Modeling data distributions is a fundamental aspect of machine learning, encompassing both discriminative modeling, which focuses on building predictive models, and generative modeling, which aims to synthesize new data that mirrors existing distributions.

The emergence of large language models in text generation has markedly transformed our technological environment, significantly impacting our daily digital interactions.

In this dissertation, we combined artificial intelligence and machine/deep learning with chemical and biological properties to develop several computational methods to solve biomedical domain problems, specifically drug repositioning, and demonstrated their efficiencies and capabilities. We developed three network-based DTI prediction methods using machine learning, graph embedding, and graph mining. These methods significantly improved prediction performance, and the best-performing method even reduces the error rate by more than 33% across all datasets compared to the best state-of-the-art method. As it is more insightful to predict continuous values that indicate how tightly the drug binds to a specific target, we conducted a comparison study of current regression-based methods that predict drug-target binding affinities (DTBA). Our methods demonstrated their efficiency and capability by achieving high prediction performance and identifying therapeutic targets for several cancer types. We further conducted a lung cancer case study of findings that support the novel predicted targets.

In this talk, I will first give an overview of the research activities in Structural and Functional Bioinformatics Group (http://sfb.kaust.edu.sa). I will then focus on our efforts on developing computational methods to tackle key open problems in Nanopore sequencing. In particular, I will introduce our recent works on developing a collection of computational methods to decode raw electrical current signal sequences into DNA sequences, to simulate raw signals of Nanopore, and to efficiently and accurately align electrical current signal sequences with DNA sequences. I will further introduce their applications in biomedicine and healthcare.

Biological knowledge is widely represented in the form of ontologies and ontology-based annotations. The structure and information contained in ontologies and their annotations make them valuable for use in machine learning, data analysis and knowledge extraction tasks. In this thesis, we propose the first approaches that can exploit all of the information encoded in ontologies, both formal and informal, to learn feature embeddings of biological concepts and biological entities based on their annotations to ontologies by applying transfer learning on the literature. To optimize learning that combines ontologies and natural language data such as the literature, we also propose a new approach that uses self-normalization with a deep Siamese neural network to improve learning from both the formal knowledge within ontologies and textual data. We validate the proposed algorithms by applying them to generate feature representations of proteins, and of genes and diseases.

In this dissertation, I present the methods I have developed for prediction of promoters for different organisms. Instead of focusing on the classification accuracy of the discrimination between promoter and non-promoter sequences, I predict the exact positions of the TSS inside the genomic sequences, testing every possible location. The developed methods significantly outperform the previous promoter prediction programs by considerably reducing the number of false positive predictions. Specifically, to reduce the false positive rate, the models are adaptively and iteratively trained by changing the distribution of samples in the training set based on the false positive errors made in the previous iteration. The new methods are used to gain insights into the design principles of the core promoters. Using model analysis, I have identified the most important core promoter elements and their effect on the promoter activity. I have developed a novel general approach to detect long range interactions in the input of a deep learning model, which was used to find related positions inside the promoter region. The final model was applied to the genomes of different species without a significant drop in the performance, demonstrating a high generality of the developed method.

With the advances in transcriptomic analysis, the monitoring of genome-wide gene expression provides a powerful approach for determining the action of drugs. In this thesis, we analyzed the transcriptional responses of cells treated with drugs either alone or in combinations to explore their effects in two different applications: breast cancer therapy and cell conversion.

Promoter is a key region that is involved in differential transcription regulation of protein-coding and RNA genes. The gene-specific architecture of promoter sequences makes it extremely difficult to devise the general strategy for their computational identification.

Malaria kills nearly one-half million people a year and over 1 billion people are at risk of becoming infected by the parasite. Plasmodial infections are difficult to treat for a myriad of reasons, but the ability of the organism to remain latent in hosts and the complex life cycles greatly contributed to the difficulty in treat malaria.

Malaria kills nearly one-half million people a year and over 1 billion people are at risk of becoming infected by the parasite. Plasmodial infections are difficult to treat for a myriad of reasons, but the ability of the organism to remain latent in hosts and the complex life cycles greatly contributed to the difficulty in treat malaria.

Biological knowledge is widely represented in the form of ontology-based annotations: ontologies describe the phenomena assumed to exist within a domain, and the annotations associate a biological entity with a set of phenomena within the domain.

Recent advances in genome editing and metabolic engineering enabled a precise construction of de novo biosynthesis pathways for high-value natural products. One important design decision to make for the engineering of heterologous biosynthesis systems is concerned with which foreign metabolic genes to introduce into a given host organism.

Drug combination therapy for the treatment of cancers and other multifactorial diseases has the potential of increasing the therapeutic effect while reducing the likelihood of drug resistance. In order to reduce the time and cost spent on comprehensive screens, methods are needed which can model additive effects of possible drug combinations.

Recent advances in genome editing and metabolic engineering enabled a precise construction of de novo biosynthesis pathways for high-value natural products. One important design decision to make for the engineering of heterologous biosynthesis systems is concerned with which foreign metabolic genes to introduce into a given host organism.

In silico prioritization of undiscovered associations can help find causal genes of newly discovered diseases. Some existing methods are based on known associations and side information of diseases and genes. We exploit the possibility of using a neural network model, Neural Inductive Matrix Completion (NIMC) in disease-gene prediction.

We are now in the fourth paradigm of science: Data Science. The massive amount of structured and unstructured data has posed new challenges and opportunities to the fields of computer science and statistics. Traditional computational and statistical methods for data storage, curation, sharing, querying, updating, visualization, analysis, and privacy have been shown to fail in the big data scenario due to the unprecedented volume, velocity, variety, veracity and value of the big data. This conference will bring together a number of prominent researchers in Computer Science and Statistics with common interests and active research in big data, as well as the researchers at KAUST who regularly generate or face big data, such as those in bioscience and red sea research.

Growth phenotype profiling of genome-wide gene-deletion strains overstresses conditions can offer a clear picture that the essentiality of genes depends on environmental conditions. In this dissertation, we first demonstrate that detecting such "co-fit" gene groups can be cast as a less well-studied problem in biclustering, i.e., constant-column biclustering. Despite significant advances in biclustering techniques, very few were designed for mining in growth phenotype data.