Webb Miller

Analysis of complete mitochondrial genomes from extinct and extant rhinoceroses reveals lack of phylogenetic resolution (2009)

Willerslev, Eske, Gilbert, M Thomas P, Binladen, Jonas, Ho, Simon YW, Campos, Paula F, Ratan, Aakrosh, ...

Abstract Background The scientific literature contains many examples where DNA sequence analyses have been used to provide definitive answers to phylogenetic problems that traditional (non-DNA based)...

Reconstructing the Evolutionary History of Complex Human Gene Clusters (2009)

Yu Zhang, Giltae Song, Eric D. Green, Adam Siepel, Webb Miller

Abstract. Clusters of genes that evolved from single progenitors via repeated segmental duplications present significant challenges to the generation of a truly complete human genome sequence. Such...

Resource zPicture: Dynamic Alignment and Visualization Tool for Analyzing Conservation Profiles (2009)

Ivan Ovcharenko, Gabriela G. Loots, Ross C. Hardison, Webb Miller, Lisa Stubbs

Comparative sequence analysis has evolved as an essential technique for identifying functional coding and noncoding elements conserved throughout evolution. Here, we introduce zPicture, an...

The mitochondrial genome sequence of the Tasmanian tiger (Thylacinus cynocephalus) (2009)

Miller, Webb, Drautz, Daniela I., Janecka, Jan E., Lesk, Arthur M., Ratan, Aakrosh, Tomsho, Lynn P., ...

We report the first two complete mitochondrial genome sequences of the thylacine (Thylacinus cynocephalus), or so-called Tasmanian tiger, extinct since 1936. The thylacine's phylogenetic position...

CleaveLand: a pipeline for using degradome data to find cleaved small RNA targets (2009)

Addo-Quaye, Charles, Miller, Webb, Axtell, Michael J.

Summary: MicroRNAs (miRNAs) are ∼20- to 22-nt long endogenous RNA sequences that play a critical role in the regulation of gene expression in eukaryotic genomes. Confident identification of miRNA...

Abstract (2008)

Eugene W. Myers, Webb Miller

Optimal alignments in linear space

Parametric Recomputing in Alignment Graphs (2008)

Xiaoqiu Tiuang, Pavel A. Pevzner, Webb Miller

Abstract. DNA/protein sequence alignments in computational molecular biology depend heavily on the settings of penalties for substitutions, inser-tions/deletions and gaps. Inappropriate choice of...

Article Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes (2008)

Adam Siepel, Gill Bejerano, Jakob S. Pedersen, Angie S. Hinrichs, Minmei Hou, Kate Rosenbloom, ...

We have conducted a comprehensive search for conserved elements in vertebrate genomes, using genome-wide multiple alignments of five vertebrate species (human, mouse, rat, chicken, and Fugu...

Human-macaque comparisons illuminate variation in neutral substitution rates (2008)

Tyekucheva, Svitlana, Makova, Kateryna D, Karro, John E, Hardison, Ross C, Miller, Webb, Chiaromonte, Francesca

Abstract Background The evolutionary distance between human and macaque is particularly attractive for investigating local variation in neutral substitution rates, because substitutions can be...

Proceedings of the 28th Annual Hawaii international Conference on System Sciences- 1995 A Database for Globin Gene Expression Data (2008)

Webb Miller, Ahmed Elsherbini, Jamie Peck, Cathy Riemer, Scott Schwartz, Nikola Stojanovic, ...

We describe a prototype database of sequence align-ments and experimental results for the P-like globin gene cluster of mammals. This data repository is in-tended to help the international community...

A Heuristic Algorithm for Reconstructing Ancestral Gene Orders with Duplications (2008)

Jian Ma, Louxin Zhang, Webb Miller

Abstract. Accurately reconstructing the large-scale gene order in an ancestral genome is a critical step to better understand genome evolution. In this paper, we propose a heuristic algorithm for...

Abstract Aligning a DNA Sequence with a Protein Sequence (2008)

Zheng Zhang, William R. Pearson, Webb Miller

We develop several algorithms for the problem of aligning a DNA sequence with a protein sequence. Our methods account for frameshift errors, but not for introns in the DNA sequence. Thus, they are...

Resource Aligning Multiple Genomic Sequences With the Threaded Blockset Aligner (2008)

Mathieu Blanchette, W. James Kent, Cathy Riemer, Laura Elnitski, Krishna M. Roskin, ...

