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Articles 31 - 35 of 35
Full-Text Articles in Genetics and Genomics
Poor Performance Of Bootstrap Confidence Intervals For The Location Of A Quantitative Trait Loucs, Ani Manichaikul, Josee Dupuis, Saunak Sen, Karl W. Broman
Poor Performance Of Bootstrap Confidence Intervals For The Location Of A Quantitative Trait Loucs, Ani Manichaikul, Josee Dupuis, Saunak Sen, Karl W. Broman
Johns Hopkins University, Dept. of Biostatistics Working Papers
The aim of many genetic studies is to locate the genomic regions (called quantitative trait loci, QTLs) that contribute to variation in a quantitative trait (such as body weight). Confidence intervals for the locations of QTLs are particularly important for the design of further experiments to identify the gene or genes responsible for the effect. Likelihood support intervals are the most widely used method to obtain confidence intervals for QTL location, but the non-parametric bootstrap has also been recommended. Through extensive computer simulation, we show that bootstrap confidence intervals are poorly behaved and so should not be used in this …
Multiple Tests Of Association With Biological Annotation Metadata, Sandrine Dudoit, Sunduz Keles, Mark J. Van Der Laan
Multiple Tests Of Association With Biological Annotation Metadata, Sandrine Dudoit, Sunduz Keles, Mark J. Van Der Laan
U.C. Berkeley Division of Biostatistics Working Paper Series
We propose a general and formal statistical framework for the multiple tests of associations between known fixed features of a genome and unknown parameters of the distribution of variable features of this genome in a population of interest. The known fixed gene-annotation profiles, corresponding to the fixed features of the genome, may concern Gene Ontology (GO) annotation, pathway membership, regulation by particular transcription factors, nucleotide sequences, or protein sequences. The unknown gene-parameter profiles, corresponding to the variable features of the genome, may be, for example, regression coefficients relating genome-wide transcript levels or DNA copy numbers to possibly censored biological and …
The Role Of An Explicit Causal Framework In Affected Sib Pair Designs With Covariates , Constantine E. Frangakis, Fan Li, Betty Q. Doan
The Role Of An Explicit Causal Framework In Affected Sib Pair Designs With Covariates , Constantine E. Frangakis, Fan Li, Betty Q. Doan
Johns Hopkins University, Dept. of Biostatistics Working Papers
The affected sib/relative pair (ASP/ARP) design is often used with covariates to find genes that can cause a disease in pathways other than through those covariates. However, such "covariates" can themselves have genetic determinants, and the validity of existing methods has so far only been argued under implicit assumptions. We propose an explicit causal formulation of the problem using potential outcomes and principal stratification. The general role of this formulation is to identify and separate the meaning of the different assumptions that can provide valid causal inference in linkage analysis. This separation helps to (a) develop better methods under explicit …
New Statistical Paradigms Leading To Web-Based Tools For Clinical/Translational Science, Knut M. Wittkowski
New Statistical Paradigms Leading To Web-Based Tools For Clinical/Translational Science, Knut M. Wittkowski
COBRA Preprint Series
As the field of functional genetics and genomics is beginning to mature, we become confronted with new challenges. The constant drop in price for sequencing and gene expression profiling as well as the increasing number of genetic and genomic variables that can be measured makes it feasible to address more complex questions. The success with rare diseases caused by single loci or genes has provided us with a proof-of-concept that new therapies can be developed based on functional genomics and genetics.
Common diseases, however, typically involve genetic epistasis, genomic pathways, and proteomic pattern. Moreover, to better understand the underlying biologi-cal …
Searching For Differentially Expressed Gene Combinations, Marcel Dettling, Edward Gabrielson, Giovanni Parmigiani
Searching For Differentially Expressed Gene Combinations, Marcel Dettling, Edward Gabrielson, Giovanni Parmigiani
Johns Hopkins University, Dept. of Biostatistics Working Papers
Background: Comparison of mRNA expression levels across biological samples is a widely used approach in genomics. Available data-analytic tools for deriving comprehensive lists of differentially expressed genes rely on data summaries formed using each gene in isolation from others. These approaches ignore biological relationships among genes and may miss important biological insight provided by genomics data.
Methods: We propose a fast, easily interpretable and scalable approach for identifying pairs of genes that are differentially expressed across phenotypes or experimental conditions. These are defined as pairs for which there is detectable phenotype discrimination using the joint distribution, but not from either …