Systems Biology Commons^™

Mutations In Braf Are Associated With Higher Levels Of Immune Infiltrates In Microsatellite-Stable Colon Cancer, Jake Rubin, Eduard Porta Parto

GW Research Days 2016 - 2020

While BRAF is among the most well-established oncogenes in human cancers, more recently it has garnered attention for its role in suppressing antitumor immunity, especially in melanoma. Because tumor-infiltrating lymphocyte (TIL) density is strongly prognostic in colorectal cancer (CRC)⁷, we decided to investigate the connection between TIL density and the BRAF-activating V600E mutation in CRC.

We used ESTIMATE to quantify immune infiltrate in samples from the TCGA colon adenocarcinoma (COAD) dataset (n = 216). This is an algorithm that uses the gene-expression signature of 141 immune-related genes to infer the presence of immune cells in the tumor infiltrate. …

Biosimp: Using Software Testing Techniques For Sampling And Inference In Biological Organisms, Mikaela Cashman, Jennie L. Catlett, Myra B. Cohen, Nicole R. Buan, Zahmeeth Sakkaff, Massimiliano Pierobon, Christine A. Kelley

School of Computing: Conference and Workshop Papers

Years of research in software engineering have given us novel ways to reason about, test, and predict the behavior of complex software systems that contain hundreds of thousands of lines of code. Many of these techniques have been inspired by nature such as genetic algorithms, swarm intelligence, and ant colony optimization. In this paper we reverse the direction and present BioSIMP, a process that models and predicts the behavior of biological organisms to aid in the emerging field of systems biology. It utilizes techniques from testing and modeling of highly-configurable software systems. Using both experimental and simulation data we show …

Global Gene Expression Profiling Of Healthy Human Brain And Its Application In Studying Neurological Disorders, Simarjeet K. Negi

Theses & Dissertations

The human brain is the most complex structure known to mankind and one of the greatest challenges in modern biology is to understand how it is built and organized. The power of the brain arises from its variety of cells and structures, and ultimately where and when different genes are switched on and off throughout the brain tissue. In other words, brain function depends on the precise regulation of gene expression in its sub-anatomical structures. But, our understanding of the complexity and dynamics of the transcriptome of the human brain is still incomplete. To fill in the need, we designed …

Network Inference Driven Drug Discovery, Gergely Zahoránszky-Kőhalmi, Tudor I. Oprea, Cristian G. Bologa, Subramani Mani, Oleg Ursu

Biomedical Sciences ETDs

The application of rational drug design principles in the era of network-pharmacology requires the investigation of drug-target and target-target interactions in order to design new drugs. The presented research was aimed at developing novel computational methods that enable the efficient analysis of complex biomedical data and to promote the hypothesis generation in the context of translational research. The three chapters of the Dissertation relate to various segments of drug discovery and development process.

The first chapter introduces the integrated predictive drug discovery platform „SmartGraph”. The novel collaborative-filtering based algorithm „Target Based Recommender (TBR)” was developed in the framework of this …

Modeling And Analysis Of Germ Layer Formations Using Finite Dynamical Systems, Alexander Garza, Megan Eberle, Eric A. Eager

Spora: A Journal of Biomathematics

The development of an embryo from a fertilised egg to a multicellular organism proceeds through numerous steps, with the formation of the three germ layers (endoderm, mesoderm, ectoderm) being one of the first. In this paper we study the mesendoderm (the tissue that collectively gives rise to both mesoderm and endoderm) gene regulatory network for two species, \textit{Xenopus laevis} and the axolotl (\textit{Ambystoma mexicanum}) using Boolean networks. We find that previously-established bistability found in these networks can be reproduced using this Boolean framework, provided that some assumptions used in previously-published differential equations models are relaxed. We conclude by discussing our …

Nasp: An Accurate, Rapid Method For The Identification Of Snps In Wgs Datasets That Supports Flexible Input And Output Formats, Jason Sahl, Darrin Lemmer, Jason Travis, James Schupp, John Gillece, Maliha Aziz, +Several Additional Authors

Environmental and Occupational Health Faculty Publications

Whole-genome sequencing (WGS) of bacterial isolates has become standard practice in many laboratories. Applications for WGS analysis include phylogeography and molecular epidemiology, using single nucleotide polymorphisms (SNPs) as the unit of evolution. NASP was developed as a reproducible method that scales well with the hundreds to thousands of WGS data typically used in comparative genomics applications. In this study, we demonstrate how NASP compares with other tools in the analysis of two real bacterial genomics datasets and one simulated dataset. Our results demonstrate that NASP produces similar, and often better, results in comparison with other pipelines, but is much more …

Computational Labeling, Partitioning, And Balancing Of Molecular Networks, Biaobin Jiang

Open Access Dissertations

Recent advances in high throughput techniques enable large-scale molecular quantification with high accuracy, including mRNAs, proteins and metabolites. Differential expression of these molecules in case and control samples provides a way to select phenotype-associated molecules with statistically significant changes. However, given the significance ranking list of molecular changes, how those molecules work together to drive phenotype formation is still unclear. In particular, the changes in molecular quantities are insufficient to interpret the changes in their functional behavior. My study is aimed at answering this question by integrating molecular network data to systematically model and estimate the changes of molecular functional …

Design Science 5 | Steam Intelligence, Schedule, Edna W. Lawrence Nature Lab

Design Science Symposia

Schedule of events.