We define a “threaded blockset, ” which is a novel generalization of the classic notion of a multiple alignment. A new computer program called TBA (for “threaded blockset aligner”) builds a...

Signi � cance of Interspecies Matches when Evolutionary Rate Varies (2008)

Jia Li, Webb Miller

We develop techniques to estimate the statistical signi � cance of gap-free alignments between two genomic DNA sequences, using human–mouse alignments as an example. The sequences are assumed to...

Journal of Computational Biology 10(3-4):537-554 Significance Of Inter-Species Matches When Evolutionary Rate Varies (2008)

Jia Li, Webb Miller

We develop techniques to estimate the statistical significance of gap-free alignments between two genomic DNA sequences, using human-mouse alignments as an example. The sequences are assumed to be...

Methods Human–Mouse Alignments with BLASTZ (2008)

Scott Schwartz, W. James Kent, Arian Smit, Zheng Zhang, Robert Baertsch, Ross C. Hardison, ...

The Mouse Genome Analysis Consortium aligned the human and mouse genome sequences for a variety of purposes, using alignment programs that suited the various needs. For investigating issues regarding...

Genome analysis of the platypus reveals unique signatures of evolution (2008)

Warren, Wesley C., Hillier, LaDeana W., Marshall Graves, Jennifer A., Birney, Ewan, Ponting, Chris P., Grützner, Frank, ...

We present a draft genome sequence of the platypus, Ornithorhynchus anatinus. This monotreme exhibits a fascinating combination of reptilian and mammalian characters. For example, platypuses have a...

Transcriptional enhancement by GATA1-occupied DNA segments is strongly associated with evolutionary constraint on the binding site motif (2008)

Cheng, Yong, King, David C., Dore, Louis C., Zhang, Xinmin, Zhou, Yuepin, Zhang, Ying, ...

Tissue development and function are exquisitely dependent on proper regulation of gene expression, but it remains controversial whether the genomic signals controlling this process are subject to...

Results Statistics (2008)

Stephen F. Altschul, Thomas L. Madden, Ro A. Schäffer, Jinghui Zhang, Zheng Zhang, Webb Miller, ...

Number of letters 2,393,238,591 Number of sequences 6,929,940 Entrez query none Karlin-Altschul statistics

1 (2007)

Jonathan Flint, Cristina Tufarelli, Rachael J. Daniels, Ross Hardison, Webb Miller, Sjaak Philipsen, ...

genome analysis delimits a chromosomal domain and identifies key regulatory elements in the globin cluster

Fast-evolving noncoding sequences in the human genome (2007)

Bird, Christine P, Stranger, Barbara E, Liu, Maureen, Thomas, Daryl J, Ingle, Catherine E, Beazley, Claude, ...

Abstract Background Gene regulation is considered one of the driving forces of evolution. Although protein-coding DNA sequences and RNA genes have been subject to recent evolutionary events in the...

A framework for collaborative analysis of ENCODE data: Making large-scale analyses biologist-friendly (2007)

Blankenberg, Daniel, Taylor, James, Schenck, Ian, He, Jianbin, Zhang, Yi, Ghent, Matthew, ...

The standardization and sharing of data and tools are the biggest challenges of large collaborative projects such as the Encyclopedia of DNA Elements (ENCODE). Here we describe a compact Web...

Analyses of deep mammalian sequence alignments and constraint predictions for 1% of the human genome (2007)

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,...

Finding cis-regulatory elements using comparative genomics: Some lessons from ENCODE data (2007)

King, David C., Taylor, James, Zhang, Ying, Cheng, Yong, Lawson, Heather A., Martin, Joel, ...

Identification of functional genomic regions using interspecies comparison will be most effective when the full span of relationships between genomic function and evolutionary constraint are...

Using genomic data to unravel the root of the placental mammal phylogeny (2007)

Murphy, William J., Pringle, Thomas H., Crider, Tess A., Springer, Mark S., Miller, Webb

The phylogeny of placental mammals is a critical framework for choosing future genome sequencing targets and for resolving the ancestral mammalian genome at the nucleotide level. Despite considerable...

Approximating the spanning star forest problem and its applications to genomic sequence alignment (2007)

C. Thach Nguyen, Jian Shen, Minmei Hou, Li Sheng, Webb Miller, Louxin Zhang

Abstract. This paper studies the algorithmic issues of the spanning star forest problem. We prove the following results: (1) There is a polynomial-time approximation scheme for planar graphs; (2)...

