Assisted assembly: how to improve a de novogenome assembly by using related species (2009)
Gnerre, Sante, Lander, Eric S, Lindblad-Toh, Kerstin, Jaffe, David B
Abstract We describe a new assembly algorithm, where a genome assembly with low sequence coverage, either throughout the genome or locally, due to cloning bias, is considerably improved through an...
Assisted assembly: how to improve a de novo genome assembly by using related species (2009)
Gnerre, Sante, Lander, Eric S., Lindbald-Toh, Kerstin, Jaffe, David B.
We describe a new assembly algorithm, where a genome assembly with low sequence coverage, either throughout the genome or locally, due to cloning bias, is considerably improved through an assisting...
Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1 (2009)
Barbie, David A., Tamayo, Pablo, Boehm, Jesse S., Kim, So Young, Moody, Susan E., Dunn, Ian F., ...
Neafsey, Daniel E, Schaffner, Stephen F, Volkman, Sarah K, Park, Daniel, Montgomery, Philip, Milner, Danny A, ...
Abstract Background The malaria parasite Plasmodium falciparum exhibits abundant genetic diversity, and this diversity is key to its success as a pathogen. Previous efforts to study genetic diversity...
Somatic mutations affect key pathways in lung adenocarcinoma (2008)
Ding, Li, Getz, Gad, Wheeler, David A., Mardis, Elaine R., McLellan, Michael D., Cibulskis, Kristian, ...
Determining the genetic basis of cancer requires comprehensive analyses of large collections of histopathologically well- classified primary tumours. Here we report the results of a collaborative...
SYMMETRIC DESIGNS AND SELF-DUAL CODES (2008)
A construction is given for associating to any symmetric (v, k, X) design a self-dual code of length v+ 1 over GF (p), where p is any divisor of the square-free part of k — k. These codes are then...
Physical Mapping Assembling Physical Maps by (2008)
Genetic mapping is only the first step toward positional cloning of a gene. Once a gene has been determined to lie between two genetic markers, the geneticist must produce a physical map—consisting...
Somatic mutations affect key pathways in lung adenocarcinoma (2008)
Ding, Li, Getz, Gad, Wheeler, David A., Mardis, Elaine R., McLellan, Michael D., Cibulskis, Kristian, ...
Genetic architecture of complex traits: large phenotypic effects and pervasive epistasis. (2008)
Shao, Haifeng, Burrage, Lindsay C., Sinasac, David S., Hill, Annie E., Ernest, Sheila R., O'Brien, William, ...
The genetic architecture of complex traits underlying physiology and disease in most organisms remains elusive. We still know little about the number of genes that underlie these traits, the...
Quality scores and SNP detection in sequencing-by-synthesis systems (2008)
Brockman, William, Alvarez, Pablo, Young, Sarah, Garber, Manuel, Giannoukos, Georgia, Lee, William L., ...
Promising new sequencing technologies, based on sequencing-by-synthesis (SBS), are starting to deliver large amounts of DNA sequence at very low cost. Polymorphism detection is a key application. We...
ALLPATHS: De novo assembly of whole-genome shotgun microreads (2008)
Butler, Jonathan, MacCallum, Iain, Kleber, Michael, Shlyakhter, Ilya A., Belmonte, Matthew K., Lander, Eric S., ...
New DNA sequencing technologies deliver data at dramatically lower costs but demand new analytical methods to take full advantage of the very short reads that they produce. We provide an initial,...
Characterizing the cancer genome in lung adenocarcinoma (2007)
Weir, Barbara A., Woo, Michele S., Getz, Gad, Perner, Sven, Ding, Li, Beroukhim, Rameen, ...
Somatic alterations in cellular DNA underlie almost all human cancers(1). The prospect of targeted therapies(2) and the development of high-resolution, genome-wide approaches(3-8) are now spurring...
Leonid Kruglyak, Mark J. Daly, Eric S. Lander, Eric S. L
this paper allows very rapid multipoint likelihood calculation in nuclear families (with or without parental consanguinity), and the accompanying software package makes multipoint mapping feasible in...
Margulies, Elliott H., Cooper, Gregory M., Asimenos, George, Thomas, Daryl J., Dewey, Colin N., Siepel, Adam, ...
A key component of the ongoing ENCODE project involves rigorous comparative sequence analyses for the initially targeted 1% of the human genome. Here, we present orthologous sequence generation,...
A second major histocompatibility complex susceptibility locus for multiple sclerosis (2007)
Gregory, Simon G, Barcellos, Lisa F, Walton, Amie, ...
Objective: Variation in the major histocompatibility complex (MHC) on chromosome 6p21 is known to influence susceptibility to multiple sclerosis with the strongest effect originating from the...
Characterizing the cancer genome in lung adenocarcinoma (2007)
Weir, Barbara A., Woo, Michele S., Getz, Gad, Perner, Sven, Ding, Li, Beroukhim, Rameen, ...
28-Way vertebrate alignment and conservation track in the UCSC Genome Browser (2007)
Miller, Webb, Rosenbloom, Kate, Hardison, Ross C., Hou, Minmei, Taylor, James, Raney, Brian, ...
This article describes a set of alignments of 28 vertebrate genome sequences that is provided by the UCSC Genome Browser. The alignments can be viewed on the Human Genome Browser (March 2006...
Symmetric Designs and Self-Dual Codes (2006)
A construction is given for associating to any symmetric (v, k,λ) design a self-dual code of length v+ 1 over GF (p), where p is any divisor of the square-free part of k−λ. These codes are then...
Identification and classification of conserved RNA secondary structures in the human genome (2006)
Pedersen, Jakob Skou, Bejerano, Gill, Siepel, Adam, Rosenbloom, Kate, Lindblad-Toh, Kerstin, Lander, Eric S, ...
The discoveries of microRNAs and riboswitches, among others, have shown functional RNAs to be biologically more important and genomically more prevalent than previously anticipated. We have developed...
Identification and Classification of Conserved RNA Secondary Structures in the Human Genome (2006)
Jakob Skou Pedersen, Gill Bejerano, Adam Siepel, Kate Rosenbloom, Kerstin Lindblad-Toh, Eric S. Lander, ...
