Systems Biology Commons^™

Ai-Powered Multi-Omics Integration For Predictive Modeling Of Genotype-Environment-Phenotype Relationships, You Wu

Dissertations, Theses, and Capstone Projects

This dissertation presents a series of machine learning frameworks for modeling genotype–environment–phenotype relationships through integrative predictive modeling of multi-omics data. The work addresses three major axes of biological complexity: modeling biological information transmission cross-levels from genes to proteins to phenotypes, predicting molecular features cross-scale from cells to tissues to organisms, and translating phenotypes cross-species from model systems to humans. Each proposed method also tackles key machine learning (ML) challenges in the biomedical domain, including data scarcity, domain shift, out-of-distribution (OOD) generalization, and hierarchical modeling. Specifically, this dissertation introduces five novel deep learning algorithms: MultiDCP predicts drug-induced transcriptomic and viability responses …

Taming Biological Complexity Through The Use Of Symmetries, Luis A. Álvarez-García

Dissertations, Theses, and Capstone Projects

The study of biological systems is, inherently, the study of very complex systems. This is essentially due to the fact that they are made up of numerous, often very complicated, interactions between an extensive number of components. Often necessitating an abundance of quantitative parameters and details for a precise description. The human brain for ex- ample, consisting of ∼ 80 billion neurons with ∼ 800 to 100 trillion connections between them, each of them depending on a large set of parameters. Even simpler examples such as bacterial organisms, such as E. coli and B. subtilis, which we focus on …

Attenuated Typicality Effect In Category-Based Inferences: Implications For Autism Spectrum Disorder, Janani Rajagopalan

Dissertations, Theses, and Capstone Projects

Individuals diagnosed with Autism Spectrum Disorder (ASD) often encounter challenges in assimilating atypical exemplars into their categorical prototypes, a cognitive hurdle that can impact their interpretative and integrative capacities. Addressing this problem, the present research sought to develop a robust methodological approach to reduce the effect of this disparity. We examined the elements embedded within the category's internal structure, with the intention of experimentally attenuating the pronounced typicality effect, which is often exaggerated in ASD.

Across four experiments, the thesis investigated the cognitive and neural underpinnings that shape the access to the typicality gradient intrinsic to a category's structure. The …

Fine Characterization Of Leafing Phenology In The Brazilian Atlantic Forest By Optical And Microwave Remote Sensing, James B. Bell

Dissertations and Theses

Tropical forests provide important ecosystem functions in the global biosphere, but they remain among the most poorly understood elements of land surface models, especially with regard to their seasonal dynamics. For instance, in seasonally dry forests, the pattern of the annual green-up in their canopies closely follows annual patterns of rainfall. The same, however, does not occur in wet forest canopies which are dominated by evergreen trees. In the latter, water is not scarce enough to limit leaf photosynthetic function. Canopy leafing phenology in these forests is therefore poorly characterized by optical remote sensing methods which are not sensitive to …

Prenatal Choline Supplementation During Maternal Obesity Alters Offspring Response To Western Diets, Hunter W. Korsmo

Dissertations, Theses, and Capstone Projects

Maternal obesity has led to an increase in adverse offspring developmental outcomes and a greater risk for long-term metabolic diseases. Choline, a semi-essential nutrient, can be incorporated into phosphatidylcholine (PC) as well as sphingomyelin (SM) and donate its labile methyl group for the remethylation of homocysteine after choline is oxidized to betaine. Prenatal choline insufficiency has been related to maternal obesity and metabolic diseases, such as metabolic associated fatty liver disease (MAFLD). Choline may interact with maternal obesity to influence the programming offspring.

