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Robert Gentleman

Bio: Robert Gentleman is an academic researcher from Genentech. The author has contributed to research in topics: Bioconductor & Gene expression profiling. The author has an hindex of 52, co-authored 139 publications receiving 48510 citations. Previous affiliations of Robert Gentleman include Harvard University & Brigham and Women's Hospital.


Papers
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Journal ArticleDOI
TL;DR: PIPA provides an analytical framework to interpret siRNA screen data by merging biologically annotated gene sets with the human interactome and provides a complementary approach to standard gene set enrichment that utilizes the additional knowledge of specific interactions within biological gene sets.
Abstract: Background A systems biology interpretation of genome-scale RNA interference (RNAi) experiments is complicated by scope, experimental variability and network signaling robustness. Over representation approaches (ORA), such as the Hypergeometric or z-score, are an established statistical framework used to associate RNA interference effectors to biologically annotated gene sets or pathways. These methods, however, do not directly take advantage of our growing understanding of the interactome. Furthermore, these methods can miss partial pathway activation and may be biased by protein complexes. Here we present a novel ORA, protein interaction permutation analysis (PIPA), that takes advantage of canonical pathways and established protein interactions to identify pathways enriched for protein interactions connecting RNAi hits.

15 citations

Journal ArticleDOI
TL;DR: The results identify novel components of the graft response to transplantation injury and rejection that are identified in genes classified as defense, communication, and metabolism.
Abstract: Little is known regarding the graft response to transplantation injury. This study investigates the posttransplantation response of genes that are constitutively expressed in the heart. Constitutiv...

15 citations

Journal ArticleDOI
TL;DR: This work is motivated by emerging requirements for data architectures and algorithm interfaces to allow flexible exploration of public and private archives of genotyping and expression arrays to allow interactively explored and analyzed using commodity hardware.
Abstract: Summary: Associations between DNA polymorphisms and mRNA abundance are a natural target of genetic investigations, and microarrays facilitate genome-wide and transcriptome-wide surveys of these associations. This work is motivated by emerging requirements for data architectures and algorithm interfaces to allow flexible exploration of public and private archives of genotyping and expression arrays. Using R/Bioconductor facilities, Phase II HapMap genotypes and Illumina 47K expression assay results archived on multiple populations may be interactively explored and analyzed using commodity hardware. Availability and Implementation: Open Source. Bioconductor 2.3 packages GGtools, GGBase, GGdata, hmyriB36. Freely available on the web at http://www.bioconductor.org Contact: stvjc@channing.harvard.edu

14 citations

Book ChapterDOI
01 Jan 2003
TL;DR: A framework for reducing and interpreting results of multiple microarray experiments and a flexible genefiltering procedure, a dynamic and extensible annotation system, and methods for visualization are provided.
Abstract: We provide a framework for reducing and interpreting results of multiple microarray experiments. The basic tools are a flexible genefiltering procedure, a dynamic and extensible annotation system, and methods for visualization. The gene-filtering procedure efficiently evaluates families of deterministic or statistical predicates on collections of expression measurements. The expression-filtering predicates may involve reference to arbitrarily complex predicates on phenotype or genotype data. The annotation system collects mappings between manufacturer-specified probe set identifiers and public use nomenclature, ontology, and bibliographic systems. Visualization tools allow the exploration of the experimental data with respect to genomic quantities such as chromosomal location or functional groupings.

14 citations

Journal ArticleDOI
TL;DR: In this article, the authors proposed a reduction technique and versions of the EM algorithm and the vertex ex change method to perform constrained nonparametric maximum likelihood estimation of the cumulative distribution function given interval censored data.
Abstract: The authors propose a reduction technique and versions of the EM algorithm and the vertex ex change method to perform constrained nonparametric maximum likelihood estimation of the cumulative distribution function given interval censored data. The constrained vertex exchange method can be used in practice to produce likelihood intervals for the cumulative distribution function. In particular, the authors show how to produce a confidence interval with known asymptotic coverage for the survival function given current status data.

13 citations


Cited by
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Journal ArticleDOI
TL;DR: This work presents DESeq2, a method for differential analysis of count data, using shrinkage estimation for dispersions and fold changes to improve stability and interpretability of estimates, which enables a more quantitative analysis focused on the strength rather than the mere presence of differential expression.
Abstract: In comparative high-throughput sequencing assays, a fundamental task is the analysis of count data, such as read counts per gene in RNA-seq, for evidence of systematic changes across experimental conditions. Small replicate numbers, discreteness, large dynamic range and the presence of outliers require a suitable statistical approach. We present DESeq2, a method for differential analysis of count data, using shrinkage estimation for dispersions and fold changes to improve stability and interpretability of estimates. This enables a more quantitative analysis focused on the strength rather than the mere presence of differential expression. The DESeq2 package is available at http://www.bioconductor.org/packages/release/bioc/html/DESeq2.html .