The discoveries of microRNAs and riboswitches, among others, have shown functional RNAs to be biologically more important and genomically more prevalent than previously anticipated. We have developed...
Identification and Classification of Conserved RNA Secondary Structures in the Human Genome (2006)
Jakob Skou Pedersen, Gill Bejerano, Adam Siepel, Kate R. Rosenbloom, Kerstin Lindblad-Toh, Eric S Lander, ...
The discovery of, e.g., microRNAs and riboswitches have shown functional RNAs to be biologically more important and genomically more prevalent than previously anticipated. We have developed a general...
The Case for Selection at CCR5-Δ32 (2005)
Pardis C. Sabeti, Emily Walsh, Steve F. Schaffner, Patrick Varilly, Ben Fry, Holli B. Hutcheson, ...
Sabeti and colleagues use dense genetic maps to show that the HIV-resistance CCR5-Δ32 allele is more than 5,000 years old and is likely to have been under mainly neutral selection.
The Case for Selection at CCR5-Δ32 (2005)
Pardis C. Sabeti, Emily Walsh, Steve F. Schaffner, Patrick Varilly, Ben Fry, Holli B. Hutcheson, ...
The C-C chemokine receptor 5, 32 base-pair deletion (CCR5-Δ32) allele confers strong resistance to infection by the AIDS virus HIV. Previous studies have suggested that CCR5-Δ32 arose within the...
Initial sequence of the chimpanzee genome and comparison with the human genome (2005)
Mikkelsen, Tarjei S., Hillier, LaDeana W., Eichler, Evan E., Zody, Michael C., Jaffe, David B., Yang, Shiaw-Pyng, ...
Here we present a draft genome sequence of the common chimpanzee (Pan troglodytes). Through comparison with the human genome, we have generated a largely complete catalogue of the genetic differences...
Mapping quantitative trait loci for anxiety in chromosome substitution strains of mice. (2005)
Singer, Jonathan B., Hill, Annie E., Nadeau, Joseph H., Lander, Eric S.
Anxious behavior in the mouse is a complex quantitative phenotype that varies widely among inbred mouse strains. We examined a panel of chromosome substitution strains bearing individual A/J...
Meissner, Alexander, Gnirke, Andreas, Bell, George W., Ramsahoye, Bernard, Lander, Eric S., Jaenisch, Rudolf
We describe a large-scale random approach termed reduced representation bisulfite sequencing (RRBS) for analyzing and comparing genomic methylation patterns. BglII restriction fragments were...
Assembly of polymorphic genomes: Algorithms and application to Ciona savignyi (2005)
Vinson, Jade P., Jaffe, David B., O'Neill, Keith, Karlsson, Elinor K., Stange-Thomann, Nicole, Anderson, Scott, ...
Whole-genome assembly is now used routinely to obtain high-quality draft sequence for the genomes of species with low levels of polymorphism. However, genome assembly remains extremely challenging...
Poirier, Christophe, Qin, Yangjun, Adams, Carolyn P., Anaya, Yanett, Singer, Jonathan B., Hill, Annie E., ...
The transgenic insertional mouse mutation Odd Sex (Ods) represents a model for the long-range regulation of Sox9. The mutation causes complete female-to-male sex reversal by inducing a male-specific...
Enhancing linkage analysis of complex disorders: An evaluation of high-density genotyping (2004)
Sawcer, Stephen J, Maranian, Mel, Singlehurst, Sarah, Yeo, TaiWai, Compston, Alastair, ...
To explore the potential value of recently developed high density linkage mapping methods in the analysis of complex disease we have regenotyped five nuclear families first studied in the 1996 UK...
Enhancing linkage analysis of complex disorders: An evaluation of high-density genotyping (2004)
Sawcer, Stephen J, Maranian, Mel, Singlehurst, Sarah, Yeo, TaiWai, Compston, Alastair, ...
To explore the potential value of recently developed high density linkage mapping methods in the analysis of complex disease we have regenotyped five nuclear families first studied in the 1996 UK...
Position specific variation in the rate of evolution in transcription factor binding sites (2003)
Moses, Alan M., Chiang, Derek Y., Kellis, Manolis, Lander, Eric S., Eisen, Michael B.
Background: The binding sites of sequence specific transcription factors are an important and relatively well-understood class of functional non-coding DNAs. Although a wide variety of experimental...
Position specific variation in the rate of evolution in transcription factor binding sites (2003)
Moses, Alan M, Chiang, Derek Y, Kellis, Manolis, Lander, Eric S, Eisen, Michael B
Abstract Background The binding sites of sequence specific transcription factors are an important and relatively well-understood class of functional non-coding DNAs. Although a wide variety of...
Chiang, Derek Y, Moses, Alan M, Kellis, Manolis, Lander, Eric S, Eisen, Michael B
Abstract Background Transcriptional regulation in eukaryotes often involves multiple transcription factors binding to the same transcription control region, and to understand the regulatory content...
BMC Evolutionary Biology BioMed Central (2003)
Alan M Moses, Derek Y Chiang, Manolis Kellis, Eric S L, Michael B Eisen, Eric S Lander, ...
Research article Position specific variation in the rate of evolution in transcription factor binding sites
Derek Y. Chiang, Dept Of Molecular, Cell Biology, Eric S. Lander
Background. Transcriptional regulation in eukaryotes is often multifactorial, involving multiple transcription factors binding to the same transcription control region (e.g., upstream activating...
Genes, Regulation, Evolution (2003)
Manolis (kellis Kamvysselis, Eric S. Lander, Bonnie A. Berger, Arthur C. Smith
BMC Evolutionary Biology BioMed Central (2003)
Alan M Moses, Derek Y Chiang, Manolis Kellis, Eric S L, Michael B Eisen, Eric S Lander, ...
Research article Position specific variation in the rate of evolution in transcription factor binding sites
Whole-Genome Sequence Assembly for Mammalian Genomes: Arachne 2 (2003)
Jaffe, David B., Butler, Jonathan, Gnerre, Sante, Mauceli, Evan, Lindblad-Toh, Kerstin, Mesirov, Jill P., ...
