilombero Valley and the implications for food security.
This dissertation uses three empirical studies to understand the process of development in the Kilombero Valley and to link the priorities and perceptions of conservation and development efforts to the material outcomes in food security and land change. The first paper of this dissertation examines the changes in land use in the Kilombero Valley between 1997 and 2014 following the privatization of agriculture and the expansion of Tanzania’s Kilimo Kwanza program. Remote sensing analysis reveals a two-fold increase in agricultural area during this short time, largely at the expense of forest. Protected areas in some parts of the Valley appear to be deterring deforestation, but rapid agricultural growth, particularly surrounding a commercial rice plantation, has led to loss of extant forest and sustained habitat fragmentation. The second paper focuses examines livelihood strategies in the Valley and claims regarding the role of agrobiodiversity in food security.
The results of household survey reveal no difference or lower food security among households that diversify their agricultural activities. Some evidence, however, emerges regarding the importance of home gardens and crop diversification for dietary diversity. The third paper considers the competing discourses surrounding conservation and development in the Kilombero Valley. Employing q-method, this paper discerns four key viewpoints among various stakeholders in the Valley. While there are some apparently intractable distinctions between among these discourses, consensus regarding the importance of wildlife corridors and the presence of boundary-crossing individuals provide the promise of collaboration and compromise.
ContributorsConnors, John Patrick (Author) / Turner, Billie Lee (Thesis advisor) / Eakin, Hallie (Committee member) / Myint, Soe (Committee member) / Arizona State University (Publisher)
Created2015
Description
The quality of real-world visual content is typically impaired by many factors including image noise and blur. Detecting and analyzing these impairments are important steps for multiple computer vision tasks. This work focuses on perceptual-based locally adaptive noise and blur detection and their application to image restoration.
In the context of noise detection, this work proposes perceptual-based full-reference and no-reference objective image quality metrics by integrating perceptually weighted local noise into a probability summation model. Results are reported on both the LIVE and TID2008 databases. The proposed metrics achieve consistently a good performance across noise types and across databases as compared to many of the best very recent quality metrics. The proposed metrics are able to predict with high accuracy the relative amount of perceived noise in images of different content.
In the context of blur detection, existing approaches are either computationally costly or cannot perform reliably when dealing with the spatially-varying nature of the defocus blur. In addition, many existing approaches do not take human perception into account. This work proposes a blur detection algorithm that is capable of detecting and quantifying the level of spatially-varying blur by integrating directional edge spread calculation, probability of blur detection and local probability summation. The proposed method generates a blur map indicating the relative amount of perceived local blurriness. In order to detect the flat
ear flat regions that do not contribute to perceivable blur, a perceptual model based on the Just Noticeable Difference (JND) is further integrated in the proposed blur detection algorithm to generate perceptually significant blur maps. We compare our proposed method with six other state-of-the-art blur detection methods. Experimental results show that the proposed method performs the best both visually and quantitatively.
This work further investigates the application of the proposed blur detection methods to image deblurring. Two selective perceptual-based image deblurring frameworks are proposed, to improve the image deblurring results and to reduce the restoration artifacts. In addition, an edge-enhanced super resolution algorithm is proposed, and is shown to achieve better reconstructed results for the edge regions.
In the context of noise detection, this work proposes perceptual-based full-reference and no-reference objective image quality metrics by integrating perceptually weighted local noise into a probability summation model. Results are reported on both the LIVE and TID2008 databases. The proposed metrics achieve consistently a good performance across noise types and across databases as compared to many of the best very recent quality metrics. The proposed metrics are able to predict with high accuracy the relative amount of perceived noise in images of different content.
In the context of blur detection, existing approaches are either computationally costly or cannot perform reliably when dealing with the spatially-varying nature of the defocus blur. In addition, many existing approaches do not take human perception into account. This work proposes a blur detection algorithm that is capable of detecting and quantifying the level of spatially-varying blur by integrating directional edge spread calculation, probability of blur detection and local probability summation. The proposed method generates a blur map indicating the relative amount of perceived local blurriness. In order to detect the flat
ear flat regions that do not contribute to perceivable blur, a perceptual model based on the Just Noticeable Difference (JND) is further integrated in the proposed blur detection algorithm to generate perceptually significant blur maps. We compare our proposed method with six other state-of-the-art blur detection methods. Experimental results show that the proposed method performs the best both visually and quantitatively.
