Genetics and Genomics Commons^™

A Law-Policy Proposal To Promote The Public Nature Of Science In An Era Of Academia-Industry Integration, Michael J. Malinowski

Michael J. Malinowski

This article addresses the impact of integration of academia, industry, and government on the public nature of research. The article concludes that, while the integration has benefited science immensely, regulatory measures should be taken to restore the public nature of research in an age of integration.

Modeling Dependent Gene Expression, Donatello Telesca, Peter Muller, Giovanni Parmigiani, Ralph S. Freedman

Harvard University Biostatistics Working Paper Series

No abstract provided.

Finding A (Pine) Needle In A Haystack: Chloroplast Genome Sequence Divergence In Rare And Widespread Pines, Justen B. Whittall, John Syring, Matthew Parks, Jason Buenrostro, Cynthia A. Dick, Aaron Liston, Richard Cronn

Biology

Critical to conservation efforts and other investigations at low taxonomic levels, DNA sequence data offer important insights into the distinctiveness, biogeographic partitioning and evolutionary histories of species. The resolving power of DNA sequences is often limited by insufficient variability at the intraspecific level. This is particularly true of studies involving plant organelles, as the conservative mutation rate of chloroplasts and mitochondria makes it difficult to detect polymorphisms necessary to track genealogical relationships among individuals, populations and closely related taxa, through space and time. Massively parallel sequencing (MPS) makes it possible to acquire entire organelle genome sequences to identify cryptic variation …

Wavelet Based Functional Models For Transcriptome Analysis With Tiling Arrays, Lieven Clement, Kristof Debeuf, Ciprian Crainiceanu, Olivier Thas, Marnik Vuylsteke, Rafael Irizarry

Johns Hopkins University, Dept. of Biostatistics Working Papers

For a better understanding of the biology of an organism a complete description is needed of all regions of the genome that are actively transcribed. Tiling arrays can be used for this purpose. Such arrays allow the discovery of novel transcripts and the assessment of differential expression between two or more experimental conditions such as genotype, treatment, tissue, etc. Much of the initial methodological efforts were designed for transcript discovery, while more recent developments also focus on differential expression. To our knowledge no methods for tiling arrays are described in the literature that can both assess transcript discovery and identify …

Gender Moderates The Association Between 5-Httlpr And Decision-Making Under Ambiguity But Not Under Risk, Scott F. Stoltenberg, Joanna M. Vandever

Faculty Publications, Department of Psychology

Decisions made under ambiguity may involve a different genetic architecture than those made under risk. Because gender moderates the effect of genetic polymorphisms on serotonin function and because there are gender differences in decision-making, the present study examined potential gender moderation of associations between polymorphisms in important serotonin system candidate genes (serotonin transporter [SLC6A4] and tryptophan hydroxylase-2 [TPH2]) and performance on a decision-making task (Iowa Gambling Task, IGT) in healthy, adults (N = 188; 62% women). Subjects were genotyped for the well-studied SLC6A4 promoter variant 5-HTTLPR and a TPH2 single nucleotide polymorphism in intron-8 (rs1386438). Genotype at rs1386438was not …

Trait Selection And Welfare Of Genetically Engineered Animals In Agriculture, Michael Greger

Genetics Collection

The release of the Final Guidance from the US Food and Drug Administration on the commercialization of genetically engineered animals has sparked renewed discussion over the ethical, consumer, and regulatory implications of transgenesis in animal agriculture. Animal welfare critiques have focused on unexpected phenotypic effects in animals used in transgenic research, rather than on the health and welfare implications of the intended productivity enhancement. Unless breeding goals are redefined to reflect social concerns, the occurrence and magnitude of undesirable side effects may increase and consumer confidence in the nascent technology may be undermined.

Proteomic Analysis Of Iron Acquisition, Metabolic And Regulatory Responses Of Yersinia Pestis To Iron Starvation, Rembert Pieper, Shih-Ting Huang, Prashanth P. Parmar, David J. Clark, Hamid Alami, Robert D. Fleischmann, Robert D. Perry, Scott N. Peterson

Microbiology, Immunology, and Molecular Genetics Faculty Publications

BACKGROUND: The Gram-negative bacterium Yersinia pestis is the causative agent of the bubonic plague. Efficient iron acquisition systems are critical to the ability of Y. pestis to infect, spread and grow in mammalian hosts, because iron is sequestered and is considered part of the innate host immune defence against invading pathogens. We used a proteomic approach to determine expression changes of iron uptake systems and intracellular consequences of iron deficiency in the Y. pestis strain KIM6+ at two physiologically relevant temperatures (26°C and 37°C).