We previously described the whole-genome assembly program Arachne, presenting assemblies of simulated data for small to mid-sized genomes. Here we describe algorithmic adaptations to the program,...
MacMurray, Armand J., Moralejo, Daniel H., Kwitek, Anne E., Rutledge, Elizabeth A., Van Yserloo, Brian, Gohlke, Paul, ...
ARACHNE: A Whole-Genome Shotgun Assembler (2002)
Batzoglou, Serafim, Jaffe, David B., Stanley, Ken, Butler, Jonathan, Gnerre, Sante, Mauceli, Evan, ...
7.012 Introduction to Biology, Fall 2001 (2001)
Lander, Eric S., Gardel, Claudette L., Mischke, Michelle D.
Cell biology, immunology, neurobiology, and an exploration into current research in cancer, genomics, and molecular medicine.
7.012 Introduction to Biology, Fall 2001 (2001)
Lander, Eric S., Gardel, Claudette L., Mischke, Michelle D.
Cell biology, immunology, neurobiology, and an exploration into current research in cancer, genomics, and molecular medicine.
Inoue, Ken, Dewar, Ken, Katsanis, Nicholas, Reiter, Lawrence T., Lander, Eric S., Devon, Keri L., ...
Class Prediction and Discovery Using Gene Expression Data (2000)
Donna K. Slonim, Pablo Tamayo, Jill P. Mesirov, Todd R. Golub, Eric S. Lander, Eric S. L
Classification of patient samples is a crucial aspect of cancer diagnosis and treatment. We present a method for classifying samples by computational analysis of gene expression data. We consider the...
Human and Mouse Gene Structure: Comparative Analysis and Application to Exon Prediction (2000)
Batzoglou, Serafim, Pachter, Lior, Mesirov, Jill P., Berger, Bonnie, Lander, Eric S.
A Dictionary Based Approach for Gene Annotation (1999)
Lior Pachter, Serafim Batzoglou, Valentin I. Spitkovsky, William S. Beebee, Eric S. Lander, Bonnie Berger, ...
This paper describes a fast and fully automated dictionary based approach to gene annotation and exon prediction. Two dictionaries are constructed, one from the nonredundant protein OWL database and...
A Dictionary Based Approach for Gene Annotation (1999)
Lior Pachter, Valentin I. Spitkovsky, Eric Banks, Eric S. Lander, Daniel J. Kleitman, Bonnie Berger
L.P. and S.B. contributed equally to this work. z
A dictionary-based approach for gene annotation (1999)
Lior Pachter, Serafim Batzoglou, Valentin I. Spitkovsky, Eric Banks, Eric S. Lander, Daniel J. Kleitman, ...
This paper describes a fast and fully automated dictionary-based approach to gene annotation and exon prediction. Two dictionaries are constructed, one from the nonredundant protein OWL database and...
Sequencing a Genome by Walking with Clone-End Sequences: A Mathematical Analysis (1999)
Batzoglou, Serafim, Berger, Bonnie, Mesirov, Jill, Lander, Eric S.
A High-Density Integrated Genetic Linkage and Radiation Hybrid Map of the Laboratory Rat (1999)
Steen, Robert G., Kwitek-Black, Anne E., Glenn, Christopher, Gullings-Handley, Jo, Van Etten, William, Atkinson, O. Scott, ...
A High-Density Integrated Genetic Linkage and Radiation Hybrid Map of the Laboratory Rat (1999)
Steen, Robert G., Kwitek-Black, Anne E., Glenn, Christopher, Gullings-Handley, Jo, Van Etten, William, Atkinson, O. Scott, ...
Recent Developments in Computational Gene Recognition (1998)
Serafim Batzoglou, Bonnie Berger, Daniel J. Kleitman, Eric S. Lander, Eric S. L, Lior Pachter
. We survey recent mathematical and computational work in the field of gene recognition, focusing on the techniques that have been developed to tackle the problem of identifying protein coding...
this article appeared in the July issue of Notices.
An automated method for DNA preparation from thousands of YAC clones (1991)
MacMurray, Armand J., Weaver, Alix, Shin, Hee-Sup, Lander, Eric S.
We describe an automated method for the preparation of yeast genomlc DNA capable of preparing thousands of DNAs in parallel from a YAC library. Briefly, the protocol involves four steps: (1) Yeast...
Prospects for the Genetic Analysis of Schizophrenia (1989)
Pato, Carlos N., Lander, Eric S., Schulz, S. Charles
This issue of the Schizophrenia Bulletin provides a forum for the presentation of early results and speculative hypotheses based on the application of molecular genetic methods for linkage studies in...
Restriction Fragment Length Polymorphism Linkage Map for Arabidopsis thaliana (1988)
Chang, Caren, Bowman, John L., DeJohn, Arthur W., Lander, Eric S., Meyerowitz, Elliot M.
We have constructed a restriction fragment length polymorphism linkage map for the nuclear genome of the flowering plant Arabidopsis thaliana. The map, containing 90 randomly distributed molecular...
Tamayo, Pablo, Slonim, Donna, Mesirov, Jill, Zhu, Qing, Kitareewan, Sutisak, Dmitrovsky, Ethan, ...
Array technologies have made it straightforward to monitor simultaneously the expression pattern of thousands of genes. The challenge now is to interpret such massive data sets. The first step is to...
Coller, Hilary A., Grandori, Carla, Tamayo, Pablo, Colbert, Trent, Lander, Eric S., Eisenman, Robert N., ...
MYC affects normal and neoplastic cell proliferation by altering gene expression, but the precise pathways remain unclear. We used oligonucleotide microarray analysis of 6,416 genes and expressed...
SBE-TAGS: An array-based method for efficient single-nucleotide polymorphism genotyping
Hirschhorn, Joel N., Sklar, Pamela, Lindblad-Toh, Kerstin, Lim, Yin-Mei, Ruiz-Gutierrez, Melisa, Bolk, Stacey, ...
Generating human single-nucleotide polymorphisms (SNPs) is no longer a rate-limiting step for genetic studies of disease. The number of SNPs in public databases already exceeds 200,000, and the total...
