Life Sciences Commons^™

A Proposal For An International Transcriptome Initiative For Forage And Turf: Microarray Tools For Expression Profiling In Ryegrass, Clover And Grass Endophytes, T. Webster, N. Nguyen, C. Rhodes, S. A. Felitti, R. Chapman, D. Edwards, G. C. Spangenberg

IGC Proceedings (1997-2023)

Knowledge of the expression pattern of genes provides a valuable insight into gene function and role in determining the observed heritable phenotype. High–density cDNA and oligonucleotide microarrays represent powerful tools for transcriptome analysis to gain an understanding of gene expression patterns for thousands of genes. Internationally coordinated efforts in transcriptome analyses and sharing of microarray resources will benefit the advancement of our understanding of gene function in forage and turf species.

Microarray-Based Transcriptome Analysis Of The Interaction Between Perrenial Ryegrass (Lolium Perenne) And The Fungal Endophyte Neotyphodium Lolii, S. Felitti, P. Tian, T. Webster, D. Edwards, G. C. Spangenberg

IGC Proceedings (1997-2023)

Neotyphodium lolii, Neotyphodium coenophialum and Epichloë festucae are common symbiotic fungal endophytes of the temperate pasture grasses perennial ryegrass (Lolium perenne), tall fescue (Festuca arundinacea) and red fescue (Festuca rubra), respectively. A genomic resource of 13,964 expressed sequence tags (ESTs), representing 7,585 unique endophyte genes, has been established for Neotyphodium and Epichloë fungal endophytes.

Statistical Approaches Of Gene Set Analysis With Quantitative Trait Loci For High-Throughput Genomic Studies., Samarendra Das

Electronic Theses and Dissertations

Recently, gene set analysis has become the first choice for gaining insights into the underlying complex biology of diseases through high-throughput genomic studies, such as Microarrays, bulk RNA-Sequencing, single cell RNA-Sequencing, etc. It also reduces the complexity of statistical analysis and enhances the explanatory power of the obtained results. Further, the statistical structure and steps common to these approaches have not yet been comprehensively discussed, which limits their utility. Hence, a comprehensive overview of the available gene set analysis approaches used for different high-throughput genomic studies is provided. The analysis of gene sets is usually carried out based on …

Differential Effects Of Influenza Virus Na, Ha Head, And Ha Stalk Antibodies On Peripheral Blood Leukocyte Gene Expression During Human Infection., Kathie-Anne Walters, Ruoqing Zhu, Michael Welge, Kelsey Scherler, Jae-Keun Park, Zainab Rahil, Hao Wang, Loretta Auvil, Colleen Bushell, Min Young Lee, David Baxter, Tyler Bristol, Luz Angela Rosas, Adriana Cervantes-Medina, Lindsay Czajkowski, Alison Han, Matthew J Memoli, Jeffery K Taubenberger, John C Kash

Articles, Abstracts, and Reports

In this study, we examined the relationships between anti-influenza virus serum antibody titers, clinical disease, and peripheral blood leukocyte (PBL) global gene expression during presymptomatic, acute, and convalescent illness in 83 participants infected with 2009 pandemic H1N1 virus in a human influenza challenge model. Using traditional statistical and logistic regression modeling approaches, profiles of differentially expressed genes that correlated with active viral shedding, predicted length of viral shedding, and predicted illness severity were identified. These analyses further demonstrated that challenge participants fell into three peripheral blood leukocyte gene expression phenotypes that significantly correlated with different clinical outcomes and prechallenge serum …

Gesture: An Online Hand-Drawing Tool For Gene Expression Pattern Search, Chunyan Wang, Yiqing Xu, Xuelin Wang, Li Zhang, Suyun Wei, Qiaolin Ye, Youxiang Zhu, Hengfu Yin, Manoj Nainwal, Luis Tanon-Reyes, Feng Cheng, Tongming Yin, Ning Ye

