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R. Alan Harris

Bio: R. Alan Harris is an academic researcher from Baylor College of Medicine. The author has contributed to research in topics: DNA methylation & Epigenomics. The author has an hindex of 43, co-authored 84 publications receiving 10907 citations. Previous affiliations of R. Alan Harris include University of Houston & Human Genome Sequencing Center.


Papers
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Journal ArticleDOI
Anshul Kundaje1, Wouter Meuleman1, Wouter Meuleman2, Jason Ernst3, Misha Bilenky4, Angela Yen2, Angela Yen1, Alireza Heravi-Moussavi4, Pouya Kheradpour2, Pouya Kheradpour1, Zhizhuo Zhang2, Zhizhuo Zhang1, Jianrong Wang1, Jianrong Wang2, Michael J. Ziller2, Viren Amin5, John W. Whitaker, Matthew D. Schultz6, Lucas D. Ward1, Lucas D. Ward2, Abhishek Sarkar2, Abhishek Sarkar1, Gerald Quon1, Gerald Quon2, Richard Sandstrom7, Matthew L. Eaton1, Matthew L. Eaton2, Yi-Chieh Wu2, Yi-Chieh Wu1, Andreas R. Pfenning1, Andreas R. Pfenning2, Xinchen Wang1, Xinchen Wang2, Melina Claussnitzer1, Melina Claussnitzer2, Yaping Liu1, Yaping Liu2, Cristian Coarfa5, R. Alan Harris5, Noam Shoresh2, Charles B. Epstein2, Elizabeta Gjoneska2, Elizabeta Gjoneska1, Danny Leung8, Wei Xie8, R. David Hawkins8, Ryan Lister6, Chibo Hong9, Philippe Gascard9, Andrew J. Mungall4, Richard A. Moore4, Eric Chuah4, Angela Tam4, Theresa K. Canfield7, R. Scott Hansen7, Rajinder Kaul7, Peter J. Sabo7, Mukul S. Bansal2, Mukul S. Bansal1, Mukul S. Bansal10, Annaick Carles4, Jesse R. Dixon8, Kai How Farh2, Soheil Feizi1, Soheil Feizi2, Rosa Karlic11, Ah Ram Kim2, Ah Ram Kim1, Ashwinikumar Kulkarni12, Daofeng Li13, Rebecca F. Lowdon13, Ginell Elliott13, Tim R. Mercer14, Shane Neph7, Vitor Onuchic5, Paz Polak15, Paz Polak2, Nisha Rajagopal8, Pradipta R. Ray12, Richard C Sallari2, Richard C Sallari1, Kyle Siebenthall7, Nicholas A Sinnott-Armstrong2, Nicholas A Sinnott-Armstrong1, Michael Stevens13, Robert E. Thurman7, Jie Wu16, Bo Zhang13, Xin Zhou13, Arthur E. Beaudet5, Laurie A. Boyer1, Philip L. De Jager2, Philip L. De Jager15, Peggy J. Farnham17, Susan J. Fisher9, David Haussler18, Steven J.M. Jones19, Steven J.M. Jones4, Wei Li5, Marco A. Marra4, Michael T. McManus9, Shamil R. Sunyaev15, Shamil R. Sunyaev2, James A. Thomson20, Thea D. Tlsty9, Li-Huei Tsai1, Li-Huei Tsai2, Wei Wang, Robert A. Waterland5, Michael Q. Zhang21, Lisa Helbling Chadwick22, Bradley E. Bernstein6, Bradley E. Bernstein15, Bradley E. Bernstein2, Joseph F. Costello9, Joseph R. Ecker11, Martin Hirst4, Alexander Meissner2, Aleksandar Milosavljevic5, Bing Ren8, John A. Stamatoyannopoulos7, Ting Wang13, Manolis Kellis2, Manolis Kellis1 
19 Feb 2015-Nature
TL;DR: It is shown that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease.
Abstract: The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease.

5,037 citations

Journal ArticleDOI
13 Apr 2007-Science
TL;DR: The genome sequence of an Indian-origin Macaca mulatta female is determined and compared with chimpanzees and humans to reveal the structure of ancestral primate genomes and to identify evidence for positive selection and lineage-specific expansions and contractions of gene families.
Abstract: The rhesus macaque (Macaca mulatta) is an abundant primate species that diverged from the ancestors of Homo sapiens about 25 million years ago. Because they are genetically and physiologically similar to humans, rhesus monkeys are the most widely used nonhuman primate in basic and applied biomedical research. We determined the genome sequence of an Indian-origin Macaca mulatta female and compared the data with chimpanzees and humans to reveal the structure of ancestral primate genomes and to identify evidence for positive selection and lineage-specific expansions and contractions of gene families. A comparison of sequences from individual animals was used to investigate their underlying genetic diversity. The complete description of the macaque genome blueprint enhances the utility of this animal model for biomedical research and improves our understanding of the basic biology of the species.