Radany, Eric H., Hong, Karen, Kesharvarzi, Sima, Lander, Eric S., Bishop, J. Michael
Hybrid mice carrying oncogenic transgenes afford powerful systems for investigating loss of heterozygosity (LOH) in tumors. Here, we apply this approach to a neoplasm of key importance in human...
Effects of p53 mutations on apoptosis in mouse intestinal and human colonic adenomas
Fazeli, Amin, Steen, Robert G., Dickinson, Stephanie L., Bautista, Dolores, Dietrich, William F., Bronson, Roderick T., ...
We have examined the effects of inactivation of the p53 tumor suppressor gene on the incidence of apoptotic cell death in two stages of the adenoma-to-carcinoma progression in the intestine: in early...
Remodeling of Yeast Genome Expression in Response to Environmental Changes
Causton, Helen C., Ren, Bing, Koh, Sang Seok, Harbison, Christopher T., Kanin, Elenita, Jennings, Ezra G., ...
We used genome-wide expression analysis to explore how gene expression in Saccharomyces cerevisiae is remodeled in response to various changes in extracellular environment, including changes in...
Deletion of cytosolic phospholipase A2 suppresses ApcMin-induced tumorigenesis
Hong, Karen H., Bonventre, Joanna C., O'Leary, Eileen, Bonventre, Joseph V., Lander, Eric S.
Although nonsteroidal antiinflammatory drugs (NSAIDs) show great promise as therapies for colon cancer, a dispute remains regarding their mechanism of action. NSAIDs are known to inhibit...
Chemosensitivity prediction by transcriptional profiling
Staunton, Jane E., Slonim, Donna K., Coller, Hilary A., Tamayo, Pablo, Angelo, Michael J., Park, Johnny, ...
In an effort to develop a genomics-based approach to the prediction of drug response, we have developed an algorithm for classification of cell line chemosensitivity based on gene expression profiles...
Bhattacharjee, Arindam, Richards, William G., Staunton, Jane, Li, Cheng, Monti, Stefano, Vasa, Priya, ...
We have generated a molecular taxonomy of lung carcinoma, the leading cause of cancer death in the United States and worldwide. Using oligonucleotide microarrays, we analyzed mRNA expression levels...
Multiclass cancer diagnosis using tumor gene expression signatures
Ramaswamy, Sridhar, Tamayo, Pablo, Rifkin, Ryan, Mukherjee, Sayan, Yeang, Chen-Hsiang, Angelo, Michael, ...
The optimal treatment of patients with cancer depends on establishing accurate diagnoses by using a complex combination of clinical and histopathological data. In some instances, this task is...
Human macrophage activation programs induced by bacterial pathogens
Nau, Gerard J., Richmond, Joan F. L., Schlesinger, Ann, Jennings, Ezra G., Lander, Eric S., Young, Richard A.
Understanding the response of innate immune cells to pathogens may provide insights to host defenses and the tactics used by pathogens to circumvent these defenses. We used DNA microarrays to explore...
On the sequencing of the human genome
Waterston, Robert H., Lander, Eric S., Sulston, John E.
Two recent papers using different approaches reported draft sequences of the human genome. The international Human Genome Project (HGP) used the hierarchical shotgun approach, whereas Celera Genomics...
Abnormal gene expression in cloned mice derived from embryonic stem cell and cumulus cell nuclei
Humpherys, David, Eggan, Kevin, Akutsu, Hidenori, Friedman, Adam, Hochedlinger, Konrad, Yanagimachi, Ryuzo, ...
To assess the extent of abnormal gene expression in clones, we assessed global gene expression by microarray analysis on RNA from the placentas and livers of neonatal cloned mice derived by nuclear...
Chen, Chang-Zheng, Li, Min, De Graaf, David, Monti, Stefano, Göttgens, Berthold, Sanchez, Maria-Jose, ...
We describe a strategy to obtain highly enriched long-term repopulating (LTR) hematopoietic stem cells (HSCs) from bone marrow side-population (SP) cells by using a transgenic reporter gene driven by...
Identification of a gene causing human cytochrome c oxidase deficiency by integrative genomics
Mootha, Vamsi K., Lepage, Pierre, Miller, Kathleen, Bunkenborg, Jakob, Reich, Michael, Hjerrild, Majbrit, ...
Identifying the genes responsible for human diseases requires combining information about gene position with clues about biological function. The recent availability of whole-genome data sets of RNA...
MacMurray, Armand J., Moralejo, Daniel H., Kwitek, Anne E., Rutledge, Elizabeth A., Van Yserloo, Brian, Gohlke, Paul, ...
The BB (BioBreeding) rat is one of the best models of spontaneous autoimmune diabetes and is used to study non-MHC loci contributing to Type 1 diabetes. Type 1 diabetes in the diabetes-prone BB...
Chiang, Derek Y, Moses, Alan M, Kellis, Manolis, Lander, Eric S, Eisen, Michael B
The determination of conserved sequences has identified individual transcription factor binding sites. The incorporation of both joint conservation and spacing constraints of sequence pairs predicts...
Position specific variation in the rate of evolution in transcription factor binding sites
Moses, Alan M, Chiang, Derek Y, Kellis, Manolis, Lander, Eric S, Eisen, Michael B
Human and Mouse Gene Structure: Comparative Analysis and Application to Exon Prediction
Batzoglou, Serafim, Pachter, Lior, Mesirov, Jill P., Berger, Bonnie, Lander, Eric S.
We describe a novel analytical approach to gene recognition based on cross-species comparison. We first undertook a comparison of orthologous genomic loci from human and mouse, studying the extent of...
Inoue, Ken, Dewar, Ken, Katsanis, Nicholas, Reiter, Lawrence T., Lander, Eric S., Devon, Keri L., ...
Duplication and deletion of the 1.4-Mb region in 17p12 that is delimited by two 24-kb low copy number repeats (CMT1A–REPs) represent frequent genomic rearrangements resulting in two common...
Mootha, Vamsi K., Handschin, Christoph, Arlow, Dan, Xie, Xiaohui, St. Pierre, Julie, Sihag, Smita, ...
Recent studies have shown that genes involved in oxidative phosphorylation (OXPHOS) exhibit reduced expression in skeletal muscle of diabetic and prediabetic humans. Moreover, these changes may be...
