Imaging genetics is an emerging and promising technique that investigates how genetic variations affect brain development, structure, and function. By exploiting disorder-related neuroimaging phenotypes, this class of studies provides a novel direction to reveal and understand the complex genetic mechanisms. Oftentimes, imaging genetics studies are challenging due to the relatively small number of subjects but extremely high-dimensionality of both imaging data and genomic data. In this dissertation, I carry on my research on imaging genetics with particular focuses on two tasks---building predictive models between neuroimaging data and genomic data, and identifying disorder-related genetic risk factors through image-based biomarkers. To this end, I consider a suite of structured sparse methods---that can produce interpretable models and are robust to overfitting---for imaging genetics. With carefully-designed sparse-inducing regularizers, different biological priors are incorporated into learning models. More specifically, in the Allen brain image--gene expression study, I adopt an advanced sparse coding approach for image feature extraction and employ a multi-task learning approach for multi-class annotation. Moreover, I propose a label structured-based two-stage learning framework, which utilizes the hierarchical structure among labels, for multi-label annotation. In the Alzheimer's disease neuroimaging initiative (ADNI) imaging genetics study, I employ Lasso together with EDPP (enhanced dual polytope projections) screening rules to fast identify Alzheimer's disease risk SNPs. I also adopt the tree-structured group Lasso with MLFre (multi-layer feature reduction) screening rules to incorporate linkage disequilibrium information into modeling. Moreover, I propose a novel absolute fused Lasso model for ADNI imaging genetics. This method utilizes SNP spatial structure and is robust to the choice of reference alleles of genotype coding. In addition, I propose a two-level structured sparse model that incorporates gene-level networks through a graph penalty into SNP-level model construction. Lastly, I explore a convolutional neural network approach for accurate predicting Alzheimer's disease related imaging phenotypes. Experimental results on real-world imaging genetics applications demonstrate the efficiency and effectiveness of the proposed structured sparse methods.

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.

Background
Drosophila melanogaster has been established as a model organism for investigating the developmental gene interactions. The spatio-temporal gene expression patterns of Drosophila melanogaster can be visualized by in situ hybridization and documented as digital images. Automated and efficient tools for analyzing these expression images will provide biological insights into the gene functions, interactions, and networks. To facilitate pattern recognition and comparison, many web-based resources have been created to conduct comparative analysis based on the body part keywords and the associated images. With the fast accumulation of images from high-throughput techniques, manual inspection of images will impose a serious impediment on the pace of biological discovery. It is thus imperative to design an automated system for efficient image annotation and comparison.
Results
We present a computational framework to perform anatomical keywords annotation for Drosophila gene expression images. The spatial sparse coding approach is used to represent local patches of images in comparison with the well-known bag-of-words (BoW) method. Three pooling functions including max pooling, average pooling and Sqrt (square root of mean squared statistics) pooling are employed to transform the sparse codes to image features. Based on the constructed features, we develop both an image-level scheme and a group-level scheme to tackle the key challenges in annotating Drosophila gene expression pattern images automatically. To deal with the imbalanced data distribution inherent in image annotation tasks, the undersampling method is applied together with majority vote. Results on Drosophila embryonic expression pattern images verify the efficacy of our approach.
Conclusion
In our experiment, the three pooling functions perform comparably well in feature dimension reduction. The undersampling with majority vote is shown to be effective in tackling the problem of imbalanced data. Moreover, combining sparse coding and image-level scheme leads to consistent performance improvement in keywords annotation.