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...

Recharacterization of ancient DNA miscoding lesions: insights in the era of sequencing-by-synthesis (2007)

Gilbert, M. Thomas P., Binladen, Jonas, Miller, Webb, Wiuf, Carsten, Willerslev, Eske, Poinar, Hendrik, ...

Although ancient DNA (aDNA) miscoding lesions have been studied since the earliest days of the field, their nature remains a source of debate. A variety of conflicting hypotheses exist about which...

Using genomic data to unravel the root of the placental mammal phylogeny (2007)

Murphy, William J., Pringle, Thomas H., Crider, Tess A., Springer, Mark S., Miller, Webb

The phylogeny of placental mammals is a critical framework for choosing future genome sequencing targets and for resolving the ancestral mammalian genome at the nucleotide level. Despite considerable...

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...

Notes (2006)

Jian Ma, Louxin Zhang, Bernard B. Suh, Brian J. Raney, Richard C. Burhans, W. James Kent, ...

Access the most recent version at doi: 10.1101/gr.5383506

Notes (2006)

Jian Ma, Louxin Zhang, Bernard B. Suh, Brian J. Raney, Richard C. Burhans, W. James Kent, ...

Access the most recent version at doi: 10.1101/gr.5383506

Controlling size when aligning multiple genomic sequences with duplications (2006)

Minmei Hou, Louxin Zhang, Webb Miller

Abstract. For a genomic region containing a tandem gene cluster, a proper set of alignments needs to align only orthologous segments, i.e., those separated by a speciation event. Otherwise, methods...

Recharacterization of ancient DNA miscoding lesions: insights in the era of sequencing-by-synthesis (2006)

Gilbert, M. Thomas P., Binladen, Jonas, Miller, Webb, Wiuf, Carsten, Willerslev, Eske, Poinar, Hendrik, ...

Although ancient DNA (aDNA) miscoding lesions have been studied since the earliest days of the field, their nature remains a source of debate. A variety of conflicting hypotheses exist about which...

Recharacterization of ancient DNA miscoding lesions: insights in the era of sequencing-by-synthesis (2006)

Gilbert, M. Thomas P., Binladen, Jonas, Miller, Webb, Wiuf, Carsten, Willerslev, Eske, Poinar, Hendrik, ...

Although ancient DNA (aDNA) miscoding lesions have been studied since the earliest days of the field, their nature remains a source of debate. A variety of conflicting hypotheses exist about which...

ESPERR: Learning strong and weak signals in genomic sequence alignments to identify functional elements (2006)

Taylor, James, Tyekucheva, Svitlana, King, David C., Hardison, Ross C., Miller, Webb, Chiaromonte, Francesca

Genomic sequence signals—such as base composition, presence of particular motifs, or evolutionary constraint—have been used effectively to identify functional elements. However, approaches based...

Experimental validation of predicted mammalian erythroid cis-regulatory modules (2006)

Wang, Hao, Zhang, Ying, Cheng, Yong, Zhou, Yuepin, King, David C., Taylor, James, ...

Multiple alignments of genome sequences are helpful guides to functional analysis, but predicting cis-regulatory modules (CRMs) accurately from such alignments remains an elusive goal. We predict...

Reconstructing contiguous regions of an ancestral genome (2006)

Ma, Jian, Zhang, Louxin, Suh, Bernard B., Raney, Brian J., Burhans, Richard C., Kent, W. James, ...

This article analyzes mammalian genome rearrangements at higher resolution than has been published to date. We identify 3171 intervals, covering ∼92% of the human genome, within which we find no...

Experimental validation of predicted mammalian erythroid cis-regulatory modules (2006)

Wang, Hao, Zhang, Ying, Cheng, Yong, Zhou, Yuepin, King, David C., Taylor, James, ...

Multiple alignments of genome sequences are helpful guides to functional analysis, but predicting cis-regulatory modules (CRMs) accurately from such alignments remains an elusive goal. We predict...

Reconstructing contiguous regions of an ancestral genome (2006)

Ma, Jian, Zhang, Louxin, Suh, Bernard B., Raney, Brian J., Burhans, Richard C., Kent, W. James, ...

This article analyzes mammalian genome rearrangements at higher resolution than has been published to date. We identify 3171 intervals, covering ∼92% of the human genome, within which we find no...