Whole-Genome Sequence Assembly for Mammalian Genomes: Arachne 2
Jaffe, David B., Butler, Jonathan, Gnerre, Sante, Mauceli, Evan, Lindblad-Toh, Kerstin, Mesirov, Jill P., ...
We previously described the whole-genome assembly program Arachne, presenting assemblies of simulated data for small to mid-sized genomes. Here we describe algorithmic adaptations to the program,...
Margulies, Elliott H., Vinson, Jade P., Miller, Webb, Jaffe, David B., Lindblad-Toh, Kerstin, Chang, Jean L., ...
With the recent completion of a high-quality sequence of the human genome, the challenge is now to understand the functional elements that it encodes. Comparative genomic analysis offers a powerful...
Assembly of polymorphic genomes: Algorithms and application to Ciona savignyi
Vinson, Jade P., Jaffe, David B., O'Neill, Keith, Karlsson, Elinor K., Stange-Thomann, Nicole, Anderson, Scott, ...
Whole-genome assembly is now used routinely to obtain high-quality draft sequence for the genomes of species with low levels of polymorphism. However, genome assembly remains extremely challenging...
Hirschhorn, Joel N., Lindgren, Cecilia M., Daly, Mark J., Kirby, Andrew, Schaffner, Stephen F., Burtt, Noel P., ...
Genomewide linkage analysis has been extremely successful at identification of the genetic variation underlying single-gene disorders. However, linkage analysis has been less successful for common...
Lee, Nana, Daly, Mark J., Delmonte, Terrye, Lander, Eric S., Xu, Fenghao, Hudson, Thomas J., ...
Leigh syndrome (LS) affects 1/40,000 newborn infants in the worldwide population and is characterized by the presence of developmental delay and lactic acidosis and by a mean life expectancy...
Ardlie, Kristin, Liu-Cordero, Shau Neen, Eberle, Michael A., Daly, Mark, Barrett, Jeff, Winchester, Ellen, ...
Understanding the pattern of linkage disequilibrium (LD) in the human genome is important both for successful implementation of disease-gene mapping approaches and for inferences about human...
Reduced representation bisulfite sequencing for comparative high-resolution DNA methylation analysis
Meissner, Alexander, Gnirke, Andreas, Bell, George W., Ramsahoye, Bernard, Lander, Eric S., Jaenisch, Rudolf
We describe a large-scale random approach termed reduced representation bisulfite sequencing (RRBS) for analyzing and comparing genomic methylation patterns. BglII restriction fragments were...
The Case for Selection at CCR5-Δ32
Sabeti, Pardis C, Walsh, Emily, Schaffner, Steve F, Varilly, Patrick, Fry, Ben, Hutcheson, Holli B, ...
The C-C chemokine receptor 5, 32 base-pair deletion (CCR5-Δ32) allele confers strong resistance to infection by the AIDS virus HIV. Previous studies have suggested that CCR5-Δ32 arose within the...
Pajukanta, Päivi, Cargill, Michele, Viitanen, Laura, Nuotio, Ilpo, Kareinen, Anu, Perola, Markus, ...
Coronary heart disease (CHD) is a complex disorder constituting a major health problem in Western societies. To assess the genetic background of CHD, we performed a genomewide linkage scan in two...
ARACHNE: A Whole-Genome Shotgun Assembler
Batzoglou, Serafim, Jaffe, David B., Stanley, Ken, Butler, Jonathan, Gnerre, Sante, Mauceli, Evan, ...
We describe a new computer system, called ARACHNE, for assembling genome sequence using paired-end whole-genome shotgun reads. ARACHNE has several key features, including an efficient and sensitive...
Subramanian, Aravind, Tamayo, Pablo, Mootha, Vamsi K., Mukherjee, Sayan, Ebert, Benjamin L., Gillette, Michael A., ...
Although genomewide RNA expression analysis has become a routine tool in biomedical research, extracting biological insight from such information remains a major challenge. Here, we describe a...
Identification and Classification of Conserved RNA Secondary Structures in the Human Genome
Pedersen, Jakob Skou, Bejerano, Gill, Siepel, Adam, Rosenbloom, Kate, Lindblad-Toh, Kerstin, Lander, Eric S, ...
The discoveries of microRNAs and riboswitches, among others, have shown functional RNAs to be biologically more important and genomically more prevalent than previously anticipated. We have developed...
A large family of ancient repeat elements in the human genome is under strong selection
Kamal, Michael, Xie, Xiaohui, Lander, Eric S.
Although conserved noncoding elements (CNEs) constitute the majority of sequences under purifying selection in the human genome, they remain poorly understood. CNEs seem to be largely unique, with no...
Poirier, Christophe, Qin, Yangjun, Adams, Carolyn P., Anaya, Yanett, Singer, Jonathan B., Hill, Annie E., ...
The transgenic insertional mouse mutation Odd Sex (Ods) represents a model for the long-range regulation of Sox9. The mutation causes complete female-to-male sex reversal by inducing a male-specific...
Mapping Quantitative Trait Loci for Anxiety in Chromosome Substitution Strains of Mice
Singer, Jonathan B., Hill, Annie E., Nadeau, Joseph H., Lander, Eric S.
Anxious behavior in the mouse is a complex quantitative phenotype that varies widely among inbred mouse strains. We examined a panel of chromosome substitution strains bearing individual A/J...
Tamayo, Pablo, Slonim, Donna, Mesirov, Jill, Zhu, Qing, Kitareewan, Sutisak, Dmitrovsky, Ethan, ...
Array technologies have made it straightforward to monitor simultaneously the expression pattern of thousands of genes. The challenge now is to interpret such massive data sets. The first step is to...
Coller, Hilary A., Grandori, Carla, Tamayo, Pablo, Colbert, Trent, Lander, Eric S., Eisenman, Robert N., ...
MYC affects normal and neoplastic cell proliferation by altering gene expression, but the precise pathways remain unclear. We used oligonucleotide microarray analysis of 6,416 genes and expressed...
