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Identifying chemical compounds that inhibit bacterial infection has recently gained a considerable amount of attention given the increased number of highly resistant bacteria and the serious health threat it poses around the world. With the development of automated microscopy and image analysis systems, the process of identifying novel therapeutic drugs

Identifying chemical compounds that inhibit bacterial infection has recently gained a considerable amount of attention given the increased number of highly resistant bacteria and the serious health threat it poses around the world. With the development of automated microscopy and image analysis systems, the process of identifying novel therapeutic drugs can generate an immense amount of data - easily reaching terabytes worth of information. Despite increasing the vast amount of data that is currently generated, traditional analytical methods have not increased the overall success rate of identifying active chemical compounds that eventually become novel therapeutic drugs. Moreover, multispectral imaging has become ubiquitous in drug discovery due to its ability to provide valuable information on cellular and sub-cellular processes using florescent reagents. These reagents are often costly and toxic to cells over an extended period of time causing limitations in experimental design. Thus, there is a significant need to develop a more efficient process of identifying active chemical compounds.

This dissertation introduces novel machine learning methods based on parallelized cellomics to analyze interactions between cells, bacteria, and chemical compounds while reducing the use of fluorescent reagents. Machine learning analysis using image-based high-content screening (HCS) data is compartmentalized into three primary components: (1) \textit{Image Analytics}, (2) \textit{Phenotypic Analytics}, and (3) \textit{Compound Analytics}. A novel software analytics tool called the Insights project is also introduced. The Insights project fully incorporates distributed processing, high performance computing, and database management that can rapidly and effectively utilize and store massive amounts of data generated using HCS biological assessments (bioassays). It is ideally suited for parallelized cellomics in high dimensional space.

Results demonstrate that a parallelized cellomics approach increases the quality of a bioassay while vastly decreasing the need for control data. The reduction in control data leads to less fluorescent reagent consumption. Furthermore, a novel proposed method that uses single-cell data points is proven to identify known active chemical compounds with a high degree of accuracy, despite traditional quality control measurements indicating the bioassay to be of poor quality. This, ultimately, decreases the time and resources needed in optimizing bioassays while still accurately identifying active compounds.
ContributorsTrevino, Robert (Author) / Liu, Huan (Thesis advisor) / Lamkin, Thomas J (Committee member) / He, Jingrui (Committee member) / Lee, Joohyung (Committee member) / Arizona State University (Publisher)
Created2016
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Description
The rapid growth in the high-throughput technologies last few decades makes the manual processing of the generated data to be impracticable. Even worse, the machine learning and data mining techniques seemed to be paralyzed against these massive datasets. High-dimensionality is one of the most common challenges for machine learning and

The rapid growth in the high-throughput technologies last few decades makes the manual processing of the generated data to be impracticable. Even worse, the machine learning and data mining techniques seemed to be paralyzed against these massive datasets. High-dimensionality is one of the most common challenges for machine learning and data mining tasks. Feature selection aims to reduce dimensionality by selecting a small subset of the features that perform at least as good as the full feature set. Generally, the learning performance, e.g. classification accuracy, and algorithm complexity are used to measure the quality of the algorithm. Recently, the stability of feature selection algorithms has gained an increasing attention as a new indicator due to the necessity to select similar subsets of features each time when the algorithm is run on the same dataset even in the presence of a small amount of perturbation. In order to cure the selection stability issue, we should understand the cause of instability first. In this dissertation, we will investigate the causes of instability in high-dimensional datasets using well-known feature selection algorithms. As a result, we found that the stability mostly data-dependent. According to these findings, we propose a framework to improve selection stability by solving these main causes. In particular, we found that data noise greatly impacts the stability and the learning performance as well. So, we proposed to reduce it in order to improve both selection stability and learning performance. However, current noise reduction approaches are not able to distinguish between data noise and variation in samples from different classes. For this reason, we overcome this limitation by using Supervised noise reduction via Low Rank Matrix Approximation, SLRMA for short. The proposed framework has proved to be successful on different types of datasets with high-dimensionality, such as microarrays and images datasets. However, this framework cannot handle unlabeled, hence, we propose Local SVD to overcome this limitation.
ContributorsAlelyani, Salem (Author) / Liu, Huan (Thesis advisor) / Xue, Guoliang (Committee member) / Ye, Jieping (Committee member) / Zhao, Zheng (Committee member) / Arizona State University (Publisher)
Created2013
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Description
Attributes - that delineating the properties of data, and connections - that describing the dependencies of data, are two essential components to characterize most real-world phenomena. The synergy between these two principal elements renders a unique data representation - the attributed networks. In many cases, people are inundated with vast

Attributes - that delineating the properties of data, and connections - that describing the dependencies of data, are two essential components to characterize most real-world phenomena. The synergy between these two principal elements renders a unique data representation - the attributed networks. In many cases, people are inundated with vast amounts of data that can be structured into attributed networks, and their use has been attractive to researchers and practitioners in different disciplines. For example, in social media, users interact with each other and also post personalized content; in scientific collaboration, researchers cooperate and are distinct from peers by their unique research interests; in complex diseases studies, rich gene expression complements to the gene-regulatory networks. Clearly, attributed networks are ubiquitous and form a critical component of modern information infrastructure. To gain deep insights from such networks, it requires a fundamental understanding of their unique characteristics and be aware of the related computational challenges.

My dissertation research aims to develop a suite of novel learning algorithms to understand, characterize, and gain actionable insights from attributed networks, to benefit high-impact real-world applications. In the first part of this dissertation, I mainly focus on developing learning algorithms for attributed networks in a static environment at two different levels: (i) attribute level - by designing feature selection algorithms to find high-quality features that are tightly correlated with the network topology; and (ii) node level - by presenting network embedding algorithms to learn discriminative node embeddings by preserving node proximity w.r.t. network topology structure and node attribute similarity. As changes are essential components of attributed networks and the results of learning algorithms will become stale over time, in the second part of this dissertation, I propose a family of online algorithms for attributed networks in a dynamic environment to continuously update the learning results on the fly. In fact, developing application-aware learning algorithms is more desired with a clear understanding of the application domains and their unique intents. As such, in the third part of this dissertation, I am also committed to advancing real-world applications on attributed networks by incorporating the objectives of external tasks into the learning process.
ContributorsLi, Jundong (Author) / Liu, Huan (Thesis advisor) / Faloutsos, Christos (Committee member) / He, Jingrui (Committee member) / Xue, Guoliang (Committee member) / Arizona State University (Publisher)
Created2019