ESPERR: Learning strong and weak signals in genomic sequence alignments to identify functional elements (2006)

Taylor, James, Tyekucheva, Svitlana, King, David C., Hardison, Ross C., Miller, Webb, Chiaromonte, Francesca

Genomic sequence signals—such as base composition, presence of particular motifs, or evolutionary constraint—have been used effectively to identify functional elements. However, approaches based...

Recharacterization of ancient DNA miscoding lesions: insights in the era of sequencing-by-synthesis (2006)

Gilbert, M. Thomas P., Binladen, Jonas, Miller, Webb, Wiuf, Carsten, Willerslev, Eske, Poinar, Hendrik, ...

Although ancient DNA (aDNA) miscoding lesions have been studied since the earliest days of the field, their nature remains a source of debate. A variety of conflicting hypotheses exist about which...

Recharacterization of ancient DNA miscoding lesions: insights in the era of sequencing-by-synthesis (2006)

Gilbert, M. Thomas P., Binladen, Jonas, Miller, Webb, Wiuf, Carsten, Willerslev, Eske, Poinar, Hendrik, ...

Although ancient DNA (aDNA) miscoding lesions have been studied since the earliest days of the field, their nature remains a source of debate. A variety of conflicting hypotheses exist about which...

Galaxy: A platform for interactive large-scale genome analysis (2005)

Belinda Giardine, Cathy Riemer, Ross C. Hardison, Richard Burhans, Prachi Shah, Yi Zhang, ...

Accessing and analyzing the exponentially expanding genomic sequence and functional data pose a challenge for biomedical researchers. Here we describe an interactive system, Galaxy, that combines the...

Improvements to GALA and dbERGE II: databases featuring genomic sequence alignment, annotation and experimental results (2005)

Elnitski, Laura, Giardine, Belinda, Shah, Prachi, Zhang, Yi, Riemer, Cathy, Weirauch, Matthew, ...

We describe improvements to two databases that give access to information on genomic sequence similarities, functional elements in DNA and experimental results that demonstrate those functions. GALA,...

Evolution and functional classification of vertebrate gene deserts (2005)

Ovcharenko, Ivan, Loots, Gabriela G., Nobrega, Marcelo A., Hardison, Ross C., Miller, Webb, Stubbs, Lisa

Large tracts of the human genome, known as gene deserts, are devoid of protein-coding genes. Dichotomy in their level of conservation with chicken separates these regions into two distinct...

Mulan: Multiple-sequence local alignment and visualization for studying function and evolution (2005)

Ovcharenko, Ivan, Loots, Gabriela G., Giardine, Belinda M., Hou, Minmei, Ma, Jian, Hardison, Ross C., ...

Multiple-sequence alignment analysis is a powerful approach for understanding phylogenetic relationships, annotating genes, and detecting functional regulatory elements. With a growing number of...

Evaluation of regulatory potential and conservation scores for detecting cis-regulatory modules in aligned mammalian genome sequences (2005)

King, David C., Taylor, James, Elnitski, Laura, Chiaromonte, Francesca, Miller, Webb, Hardison, Ross C.

Techniques of comparative genomics are being used to identify candidate functional DNA sequences, and objective evaluations are needed to assess their effectiveness. Different analytical methods...

Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes (2005)

Siepel, Adam, Bejerano, Gill, Pedersen, Jakob S., Hinrichs, Angie S., Hou, Minmei, Rosenbloom, Kate, ...

We have conducted a comprehensive search for conserved elements in vertebrate genomes, using genome-wide multiple alignments of five vertebrate species (human, mouse, rat, chicken, and Fugu...

Galaxy: A platform for interactive large-scale genome analysis (2005)

Giardine, Belinda, Riemer, Cathy, Hardison, Ross C., Burhans, Richard, Elnitski, Laura, Shah, Prachi, ...

Accessing and analyzing the exponentially expanding genomic sequence and functional data pose a challenge for biomedical researchers. Here we describe an interactive system, Galaxy, that combines the...

Galaxy: A platform for interactive large-scale genome analysis (2005)

Giardine, Belinda, Riemer, Cathy, Hardison, Ross C., Burhans, Richard, Elnitski, Laura, Shah, Prachi, ...

Accessing and analyzing the exponentially expanding genomic sequence and functional data pose a challenge for biomedical researchers. Here we describe an interactive system, Galaxy, that combines the...

Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes (2005)

Siepel, Adam, Bejerano, Gill, Pedersen, Jakob S., Hinrichs, Angie S., Hou, Minmei, Rosenbloom, Kate, ...