This work further investigates the application of the proposed blur detection methods to image deblurring. Two selective perceptual-based image deblurring frameworks are proposed, to improve the image deblurring results and to reduce the restoration artifacts. In addition, an edge-enhanced super resolution algorithm is proposed, and is shown to achieve better reconstructed results for the edge regions.
ContributorsZhu, Tong (Author) / Karam, Lina (Thesis advisor) / Li, Baoxin (Committee member) / Bliss, Daniel (Committee member) / Myint, Soe (Committee member) / Arizona State University (Publisher)
Created2016
Description
The combination of rapid urban growth and climate change places stringent constraints on multisector sustainability of cities. Green infrastructure provides a great potential for mitigating anthropogenic-induced urban environmental problems; nevertheless, studies at city and regional scales are inhibited by the deficiency in modelling the complex transport coupled water and energy inside urban canopies. This dissertation is devoted to incorporating hydrological processes and urban green infrastructure into an integrated atmosphere-urban modelling system, with the goal to improve the reliability and predictability of existing numerical tools. Based on the enhanced numerical tool, the effects of urban green infrastructure on environmental sustainability of cities are examined.
Findings indicate that the deployment of green roofs will cool the urban environment in daytime and warm it at night, via evapotranspiration and soil insulation. At the annual scale, green roofs are effective in decreasing building energy demands for both summer cooling and winter heating. For cities in arid and semiarid environments, an optimal trade-off between water and energy resources can be achieved via innovative design of smart urban irrigation schemes, enabled by meticulous analysis of the water-energy nexus. Using water-saving plants alleviates water shortage induced by population growth, but comes at the price of an exacerbated urban thermal environment. Realizing the potential water buffering capacity of urban green infrastructure is crucial for the long-term water sustainability and subsequently multisector sustainability of cities. Environmental performance of urban green infrastructure is determined by land-atmosphere interactions, geographic and meteorological conditions, and hence it is recommended that analysis should be conducted on a city-by-city basis before actual implementation of green infrastructure.
Findings indicate that the deployment of green roofs will cool the urban environment in daytime and warm it at night, via evapotranspiration and soil insulation. At the annual scale, green roofs are effective in decreasing building energy demands for both summer cooling and winter heating. For cities in arid and semiarid environments, an optimal trade-off between water and energy resources can be achieved via innovative design of smart urban irrigation schemes, enabled by meticulous analysis of the water-energy nexus. Using water-saving plants alleviates water shortage induced by population growth, but comes at the price of an exacerbated urban thermal environment. Realizing the potential water buffering capacity of urban green infrastructure is crucial for the long-term water sustainability and subsequently multisector sustainability of cities. Environmental performance of urban green infrastructure is determined by land-atmosphere interactions, geographic and meteorological conditions, and hence it is recommended that analysis should be conducted on a city-by-city basis before actual implementation of green infrastructure.