A story is defined as "an actor(s) taking action(s) that culminates in a resolution(s)''. I present novel sets of features to facilitate story detection among text via supervised classification and further reveal different forms within stories via unsupervised clustering. First, I investigate the utility of a new set of semantic features compared to standard keyword features combined with statistical features, such as density of part-of-speech (POS) tags and named entities, to develop a story classifier. The proposed semantic features are based on triplets that can be extracted using a shallow parser. Experimental results show that a model of memory-based semantic linguistic features alongside statistical features achieves better accuracy. Next, I further improve the performance of story detection with a novel algorithm which aggregates the triplets producing generalized concepts and relations. A major challenge in automated text analysis is that different words are used for related concepts. Analyzing text at the surface level would treat related concepts (i.e. actors, actions, targets, and victims) as different objects, potentially missing common narrative patterns. The algorithm clusters triplets into generalized concepts by utilizing syntactic criteria based on common contexts and semantic corpus-based statistical criteria based on "contextual synonyms''. Generalized concepts representation of text (1) overcomes surface level differences (which arise when different keywords are used for related concepts) without drift, (2) leads to a higher-level semantic network representation of related stories, and (3) when used as features, they yield a significant (36%) boost in performance for the story detection task. Finally, I implement co-clustering based on generalized concepts/relations to automatically detect story forms. Overlapping generalized concepts and relationships correspond to archetypes/targets and actions that characterize story forms. I perform co-clustering of stories using standard unigrams/bigrams and generalized concepts. I show that the residual error of factorization with concept-based features is significantly lower than the error with standard keyword-based features. I also present qualitative evaluations by a subject matter expert, which suggest that concept-based features yield more coherent, distinctive and interesting story forms compared to those produced by using standard keyword-based features.

Understanding the complexity of temporal and spatial characteristics of gene expression over brain development is one of the crucial research topics in neuroscience. An accurate description of the locations and expression status of relative genes requires extensive experiment resources. The Allen Developing Mouse Brain Atlas provides a large number of in situ hybridization (ISH) images of gene expression over seven different mouse brain developmental stages. Studying mouse brain models helps us understand the gene expressions in human brains. This atlas collects about thousands of genes and now they are manually annotated by biologists. Due to the high labor cost of manual annotation, investigating an efficient approach to perform automated gene expression annotation on mouse brain images becomes necessary. In this thesis, a novel efficient approach based on machine learning framework is proposed. Features are extracted from raw brain images, and both binary classification and multi-class classification models are built with some supervised learning methods. To generate features, one of the most adopted methods in current research effort is to apply the bag-of-words (BoW) algorithm. However, both the efficiency and the accuracy of BoW are not outstanding when dealing with large-scale data. Thus, an augmented sparse coding method, which is called Stochastic Coordinate Coding, is adopted to generate high-level features in this thesis. In addition, a new multi-label classification model is proposed in this thesis. Label hierarchy is built based on the given brain ontology structure. Experiments have been conducted on the atlas and the results show that this approach is efficient and classifies the images with a relatively higher accuracy.

Software-as-a-Service (SaaS) has received significant attention in recent years as major computer companies such as Google, Microsoft, Amazon, and Salesforce are adopting this new approach to develop software and systems. Cloud computing is a computing infrastructure to enable rapid delivery of computing resources as a utility in a dynamic, scalable, and virtualized manner. Computer Simulations are widely utilized to analyze the behaviors of software and test them before fully implementations. Simulation can further benefit SaaS application in a cost-effective way taking the advantages of cloud such as customizability, configurability and multi-tendency.

This research introduces Modeling, Simulation and Analysis for Software-as-Service in Cloud. The researches cover the following topics: service modeling, policy specification, code generation, dynamic simulation, timing, event and log analysis. Moreover, the framework integrates current advantages of cloud: configurability, Multi-Tenancy, scalability and recoverability.

The following chapters are provided in the architecture:

Multi-Tenancy Simulation Software-as-a-Service.

Policy Specification for MTA simulation environment.

Model Driven PaaS Based SaaS modeling.

Dynamic analysis and dynamic calibration for timing analysis.

Event-driven Service-Oriented Simulation Framework.

LTBD: A Triage Solution for SaaS.