We have conducted a comprehensive search for conserved elements in vertebrate genomes, using genome-wide multiple alignments of five vertebrate species (human, mouse, rat, chicken, and Fugu...

Evaluation of regulatory potential and conservation scores for detecting cis-regulatory modules in aligned mammalian genome sequences (2005)

King, David C., Taylor, James, Elnitski, Laura, Chiaromonte, Francesca, Miller, Webb, Hardison, Ross C.

Techniques of comparative genomics are being used to identify candidate functional DNA sequences, and objective evaluations are needed to assess their effectiveness. Different analytical methods...

zPicture: Dynamic Alignment and Visualization Tool for Analyzing Conservation Profiles (2004)

Ovcharenko, Ivan, Loots, Gabriela G., Hardison, Ross C., Miller, Webb, Stubbs, Lisa

Comparative sequence analysis has evolved as an essential technique for identifying functional coding and noncoding elements conserved throughout evolution. Here, we introduce zPicture, an...

Patterns of Insertions and Their Covariation With Substitutions in the Rat, Mouse, and Human Genomes (2004)

Yang, Shan, Smit, Arian F., Schwartz, Scott, Chiaromonte, Francesca, Roskin, Krishna M., Haussler, David, ...

The rates at which human genomic DNA changes by neutral substitution and insertion of certain families of transposable elements covary in large, megabase-sized segments. We used the rat, mouse, and...

Comparative Analysis of the {alpha}-Like Globin Clusters in Mouse, Rat, and Human Chromosomes Indicates a Mechanism Underlying Breaks in Conserved Synteny (2004)

Tufarelli, Cristina, Hardison, Ross, Miller, Webb, Hughes, Jim, Clark, Kevin, Ventress, Nicki, ...

We have sequenced and fully annotated a 65,871-bp region of mouse Chromosome 17 including the Hba-ps4 α-globin pseudogene. Comparative sequence analysis with the functional α-globin loci at human...

Regulatory Potential Scores From Genome-Wide Three-Way Alignments of Human, Mouse, and Rat (2004)

Kolbe, Diana, Taylor, James, Elnitski, Laura, Eswara, Pallavi, Li, Jia, Miller, Webb, ...

We generalize the computation of the Regulatory Potential (RP) score from two-way alignments of human and mouse to three-way alignments of human, mouse, and rat. This requires overcoming technical...

Aligning Multiple Genomic Sequences With the Threaded Blockset Aligner (2004)

Blanchette, Mathieu, Kent, W. James, Riemer, Cathy, Elnitski, Laura, Smit, Arian F.A., Roskin, Krishna M., ...

We define a “threaded blockset,” which is a novel generalization of the classic notion of a multiple alignment. A new computer program called TBA (for “threaded blockset aligner”) builds a...

Reconstructing large regions of an ancestral mammalian genome in silico (2004)

Blanchette, Mathieu, Green, Eric D., Miller, Webb, Haussler, David

It is believed that most modern mammalian lineages arose from a series of rapid speciation events near the Cretaceous-Tertiary boundary. It is shown that such a phylogeny makes the common ancestral...

Improvements in the HbVar database of human hemoglobin variants and thalassemia mutations for population and sequence variation studies (2004)

Patrinos, George P., Giardine, Belinda, Riemer, Cathy, Miller, Webb, Chui, David H. K., Anagnou, Nicholas P., ...

HbVar (http://globin.cse.psu.edu/globin/hbvar/) is a relational database developed by a multi‐center academic effort to provide up‐to‐date and high quality information on the genomic...

Mulan: Multiple-sequence local alignment and visualization for studying function and evolution (2004)

Ovcharenko, Ivan, Loots, Gabriela G., Giardine, Belinda M., Hou, Minmei, Ma, Jian, Hardison, Ross C., ...

Multiple-sequence alignment analysis is a powerful approach for understanding phylogenetic relationships, annotating genes, and detecting functional regulatory elements. With a growing number of...

Evolution and functional classification of vertebrate gene deserts (2004)

Ovcharenko, Ivan, Loots, Gabriela G., Nobrega, Marcelo A., Hardison, Ross C., Miller, Webb, Stubbs, Lisa

Large tracts of the human genome, known as gene deserts, are devoid of protein-coding genes. Dichotomy in their level of conservation with chicken separates these regions into two distinct...