ContributorsYang, Jiachuan (Author) / Wang, Zhihua (Thesis advisor) / Kaloush, Kamil (Committee member) / Myint, Soe (Committee member) / Huang, Huei-Ping (Committee member) / Mascaro, Giuseppe (Committee member) / Arizona State University (Publisher)
Created2016
Description
Ephemeral streams in Arizona that are perpendicularly intersected by the Central Arizona Project (CAP) canal have been altered due to partial or complete damming of the stream channel. The dammed upstream channels have experienced decades long cycles of sediment deposition and waterlogging during storm events causing the development of "green-up" zones. This dissertation examines the biogeomorphological effects of damming ephemeral streams caused by the CAP canal by investigating: (1) changes in the preexisting spatial cover of riparian vegetation and how these changes are affected by stream geometry; (2) green-up initiation and evolution; and (3) changes in plant species and community level changes. To the author's knowledge, this is the only study that undertakes an interdisciplinary approach to understanding the environmental responses to anthropogenically-altered ephemeral stream channels. The results presented herein show that vegetation along the upstream section increased by an average of 200,872 m2 per kilometer of the CAP canal over a 28 year period. Vegetation growth was compared to channel widths which share a quasi-linear relationship. Remote sensing analysis of Landsat TM images using an object-oriented approach shows that riparian vegetation cover gradually increased over 28 years. Field studies reveal that the increases in vegetation are attributed to the artificial rise in local base-level upstream created by the canal, which causes water to spill laterally onto the desert floor. Vegetation within the green-up zone varies considerably in comparison to pre-canal construction. Changes are most notable in vegetation community shifts and abundance. The wettest section of the green-up zone contains the greatest density of woody plant stems, the greatest vegetation volume, and a high percentage of herbaceous cover. Vegetation within wetter zones changed from a tree-shrub to a predominantly tree-herb assemblage, whereas desert shrubs located in zones with intermediate moisture have developed larger stems. Results from this study lend valuable insight to green-up processes associated with damming ephemeral streams, which can be applied to planning future canal or dam projects in drylands. Also, understanding the development of the green-up zones provide awareness to potentially avoiding flood damage to infrastructure that may be unknowingly constructed within the slow-growing green-up zone.
ContributorsHamdan, Abeer (Author) / Schmeeckle, Mark (Thesis advisor) / Myint, Soe (Thesis advisor) / Dorn, Ronald (Committee member) / Stromberg, Juliet (Committee member) / Arizona State University (Publisher)
Created2014
Description
The processes of a human somatic cell are very complex with various genetic mechanisms governing its fate. Such cells undergo various genetic mutations, which translate to the genetic aberrations that we see in cancer. There are more than 100 types of cancer, each having many more subtypes with aberrations being unique to each. In the past two decades, the widespread application of high-throughput genomic technologies, such as micro-arrays and next-generation sequencing, has led to the revelation of many such aberrations. Known types and subtypes can be readily identified using gene-expression profiling and more importantly, high-throughput genomic datasets have helped identify novel sub-types with distinct signatures. Recent studies showing usage of gene-expression profiling in clinical decision making in breast cancer patients underscore the utility of high-throughput datasets. Beyond prognosis, understanding the underlying cellular processes is essential for effective cancer treatment. Various high-throughput techniques are now available to look at a particular aspect of a genetic mechanism in cancer tissue. To look at these mechanisms individually is akin to looking at a broken watch; taking apart each of its parts, looking at them individually and finally making a list of all the faulty ones. Integrative approaches are needed to transform one-dimensional cancer signatures into multi-dimensional interaction and regulatory networks, consequently bettering our understanding of cellular processes in cancer. Here, I attempt to (i) address ways to effectively identify high quality variants when multiple assays on the same sample samples are available through two novel tools, snpSniffer and NGSPE; (ii) glean new biological insight into multiple myeloma through two novel integrative analysis approaches making use of disparate high-throughput datasets. While these methods focus on multiple myeloma datasets, the informatics approaches are applicable to all cancer datasets and will thus help advance cancer genomics.