Chapter 1 presents an introduction of choline and the various clinical outcomes associated with choline supplementation during …

Symmetry-Inspired Analysis Of Biological Networks, Ian Leifer

Dissertations, Theses, and Capstone Projects

The description of a complex system like gene regulation of a cell or a brain of an animal in terms of the dynamics of each individual element is an insurmountable task due to the complexity of interactions and the scores of associated parameters. Recent decades brought about the description of these systems that employs network models. In such models the entire system is represented by a graph encapsulating a set of independently functioning objects and their interactions. This creates a level of abstraction that makes the analysis of such large scale system possible. Common practice is to draw conclusions about …

Three Lc-Ms Plant Metabolomics Studies Of Hop (Humulus) Species: Wild H. Neomexicanus, Drought Stress, And Agricultural Terroir, Taylan Morcol

Dissertations, Theses, and Capstone Projects

The hop plant (Humulus L., Cannabaceae) is a dioecious, perennial, twining vine with a long history of human use. Nowadays, hop plants are generally grown for their inflorescences (“cones”), which are used in brewing for their phytochemical metabolites. Many of these metabolites are involved in plant stress response and communication. Genetics and environment are two major factors that affect plant metabolism. In three separate metabolomics studies, this project examined the effects of both genetic and environmental factors on hop phytochemistry.

In the first study, 23 hop genotypes were grown in two different locations in the Pacific Northwest region of …

Resilience: Insights From The U.S. Longterm Ecological Research Network, Jane Cowles, Laura Templeton, John J. Battles, Peter J. Edmunds, Robert C. Carpenter, Stephen R. Carpenter, Michael Paul Nelson, Natalie L. Cleavitt, Timothy J. Fahey, Peter M. Groffman, Joe H. Sullivan, Maile C. Neel, Gretchen J. A. Hansen, Sarah Hobbie, Sally J. Holbrook, Clare E. Kazanski, Eric W. Seabloom, Russell J. Schmitt, Emily H. Stanley, Alan J. Tepley, Natalie S. Van Doorn, Jake M. Vander Zanden

Advanced Science Research Center

Ecosystems are changing in complex and unpredictable ways, and analysis of these changes is facilitated by coordinated, long-term research. Meeting diverse societal needs requires an understanding of what populations and communities will be dominant in 20, 50, and 100 yr. This paper is a product of a synthesis effort of the U.S. National Science Foundation funded Long-Term Ecological Research (LTER) network addressing the LTER core research area of populations and communities. This analysis revealed that each LTER site had at least one compelling story about what their site would look like in 50 or 100 yr. As the stories were …

A New Mathematical Theory For The Dynamics Of Large Tumor Populations, A Potential Mechanism For Cancer Dormancy & Recurrence And Experimental Observation Of Melanoma Progression In Zebrafish, Adeyinka A. Lesi

Dissertations and Theses

Cancer, a family of over a hundred disease varieties, results in 600,000 deaths in the U.S. alone. Yet, improvements in imaging technology to detect disease earlier, pharmaceutical developments to shrink or eliminate tumors, and modeling of biological interactions to guide treatment have prevented millions of deaths. Cancer patients with initially similar disease can experience vastly different outcomes, including sustained recovery, refractory disease or, remarkably, recurrence years after apparently successful treatment. The current understanding of such recurrences is that they depend on the random occurrence of critical mutations. Clearly, these biological changes appear to be sufficient for recurrence, but are they …

Machine Learning Applications For Drug Repurposing, Hansaim Lim

Dissertations, Theses, and Capstone Projects

The cost of bringing a drug to market is astounding and the failure rate is intimidating. Drug discovery has been of limited success under the conventional reductionist model of one-drug-one-gene-one-disease paradigm, where a single disease-associated gene is identified and a molecular binder to the specific target is subsequently designed. Under the simplistic paradigm of drug discovery, a drug molecule is assumed to interact only with the intended on-target. However, small molecular drugs often interact with multiple targets, and those off-target interactions are not considered under the conventional paradigm. As a result, drug-induced side effects and adverse reactions are often neglected …

Combinatorial Discovery And Validation Of Heptapeptides With Utp Binding Induced Structure, Daniela Kroiss, James Aramini, Sangitaa Ragoonath, Rein V. Ulijn, Tell Tuttle

Advanced Science Research Center

In biology, supramolecular recognition typically involves an ‘induced-fit’ mechanism, where structures rearrange upon complexation to accommodate binding ligands. Designing minimalistic compounds with such adaptability is challenging as they involve subtle conformational changes that are energetically similar. Here, we demonstrate the integration of combinatorial screening with molecular modelling to identify heptapeptides that form a stable loop upon recognition of uridine triphosphate (UTP). Peptide sequences selected using phage display were refined computationally and correlated with experimental KD values. This combined approach may serve as a method for the de novo selection and subsequent rationalization of the compositional and organizational principles that dictate …

