Statistical Models Commons^™

Hierarchical Modeling And Differential Expression Analysis For Rna-Seq Experiments With Inbred And Hybrid Genotypes, Andrew Lithio, Dan Nettleton

Dan Nettleton

The performance of inbred and hybrid genotypes is of interest in plant breeding and genetics. High-throughput sequencing of RNA (RNA-seq) has proven to be a useful tool in the study of the molecular genetic responses of inbreds and hybrids to environmental stresses. Commonly used experimental designs and sequencing methods lead to complex data structures that require careful attention in data analysis. We demonstrate an analysis of RNA-seq data from a split-plot design involving drought stress applied to two inbred genotypes and two hybrids formed by crosses between the inbreds. Our generalized linear modeling strategy incorporates random effects for whole-plot experimental …

Root Type-Specific Reprogramming Of Maize Pericycle Transcriptomes By Local High Nitrate Results In Disparate Lateral Root Branching Patterns, Peng Yu, Jutta A. Baldauf, Andrew Lithio, Caroline Marcon, Dan Nettleton, Chunjian Li, Frank Hochholdinger

Dan Nettleton

The adaptability of root system architecture to unevenly distributed mineral nutrients in soil is a key determinant of plant performance. The molecular mechanisms underlying nitrate dependent plasticity of lateral root branching across the different root types of maize are only poorly understood. In this study, detailed morphological and anatomical analyses together with cell type-specific transcriptome profiling experiments combining laser capture microdissection with RNA-seq were performed to unravel the molecular signatures of lateral root formation in primary, seminal, crown, and brace roots of maize (Zea mays) upon local high nitrate stimulation. The four maize root types displayed divergent branching …

Genomic Neighborhoods For Arabidopsisretrotransposons: A Role For Targeted Integration In The Distribution Of The Metaviridae, Brooke D. Peterson-Burch, Dan Nettleton, Daniel F. Voytas

Dan Nettleton

Background: Retrotransposons are an abundant component of eukaryotic genomes. The high quality of the Arabidopsis thaliana genome sequence makes it possible to comprehensively characterize retroelement populations and explore factors that contribute to their genomic distribution.

Results: We identified the full complement of A. thaliana long terminal repeat (LTR) retroelements using RetroMap, a software tool that iteratively searches genome sequences for reverse transcriptases and then defines retroelement insertions. Relative ages of full-length elements were estimated by assessing sequence divergence between LTRs: the Pseudoviridae were significantly younger than the Metaviridae. All retroelement insertions were mapped onto the genome sequence and their distribution …

Complementation Contributes To Transcriptome Complexity In Maize (Zea Mays L.) Hybrids Relative To Their Inbred Parents, Anja Paschold, Yi Jia, Caroline Marcon, Steve Lund, Nick B. Larson, Cheng-Ting Yeh, Stephan Ossowski, Christa Lanz, Dan Nettleton, Patrick S. Schnable, Frank Hochholdinger

Dan Nettleton

Typically, F₁-hybrids are more vigorous than their homozygous, genetically distinct parents, a phenomenon known as heterosis. In the present study, the transcriptomes of the reciprocal maize (Zea mays L.) hybrids B73×Mo17 and Mo17×B73 and their parental inbred lines B73 and Mo17 were surveyed in primary roots, early in the developmental manifestation of heterotic root traits. The application of statistical methods and a suitable experimental design established that 34,233 (i.e., 86%) of all high-confidence maize genes were expressed in at least one genotype. Nearly 70% of all expressed genes were differentially expressed between the two parents and 42%–55% …

Estimation And Testing Of Gene Expression Heterosis, Tieming Ji, Peng Liu, Dan Nettleton

Dan Nettleton

Heterosis, also known as the hybrid vigor, occurs when the mean phenotype of hybrid offspring is superior to that of its two inbred parents. The heterosis phenomenon is extensively utilized in agriculture though the molecular basis is still unknown. In an effort to understand phenotypic heterosis at the molecular level, researchers have begun to compare expression levels of thousands of genes between parental inbred lines and their hybrid offspring to search for evidence of gene expression heterosis. Standard statistical approaches for separately analyzing expression data for each gene can produce biased and highly variable estimates and unreliable tests of heterosis. …

Non-Syntenic Genes Drive Rtcs-Dependent Regulation Of The Embryo Transcriptome During Formation Of Seminal Root Primordia In Maize (Zea Mays L.), Huanhuan Tai, Nina Opitz, Andrew Lithio, Xin Lu, Dan Nettleton, Frank Hochholdinger

Dan Nettleton

Seminal roots of maize are pivotal for early seedling establishment. The maize mutant rootless concerning crown and seminal roots (rtcs) is defective in seminal root initiation during embryogenesis. In this study, the transcriptomes of wild-type and rtcs embryos were analyzed by RNA-Seq based on histological results at three stages of seminal root primordia formation. Hierarchical clustering highlighted that samples of each genotype grouped together along development. Determination of their gene activity status revealed hundreds of genes specifically transcribed in wild-type or rtcs embryos, while K-mean clustering revealed changes in gene expression dynamics between wild-type and rtcs during embryo …