ContributorsYellapantula, Venkata (Author) / Dinu, Valentin (Thesis advisor) / Scotch, Matthew (Committee member) / Wallstrom, Garrick (Committee member) / Keats, Jonathan (Committee member) / Arizona State University (Publisher)
Created2014
Description
Genomic structural variation (SV) is defined as gross alterations in the genome broadly classified as insertions/duplications, deletions inversions and translocations. DNA sequencing ushered structural variant discovery beyond laboratory detection techniques to high resolution informatics approaches. Bioinformatics tools for computational discovery of SVs however are still missing variants in the complex cancer genome. This study aimed to define genomic context leading to tool failure and design novel algorithm addressing this context. Methods: The study tested the widely held but unproven hypothesis that tools fail to detect variants which lie in repeat regions. Publicly available 1000-Genomes dataset with experimentally validated variants was tested with SVDetect-tool for presence of true positives (TP) SVs versus false negative (FN) SVs, expecting that FNs would be overrepresented in repeat regions. Further, the novel algorithm designed to informatically capture the biological etiology of translocations (non-allelic homologous recombination and 3&ndashD; placement of chromosomes in cells –context) was tested using simulated dataset. Translocations were created in known translocation hotspots and the novel&ndashalgorithm; tool compared with SVDetect and BreakDancer. Results: 53% of false negative (FN) deletions were within repeat structure compared to 81% true positive (TP) deletions. Similarly, 33% FN insertions versus 42% TP, 26% FN duplication versus 57% TP and 54% FN novel sequences versus 62% TP were within repeats. Repeat structure was not driving the tool's inability to detect variants and could not be used as context. The novel algorithm with a redefined context, when tested against SVDetect and BreakDancer was able to detect 10/10 simulated translocations with 30X coverage dataset and 100% allele frequency, while SVDetect captured 4/10 and BreakDancer detected 6/10. For 15X coverage dataset with 100% allele frequency, novel algorithm was able to detect all ten translocations albeit with fewer reads supporting the same. BreakDancer detected 4/10 and SVDetect detected 2/10 Conclusion: This study showed that presence of repetitive elements in general within a structural variant did not influence the tool's ability to capture it. This context-based algorithm proved better than current tools even with half the genome coverage than accepted protocol and provides an important first step for novel translocation discovery in cancer genome.
ContributorsShetty, Sheetal (Author) / Dinu, Valentin (Thesis advisor) / Bussey, Kimberly (Committee member) / Scotch, Matthew (Committee member) / Wallstrom, Garrick (Committee member) / Arizona State University (Publisher)
Created2014
Description
Skeletal muscle (SM) mitochondria generate the majority of adenosine triphosphate (ATP) in SM, and help regulate whole-body energy expenditure. Obesity is associated with alterations in SM mitochondria, which are unique with respect to their arrangement within cells; some mitochondria are located directly beneath the sarcolemma (i.e., subsarcolemmal (SS) mitochondria), while other are nested between the myofibrils (i.e., intermyofibrillar (IMF) mitochondria). Functional and proteome differences specific to SS versus IMF mitochondria in obese individuals may contribute to reduced capacity for muscle ATP production seen in obesity. The overall goals of this work were to (1) isolate functional muscle SS and IMF mitochondria from lean and obese individuals, (2) assess enzyme activities associated with the electron transport chain and ATP production, (3) determine if elevated plasma amino acids enhance SS and IMF mitochondrial respiration and ATP production rates in SM of obese humans, and (4) determine differences in mitochondrial proteome regulating energy metabolism and key biological processes associated with SS and IMF mitochondria between lean and obese humans.
Polarography was used to determine functional differences in isolated SS and IMF mitochondria between lean (37 ± 3 yrs; n = 10) and obese (35 ± 3 yrs; n = 11) subjects during either saline (control) or amino acid (AA) infusions. AA infusion increased ADP-stimulated respiration (i.e., coupled respiration), non-ADP stimulated respiration (i.e., uncoupled respiration), and ATP production rates in SS, but not IMF mitochondria in lean (n = 10; P < 0.05). Neither infusion increased any of the above parameters in muscle SS or IMF mitochondria of the obese subjects.
Using label free quantitative mass spectrometry, we determined differences in proteomes of SM SS and IMF mitochondria between lean (33 ± 3 yrs; n = 16) and obese (32 ± 3 yrs; n = 17) subjects. Differentially-expressed mitochondrial proteins in SS versus IMF mitochondria of obese subjects were associated with biological processes that regulate: electron transport chain (P<0.0001), citric acid cycle (P<0.0001), oxidative phosphorylation (P<0.001), branched-chain amino acid degradation, (P<0.0001), and fatty acid degradation (P<0.001). Overall, these findings show that obesity is associated with redistribution of key biological processes within the mitochondrial reticulum responsible for regulating energy metabolism in human skeletal muscle.