RESULTS: Differential protein display was performed for three Y. pestis subcellular fractions. Five characterized Y. pestis …

Farnesol Induces Hydrogen Peroxide Resistance In Candida Albicans Yeast By Inhibiting The Ras-Cyclic Amp Signaling Pathway, Aurélie Deveau, Amy E. Piispanen, Angelyca A. Jackson, Deborah A. Hogan

Dartmouth Scholarship

Farnesol, a Candida albicans cell-cell signaling molecule that participates in the control of morphology, has an additional role in protection of the fungus against oxidative stress. In this report, we show that although farnesol induces the accumulation of intracellular reactive oxygen species (ROS), ROS generation is not necessary for the induction of catalase (Cat1)-mediated oxidative-stress resistance. Two antioxidants, α-tocopherol and, to a lesser extent, ascorbic acid effectively reduced intracellular ROS generation by farnesol but did not alter farnesol-induced oxidative-stress resistance. Farnesol inhibits the Ras1-adenylate cyclase (Cyr1) signaling pathway to achieve its effects on morphology under hypha-inducing conditions, and we demonstrate …

Implications Of The Plastid Genome Sequence Of Typha (Typhaceae, Poales) For Understanding Genome Evolution In Poaceae, Mary M. Guisinger, Timothy W. Chumley, Jennifer V. Kuehl, Jeffrey L. Boore, Robert K. Jansen

All Faculty Scholarship for the College of the Sciences

Plastid genomes of the grasses (Poaceae) are unusual in their organization and rates of sequence evolution. There has been a recent surge in the availability of grass plastid genome sequences, but a comprehensive comparative analysis of genome evolution has not been performed that includes any related families in the Poales. We report on the plastid genome of Typha latifolia, the first non-grass Poales sequenced to date, and we present comparisons of genome organization and sequence evolution within Poales. Our results confirm that grass plastid genomes exhibit acceleration in both genomic rearrangements and nucleotide substitutions. Poaceae have multiple structural rearrangements, including …

Genetic Variation At Nuclear Loci Fails To Distinguish Two Morphologically Distinct Species Of Aquilegia, Elizabeth A. Cooper, Justen B. Whittall, Scott A. Hodges, Magnus Nordborg

Biology

Aquilegia formosa and pubescens are two closely related species belonging to the columbine genus. Despite their morphological and ecological differences, previous studies have revealed a large degree of intercompatibility, as well as little sequence divergence between these two taxa [1,2]. We compared the inter- and intraspecific patterns of variation for 9 nuclear loci, and found that the two species were practically indistinguishable at the level of DNA sequence polymorphism, indicating either very recent speciation or continued gene flow. As a comparison, we also analyzed variation at two loci across 30 other Aquilegia taxa; this revealed slightly more differentiation among taxa, …

Genetic Variation In Past And Current Landscapes: Conservation Implications Based On Six Endemic Florida Scrub Plants, Eric S. Menges, Rebecca W. Dolan, Robert Pickert, Rebecca Yahr, Doria R. Gordon

Scholarship and Professional Work - LAS

If genetic variation is often positively correlated with population sizes and the presence of nearby populations and suitable habitats, landscape proxies could inform conservation decisions without genetic analyses. For six Florida scrub endemic plants (Dicerandra frutescens, Eryngium cuneifolium, Hypericum cumulicola, Liatris ohlingerae, Nolina brittoniana, and Warea carteri), we relate two measures of genetic variation, expected heterozygosity and alleles per polymorphic locus (APL), to population size and landscape variables. Presettlement areas were estimated based on soil preferences and GIS soils maps. Four species showed no genetic patterns related to population or landscape factors. The …

Joint Estimation Of Dna Copy Number From Multiple Platforms, Nancy Zhang, Yasin Senbabaoglu, Jun Z. Li

Statistics Papers

DNA copy number variants (CNV) are gains and losses of segments of chromosomes, and comprise an important class of genetic variation. Recently, various microarray hybridization based techniques have been developed for high throughput measurement of DNA copy number. In many studies, multiple technical platforms or different versions of the same platform were used to interrogate the same samples; and it became necessary to pool information across these multiple sources to derive a consensus molecular profile for each sample. An integrated analysis is expected to maximize resolution and accuracy, yet currently there is no well formulated statistical method to address the …

Bayesian Methods For Network-Structured Genomics Data, Stefano Monni, Hongzhe Li

UPenn Biostatistics Working Papers

Graphs and networks are common ways of depicting information. In biology, many different processes are represented by graphs, such as regulatory networks, metabolic pathways and protein-protein interaction networks. This information provides useful supplement to the standard numerical genomic data such as microarray gene expression data. Effectively utilizing such an information can lead to a better identification of biologically relevant genomic features in the context of our prior biological knowledge. In this paper, we present a Bayesian variable selection procedure for network-structured covariates for both Gaussian linear and probit models. The key of our approach is the introduction of a Markov …

Wavelet-Based Functional Linear Mixed Models: An Application To Measurement Error–Corrected Distributed Lag Models, Elizabeth J. Malloy, Jeffrey S. Morris, Sara D. Adar, Helen Suh, Diane R. Gold, Brent A. Coull