Human-Mouse Alignments with BLASTZ (2003)

Schwartz, Scott, Kent, W. James, Smit, Arian, Zhang, Zheng, Baertsch, Robert, Hardison, Ross C., ...

The Mouse Genome Analysis Consortium aligned the human and mouse genome sequences for a variety of purposes, using alignment programs that suited the various needs. For investigating issues regarding...

Covariation in Frequencies of Substitution, Deletion, Transposition, and Recombination During Eutherian Evolution (2003)

Hardison, Ross C., Roskin, Krishna M., Yang, Shan, Diekhans, Mark, Kent, W. James, Weber, Ryan, ...

Six measures of evolutionary change in the human genome were studied, three derived from the aligned human and mouse genomes in conjunction with the Mouse Genome Sequencing Consortium, consisting of...

Distinguishing Regulatory DNA From Neutral Sites (2003)

Elnitski, Laura, Hardison, Ross C., Li, Jia, Yang, Shan, Kolbe, Diana, Eswara, Pallavi, ...

We explore several computational approaches to analyzing interspecies genomic sequence alignments, aiming to distinguish regulatory regions from neutrally evolving DNA. Human–mouse genomic...

MultiPipMaker and supporting tools: alignments and analysis of multiple genomic DNA sequences (2003)

Schwartz, Scott, Elnitski, Laura, Li, Mei, Weirauch, Matt, Riemer, Cathy, Smit, Arian, ...

Analysis of multiple sequence alignments can generate important, testable hypotheses about the phylogenetic history and cellular function of genomic sequences. We describe the MultiPipMaker server,...

EnteriX 2003: visualization tools for genome alignments of Enterobacteriaceae (2003)

Florea, Liliana, McClelland, Michael, Riemer, Cathy, Schwartz, Scott, Miller, Webb

We describe EnteriX, a suite of three web-based visualization tools for graphically portraying alignment information from comparisons among several fixed and user-supplied sequences from related...

Gene Length and Proximity to Neighbors Affect Genome-Wide Expression Levels (2003)

Chiaromonte, Francesca, Miller, Webb

Steady-state levels of mRNA in cells theoretically depend on the rate and efficiency of transcription and posttranscriptional processing, on mRNA stability, on transcriptional interference from other...

GALA, a Database for Genomic Sequence Alignments and Annotations (2003)

Giardine, Belinda, Elnitski, Laura, Riemer, Cathy, Makalowska, Izabela, Schwartz, Scott, Miller, Webb, ...

We have developed a relational database to contain whole genome sequence alignments between human and mouse with extensive annotations of the human sequence. Complex queries are supported on recorded...

Gene Length and Proximity to Neighbors Affect Genome-Wide Expression Levels (2003)

Chiaromonte, Francesca, Miller, Webb, Bouhassira, Eric E.

Steady-state levels of mRNA in cells theoretically depend on the rate and efficiency of transcription and posttranscriptional processing, on mRNA stability, on transcriptional interference from other...

Significance of inter-species matches when evolutionary rate varies (2002)

Jia Li, Webb Miller

We develop techniques to estimate the statistical signi cance of gap-free alignments between two genomic DNA sequences, using human-mouse alignments as an example. The sequences are assumed to be su...

Significance of inter-species matches when evolutionary rate varies (2002)

Jia Li, Webb Miller

We develop techniques to estimate the statistical significance of gap-free alignments between two genomic DNA sequences, using human-mouse alignments as an example. The sequences are assumed to be...

Comparison of genomic DNA sequences: solved and unsolved problems (2001)

Miller, Webb

Motivation: The DNA sequences of entire genomes are being determined at a rapid rate. Whereas initial genome sequencing efforts were for organisms chosen to be widely spaced in the tree of life,...

Comparative analysis of the gene-dense ACHE/TFR2 region on human chromosome 7q22 with the orthologous region on mouse chromosome 5 (2001)

Wilson, Michael D., Riemer, Cathy, Martindale, Duane W., Schnupf, Pamela, Boright, Andrew P., Cheung, Tony L., ...

Chromosome 7q22 has been the focus of many cytogenetic and molecular studies aimed at delineating regions commonly deleted in myeloid leukemias and myelodysplastic syndromes. We have compared a...

Comparative genome analysis delimits a chromosomal domain and identifies key regulatory elements in the {{alpha}} globin cluster (2001)

Flint, Jonathan, Tufarelli, Cristina, Peden, John, Clark, Kevin, Daniels, Rachael J., Hardison, Ross, ...