Polarography was used to determine functional differences in isolated SS and IMF mitochondria between lean (37 ± 3 yrs; n = 10) and obese (35 ± 3 yrs; n = 11) subjects during either saline (control) or amino acid (AA) infusions. AA infusion increased ADP-stimulated respiration (i.e., coupled respiration), non-ADP stimulated respiration (i.e., uncoupled respiration), and ATP production rates in SS, but not IMF mitochondria in lean (n = 10; P < 0.05). Neither infusion increased any of the above parameters in muscle SS or IMF mitochondria of the obese subjects.
Using label free quantitative mass spectrometry, we determined differences in proteomes of SM SS and IMF mitochondria between lean (33 ± 3 yrs; n = 16) and obese (32 ± 3 yrs; n = 17) subjects. Differentially-expressed mitochondrial proteins in SS versus IMF mitochondria of obese subjects were associated with biological processes that regulate: electron transport chain (P<0.0001), citric acid cycle (P<0.0001), oxidative phosphorylation (P<0.001), branched-chain amino acid degradation, (P<0.0001), and fatty acid degradation (P<0.001). Overall, these findings show that obesity is associated with redistribution of key biological processes within the mitochondrial reticulum responsible for regulating energy metabolism in human skeletal muscle.
ContributorsKras, Katon Anthony (Author) / Katsanos, Christos (Thesis advisor) / Chandler, Douglas (Committee member) / Dinu, Valentin (Committee member) / Mor, Tsafrir S. (Committee member) / Arizona State University (Publisher)
Created2017
Description
Random forest (RF) is a popular and powerful technique nowadays. It can be used for classification, regression and unsupervised clustering. In its original form introduced by Leo Breiman, RF is used as a predictive model to generate predictions for new observations. Recent researches have proposed several methods based on RF for feature selection and for generating prediction intervals. However, they are limited in their applicability and accuracy. In this dissertation, RF is applied to build a predictive model for a complex dataset, and used as the basis for two novel methods for biomarker discovery and generating prediction interval.
Firstly, a biodosimetry is developed using RF to determine absorbed radiation dose from gene expression measured from blood samples of potentially exposed individuals. To improve the prediction accuracy of the biodosimetry, day-specific models were built to deal with day interaction effect and a technique of nested modeling was proposed. The nested models can fit this complex data of large variability and non-linear relationships.
Secondly, a panel of biomarkers was selected using a data-driven feature selection method as well as handpick, considering prior knowledge and other constraints. To incorporate domain knowledge, a method called Know-GRRF was developed based on guided regularized RF. This method can incorporate domain knowledge as a penalized term to regulate selection of candidate features in RF. It adds more flexibility to data-driven feature selection and can improve the interpretability of models. Know-GRRF showed significant improvement in cross-species prediction when cross-species correlation was used to guide selection of biomarkers. The method can also compete with existing methods using intrinsic data characteristics as alternative of domain knowledge in simulated datasets.
Lastly, a novel non-parametric method, RFerr, was developed to generate prediction interval using RF regression. This method is widely applicable to any predictive models and was shown to have better coverage and precision than existing methods on the real-world radiation dataset, as well as benchmark and simulated datasets.
Firstly, a biodosimetry is developed using RF to determine absorbed radiation dose from gene expression measured from blood samples of potentially exposed individuals. To improve the prediction accuracy of the biodosimetry, day-specific models were built to deal with day interaction effect and a technique of nested modeling was proposed. The nested models can fit this complex data of large variability and non-linear relationships.
Secondly, a panel of biomarkers was selected using a data-driven feature selection method as well as handpick, considering prior knowledge and other constraints. To incorporate domain knowledge, a method called Know-GRRF was developed based on guided regularized RF. This method can incorporate domain knowledge as a penalized term to regulate selection of candidate features in RF. It adds more flexibility to data-driven feature selection and can improve the interpretability of models. Know-GRRF showed significant improvement in cross-species prediction when cross-species correlation was used to guide selection of biomarkers. The method can also compete with existing methods using intrinsic data characteristics as alternative of domain knowledge in simulated datasets.