Post-Weaning Blood Transcriptomic Differences Between Yorkshire Pigs Divergently Selected For Residual Feed Intake, Haibo Liu, Yet T. Nguyen, Dan Nettleton, Jack C. M. Dekkers, Christopher K. Tuggle

Dan Nettleton

Background: Improving feed efficiency (FE) of pigs by genetic selection is of economic and environmental significance. An increasingly accepted measure of feed efficiency is residual feed intake (RFI). Currently, the molecular mechanisms underlying RFI are largely unknown. Additionally, to incorporate RFI into animal breeding programs, feed intake must be recorded on individual pigs, which is costly and time-consuming. Thus, convenient and predictive biomarkers for RFI that can be measured at an early age are greatly desired. In this study, we aimed to explore whether differences exist in the global gene expression profiles of peripheral blood of 35 to 42 day-old …

Substantial Contribution Of Genetic Variation In The Expression Of Transcription Factors To Phenotypic Variation Revealed By Erd-Gwas, Hung-Ying Lin, Qiang Liu, Xiao Li, Jinliang Yang, Sanzhen Liu, Yinlian Huang, Michael J. Scanlon, Dan Nettleton, Patrick S. Schnable

Dan Nettleton

Background: There are significant limitations in existing methods for the genome-wide identification of genes whose expression patterns affect traits.

Results: The transcriptomes of five tissues from 27 genetically diverse maize inbred lines were deeply sequenced to identify genes exhibiting high and low levels of expression variation across tissues or genotypes. Transcription factors are enriched among genes with the most variation in expression across tissues, as well as among genes with higher-than-median levels of variation in expression across genotypes. In contrast, transcription factors are depleted among genes whose expression is either highly stable or highly variable across genotypes. We developed a …

Inferring Processes Of Coevolutionary Diversification In A Community Of Panamanian Strangler Figs And Associated Pollinating Wasps, Jordan D. Satler, Edward Allen Herre, K. Charlotte Jandér, Deren A. R. Eaton, Carlos A. Machado, Tracy A. Heath, John D. Nason

Tracy Heath

The fig and pollinator wasp obligate mutualism is diverse (~750 described species), ecologically important, and ancient (~80-90 Ma), providing model systems for generating and testing many questions in evolution and ecology. Once thought to be a prime example of strict one-to-one cospeciation, current thinking suggests that genera of pollinator wasps coevolve with corresponding subsections of figs, but the degree to which cospeciation or other processes contributes to the association at finer scales is unclear. Here we use genome-wide sequence data from a community of Panamanian strangler figs (Ficus subgenus Urostigma, section Americana) and associated fig wasp pollinators …

The Fossilized Birth-Death Model For The Analysis Of Stratigraphic Range Data Under Different Speciation Modes, Tanja Stadler, Alexandra Gavryushkina, Rachel C. M. Warnock, Alexei J. Drummond, Tracy A. Heath

Tracy Heath

A birth-death-sampling model gives rise to phylogenetic trees with samples from the past and the present. Interpreting “birth” as branching speciation, “death” as extinction, and “sampling” as fossil preservation and recovery, this model – also referred to as the fossilized birth-death (FBD) model – gives rise to phylogenetic trees on extant and fossil samples. The model has been mathematically analyzed and successfully applied to a range of datasets on different taxonomic levels, such as penguins, plants, and insects. However, the current mathematical treatment of this model does not allow for a group of temporally distinct fossil specimens to be assigned …

A Gene-Based Association Method For Mapping Traits Using Reference Transcriptome Data, Eric R. Gamazon, Heather Wheeler, Kaanan P. Shah, Sahar V. Mozaffari, Keston Aquino-Michaels, Robert J. Carroll, Anne E. Eyler, Joshua C. Denny, Dan L. Nicolae, Nancy J. Cox, Hae Kyung Im

Heather Wheeler

Genome-wide association studies (GWAS) have identified thousands of variants robustly associated with complex traits. However, the biological mechanisms underlying these associations are, in general, not well understood. We propose a gene-based association method called PrediXcan that directly tests the molecular mechanisms through which genetic variation affects phenotype. The approach estimates the component of gene expression determined by an individual’s genetic profile and correlates ‘imputed’ gene expression with the phenotype under investigation to identify genes involved in the etiology of the phenotype. Genetically regulated gene expression is estimated using whole-genome tissue-dependent prediction models trained with reference transcriptome data sets. PrediXcan enjoys …

Bayesian Methods For Expression-Based Integration, Elizabeth M. Jennings, Jeffrey S. Morris, Raymond J. Carroll, Ganiraju C. Manyam, Veera Baladandayuthapani

Jeffrey S. Morris

We propose methods to integrate data across several genomic platforms using a hierarchical Bayesian analysis framework that incorporates the biological relationships among the platforms to identify genes whose expression is related to clinical outcomes in cancer. This integrated approach combines information across all platforms, leading to increased statistical power in finding these predictive genes, and further provides mechanistic information about the manner in which the gene affects the outcome. We demonstrate the advantages of the shrinkage estimation used by this approach through a simulation, and finally, we apply our method to a Glioblastoma Multiforme dataset and identify several genes potentially …