47,038 citations

Journal ArticleDOI
TL;DR: EdgeR as mentioned in this paper is a Bioconductor software package for examining differential expression of replicated count data, which uses an overdispersed Poisson model to account for both biological and technical variability and empirical Bayes methods are used to moderate the degree of overdispersion across transcripts, improving the reliability of inference.
Abstract: Summary: It is expected that emerging digital gene expression (DGE) technologies will overtake microarray technologies in the near future for many functional genomics applications. One of the fundamental data analysis tasks, especially for gene expression studies, involves determining whether there is evidence that counts for a transcript or exon are significantly different across experimental conditions. edgeR is a Bioconductor software package for examining differential expression of replicated count data. An overdispersed Poisson model is used to account for both biological and technical variability. Empirical Bayes methods are used to moderate the degree of overdispersion across transcripts, improving the reliability of inference. The methodology can be used even with the most minimal levels of replication, provided at least one phenotype or experimental condition is replicated. The software may have other applications beyond sequencing data, such as proteome peptide count data. Availability: The package is freely available under the LGPL licence from the Bioconductor web site (http://bioconductor.org).

29,413 citations

Journal ArticleDOI
TL;DR: The philosophy and design of the limma package is reviewed, summarizing both new and historical features, with an emphasis on recent enhancements and features that have not been previously described.
Abstract: limma is an R/Bioconductor software package that provides an integrated solution for analysing data from gene expression experiments. It contains rich features for handling complex experimental designs and for information borrowing to overcome the problem of small sample sizes. Over the past decade, limma has been a popular choice for gene discovery through differential expression analyses of microarray and high-throughput PCR data. The package contains particularly strong facilities for reading, normalizing and exploring such data. Recently, the capabilities of limma have been significantly expanded in two important directions. First, the package can now perform both differential expression and differential splicing analyses of RNA sequencing (RNA-seq) data. All the downstream analysis tools previously restricted to microarray data are now available for RNA-seq as well. These capabilities allow users to analyse both RNA-seq and microarray data with very similar pipelines. Second, the package is now able to go past the traditional gene-wise expression analyses in a variety of ways, analysing expression profiles in terms of co-regulated sets of genes or in terms of higher-order expression signatures. This provides enhanced possibilities for biological interpretation of gene expression differences. This article reviews the philosophy and design of the limma package, summarizing both new and historical features, with an emphasis on recent enhancements and features that have not been previously described.

22,147 citations

Journal ArticleDOI
TL;DR: The GATK programming framework enables developers and analysts to quickly and easily write efficient and robust NGS tools, many of which have already been incorporated into large-scale sequencing projects like the 1000 Genomes Project and The Cancer Genome Atlas.
Abstract: Next-generation DNA sequencing (NGS) projects, such as the 1000 Genomes Project, are already revolutionizing our understanding of genetic variation among individuals. However, the massive data sets generated by NGS—the 1000 Genome pilot alone includes nearly five terabases—make writing feature-rich, efficient, and robust analysis tools difficult for even computationally sophisticated individuals. Indeed, many professionals are limited in the scope and the ease with which they can answer scientific questions by the complexity of accessing and manipulating the data produced by these machines. Here, we discuss our Genome Analysis Toolkit (GATK), a structured programming framework designed to ease the development of efficient and robust analysis tools for next-generation DNA sequencers using the functional programming philosophy of MapReduce. The GATK provides a small but rich set of data access patterns that encompass the majority of analysis tool needs. Separating specific analysis calculations from common data management infrastructure enables us to optimize the GATK framework for correctness, stability, and CPU and memory efficiency and to enable distributed and shared memory parallelization. We highlight the capabilities of the GATK by describing the implementation and application of robust, scale-tolerant tools like coverage calculators and single nucleotide polymorphism (SNP) calling. We conclude that the GATK programming framework enables developers and analysts to quickly and easily write efficient and robust NGS tools, many of which have already been incorporated into large-scale sequencing projects like the 1000 Genomes Project and The Cancer Genome Atlas.

20,557 citations

Posted ContentDOI
17 Nov 2014-bioRxiv
TL;DR: This work presents DESeq2, a method for differential analysis of count data, using shrinkage estimation for dispersions and fold changes to improve stability and interpretability of estimates, which enables a more quantitative analysis focused on the strength rather than the mere presence of differential expression.
Abstract: In comparative high-throughput sequencing assays, a fundamental task is the analysis of count data, such as read counts per gene in RNA-Seq data, for evidence of systematic changes across experimental conditions. Small replicate numbers, discreteness, large dynamic range and the presence of outliers require a suitable statistical approach. We present DESeq2, a method for differential analysis of count data. DESeq2 uses shrinkage estimation for dispersions and fold changes to improve stability and interpretability of the estimates. This enables a more quantitative analysis focused on the strength rather than the mere presence of differential expression and facilitates downstream tasks such as gene ranking and visualization. DESeq2 is available as an R/Bioconductor package.

17,014 citations