Jeffrey S. Morris

Frequently, exposure data are measured over time on a grid of discrete values that collectively define a functional observation. In many applications, researchers are interested in using these measurements as covariates to predict a scalar response in a regression setting, with interest focusing on the most biologically relevant time window of exposure. One example is in panel studies of the health effects of particulate matter (PM), where particle levels are measured over time. In such studies, there are many more values of the functional data than observations in the data set so that regularization of the corresponding functional regression coefficient …

Members’ Discoveries: Fatal Flaws In Cancer Research, Jeffrey S. Morris

Jeffrey S. Morris

A recent article published in The Annals of Applied Statistics (AOAS) by two MD Anderson researchers—Keith Baggerly and Kevin Coombes—dissects results from a highly-influential series of medical papers involving genomics-driven personalized cancer therapy, and outlines a series of simple yet fatal flaws that raises serious questions about the veracity of the original results. Having immediate and strong impact, this paper, along with related work, is providing the impetus for new standards of reproducibility in scientific research.

Statistical Contributions To Proteomic Research, Jeffrey S. Morris, Keith A. Baggerly, Howard B. Gutstein, Kevin R. Coombes

Jeffrey S. Morris

Proteomic profiling has the potential to impact the diagnosis, prognosis, and treatment of various diseases. A number of different proteomic technologies are available that allow us to look at many proteins at once, and all of them yield complex data that raise significant quantitative challenges. Inadequate attention to these quantitative issues can prevent these studies from achieving their desired goals, and can even lead to invalid results. In this chapter, we describe various ways the involvement of statisticians or other quantitative scientists in the study team can contribute to the success of proteomic research, and we outline some of the …

Informatics And Statistics For Analyzing 2-D Gel Electrophoresis Images, Andrew W. Dowsey, Jeffrey S. Morris, Howard G. Gutstein, Guang Z. Yang

Jeffrey S. Morris

Whilst recent progress in ‘shotgun’ peptide separation by integrated liquid chromatography and mass spectrometry (LC/MS) has enabled its use as a sensitive analytical technique, proteome coverage and reproducibility is still limited and obtaining enough replicate runs for biomarker discovery is a challenge. For these reasons, recent research demonstrates the continuing need for protein separation by two-dimensional gel electrophoresis (2-DE). However, with traditional 2-DE informatics, the digitized images are reduced to symbolic data though spot detection and quantification before proteins are compared for differential expression by spot matching. Recently, a more robust and automated paradigm has emerged where gels are directly …

Bayesian Random Segmentationmodels To Identify Shared Copy Number Aberrations For Array Cgh Data, Veerabhadran Baladandayuthapani, Yuan Ji, Rajesh Talluri, Luis E. Nieto-Barajas, Jeffrey S. Morris

Jeffrey S. Morris

Array-based comparative genomic hybridization (aCGH) is a high-resolution high-throughput technique for studying the genetic basis of cancer. The resulting data consists of log fluorescence ratios as a function of the genomic DNA location and provides a cytogenetic representation of the relative DNA copy number variation. Analysis of such data typically involves estimation of the underlying copy number state at each location and segmenting regions of DNA with similar copy number states. Most current methods proceed by modeling a single sample/array at a time, and thus fail to borrow strength across multiple samples to infer shared regions of copy number aberrations. …

Quantitative Comparison Of Genomic-Wide Protein Domain Distributions, Arli A. Parikesit, Peter F. Stadler, Sonja J. Prohaska

Arli A Parikesit

Investigations into the origins and evolution of regulatory mechanisms require quantitative estimates of the abundance and co-occurrence of functional protein domains among distantly related genomes. Currently available databases, such as the SUPERFAMILY, are not designed for quantitative comparisons since they are built upon transcript and protein annotations provided by the various different genome annotation projects. Large biases are introduced by the differences in genome annotation protocols, which strongly depend on the availability of transcript information and well-annotated closely related organisms. Here we show that the combination of de novo gene predictors and subsequent HMM-based annotation of SCOP domains in the …

Paraoxonase 1 Activity As A Predictor Of Cardiovascular Disease In Type 2 Diabetes, Rozaida @ Poh Yuen Ying

Rozaida @ Poh Yuen Ying

The role of paraoxonase 1 in cardiovascular disease complications in type 2 diabetes mellitus is not fully understood. We studied paraoxonase activity towards paraoxon in 188 non-diabetic and 140 diabetic subjects using general linear models and univariate analysis. Adjusting for age revealed a reduction in activity towards paraoxon was associated with a significant increase in risk (p=0.023) for cardiovascular disease complications in diabetic patients. Multivariate analysis of two plasma measures of paraoxonase activity using paraoxon and diazoxon also showed reduced paraoxonase activity towards paraoxon was associated with a significant increase in risk (p=0.045) for cardiovascular disease complications in diabetic patients. …