Discriminative learning when training and test data belong to different distributions is a challenging and complex task. Often times we have very few or no labeled data from the test or target distribution, but we may have plenty of labeled data from one or multiple related sources with different distributions. Due to its capability of migrating knowledge from related domains, transfer learning has shown to be effective for cross-domain learning problems. In this dissertation, I carry out research along this direction with a particular focus on designing efficient and effective algorithms for BioImaging and Bilingual applications. Specifically, I propose deep transfer learning algorithms which combine transfer learning and deep learning to improve image annotation performance. Firstly, I propose to generate the deep features for the Drosophila embryo images via pretrained deep models and build linear classifiers on top of the deep features. Secondly, I propose to fine-tune the pretrained model with a small amount of labeled images. The time complexity and performance of deep transfer learning methodologies are investigated. Promising results have demonstrated the knowledge transfer ability of proposed deep transfer algorithms. Moreover, I propose a novel Robust Principal Component Analysis (RPCA) approach to process the noisy images in advance. In addition, I also present a two-stage re-weighting framework for general domain adaptation problems. The distribution of source domain is mapped towards the target domain in the first stage, and an adaptive learning model is proposed in the second stage to incorporate label information from the target domain if it is available. Then the proposed model is applied to tackle cross lingual spam detection problem at LinkedIn’s website. Our experimental results on real data demonstrate the efficiency and effectiveness of the proposed algorithms.

One of the most remarkable outcomes resulting from the evolution of the web into Web 2.0, has been the propelling of blogging into a widely adopted and globally accepted phenomenon. While the unprecedented growth of the Blogosphere has added diversity and enriched the media, it has also added complexity. To cope with the relentless expansion, many enthusiastic bloggers have embarked on voluntarily writing, tagging, labeling, and cataloguing their posts in hopes of reaching the widest possible audience. Unbeknown to them, this reaching-for-others process triggers the generation of a new kind of collective wisdom, a result of shared collaboration, and the exchange of ideas, purpose, and objectives, through the formation of associations, links, and relations. Mastering an understanding of the Blogosphere can greatly help facilitate the needs of the ever growing number of these users, as well as producers, service providers, and advertisers into facilitation of the categorization and navigation of this vast environment. This work explores a novel method to leverage the collective wisdom from the infused label space for blog search and discovery. The work demonstrates that the wisdom space can provide a most unique and desirable framework to which to discover the highly sought after background information that could aid in the building of classifiers. This work incorporates this insight into the construction of a better clustering of blogs which boosts the performance of classifiers for identifying more relevant labels for blogs, and offers a mechanism that can be incorporated into replacing spurious labels and mislabels in a multi-labeled space.

Social networking services have emerged as an important platform for large-scale information sharing and communication. With the growing popularity of social media, spamming has become rampant in the platforms. Complex network interactions and evolving content present great challenges for social spammer detection. Different from some existing well-studied platforms, distinct characteristics of newly emerged social media data present new challenges for social spammer detection. First, texts in social media are short and potentially linked with each other via user connections. Second, it is observed that abundant contextual information may play an important role in distinguishing social spammers and normal users. Third, not only the content information but also the social connections in social media evolve very fast. Fourth, it is easy to amass vast quantities of unlabeled data in social media, but would be costly to obtain labels, which are essential for many supervised algorithms. To tackle those challenges raise in social media data, I focused on developing effective and efficient machine learning algorithms for social spammer detection.

I provide a novel and systematic study of social spammer detection in the dissertation. By analyzing the properties of social network and content information, I propose a unified framework for social spammer detection by collectively using the two types of information in social media. Motivated by psychological findings in physical world, I investigate whether sentiment analysis can help spammer detection in online social media. In particular, I conduct an exploratory study to analyze the sentiment differences between spammers and normal users; and present a novel method to incorporate sentiment information into social spammer detection framework. Given the rapidly evolving nature, I propose a novel framework to efficiently reflect the effect of newly emerging social spammers. To tackle the problem of lack of labeling data in social media, I study how to incorporate network information into text content modeling, and design strategies to select the most representative and informative instances from social media for labeling. Motivated by publicly available label information from other media platforms, I propose to make use of knowledge learned from cross-media to help spammer detection on social media.