Molecular Biosciences Faculty Publications

Gene expression profiling data provide useful information for the investigation of biological function and process. However, identifying a specific expression pattern from extensive time series gene expression data is not an easy task. Clustering, a popular method, is often used to classify similar expression genes, however, genes with a ‘desirable’ or ‘user-defined’ pattern cannot be efficiently detected by clustering methods. To address these limitations, we developed an online tool called GEsture. Users can draw, or graph a curve using a mouse instead of inputting abstract parameters of clustering methods. GEsture explores genes showing similar, opposite and time-delay expression patterns with …

Region Based Gene Expression Via Reanalysis Of Publicly Available Microarray Data Sets., Ernur Saka

Electronic Theses and Dissertations

A DNA microarray is a high-throughput technology used to identify relative gene expression. One of the most widely used platforms is the Affymetrix® GeneChip® technology which detects gene expression levels based on probe sets composed of a set of twenty-five nucleotide probes designed to hybridize with specific gene targets. Given a particular Affymetrix® GeneChip® platform, the design of the probes is fixed. However, the method of analysis is dynamic in nature due to the ability to annotate and group probes into uniquely defined groupings. This is particularly important since publicly available repositories of microarray datasets, such as ArrayExpress and NCBI’s …

Itar: A Web Server For Identifying Target Genes Of Transcription Factors Using Chip-Seq Or Chip-Chip Data, Chia-Chun Yang, Erik H. Andrews, Min-Hsuan Chen, Wan-Yu Wang

Dartmouth Scholarship

Chromatin immunoprecipitation followed by massively parallel DNA sequencing (ChIP-seq) or microarray hybridization (ChIP-chip) has been widely used to determine the genomic occupation of transcription factors (TFs). We have previously developed a probabilistic method, called TIP (Target Identification from Profiles), to identify TF target genes using ChIP-seq/ChIP-chip data. To achieve high specificity, TIP applies a conservative method to estimate significance of target genes, with the trade-off being a relatively low sensitivity of target gene identification compared to other methods. Additionally, TIP’s output does not render binding-peak locations or intensity, information highly useful for visualization and general experimental biological use, while the …

Fastpop: A Rapid Principal Component Derived Method To Infer Intercontinental Ancestry Using Genetic Data, Yafang Li, Jinyoung Byun, Guoshuai Cai, Xiangjun Xiao, Younghun Han, Olivier Cornelis, James E. Dinulos, Joe Dennis, Douglas Easton, Ivan Gorlov, Michael F. Seldin, Christopher I. Amos

Dartmouth Scholarship

Identifying subpopulations within a study and inferring intercontinental ancestry of the samples are important steps in genome wide association studies. Two software packages are widely used in analysis of substructure: Structure and Eigenstrat. Structure assigns each individual to a population by using a Bayesian method with multiple tuning parameters. It requires considerable computational time when dealing with thousands of samples and lacks the ability to create scores that could be used as covariates. Eigenstrat uses a principal component analysis method to model all sources of sampling variation. However, it does not readily provide information directly relevant to ancestral origin; the …

Systems Biology Approaches For The Analysis Of High-Throughput Biological Data, Michele Donato

Wayne State University Dissertations

The identification of biological processes involved with a certain phenotype, such as a disease or drug treatment, is the goal of the majority of life sciences experiments.

Pathway analysis methods are used to interpret high-throughput biological data to identify such processes by incorporating information on biological systems to translate data into biological knowledge.

Although widely used, current methods share a number of limitations.

First, they do not take into account the individual contribution of each gene to the phenotype in analysis.

Second, most of the methods include parameters of difficult interpretation, often arbitrarily set.