SBE-TAGS: An array-based method for efficient single-nucleotide polymorphism genotyping
Hirschhorn, Joel N., Sklar, Pamela, Lindblad-Toh, Kerstin, Lim, Yin-Mei, Ruiz-Gutierrez, Melisa, Bolk, Stacey, ...
Generating human single-nucleotide polymorphisms (SNPs) is no longer a rate-limiting step for genetic studies of disease. The number of SNPs in public databases already exceeds 200,000, and the total...
Radany, Eric H., Hong, Karen, Kesharvarzi, Sima, Lander, Eric S., Bishop, J. Michael
Hybrid mice carrying oncogenic transgenes afford powerful systems for investigating loss of heterozygosity (LOH) in tumors. Here, we apply this approach to a neoplasm of key importance in human...
Effects of p53 mutations on apoptosis in mouse intestinal and human colonic adenomas
Fazeli, Amin, Steen, Robert G., Dickinson, Stephanie L., Bautista, Dolores, Dietrich, William F., Bronson, Roderick T., ...
We have examined the effects of inactivation of the p53 tumor suppressor gene on the incidence of apoptotic cell death in two stages of the adenoma-to-carcinoma progression in the intestine: in early...
Remodeling of Yeast Genome Expression in Response to Environmental Changes
Causton, Helen C., Ren, Bing, Koh, Sang Seok, Harbison, Christopher T., Kanin, Elenita, Jennings, Ezra G., ...
We used genome-wide expression analysis to explore how gene expression in Saccharomyces cerevisiae is remodeled in response to various changes in extracellular environment, including changes in...
Deletion of cytosolic phospholipase A2 suppresses ApcMin-induced tumorigenesis
Hong, Karen H., Bonventre, Joanna C., O'Leary, Eileen, Bonventre, Joseph V., Lander, Eric S.
Although nonsteroidal antiinflammatory drugs (NSAIDs) show great promise as therapies for colon cancer, a dispute remains regarding their mechanism of action. NSAIDs are known to inhibit...
Chemosensitivity prediction by transcriptional profiling
Staunton, Jane E., Slonim, Donna K., Coller, Hilary A., Tamayo, Pablo, Angelo, Michael J., Park, Johnny, ...
In an effort to develop a genomics-based approach to the prediction of drug response, we have developed an algorithm for classification of cell line chemosensitivity based on gene expression profiles...
Bhattacharjee, Arindam, Richards, William G., Staunton, Jane, Li, Cheng, Monti, Stefano, Vasa, Priya, ...
We have generated a molecular taxonomy of lung carcinoma, the leading cause of cancer death in the United States and worldwide. Using oligonucleotide microarrays, we analyzed mRNA expression levels...
Multiclass cancer diagnosis using tumor gene expression signatures
Ramaswamy, Sridhar, Tamayo, Pablo, Rifkin, Ryan, Mukherjee, Sayan, Yeang, Chen-Hsiang, Angelo, Michael, ...
The optimal treatment of patients with cancer depends on establishing accurate diagnoses by using a complex combination of clinical and histopathological data. In some instances, this task is...
Human macrophage activation programs induced by bacterial pathogens
Nau, Gerard J., Richmond, Joan F. L., Schlesinger, Ann, Jennings, Ezra G., Lander, Eric S., Young, Richard A.
Understanding the response of innate immune cells to pathogens may provide insights to host defenses and the tactics used by pathogens to circumvent these defenses. We used DNA microarrays to explore...
On the sequencing of the human genome
Waterston, Robert H., Lander, Eric S., Sulston, John E.
Two recent papers using different approaches reported draft sequences of the human genome. The international Human Genome Project (HGP) used the hierarchical shotgun approach, whereas Celera Genomics...
Abnormal gene expression in cloned mice derived from embryonic stem cell and cumulus cell nuclei
Humpherys, David, Eggan, Kevin, Akutsu, Hidenori, Friedman, Adam, Hochedlinger, Konrad, Yanagimachi, Ryuzo, ...
To assess the extent of abnormal gene expression in clones, we assessed global gene expression by microarray analysis on RNA from the placentas and livers of neonatal cloned mice derived by nuclear...
Chen, Chang-Zheng, Li, Min, De Graaf, David, Monti, Stefano, Göttgens, Berthold, Sanchez, Maria-Jose, ...
We describe a strategy to obtain highly enriched long-term repopulating (LTR) hematopoietic stem cells (HSCs) from bone marrow side-population (SP) cells by using a transgenic reporter gene driven by...
Identification of a gene causing human cytochrome c oxidase deficiency by integrative genomics
Mootha, Vamsi K., Lepage, Pierre, Miller, Kathleen, Bunkenborg, Jakob, Reich, Michael, Hjerrild, Majbrit, ...
Identifying the genes responsible for human diseases requires combining information about gene position with clues about biological function. The recent availability of whole-genome data sets of RNA...
ARACHNE: A Whole-Genome Shotgun Assembler
Batzoglou, Serafim, Jaffe, David B., Stanley, Ken, Butler, Jonathan, Gnerre, Sante, Mauceli, Evan, ...
We describe a new computer system, called ARACHNE, for assembling genome sequence using paired-end whole-genome shotgun reads. ARACHNE has several key features, including an efficient and sensitive...
MacMurray, Armand J., Moralejo, Daniel H., Kwitek, Anne E., Rutledge, Elizabeth A., Van Yserloo, Brian, Gohlke, Paul, ...
The BB (BioBreeding) rat is one of the best models of spontaneous autoimmune diabetes and is used to study non-MHC loci contributing to Type 1 diabetes. Type 1 diabetes in the diabetes-prone BB...
Chiang, Derek Y, Moses, Alan M, Kellis, Manolis, Lander, Eric S, Eisen, Michael B
The determination of conserved sequences has identified individual transcription factor binding sites. The incorporation of both joint conservation and spacing constraints of sequence pairs predicts...
Position specific variation in the rate of evolution in transcription factor binding sites
Moses, Alan M, Chiang, Derek Y, Kellis, Manolis, Lander, Eric S, Eisen, Michael B
Human and Mouse Gene Structure: Comparative Analysis and Application to Exon Prediction
Batzoglou, Serafim, Pachter, Lior, Mesirov, Jill P., Berger, Bonnie, Lander, Eric S.