We have cloned, sequenced and annotated segments of DNA spanning the mouse, chicken and pufferfish α globin gene clusters and compared them with the corresponding region in man. This has defined a...

A greedy algorithm for aligning DNA sequences (2000)

Zheng Zhang, Scott Schwartz, Lukas Wagner, Webb Miller

For aligning DNA sequences that differ only by sequencing errors, or by equivalent errors from other sources, a greedy algorithm can be much faster than traditional dynamic programming approaches and...

Comparison of the Escherichia coli K-12 genome with sampled genomes of a Klebsiella pneumoniae and three Salmonella enterica serovars, Typhimurium, Typhi and Paratyphi (2000)

McClelland, Michael, Florea, Liliana, Sanderson, Ken, Clifton, Sandra W., Parkhill, Julian, Churcher, Carol, ...

The Escherichia coli K-12 genome (ECO) was compared with the sampled genomes of the sibling species Salmonella enterica serovars Typhimurium, Typhi and Paratyphi A (collectively referred to as SAL)...

Web-based visualization tools for bacterial genome alignments (2000)

Florea, Liliana, Riemer, Cathy, Schwartz, Scott, Zhang, Zheng, Stojanovic, Nikola, Miller, Webb, ...

With the increase in the flow of sequence data, both in contigs and whole genomes, visual aids for comparison and analysis studies are becoming imperative. We describe three web-based tools for...

Genome sequence comparisons: Hurdles in the fast lane to functional genomics (2000)

Wiehe, Thomas, Guigó, Roderic, Miller, Webb

An important computational technique for extracting the wealth of information hidden in human genomic sequence data is to compare the sequence with that from the corresponding region of the mouse...

Post-processing long pairwise alignments (1999)

Zhang, Zheng, Berman, Piotr, Wiehe, Thomas, Miller, Webb

Motivation: The local alignment problem for two sequences requires determining similar regions, one from each sequence, and aligning those regions. For alignments computed by dynamic programming,...

Protein sequence similarity searches using patterns as seeds (1998)

Zheng Zhang, Ro A. Schäffer, Webb Miller, Thomas L. Madden, David J. Lipman, Eugene V. Koonin, ...

Protein families often are characterized by conserved sequence patterns or motifs. A researcher frequently wishes to evaluate the significance of a specific pattern within a protein, or to exploit...

Gapped blast and psi-blast: a new generation of protein database search programs (1997)

Stephen F. Altschul, Thomas L. Madden, Ro A. Schäffer, Jinghui Zhang, Zheng Zhang, Webb Miller, ...

The BLAST programs are widely used tools for searching protein and DNA databases for sequence similarities. For protein comparisons, a variety of definitional, algorithmic and statistical refinements...

A tool for aligning very similar DNA sequences (1997)

Chao, Kun-Mao, Zhang, Jinghui, Ostell, James, Miller, Webb

Results: We have produced a computer program, named sim3, that solves the following computational problem. Two DNA sequences are given, where the shorter sequence is very similar to some contiguous...

Progressive Multiple Alignment with Constraints (1996)

Gene Myers, Sanford Selznick, Zheng Zhang, Webb Miller

A progressive alignment algorithm produces a multi-alignment of a set of sequences by repeatedly aligning pairs of sequences and/or previously generated alignments. We describe a method for...

A local alignment tool for very long DNA sequences (1995)

Kun-mao Chao, Jinghui Zhang, James Ostell, Webb Miller

Abstract. This paper presents a practical program, called sim2, for building local alignments of two sequences, each of which may be hundreds of kilobases long. Sim2 first constructs n best...

Chaining Multiple-Alignment Fragments in Sub-Quadratic Time (1995)

Gene Myers And Webb Miller, Gene Myers, Webb Miller

We describe a multiple-sequence alignment algorithm for determining the highest-scoring alignment that can be obtained by chaining together non-overlapping subalignments selected from a given...

A local alignment tool for very long DNA sequences (1995)

Chao, Kun-Mao, Zhang, Jinghui, Ostell, James, Miller, Webb

This paper presents a practical program, called sim2, for building local alignments of two sequences, each of which may be hundreds of kilobases long. sim2 first constructs n best non-intersecting...

Recent developments in linear-space alignment methods: A survey (1994)

Kun-mao Chao, Ross C. Hardison, Webb Miller

A dynamic-programming strategy for sequence alignment first proposed in 1975 by Dan Hirschberg can be adapted to yield a number of extremely space-efficient algorithms. Specifically, these algorithms...