Third, the results of all methods …

Genome-Wide Compensatory Changes Accompany Drugselected Mutations In The Plasmodium Falciparum Crt Gene, Hongying Jiang, Jigar J. Patel, Ming Yi, Jianbing Mu, Jinhui Ding, Robert Stephens, Roland Cooper, Michael T. Ferdig, Xin-Zhuan Su

Roland A. Cooper

Mutations in PfCRT (Plasmodium falciparum chloroquine-resistant transporter), particularly the substitution at amino acid position 76, confer chloroquine (CQ) resistance in P. falciparum. Point mutations in the homolog of the mammalian multidrug resistance gene (pfmdr1) can also modulate the levels of CQ response. Moreover, parasites with the same pfcrt and pfmdr1 alleles exhibit a wide range of drug sensitivity, suggesting that additional genes contribute to levels of CQ resistance (CQR). Reemergence of CQ sensitive parasites after cessation of CQ use indicates that changes in PfCRT are deleterious to the parasite. Some CQR parasites, however, persist in the field and grow well …

Distinguishing Melanocytic Nevi From Melanoma By Dna Copy Number Changes: Array-Comparative Genomic Hybridization As A Research Tool, Ahmed Ibrahim Mahas

Browse all Theses and Dissertations

Skin melanocytes can give rise to different benign and malignant neoplasms. Discrimination of an early melanoma from an unusual/atypical benign nevus can represent a significant challenge. However, previous studies have shown that in contrast to benign nevi, melanoma demonstrates pervasive chromosomal aberrations. This substantial difference between melanoma and benign nevi formed the idea of exploiting this difference to discriminate between melanoma and benign nevi. Array-comparative genomic hybridization (aCGH) is an approach that can be used on DNA extracted from formalin-fixed paraffin-embedded (FFPE) tissues to assess the entire genome for the presence of changes in DNA copy number. In this study, …

Cell-Type Specific Transcriptomic Profiling To Dissect Mechanisms Of Differential Dendritogenesis, Surajit Bhattacharya, Eswar Prasad R. Iyer, Srividya Chandramouli Iyer, Daniel N. Cox

Neuroscience Institute Faculty Publications

The establishment, maintenance and modulation of cell-type specific neural architectures are critically important to the formation of functional neural networks. At the neuroanatomical level, differential patterns of dendritic arborization directly impact neural function and connectivity, however the molecular mechanisms underlying the specification of distinct dendrite morphologies remain incompletely understood. To address this question, we analyzed global gene expression from purified populations of wild-type class I and class IV Drosophila melanogaster dendritic arborization (da) sensory neurons compared to wild-type whole larval RNA using oligo DNA microarray expression profiling. Herein we present detailed experimental methods and bioinformatic anal- yses to correspond with …

Oligonucleotide Design For Whole Genome Tiling Arrays, Qin Dong

Electronic Thesis and Dissertation Repository

Oligonucleotides are short, single-stranded fragments of DNA or RNA, designed to readily bind with a unique part in the target sequence. They have many important applications including PCR (polymerase chain reaction) amplification, microarrays, or FISH (fluorescence in situ hybridization) probes. While traditional microarrays are commonly used for measuring gene expression levels by probing for sequences of known and predicted genes, high-density, whole genome tiling arrays probe intensively for sequences that are known to exist in a contiguous region. Current programs for designing oligonucleotides for tiling arrays are not able to produce results that are close to optimal since they allow …

Using Expression Profiling To Understand The Effects Of Chronic Cadmium Exposure On Mcf-7 Breast Cancer Cells, Zelmina Lubovac-Pilav, Daniel M. Borras, Esmeralda Ponce, Maggie Louie

Collected Faculty and Staff Scholarship

Cadmium is a metalloestrogen known to activate the estrogen receptor and promote breast cancer cell growth. Previous studies have implicated cadmium in the development of more malignant tumors; however the molecular mechanisms behind this cadmium-induced malignancy remain elusive. Using clonal cell lines derived from exposing breast cancer cells to cadmium for over 6 months (MCF-7-Cd4, -Cd6, -Cd7, -Cd8 and -Cd12), this study aims to identify gene expression signatures associated with chronic cadmium exposure. Our results demonstrate that prolonged cadmium exposure does not merely result in the deregulation of genes but actually leads to a distinctive expression profile. The genes deregulated …