We describe a novel analytical approach to gene recognition based on cross-species comparison. We first undertook a comparison of orthologous genomic loci from human and mouse, studying the extent of...
Inoue, Ken, Dewar, Ken, Katsanis, Nicholas, Reiter, Lawrence T., Lander, Eric S., Devon, Keri L., ...
Duplication and deletion of the 1.4-Mb region in 17p12 that is delimited by two 24-kb low copy number repeats (CMT1A–REPs) represent frequent genomic rearrangements resulting in two common...
Mootha, Vamsi K., Handschin, Christoph, Arlow, Dan, Xie, Xiaohui, St. Pierre, Julie, Sihag, Smita, ...
Recent studies have shown that genes involved in oxidative phosphorylation (OXPHOS) exhibit reduced expression in skeletal muscle of diabetic and prediabetic humans. Moreover, these changes may be...
Whole-Genome Sequence Assembly for Mammalian Genomes: Arachne 2
Jaffe, David B., Butler, Jonathan, Gnerre, Sante, Mauceli, Evan, Lindblad-Toh, Kerstin, Mesirov, Jill P., ...
We previously described the whole-genome assembly program Arachne, presenting assemblies of simulated data for small to mid-sized genomes. Here we describe algorithmic adaptations to the program,...
Margulies, Elliott H., Vinson, Jade P., Miller, Webb, Jaffe, David B., Lindblad-Toh, Kerstin, Chang, Jean L., ...
With the recent completion of a high-quality sequence of the human genome, the challenge is now to understand the functional elements that it encodes. Comparative genomic analysis offers a powerful...
Giallourakis, Cosmas, Stoll, Monika, Miller, Katie, Hampe, Jochen, Lander, Eric S., Daly, Mark J., ...
Inflammatory bowel disease (IBD) refers to complex chronic relapsing autoimmune disorders of the gastrointestinal tract that have been traditionally classified into Crohn disease (CD) and ulcerative...
An Integrated Haplotype Map of the Human Major Histocompatibility Complex
Walsh, Emily C., Mather, Kristie A., Schaffner, Stephen F., Farwell, Lisa, Daly, Mark J., Patterson, Nick, ...
Numerous studies have clearly indicated a role for the major histocompatibility complex (MHC) in susceptibility to autoimmune diseases. Such studies have focused on the genetic variation of a small...
Assembly of polymorphic genomes: Algorithms and application to Ciona savignyi
Vinson, Jade P., Jaffe, David B., O'Neill, Keith, Karlsson, Elinor K., Stange-Thomann, Nicole, Anderson, Scott, ...
Whole-genome assembly is now used routinely to obtain high-quality draft sequence for the genomes of species with low levels of polymorphism. However, genome assembly remains extremely challenging...
Miretti, Marcos M., Walsh, Emily C., Ke, Xiayi, Delgado, Marcos, Griffiths, Mark, Hunt, Sarah, ...
Autoimmune, inflammatory, and infectious diseases present a major burden to human health and are frequently associated with loci in the human major histocompatibility complex (MHC). Here, we report a...
Hirschhorn, Joel N., Lindgren, Cecilia M., Daly, Mark J., Kirby, Andrew, Schaffner, Stephen F., Burtt, Noel P., ...
Genomewide linkage analysis has been extremely successful at identification of the genetic variation underlying single-gene disorders. However, linkage analysis has been less successful for common...
Lee, Nana, Daly, Mark J., Delmonte, Terrye, Lander, Eric S., Xu, Fenghao, Hudson, Thomas J., ...
Leigh syndrome (LS) affects 1/40,000 newborn infants in the worldwide population and is characterized by the presence of developmental delay and lactic acidosis and by a mean life expectancy...
Ardlie, Kristin, Liu-Cordero, Shau Neen, Eberle, Michael A., Daly, Mark, Barrett, Jeff, Winchester, Ellen, ...
Understanding the pattern of linkage disequilibrium (LD) in the human genome is important both for successful implementation of disease-gene mapping approaches and for inferences about human...
Subramanian, Aravind, Tamayo, Pablo, Mootha, Vamsi K., Mukherjee, Sayan, Ebert, Benjamin L., Gillette, Michael A., ...
Although genomewide RNA expression analysis has become a routine tool in biomedical research, extracting biological insight from such information remains a major challenge. Here, we describe a...
Reduced representation bisulfite sequencing for comparative high-resolution DNA methylation analysis
Meissner, Alexander, Gnirke, Andreas, Bell, George W., Ramsahoye, Bernard, Lander, Eric S., Jaenisch, Rudolf
We describe a large-scale random approach termed reduced representation bisulfite sequencing (RRBS) for analyzing and comparing genomic methylation patterns. BglII restriction fragments were...
The Case for Selection at CCR5-Δ32
Sabeti, Pardis C, Walsh, Emily, Schaffner, Steve F, Varilly, Patrick, Fry, Ben, Hutcheson, Holli B, ...
The C-C chemokine receptor 5, 32 base-pair deletion (CCR5-Δ32) allele confers strong resistance to infection by the AIDS virus HIV. Previous studies have suggested that CCR5-Δ32 arose within the...
Pajukanta, Päivi, Cargill, Michele, Viitanen, Laura, Nuotio, Ilpo, Kareinen, Anu, Perola, Markus, ...
Coronary heart disease (CHD) is a complex disorder constituting a major health problem in Western societies. To assess the genetic background of CHD, we performed a genomewide linkage scan in two...
A large family of ancient repeat elements in the human genome is under strong selection
Kamal, Michael, Xie, Xiaohui, Lander, Eric S.
Although conserved noncoding elements (CNEs) constitute the majority of sequences under purifying selection in the human genome, they remain poorly understood. CNEs seem to be largely unique, with no...
Identification and Classification of Conserved RNA Secondary Structures in the Human Genome
Pedersen, Jakob Skou, Bejerano, Gill, Siepel, Adam, Rosenbloom, Kate, Lindblad-Toh, Kerstin, Lander, Eric S, ...
The discoveries of microRNAs and riboswitches, among others, have shown functional RNAs to be biologically more important and genomically more prevalent than previously anticipated. We have developed...