A Pipeline For Creation Of Genome-Scale Metabolic Reconstructions, Shaun W. Norris

Theses and Dissertations

The decreasing costs of next generation sequencing technologies and the increasing speeds at which they work have lead to an abundance of 'omic datasets. The need for tools and methods to analyze, annotate, and model these datasets to better understand biological systems is growing. Here we present a novel software pipeline to reconstruct the metabolic model of an organism in silico starting from its genome sequence and a novel compilation of biological databases to better serve the generation of metabolic models. We validate these methods using five Gardnerella vaginalis strains and compare the gene annotation results to NCBI and the …

Classification Of Breast Cancer Patients Using Somatic Mutation Profiles And Machine Learning Approaches, Suleyman Vural

Theses & Dissertations

The high degree of heterogeneity observed in breast cancers makes it very difficult to classify cancer patients into distinct clinical subgroups and consequently limits the ability to devise effective therapeutic strategies. In this study, we explore the use of gene mutation profiles to classify, characterize and predict the subgroups of breast cancers. We analyzed the whole exome sequencing data from 358 ethnically similar breast cancer patients in The Cancer Genome Atlas (TCGA) project. Identified somatic and non-synonymous single nucleotide variants were assigned a quantitative score (C-score) that represents the extent of negative impact on the function of the gene. Using …

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 …

Graph-Based Regularization In Machine Learning: Discovering Driver Modules In Biological Networks, Xi Gao

Theses and Dissertations

Curiosity of human nature drives us to explore the origins of what makes each of us different. From ancient legends and mythology, Mendel's law, Punnett square to modern genetic research, we carry on this old but eternal question. Thanks to technological revolution, today's scientists try to answer this question using easily measurable gene expression and other profiling data. However, the exploration can easily get lost in the data of growing volume, dimension, noise and complexity. This dissertation is aimed at developing new machine learning methods that take data from different classes as input, augment them with knowledge of feature relationships, …

Genetic Predictors Of Metabolic Side Effects Of Diuretic Therapy, Jorge L. Del Aguila

Dissertations and Theses (Open Access)

Thiazide diuretics are a recommended first-line monotherapy for hypertension (i.e.SBP>140 mmHg or DBP>90 mmHg). Even so, diuretics are associated with adverse metabolic side effects, such as hyperlipidemia, hyperglycemia and hypokalemia which increase the risk of developing type II diabetes. This thesis used three analytical strategies to identify and quantify genetic factors that contribute to the development of adverse metabolic effects due to thiazide diuretic treatment. I performed a genome-wide association study (GWAS) and meta-analysis of the change in fasting plasma glucose and triglycerides in response to HCTZ from two different clinical trials: the Pharmacogenomic Evaluation of Antihypertensive Responses …

Systems Biology Approaches To Probe Gene Regulation In Bacteria, Diogo F. Troggian Veiga

Dissertations and Theses (Open Access)

Mechanisms that allow pathogens to colonize the host are not the product of isolated genes, but instead emerge from the concerted operation of regulatory networks. Therefore, identifying components and the systemic behavior of networks is necessary to a better understanding of gene regulation and pathogenesis. To this end, I have developed systems biology approaches to study transcriptional and post-transcriptional gene regulation in bacteria, with an emphasis in the human pathogen Mycobacterium tuberculosis (Mtb).

First, I developed a network response method to identify parts of the Mtb global transcriptional regulatory network utilized by the pathogen to counteract phagosomal stresses …

Gene Duplication And The Evolution Of The Higher Diptera, Riyue Bao

Wayne State University Dissertations

Gene duplication is an important source of evolutionary innovation. Using the publicly available genomic information, I studied lineage-specific gene duplications in Drosophila melanogaster (fruit fly), Anopheles gambiae (mosquito), Tribolium castaneum (red flour beetle), and Apis mellifera (honey bee) at three scales: eye-specific genes, developmental genes, and genome-wide. All three studies consistently show that the Drosophila genome contains an exceptionally high number of lineage-specific yet ancient gene duplicates, the majority of which must have originated during the early diversification of the higher Diptera (Brachycera) at least 100 million years ago. Genetic data suggest that gene duplication played an important role in …

Multivariate Models And Algorithms For Systems Biology, Lipi Rani Acharya

LSU New Orleans Theses and Dissertations

Rapid advances in high-throughput data acquisition technologies, such as microarraysand next-generation sequencing, have enabled the scientists to interrogate the expression levels of tens of thousands of genes simultaneously. However, challenges remain in developingeffective computational methods for analyzing data generated from such platforms. In thisdissertation, we address some of these challenges. We divide our work into two parts. Inthe first part, we present a suite of multivariate approaches for a reliable discovery of geneclusters, often interpreted as pathway components, from molecular profiling data with replicated measurements. We translate our goal into learning an optimal correlation structure from replicated complete and incomplete …

The Time Invariance Principle, Ecological (Non)Chaos, And A Fundamental Pitfall Of Discrete Modeling, Bo Deng

Department of Mathematics: Faculty Publications

This paper is to show that most discrete models used for population dynamics in ecology are inherently pathological that their predications cannot be independently verified by experiments because they violate a fundamental principle of physics. The result is used to tackle an on-going controversy regarding ecological chaos. Another implication of the result is that all continuous dynamical systems must be modeled by differential equations. As a result it suggests that researches based on discrete modeling must be closely scrutinized and the teaching of calculus and differential equations must be emphasized for students of biology.