A Review Of Apomixis And Differential Expression Analyses Using Microarrays, Jonathan Harris Cardwell

All Graduate Plan B and other Reports, Spring 1920 to Spring 2023

Apomixis is a complex trait of great interest to the agricultural community, as it has the potential to fix hybrid vigor in many agriculturally significant crops. Although apomixis has been studied extensively morphologically, the genetic and epigenetic factors responsible for apomixis are still very poorly understood. As no apomictic species has been sequenced and annotated, various low-cost tools and techniques are being utilized to begin profiling the trait. These include cross-species microarrays using probe masking, which deletes information from array probes that do not hybridize to the genomic DNA of the cross species. Despite their limitations, these tools are providing …

Reactin: Regulatory Activity Inference Of Transcription Factors Underlying Human Diseases With Application To Breast Cancer, Mingzhu Zhu, Chun-Chi Liu, Chao Cheng

Dartmouth Scholarship

Genetic alterations of transcription factors (TFs) have been implicated in the tumorigenesis of cancers. In many cancers, alteration of TFs results in aberrant activity of them without changing their gene expression level. Gene expression data from microarray or RNA-seq experiments can capture the expression change of genes, however, it is still challenge to reveal the activity change of TFs. Here we propose a method, called REACTIN (REgulatory ACTivity INference), which integrates TF binding data with gene expression data to identify TFs with significantly differential activity between disease and normal samples. REACTIN successfully detect differential activity of estrogen receptor (ER) between …

Transcription Factor Binding Profiles Reveal Cyclic Expression Of Human Protein-Coding Genes And Non-Coding Rnas, Chao Cheng, Matthew Ung, Gavin D. Grant, Michael L. Whitfield

Dartmouth Scholarship

Cell cycle is a complex and highly supervised process that must proceed with regulatory precision to achieve successful cellular division. Despite the wide application, microarray time course experiments have several limitations in identifying cell cycle genes. We thus propose a computational model to predict human cell cycle genes based on transcription factor (TF) binding and regulatory motif information in their promoters. We utilize ENCODE ChIP-seq data and motif information as predictors to discriminate cell cycle against non-cell cycle genes. Our results show that both the trans- TF features and the cis- motif features are predictive of cell cycle genes, and …

Keratin Gene Expression Profiles After Digit Amputation In C57bl/6 Vs. Regenerative Mrl Mice Imply An Early Regenerative Keratinocyte Activated-Like State, Chia-Ho Cheng, John Leferovich, Xiangming Zhang, Khamilia Bedelbaeva, Dmitri Gourevitch, Cathy J. Hatcher, Craig T. Basson, Ellen Heber-Katz, Kenneth A. Marx

PCOM Scholarly Papers

Mouse strains C57BL/6 (B6) and MRL were studied by whole mouse genome chip microarray analyses of RNA isolated from amputation sites at different times pre-and postamputation at the midsecond phalange of the middle digit. Many keratin genes were highly differentially expressed. All keratin genes were placed into three temporal response classes determined by injury/preinjury ratios. One class, containing only Krt6 and Krt16, were uniquely expressed relative to the other two classes and exhibited different temporal responses in MRL vs. B6. Immunohistochemical staining for Krt6 and Krt16 in tissue sections, including normal digit, flank skin, and small intestine, and from normal …

The Nuances Of Statistically Analyzing Next-Generation Sequencing Data, Sanvesh Srivastava, R. W. Doerge

Conference on Applied Statistics in Agriculture

High-throughput sequencing technologies, in particular next-generation sequencing (NGS) technologies, have emerged as the preferred approach for exploring both gene function and pathway organization. Data from NGS technologies pose new computational and statistical challenges because of their massive size, limited replicate information, large number of genes (high-dimensionality), and discrete form. They are more complex than data from previous high-throughput technologies such as microarrays. In this work we focus on the statistical issues in analyzing and modeling NGS data for selecting genes suitable for further exploration and present a brief review of the relevant statistical methods. We discuss visualization methods to assess …

James-Stein Estimation And The Benjamini-Hochberg Procedure, Debashis Ghosh

Debashis Ghosh

For the problem of multiple testing, the Benjamini-Hochberg (B-H) procedure has become a very popular method in applications. Based on a spacings theory representation of the B-H procedure, we are able to motivate the use of shrinkage estimators for modifying the B-H procedure. Several generalizations in the paper are discussed, and the methodology is applied to real and simulated datasets.