Poirier, Christophe, Qin, Yangjun, Adams, Carolyn P., Anaya, Yanett, Singer, Jonathan B., Hill, Annie E., ...
The transgenic insertional mouse mutation Odd Sex (Ods) represents a model for the long-range regulation of Sox9. The mutation causes complete female-to-male sex reversal by inducing a male-specific...
Mapping Quantitative Trait Loci for Anxiety in Chromosome Substitution Strains of Mice
Singer, Jonathan B., Hill, Annie E., Nadeau, Joseph H., Lander, Eric S.
Anxious behavior in the mouse is a complex quantitative phenotype that varies widely among inbred mouse strains. We examined a panel of chromosome substitution strains bearing individual A/J...
A family of conserved noncoding elements derived from an ancient transposable element
Xie, Xiaohui, Kamal, Michael, Lander, Eric S.
The evolutionary origin of the conserved noncoding elements (CNEs) in the human genome remains poorly understood but may hold important clues to their biological functions. Here, we report the...
Xie, Xiaohui, Mikkelsen, Tarjei S., Gnirke, Andreas, Lindblad-Toh, Kerstin, Kellis, Manolis, Lander, Eric S.
Conserved noncoding elements (CNEs) constitute the majority of sequences under purifying selection in the human genome, yet their function remains largely unknown. Experimental evidence suggests that...
Analyses of deep mammalian sequence alignments and constraint predictions for 1% of the human genome
Margulies, Elliott H., Cooper, Gregory M., Asimenos, George, Thomas, Daryl J., Dewey, Colin N., Siepel, Adam, ...
A key component of the ongoing ENCODE project involves rigorous comparative sequence analyses for the initially targeted 1% of the human genome. Here, we present orthologous sequence generation,...
28-Way vertebrate alignment and conservation track in the UCSC Genome Browser
Miller, Webb, Rosenbloom, Kate, Hardison, Ross C., Hou, Minmei, Taylor, James, Raney, Brian, ...
This article describes a set of alignments of 28 vertebrate genome sequences that is provided by the UCSC Genome Browser. The alignments can be viewed on the Human Genome Browser (March 2006...
Distinguishing protein-coding and noncoding genes in the human genome
Clamp, Michele, Fry, Ben, Kamal, Mike, Xie, Xiaohui, Cuff, James, Lin, Michael F., ...
Although the Human Genome Project was completed 4 years ago, the catalog of human protein-coding genes remains a matter of controversy. Current catalogs list a total of ≈24,500 putative...
Beroukhim, Rameen, Getz, Gad, Nghiemphu, Leia, Barretina, Jordi, Hsueh, Teli, Linhart, David, ...
Comprehensive knowledge of the genomic alterations that underlie cancer is a critical foundation for diagnostics, prognostics, and targeted therapeutics. Systematic efforts to analyze cancer genomes...
Genomewide Analysis of PRC1 and PRC2 Occupancy Identifies Two Classes of Bivalent Domains
Ku, Manching, Koche, Richard P., Rheinbay, Esther, Mendenhall, Eric M., Endoh, Mitsuhiro, Mikkelsen, Tarjei S., ...
In embryonic stem (ES) cells, bivalent chromatin domains with overlapping repressive (H3 lysine 27 tri-methylation) and activating (H3 lysine 4 tri-methylation) histone modifications mark the...
ALLPATHS: De novo assembly of whole-genome shotgun microreads
Butler, Jonathan, MacCallum, Iain, Kleber, Michael, Shlyakhter, Ilya A., Belmonte, Matthew K., Lander, Eric S., ...
New DNA sequencing technologies deliver data at dramatically lower costs but demand new analytical methods to take full advantage of the very short reads that they produce. We provide an initial,...
Quality scores and SNP detection in sequencing-by-synthesis systems
Brockman, William, Alvarez, Pablo, Young, Sarah, Garber, Manuel, Giannoukos, Georgia, Lee, William L., ...
Promising new sequencing technologies, based on sequencing-by-synthesis (SBS), are starting to deliver large amounts of DNA sequence at very low cost. Polymorphism detection is a key application. We...
Neafsey, Daniel E, Schaffner, Stephen F, Volkman, Sarah K, Park, Daniel, Montgomery, Philip, Milner, Danny A, ...
An array-based SNP genotyping platform for Plasmodium falciparum is reported together with an analysis of SNP diversity in global population samples.
Highly parallel identification of essential genes in cancer cells
Luo, Biao, Cheung, Hiu Wing, Subramanian, Aravind, Sharifnia, Tanaz, Okamoto, Michael, Yang, Xiaoping, ...
More complete knowledge of the molecular mechanisms underlying cancer will improve prevention, diagnosis and treatment. Efforts such as The Cancer Genome Atlas are systematically characterizing the...
Genetic architecture of complex traits: Large phenotypic effects and pervasive epistasis
Shao, Haifeng, Burrage, Lindsay C., Sinasac, David S., Hill, Annie E., Ernest, Sheila R., O'Brien, William, ...
The genetic architecture of complex traits underlying physiology and disease in most organisms remains elusive. We still know little about the number of genes that underlie these traits, the...
Khalil, Ahmad M., Guttman, Mitchell, Huarte, Maite, Garber, Manuel, Raj, Arjun, Rivea Morales, Dianali, ...
We recently showed that the mammalian genome encodes >1,000 large intergenic noncoding (linc)RNAs that are clearly conserved across mammals and, thus, functional. Gene expression patterns have...
Systematic RNA interference reveals that oncogenic KRASdriven cancers require TBK1
Barbie, David A., Tamayo, Pablo, Boehm, Jesse S., Kim, So Young, Moody, Susan E., Dunn, Ian F., ...
A second major histocompatibility complex susceptibility locus for multiple sclerosis
Yeo, Tai Wai, De Jager, Philip L, Gregory, Simon G, Barcellos, Lisa F, Walton, Amie, Goris, An, ...
Assisted assembly: how to improve a de novo genome assembly by using related species
Gnerre, Sante, Lander, Eric S, Lindblad-Toh, Kerstin, Jaffe, David B
A method is described for improving low sequence coverage genome assemblies