Lastly, a novel non-parametric method, RFerr, was developed to generate prediction interval using RF regression. This method is widely applicable to any predictive models and was shown to have better coverage and precision than existing methods on the real-world radiation dataset, as well as benchmark and simulated datasets.
ContributorsGuan, Xin (Author) / Liu, Li (Thesis advisor) / Runger, George C. (Thesis advisor) / Dinu, Valentin (Committee member) / Arizona State University (Publisher)
Created2017
Description
Obesity and its underlying insulin resistance are caused by environmental and genetic factors. DNA methylation provides a mechanism by which environmental factors can regulate transcriptional activity. The overall goal of the work herein was to (1) identify alterations in DNA methylation in human skeletal muscle with obesity and its underlying insulin resistance, (2) to determine if these changes in methylation can be altered through weight-loss induced by bariatric surgery, and (3) to identify DNA methylation biomarkers in whole blood that can be used as a surrogate for skeletal muscle.
Assessment of DNA methylation was performed on human skeletal muscle and blood using reduced representation bisulfite sequencing (RRBS) for high-throughput identification and pyrosequencing for site-specific confirmation. Sorbin and SH3 homology domain 3 (SORBS3) was identified in skeletal muscle to be increased in methylation (+5.0 to +24.4 %) in the promoter and 5’untranslated region (UTR) in the obese participants (n= 10) compared to lean (n=12), and this finding corresponded with a decrease in gene expression (fold change: -1.9, P=0.0001). Furthermore, SORBS3 was demonstrated in a separate cohort of morbidly obese participants (n=7) undergoing weight-loss induced by surgery, to decrease in methylation (-5.6 to -24.2%) and increase in gene expression (fold change: +1.7; P=0.05) post-surgery. Moreover, SORBS3 promoter methylation was demonstrated in vitro to inhibit transcriptional activity (P=0.000003). The methylation and transcriptional changes for SORBS3 were significantly (P≤0.05) correlated with obesity measures and fasting insulin levels. SORBS3 was not identified in the blood methylation analysis of lean (n=10) and obese (n=10) participants suggesting that it is a muscle specific marker. However, solute carrier family 19 member 1 (SLC19A1) was identified in blood and skeletal muscle to have decreased 5’UTR methylation in obese participants, and this was significantly (P≤0.05) predicted by insulin sensitivity.
These findings suggest SLC19A1 as a potential blood-based biomarker for obese, insulin resistant states. The collective findings of SORBS3 DNA methylation and gene expression present an exciting novel target in skeletal muscle for further understanding obesity and its underlying insulin resistance. Moreover, the dynamic changes to SORBS3 in response to metabolic improvements and weight-loss induced by surgery.
Assessment of DNA methylation was performed on human skeletal muscle and blood using reduced representation bisulfite sequencing (RRBS) for high-throughput identification and pyrosequencing for site-specific confirmation. Sorbin and SH3 homology domain 3 (SORBS3) was identified in skeletal muscle to be increased in methylation (+5.0 to +24.4 %) in the promoter and 5’untranslated region (UTR) in the obese participants (n= 10) compared to lean (n=12), and this finding corresponded with a decrease in gene expression (fold change: -1.9, P=0.0001). Furthermore, SORBS3 was demonstrated in a separate cohort of morbidly obese participants (n=7) undergoing weight-loss induced by surgery, to decrease in methylation (-5.6 to -24.2%) and increase in gene expression (fold change: +1.7; P=0.05) post-surgery. Moreover, SORBS3 promoter methylation was demonstrated in vitro to inhibit transcriptional activity (P=0.000003). The methylation and transcriptional changes for SORBS3 were significantly (P≤0.05) correlated with obesity measures and fasting insulin levels. SORBS3 was not identified in the blood methylation analysis of lean (n=10) and obese (n=10) participants suggesting that it is a muscle specific marker. However, solute carrier family 19 member 1 (SLC19A1) was identified in blood and skeletal muscle to have decreased 5’UTR methylation in obese participants, and this was significantly (P≤0.05) predicted by insulin sensitivity.