Shrinkage In Adaptive Procedures For False Discovery Rate Estimation In Multiple Testing: Structure And Synthesis, Debashis Ghosh

Debashis Ghosh

There has been much interest in the study of adaptive estimation procedures for controlling the false discovery rate (FDR). In this article, we take the direct approach to estimation of FDR of Storey (2002) and show how it can reexpressed as a particular type of shrinkage estimator. This representation leads to natural conditions on finite-sample FDR control for a general class of shrinkage estimators. In addition, many previous proposals from the literature can be unified under this framework for which finite-sample FDR results can be developed. Some asymptotic results are also provided.

A Hierarchical Bayesian Approach For Detecting Differential Gene Expression In Unreplicated Rna-Sequencing Data, Sanvesh Srivastava, R. W. Doerge

Conference on Applied Statistics in Agriculture

Next-generation sequencing technologies have emerged as a promising technology in a variety of fields, including genomics, epigenomics, and transcriptomics. These technologies play an important role in understanding cell organization and functionality. Unlike data from earlier technologies (e.g., microarrays), data from next-generation sequencing technologies are highly replicable with little technical variation. One application of next-generation sequencing technologies is RNA-Sequencing (RNA-Seq). It is used for detecting differential gene expression between different biological conditions. While statistical methods for detecting differential expression in RNA-Seq data exist, one serious limitation to these methods is the absence of biological replication. At present, the high cost of …

Analysis Of Common And Specific Mechanisms Of Liver Function Affected By Nitrotoluene Compounds, Youping Deng, Sharon A. Meyer, Xin Guan, Barbara Lynn Escalon, Junmei Ai, Mitchell S. Wilbanks, Ruth Welti, Natàlia Garcia-Reyero, Edward J. Perkins

Faculty Publications

Background: Nitrotoluenes are widely used chemical manufacturing and munitions applications. This group of chemicals has been shown to cause a range of effects from anemia and hypercholesterolemia to testicular atrophy. We have examined the molecular and functional effects of five different, but structurally related, nitrotoluenes on using an integrative systems biology approach to gain insight into common and disparate mechanisms underlying effects caused by these chemicals.

Methodology/Principal Findings: Sprague-Dawley female rats were exposed via gavage to one of five concentrations of one of five nitrotoluenes [2,4,6-trinitrotoluene (TNT), 2-amino-4,6-dinitrotoluene (2ADNT) 4-amino-2,6-dinitrotoulene (4ADNT), 2,4-dinitrotoluene (2,4DNT) and 2,6-dinitrotoluene (2,6DNT)] with necropsy …

Generalized Benjamini-Hochberg Procedures Using Spacings, Debashis Ghosh

Debashis Ghosh

For the problem of multiple testing, the Benjamini-Hochberg (B-H) procedure has become a very popular method in applications. We show how the B-H procedure can be interpreted as a test based on the spacings corresponding to the p-value distributions. Using this equivalence, we develop a class of generalized B-H procedures that maintain control of the false discovery rate in finite-samples. We also consider the effect of correlation on the procedure; simulation studies are used to illustrate the methodology.

Software For Assumption Weighting For Meta-Analysis Of Genomic Data, Debashis Ghosh, Yihan Li

Debashis Ghosh

This is the software that accompanies Li and Ghosh, "Assumption weighting for incorporating heterogeneity into meta-analysis of genomic data."