1,297 citations

Journal ArticleDOI
TL;DR: This work combined MeDIP-seq with methylation-sensitive restriction enzyme (MRE-seq) sequencing for comprehensive methylome coverage at lower cost and detected regions with allele-specific epigenetic states, identifying most known imprinted regions and new loci with Monoallelic epigenetic marks and monoallelic expression.
Abstract: Analysis of DNA methylation patterns relies increasingly on sequencing-based profiling methods. The four most frequently used sequencing-based technologies are the bisulfite-based methods MethylC-seq and reduced representation bisulfite sequencing (RRBS), and the enrichment-based techniques methylated DNA immunoprecipitation sequencing (MeDIP-seq) and methylated DNA binding domain sequencing (MBD-seq). We applied all four methods to biological replicates of human embryonic stem cells to assess their genome-wide CpG coverage, resolution, cost, concordance and the influence of CpG density and genomic context. The methylation levels assessed by the two bisulfite methods were concordant (their difference did not exceed a given threshold) for 82% for CpGs and 99% of the non-CpG cytosines. Using binary methylation calls, the two enrichment methods were 99% concordant and regions assessed by all four methods were 97% concordant. We combined MeDIP-seq with methylation-sensitive restriction enzyme (MRE-seq) sequencing for comprehensive methylome coverage at lower cost. This, along with RNA-seq and ChIP-seq of the ES cells enabled us to detect regions with allele-specific epigenetic states, identifying most known imprinted regions and new loci with monoallelic epigenetic marks and monoallelic expression.

676 citations

Journal ArticleDOI
TL;DR: This study reinforces the importance of DNA methylation in regulating cellular phenotype across tissues, and highlights genomic patterns of epigenetic variation across functionally distinct regions of the brain, providing a resource for the epigenetics and neuroscience research communities.
Abstract: Background Dynamic changes to the epigenome play a critical role in establishing and maintaining cellular phenotype during differentiation, but little is known about the normal methylomic differences that occur between functionally distinct areas of the brain. We characterized intra- and inter-individual methylomic variation across whole blood and multiple regions of the brain from multiple donors.

610 citations

Journal ArticleDOI
TL;DR: DNA methylation at MEs was elevated in individuals conceived during the nutritionally challenged rainy season, providing the first evidence of a permanent, systemic effect of periconceptional environment on human epigenotype.
Abstract: Throughout most of the mammalian genome, genetically regulated developmental programming establishes diverse yet predictable epigenetic states across differentiated cells and tissues. At metastable epialleles (MEs), conversely, epigenotype is established stochastically in the early embryo then maintained in differentiated lineages, resulting in dramatic and systemic interindividual variation in epigenetic regulation. In the mouse, maternal nutrition affects this process, with permanent phenotypic consequences for the offspring. MEs have not previously been identified in humans. Here, using an innovative 2-tissue parallel epigenomic screen, we identified putative MEs in the human genome. In autopsy samples, we showed that DNA methylation at these loci is highly correlated across tissues representing all 3 embryonic germ layer lineages. Monozygotic twin pairs exhibited substantial discordance in DNA methylation at these loci, suggesting that their epigenetic state is established stochastically. We then tested for persistent epigenetic effects of periconceptional nutrition in rural Gambians, who experience dramatic seasonal fluctuations in nutritional status. DNA methylation at MEs was elevated in individuals conceived during the nutritionally challenged rainy season, providing the first evidence of a permanent, systemic effect of periconceptional environment on human epigenotype. At MEs, epigenetic regulation in internal organs and tissues varies among individuals and can be deduced from peripheral blood DNA. MEs should therefore facilitate an improved understanding of the role of interindividual epigenetic variation in human disease.

412 citations


Cited by
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28 Jul 2005
TL;DR: PfPMP1)与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作�ly.
Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1(PfPMP1)与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员,通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

18,940 citations

Journal ArticleDOI
TL;DR: FeatureCounts as discussed by the authors is a read summarization program suitable for counting reads generated from either RNA or genomic DNA sequencing experiments, which implements highly efficient chromosome hashing and feature blocking techniques.
Abstract: MOTIVATION: Next-generation sequencing technologies generate millions of short sequence reads, which are usually aligned to a reference genome. In many applications, the key information required for downstream analysis is the number of reads mapping to each genomic feature, for example to each exon or each gene. The process of counting reads is called read summarization. Read summarization is required for a great variety of genomic analyses but has so far received relatively little attention in the literature. RESULTS: We present featureCounts, a read summarization program suitable for counting reads generated from either RNA or genomic DNA sequencing experiments. featureCounts implements highly efficient chromosome hashing and feature blocking techniques. It is considerably faster than existing methods (by an order of magnitude for gene-level summarization) and requires far less computer memory. It works with either single or paired-end reads and provides a wide range of options appropriate for different sequencing applications. AVAILABILITY AND IMPLEMENTATION: featureCounts is available under GNU General Public License as part of the Subread (http://subread.sourceforge.net) or Rsubread (http://www.bioconductor.org) software packages.

