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 …

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 …

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 …

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 …

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, …

A Non-Parametric Empirical Bayes Approach For Estimating Transcript Abundance In Un-Replicated Next-Generation Sequencing Data, Sanvesh Srivastava, R. W. Doerge

Conference on Applied Statistics in Agriculture

Empirical Bayes approaches have been widely used to analyze data from high throughput sequencing devices. These approaches rely on borrowing information available for all the genes across samples to get better estimates of gene level expression. To date, transcript abundance in data from next generation sequencing (NGS) technologies has been estimated using parametric approaches for analyzing count data, namely – gamma-Poisson model, negative binomial model, and over-dispersed logistic model. One serious limitation of these approaches is they cannot be applied in absence of replication. The high cost of NGS technologies imposes a serious restriction on the number of biological replicates …

Discrete Nonparametric Algorithms For Outlier Detection With Genomic Data, Debashis Ghosh

Debashis Ghosh

In high-throughput studies involving genetic data such as from gene expression mi- croarrays, dierential expression analysis between two or more experimental conditions has been a very common analytical task. Much of the resulting literature on multiple comparisons has paid relatively little attention to the choice of test statistic. In this article, we focus on the issue of choice of test statistic based on a special pattern of dierential expression. The approach here is based on recasting multiple comparisons procedures for assessing outlying expression values. A major complication is that the resulting p-values are discrete; some theoretical properties of sequential testing …

Detecting Outlier Genes From High-Dimensional Data: A Fuzzy Approach, Debashis Ghosh

Debashis Ghosh

A recent nding in cancer research has been the characterization of previously undis- covered chromosomal abnormalities in several types of solid tumors. This was found based on analyses of high-throughput data from gene expression microarrays and motivated the development of so-called `outlier' tests for dierential expression. One statistical issue was the potential discreteness of the test statistics. Using ideas from fuzzy set theory, we develop fuzzy outlier detection algorithms that have links to ideas in multiple comparisons. Two- and K-sample extensions are considered. The methodology is illustrated by application to two microarray studies.

Discrete Nonparametric Algorithms For Outlier Detection With Genomic Data, Debashis Ghosh

Debashis Ghosh

In high-throughput studies involving genetic data such as from gene expression microarrays, differential expression analysis between two or more experimental conditions has been a very common analytical task. Much of the resulting literature on multiple comparisons has paid relatively little attention to the choice of test statistic. In this article, we focus on the issue of choice of test statistic based on a special pattern of differential expression. The approach here is based on recasting multiple comparisons procedures for assessing outlying expression values. A major complication is that the resulting p-values are discrete; some theoretical properties of sequential testing procedures …

Discrete Nonparametric Algorithms For Outlier Detection With Genomic Data, Debashis Ghosh

Debashis Ghosh

In high-throughput studies involving genetic data such as from gene expression microarrays, differential expression analysis between two or more experimental conditions has been a very common analytical task. Much of the resulting literature on multiple comparisons has paid relatively little attention to the choice of test statistic. In this article, we focus on the issue of choice of test statistic based on a special pattern of differential expression. The approach here is based on recasting multiple comparisons procedures for assessing outlying expression values. A major complication is that the resulting p-values are discrete; some theoretical properties of sequential testing procedures …

Identification Of Yeast Transcriptional Regulation Networks Using Multivariate Random Forests, Yuanyuan Xiao, Mark Segal

Mark R Segal

The recent availability of whole-genome scale data sets that investigate complementary and diverse aspects of transcriptional regulation has spawned an increased need for new and effective computational approaches to analyze and integrate these large scale assays. Here, we propose a novel algorithm, based on random forest methodology, to relate gene expression (as derived from expression microarrays) to sequence features residing in gene promoters (as derived from DNA motif data) and transcription factor binding to gene promoters (as derived from tiling microarrays). We extend the random forest approach to model a multivariate response as represented, for example, by time-course gene expression …

A Robust Measure Of Correlation Between Two Genes On A Microarray, Johanna S. Hardin, Aya Mitani '06, Leanne Hicks, Brian Vankoten

Pomona Faculty Publications and Research

Background

The underlying goal of microarray experiments is to identify gene expression patterns across different experimental conditions. Genes that are contained in a particular pathway or that respond similarly to experimental conditions could be co-expressed and show similar patterns of expression on a microarray. Using any of a variety of clustering methods or gene network analyses we can partition genes of interest into groups, clusters, or modules based on measures of similarity. Typically, Pearson correlation is used to measure distance (or similarity) before implementing a clustering algorithm. Pearson correlation is quite susceptible to outliers, however, an unfortunate characteristic when dealing …

Analyzing Dna Microarrays With Undergraduate Statisticians, Johanna S. Hardin, Laura Hoopes, Ryan Murphy '06

Pomona Faculty Publications and Research

With advances in technology, biologists have been saddled with high dimensional data that need modern statistical methodology for analysis. DNA microarrays are able to simultaneously measure thousands of genes (and the activity of those genes) in a single sample. Biologists use microarrays to trace connections between pathways or to identify all genes that respond to a signal. The statistical tools we usually teach our undergraduates are inadequate for analyzing thousands of measurements on tens of samples. The project materials include readings on microarrays as well as computer lab activities. The topics covered include image analysis, filtering and normalization techniques, and …

Differential Expression With The Bioconductor Project, Anja Von Heydebreck, Wolfgang Huber, Robert Gentleman

Bioconductor Project Working Papers

A basic, yet challenging task in the analysis of microarray gene expression data is the identification of changes in gene expression that are associated with particular biological conditions. We discuss different approaches to this task and illustrate how they can be applied using software from the Bioconductor Project. A central problem is the high dimensionality of gene expression space, which prohibits a comprehensive statistical analysis without focusing on particular aspects of the joint distribution of the genes expression levels. Possible strategies are to do univariate gene-by-gene analysis, and to perform data-driven nonspecific filtering of genes before the actual statistical analysis. …

Genetic Mapping Of Gene Expression Levels: Expression Level Polymorphism Analysis For Dissecting Regulatory Networks Of Plant Disease Resistance, Kyunga Kim, Marilyn A. L. West, Richard W. Michelmore, Dina A. St. Clair, R. W. Doerge

Conference on Applied Statistics in Agriculture

The genetic basis of inherited traits has been studied through di erent approaches in many areas of science. Examples include quantitative trait locus (QTL) analysis and mutant analysis in genetics, genome sequencing and gene expression analysis in genomics. Each of these approaches is used for the investigation of complex traits, such as disease resistance, but also provides knowledge on components of complex biological systems. We introduce a novel functional genomics approach that integrates two areas, genetics and genomics, by applying QTL analysis to quantitative di erences in the mRNA abundance of trait-related genes. This approach allows comprehensive dissection of regulatory …