Class Discovery And Prediction Of Tumor With Microarray Data, Bo Liu

All Graduate Theses, Dissertations, and Other Capstone Projects

Current microarray technology is able take a single tissue sample to construct an Affymetrix oglionucleotide array containing (estimated) expression levels of thousands of different genes for that tissue. The objective is to develop a more systematic approach to cancer classification based on Affymetrix oglionucleotide microarrays. For this purpose, I studied published colon cancer microarray data. Colon cancer, with 655,000 deaths worldwide per year, has become the fourth most common form of cancer in the United States and the third leading cause of cancer - related death in the Western world. This research has been focuses in two areas: class discovery, …

Rnai Screen Indicates Widespread Biological Function For Human Natural Antisense Transcripts, Mohammad A. Faghihi, Jannet Kocerha, F. Modarresi, P. G. Engstrom, A. M. Chalk, S. P. Brothers, E. Koesema, G. St. Laurent, Claes Wahlestedt

Jannet Kocerha

Natural antisense transcripts represent a class of regulatory RNA molecules, which are characterized by their complementary sequence to another RNA transcript. Extensive sequencing efforts suggest that natural antisense transcripts are prevalent throughout the mammalian genome; however, their biological significance has not been well defined. We performed a loss-of-function RNA interference (RNAi) screen, which targeted 797 evolutionary conserved antisense transcripts, and found evidence for a regulatory role for a number of natural antisense transcripts. Specifically, we found that natural antisense transcripts for CCPG1 and RAPGEF3 may functionally disrupt signaling pathways and corresponding biological phenotypes, such as cell viability, either independently or …

A Novel Multifunctional Oligonucleotide Microarray For Toxoplasma Gondii, Amit Bahl, Paul H. Davis, Michael Behnke, Florence Dzierszinski, Manjunatha Jagalur, Feng Chen, Dhanasekaran Shanmugam, Michael W. White, David Kulp, David S. Roos

Biology Faculty Publications

Background: Microarrays are invaluable tools for genome interrogation, SNP detection, and expression analysis, among other applications. Such broad capabilities would be of value to many pathogen research communities, although the development and use of genome-scale microarrays is often a costly undertaking. Therefore, effective methods for reducing unnecessary probes while maintaining or expanding functionality would be relevant to many investigators.

Results: Taking advantage of available genome sequences and annotation for Toxoplasma gondii (a pathogenic parasite responsible for illness in immunocompromised individuals) and Plasmodium falciparum (a related parasite responsible for severe human malaria), we designed a single oligonucleotide microarray capable of supporting …

Molecular Mechanisms Involved Involved In The Interaction Effects Of Hcv And Ethanol On Liver Cirrhosis, Ryan Fassnacht

Theses and Dissertations

The leading causes of liver disease are Hepatitis C virus infection and chronic alcohol abuse. Alcohol accelerates liver disease in HCV but the mechanisms are poorly understood. The identification of molecular gene expression profiles on human liver tissue was performed using microarrays. Samples were obtained from alcoholic-cirrhotic, HCV-cirrhotic, HCV/alcohol-cirrhotic and control non-cirrhotic liver tissue. Probe set expression summaries were calculated using RMA. Probe set level linear models were fit where probe set expression was modeled by HCV status, alcohol status, and the interaction between HCV and Alcohol. HCV cirrhosis was associated with up-regulation of genes related to viral and immune …

Comparative Transcriptional Profiling Identifies Takeout As A Gene That Regulates Life Span, Johannes Bauer, Michael Antosh, Chengyi Chang, Christoph Schorl, Santharam Kolli, Nicola Neretti, Stephen L. Helfand

Biosciences Research

A major challenge in translating the positive effects of dietary restriction (DR) for the improvement of human health is the development of therapeutic mimics. One approach to finding DR mimics is based upon identification of the proximal effectors of DR life span extension. Whole genome profiling of DR in Drosophila shows a large number of changes in gene expression, making it difficult to establish which changes are involved in life span determination as opposed to other unrelated physiological changes. We used comparative whole genome expression profiling to discover genes whose change in expression is shared between DR and two molecular …