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- Genre: Academic theses
- Creators: Li, Baoxin
- Status: Published
Description
In species with highly heteromorphic sex chromosomes, the degradation of one of the sex chromosomes can result in unequal gene expression between the sexes (e.g., between XX females and XY males) and between the sex chromosomes and the autosomes. Dosage compensation is a process whereby genes on the sex chromosomes achieve equal gene expression which prevents deleterious side effects from having too much or too little expression of genes on sex chromsomes. The green anole is part of a group of species that recently underwent an adaptive radiation. The green anole has XX/XY sex determination, but the content of the X chromosome and its evolution have not been described. Given its status as a model species, better understanding the green anole genome could reveal insights into other species. Genomic analyses are crucial for a comprehensive picture of sex chromosome differentiation and dosage compensation, in addition to understanding speciation.
In order to address this, multiple comparative genomics and bioinformatics analyses were conducted to elucidate patterns of evolution in the green anole and across multiple anole species. Comparative genomics analyses were used to infer additional X-linked loci in the green anole, RNAseq data from male and female samples were anayzed to quantify patterns of sex-biased gene expression across the genome, and the extent of dosage compensation on the anole X chromosome was characterized, providing evidence that the sex chromosomes in the green anole are dosage compensated.
In addition, X-linked genes have a lower ratio of nonsynonymous to synonymous substitution rates than the autosomes when compared to other Anolis species, and pairwise rates of evolution in genes across the anole genome were analyzed. To conduct this analysis a new pipeline was created for filtering alignments and performing batch calculations for whole genome coding sequences. This pipeline has been made publicly available.
In order to address this, multiple comparative genomics and bioinformatics analyses were conducted to elucidate patterns of evolution in the green anole and across multiple anole species. Comparative genomics analyses were used to infer additional X-linked loci in the green anole, RNAseq data from male and female samples were anayzed to quantify patterns of sex-biased gene expression across the genome, and the extent of dosage compensation on the anole X chromosome was characterized, providing evidence that the sex chromosomes in the green anole are dosage compensated.
In addition, X-linked genes have a lower ratio of nonsynonymous to synonymous substitution rates than the autosomes when compared to other Anolis species, and pairwise rates of evolution in genes across the anole genome were analyzed. To conduct this analysis a new pipeline was created for filtering alignments and performing batch calculations for whole genome coding sequences. This pipeline has been made publicly available.
ContributorsRupp, Shawn Michael (Author) / Wilson Sayres, Melissa A (Thesis advisor) / Kusumi, Kenro (Committee member) / DeNardo, Dale (Committee member) / Arizona State University (Publisher)
Created2016
Description
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.
ContributorsZhao, Xinlin (Author) / Ye, Jieping (Thesis advisor) / Wang, Yalin (Thesis advisor) / Li, Baoxin (Committee member) / Arizona State University (Publisher)
Created2016
Description
The regulation of gene expression, timing, location, and amount of a given project, ultimately affects the cellular structure and function. More broadly, gene regulation is the basis for cellular differentiation and development. However, gene expression is not uniform among individuals and varies greatly between genetic males and females. Males are hemizygous for the X chromosome, whereas females have two X chromosome copies. Contributing to the sex differences in gene expression between males and females are the sex chromosomes, X and Y. Gene expression differences on the autosomes and the X chromosome between males (46, XY) and females (46, XX) may help inform on the mechanisms of sex differences in human health and disease. For example, XX females are more likely to suffer from autoimmune diseases, and genetic XY males are more likely to develop cancer. Characterizing sex-specific gene expression among human tissues will help inform the molecular mechanisms driving sex differences in human health and disease. This dissertation covers a range of critical aspects in gene expression. In chapter 1, I will introduce a method to align RNA-Seq reads to a sex chromosome complement informed reference genome that considers the X and Y chromosomes' shared evolutionary history. Using this approach, I show that more genes are called as sex differentially expressed in several human adult tissues compared to a default reference alignment. In chapter 2, I characterize gene expression in an early formed tissue, the human placenta. The placenta is the DNA of the developing fetus and is typically XY male or XX female. There are well-documented sex differences in pregnancy complications, yet, surprisingly, there is no observable sex difference in expression of innate immune genes, suggesting expression of these genes is conserved. In chapter 3, I investigate gene expression in breast cancer cell lines. Cancer arises in part due to the disruption of gene expression. Here I show 19 tumor suppressor genes become upregulated in response to a synthetic protein treatment. In chapter 4, I discuss gene and allele-specific expression in Nasonia jewel wasp. Chapter 4 is a replication and extension study and discusses the importance of reproducibility.
ContributorsOlney, Kimberly (Author) / Wilson, Melissa A (Thesis advisor) / Hinde, Katherine (Committee member) / Buetow, Kenneth (Committee member) / Banovich, Nicholas (Committee member) / Arizona State University (Publisher)
Created2021
Description
Drosophila melanogaster, as an important model organism, is used to explore the mechanism which governs cell differentiation and embryonic development. Understanding the mechanism will help to reveal the effects of genes on other species or even human beings. Currently, digital camera techniques make high quality Drosophila gene expression imaging possible. On the other hand, due to the advances in biology, gene expression images which can reveal spatiotemporal patterns are generated in a high-throughput pace. Thus, an automated and efficient system that can analyze gene expression will become a necessary tool for investigating the gene functions, interactions and developmental processes. One investigation method is to compare the expression patterns of different developmental stages. Recently, however, the expression patterns are manually annotated with rough stage ranges. The work of annotation requires professional knowledge from experienced biologists. Hence, how to transfer the domain knowledge in biology into an automated system which can automatically annotate the patterns provides a challenging problem for computer scientists. In this thesis, the problem of stage annotation for Drosophila embryo is modeled in the machine learning framework. Three sparse learning algorithms and one ensemble algorithm are used to attack the problem. The sparse algorithms are Lasso, group Lasso and sparse group Lasso. The ensemble algorithm is based on a voting method. Besides that the proposed algorithms can annotate the patterns to stages instead of stage ranges with high accuracy; the decimal stage annotation algorithm presents a novel way to annotate the patterns to decimal stages. In addition, some analysis on the algorithm performance are made and corresponding explanations are given. Finally, with the proposed system, all the lateral view BDGP and FlyFish images are annotated and several interesting applications of decimal stage value are revealed.
ContributorsPan, Cheng (Author) / Ye, Jieping (Thesis advisor) / Li, Baoxin (Committee member) / Farin, Gerald (Committee member) / Arizona State University (Publisher)
Created2012