14,103 citations

Journal ArticleDOI
Anshul Kundaje1, Wouter Meuleman1, Wouter Meuleman2, Jason Ernst3, Misha Bilenky4, Angela Yen2, Angela Yen1, Alireza Heravi-Moussavi4, Pouya Kheradpour2, Pouya Kheradpour1, Zhizhuo Zhang1, Zhizhuo Zhang2, Jianrong Wang1, Jianrong Wang2, Michael J. Ziller2, Viren Amin5, John W. Whitaker, Matthew D. Schultz6, Lucas D. Ward1, Lucas D. Ward2, Abhishek Sarkar1, Abhishek Sarkar2, Gerald Quon1, Gerald Quon2, Richard Sandstrom7, Matthew L. Eaton2, Matthew L. Eaton1, Yi-Chieh Wu2, Yi-Chieh Wu1, Andreas R. Pfenning1, Andreas R. Pfenning2, Xinchen Wang2, Xinchen Wang1, Melina Claussnitzer1, Melina Claussnitzer2, Yaping Liu1, Yaping Liu2, Cristian Coarfa5, R. Alan Harris5, Noam Shoresh2, Charles B. Epstein2, Elizabeta Gjoneska2, Elizabeta Gjoneska1, Danny Leung8, Wei Xie8, R. David Hawkins8, Ryan Lister6, Chibo Hong9, Philippe Gascard9, Andrew J. Mungall4, Richard A. Moore4, Eric Chuah4, Angela Tam4, Theresa K. Canfield7, R. Scott Hansen7, Rajinder Kaul7, Peter J. Sabo7, Mukul S. Bansal1, Mukul S. Bansal2, Mukul S. Bansal10, Annaick Carles4, Jesse R. Dixon8, Kai How Farh2, Soheil Feizi2, Soheil Feizi1, Rosa Karlic11, Ah Ram Kim1, Ah Ram Kim2, Ashwinikumar Kulkarni12, Daofeng Li13, Rebecca F. Lowdon13, Ginell Elliott13, Tim R. Mercer14, Shane Neph7, Vitor Onuchic5, Paz Polak15, Paz Polak2, Nisha Rajagopal8, Pradipta R. Ray12, Richard C Sallari1, Richard C Sallari2, Kyle Siebenthall7, Nicholas A Sinnott-Armstrong2, Nicholas A Sinnott-Armstrong1, Michael Stevens13, Robert E. Thurman7, Jie Wu16, Bo Zhang13, Xin Zhou13, Arthur E. Beaudet5, Laurie A. Boyer1, Philip L. De Jager2, Philip L. De Jager15, Peggy J. Farnham17, Susan J. Fisher9, David Haussler18, Steven J.M. Jones19, Steven J.M. Jones4, Wei Li5, Marco A. Marra4, Michael T. McManus9, Shamil R. Sunyaev15, Shamil R. Sunyaev2, James A. Thomson20, Thea D. Tlsty9, Li-Huei Tsai2, Li-Huei Tsai1, Wei Wang, Robert A. Waterland5, Michael Q. Zhang21, Lisa Helbling Chadwick22, Bradley E. Bernstein6, Bradley E. Bernstein2, Bradley E. Bernstein15, Joseph F. Costello9, Joseph R. Ecker11, Martin Hirst4, Alexander Meissner2, Aleksandar Milosavljevic5, Bing Ren8, John A. Stamatoyannopoulos7, Ting Wang13, Manolis Kellis2, Manolis Kellis1 
19 Feb 2015-Nature
TL;DR: It is shown that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease.
Abstract: The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease.

5,037 citations

01 Aug 2000
TL;DR: Assessment of medical technology in the context of commercialization with Bioentrepreneur course, which addresses many issues unique to biomedical products.
Abstract: BIOE 402. Medical Technology Assessment. 2 or 3 hours. Bioentrepreneur course. Assessment of medical technology in the context of commercialization. Objectives, competition, market share, funding, pricing, manufacturing, growth, and intellectual property; many issues unique to biomedical products. Course Information: 2 undergraduate hours. 3 graduate hours. Prerequisite(s): Junior standing or above and consent of the instructor.

4,833 citations