These findings suggest SLC19A1 as a potential blood-based biomarker for obese, insulin resistant states. The collective findings of SORBS3 DNA methylation and gene expression present an exciting novel target in skeletal muscle for further understanding obesity and its underlying insulin resistance. Moreover, the dynamic changes to SORBS3 in response to metabolic improvements and weight-loss induced by surgery.
ContributorsDay, Samantha Elaine (Author) / Coletta, Dawn K. (Thesis advisor) / Katsanos, Christos (Committee member) / Mandarino, Lawrence J. (Committee member) / Shaibi, Gabriel Q. (Committee member) / Dinu, Valentin (Committee member) / Arizona State University (Publisher)
Created2017
Description
Rewired biological pathways and/or rewired microRNA (miRNA)-mRNA interactions might also influence the activity of biological pathways. Here, rewired biological pathways is defined as differential (rewiring) effect of genes on the topology of biological pathways between controls and cases. Similarly, rewired miRNA-mRNA interactions are defined as the differential (rewiring) effects of miRNAs on the topology of biological pathways between controls and cases. In the dissertation, it is discussed that how rewired biological pathways (Chapter 1) and/or rewired miRNA-mRNA interactions (Chapter 2) aberrantly influence the activity of biological pathways and their association with disease.
This dissertation proposes two PageRank-based analytical methods, Pathways of Topological Rank Analysis (PoTRA) and miR2Pathway, discussed in Chapter 1 and Chapter 2, respectively. PoTRA focuses on detecting pathways with an altered number of hub genes in corresponding pathways between two phenotypes. The basis for PoTRA is that the loss of connectivity is a common topological trait of cancer networks, as well as the prior knowledge that a normal biological network is a scale-free network whose degree distribution follows a power law where a small number of nodes are hubs and a large number of nodes are non-hubs. However, from normal to cancer, the process of the network losing connectivity might be the process of disrupting the scale-free structure of the network, namely, the number of hub genes might be altered in cancer compared to that in normal samples. Hence, it is hypothesized that if the number of hub genes is different in a pathway between normal and cancer, this pathway might be involved in cancer. MiR2Pathway focuses on quantifying the differential effects of miRNAs on the activity of a biological pathway when miRNA-mRNA connections are altered from normal to disease and rank disease risk of rewired miRNA-mediated biological pathways. This dissertation explores how rewired gene-gene interactions and rewired miRNA-mRNA interactions lead to aberrant activity of biological pathways, and rank pathways for their disease risk. The two methods proposed here can be used to complement existing genomics analysis methods to facilitate the study of biological mechanisms behind disease at the systems-level.
This dissertation proposes two PageRank-based analytical methods, Pathways of Topological Rank Analysis (PoTRA) and miR2Pathway, discussed in Chapter 1 and Chapter 2, respectively. PoTRA focuses on detecting pathways with an altered number of hub genes in corresponding pathways between two phenotypes. The basis for PoTRA is that the loss of connectivity is a common topological trait of cancer networks, as well as the prior knowledge that a normal biological network is a scale-free network whose degree distribution follows a power law where a small number of nodes are hubs and a large number of nodes are non-hubs. However, from normal to cancer, the process of the network losing connectivity might be the process of disrupting the scale-free structure of the network, namely, the number of hub genes might be altered in cancer compared to that in normal samples. Hence, it is hypothesized that if the number of hub genes is different in a pathway between normal and cancer, this pathway might be involved in cancer. MiR2Pathway focuses on quantifying the differential effects of miRNAs on the activity of a biological pathway when miRNA-mRNA connections are altered from normal to disease and rank disease risk of rewired miRNA-mediated biological pathways. This dissertation explores how rewired gene-gene interactions and rewired miRNA-mRNA interactions lead to aberrant activity of biological pathways, and rank pathways for their disease risk. The two methods proposed here can be used to complement existing genomics analysis methods to facilitate the study of biological mechanisms behind disease at the systems-level.
ContributorsLi, Chaoxing (Author) / Dinu, Valentin (Thesis advisor) / Kuang, Yang (Thesis advisor) / Liu, Li (Committee member) / Wang, Xiao (Committee member) / Arizona State University (Publisher)
Created2017