Phylogenetic Trees And Networks Can Serve As Powerful And Complementary Approaches For Analysis Of Genomic Data, Christopher Blair, Cécile Ané

Publications and Research

Genomic data have had a profound impact on nearly every biological discipline. In systematics and phylogenetics, the thousands of loci that are now being sequenced can be analyzed under the multispecies coalescent model (MSC) to explicitly account for gene tree discordance due to incomplete lineage sorting (ILS). However, the MSC assumes no gene flow post divergence, calling for additional methods that can accommodate this limitation. Explicit phylogenetic network methods have emerged, which can simultaneously account for ILS and gene flow by representing evolutionary history as a directed acyclic graph. In this point-of-view we highlight some of the strengths and limitations …

The International Conference On Intelligent Biology And Medicine (Icibm) 2018: Bioinformatics Towards Translational Applications, Xiaoming Liu, Lei Xie, Zhijin Wu, Kai Wang, Zhongming Zhao, Jianhuan Ruan, Degui Zhi

Publications and Research

The 2018 International Conference on Intelligent Biology and Medicine (ICIBM 2018) was held on June 10–12, 2018, in Los Angeles, California, USA. The conference consisted of a total of eleven scientific sessions, four tutorials, one poster session, four keynote talks and four eminent scholar talks, which covered a wild range of aspects of bioinformatics, medical informatics, systems biology and intelligent computing. Here, we summarize nine research articles selected for publishing in BMC Bioinformatics.

Editorial: Systems Biology And Ecology Of Microbial Mat Communities, Martin G. Klotz, Donald A. Bryant, Jim K. Fredrickson, William P. Inskeep, Michael Kühl

Publications and Research

No abstract provided.

Integrating Phylogenomics, Biogeography And Systematics To Explore The Taxonomy And The Rise Of The Ratsnakes, Xin Chen

Dissertations, Theses, and Capstone Projects

Understanding the evolutionary processes that create the spectacular diversity of organisms, both in species numbers and form, is a primary goal for biologists. Global ratsnakes are a species-rich assemblage with high morphological and ecological diversity and a distribution that encompasses both the Old World (OW) and the New World (NW). To explore the mechanism leading to the divergence of the ratsnakes, I tested the hypotheses regarding the area of origin and global dispersal, and examined the patterns of diversification and trait evolution. Given adaptive radiation via ecological opportunity, a diversity-dependent diversification pattern and an early burst trait evolutionary pattern are …

Comparative Phylogeography, Phylogenetics, And Population Genomics Of East African Montane Small Mammals, Terrence Constant Demos

Dissertations, Theses, and Capstone Projects

The Eastern Afromontane region of Africa is characterized by striking levels of endemism and species richness which rank it as a global biodiversity hotspot for diverse plants and animals including mammals, but has been poorly sampled and little studied to date. Using mtDNA and multi-locus nDNA sequence data, genome-wide RAD-Seq SNP data, and morphological data, I identify major cryptic biogeographic patterns within and between 11 co-distributed small mammal species/species groups across the Eastern Afromontane region. I focus on two endemic montane small mammal species complexes, Hylomyscus mice and Sylvisorex shrews, co-distributed across the Albertine Rift (AR) and Kenya Highlands (KH) …

A Systematic Revision Of North American Tolypella A. Braun (Charophyceae, Charophyta), William Perez

Dissertations, Theses, and Capstone Projects

Charophyta comprises the algal classes Mesostigmatophyceae, Chlorokybophyceae, Klebsormidiophyceae, Coleochaetophyceae and Zygnematophyceae and the land plants. However, the precise phylogenetic position of these algal classes with respect to land plants is unresolved as are the phylogenetic relationships among genera in Charophyceae (Characeae). Characeae contains two tribes with six genera: tribe Chareae (Chara, Lamprothamnium, Lychnothamnus and Nitellopsis) and tribe Nitelleae (Nitella and Tolypella). Tolypella was considered the third most species-rich genus but, in the most comprehensive taxonomic treatment of Characeae, 16 Tolypella species were consolidated into two species, T. nidifica and T. intricata in sections Rothia …