A note about computing all local alignments (1994)

Miller, Webb, Boguski, Mark

A recent paper in this journal by G. Barton proposed an efficient algorithm for locating locally optimal alignments between two sequences. Although the paper claims that all such alignments are...

Locating well-conserved regions within a pairwise alignment (1993)

Chao, Kun-Mao, Hardison, Ross C., Miller, Webb

Within a single alignment of two DNA sequences or two protein sequences, some regions may be much better conserved than others. Such strong conservation may reveal a region that possesses an...

Comparative analysis of the locus control region of the rabbit {beta}-like globin gene cluster: HS3 increases transient expression of an embryonic {varepsilon}-globin gene (1993)

Hardison, Ross, Xu, Jia, Jackson, John, Mansberger, James, Selifonova, Olga, Grotch, Brent, ...

The rabbit homolog to the locus control region (LCR) of the human β-like globln gene cluster was isolated, and long segments containing the DNase I hypersensitive sites (HS) were sequenced. The...

Building multiple alignments from pairwise alignments (1993)

Miller, Webb

Given a family of related sequences, one can first determine alignments between various pairs of those sequences, then construct a simultaneous alignment of all the sequences that is determined in a...

Aligning two sequences within a specified diagonal band (1992)

Chao, Kun-Mao, Pearson, William R., Miller, Webb

We describe an algorithm for aligning two sequences within a diagonal band that requires only O(NW) computation time and O(N) space, where N is the length of the shorter of the two sequences and W is...

Improved algorithms for searching restriction maps (1991)

Miller, Webb, Barr, John, Rudd, Kenneth E.

We present algorithms for searching a DNA restriction enzyme map for a region that best matches a shorter ‘probe’ map. Our algorithms utilize a new model of map alignments, and extensive...

Software tools for analyzing pairwise alignments of long sequences (1991)

Schwartz, Scott, Miller, Webb, Yang, Cher-Ming, Hardison, Ross C.

Pairwise comparison of long stretches of genomic DNA sequence can Identify regions conserved across species, which often indicate functional significance. However, the novel insights frequently must...

Mapping sequenced E.coli genes by computer: software, strategies and examples (1991)

Rudd, Kenneth E., Miller, Webb, Werner, Craig, Ostell, James, Tolstoshev, Carolyn, Satterfield, Steven G.

Methods are presented for organizing and integrating DNA sequence data, restriction maps, and genetic maps for the same organism but from a variety of sources (databases, publications, personal...

Kdional Library of Medicine, National Institutes of Health (1990)

Stephen F. Altschul, Warren Gish, Webb Miller, Eugene W. Myers, David J. Lipmanl

A ne & approach to rapid sequence comparison, basic local alignment search tool (BLAST), directly approsimates alignments that optimize a measure of local similarity, the maximal segment pair...

Alignment of Escherichia coli K12 DNA sequences to a genomic restriction map (1990)

Rudd, Kenneth E., Miller, Webb, Ostell, James, Benson, Dennis A.

We use the extensive published information describing the genome of Escherichia coli and new restriction map alignment software to align DNA sequence, genetic, and physical maps. Restriction map...

An algorithm for searching restriction maps (1990)

Miller, Webb, Ostell, Jim, Rudd, Kenneth E.

This paper presents an algorithm thai searches a DNA restriction enzyme map for regions that approximately match a shorter 'probe' map. Both the map and the probe consist of a sequence of...

A space-efficient algorithm for local similarities (1990)

Huang, Xiaoqiu, Hardison, Ross C., Miller, Webb

Existing dynamic-programming algorithms for identifying similar regions of two sequences require time and space proportional to the product of the sequence lengths. Often this space requirement is...

Optimal alignments in linear space (1988)

Eugene W. Myers, Webb Miller

Space, not time, is often the limiting factor when computing optimal sequence alignments, and a number of recent papers in the biology literature have proposed space-saving strategies. However, a...

Optimal alignments in linear space (1988)

Myers, Eugene W., Miller, Webb

Space, not time, is often the limiting factor when computing optimal sequence alignments, and a number of recent papers in the biology literature have proposed space-saving strategies. However, a...

Comparative genomic sequence analysis of the human and mouse cystic fibrosis transmembrane conductance regulator genes

Ellsworth, Rachel E., Jamison, D. Curtis, Touchman, Jeffrey W., Chissoe, Stephanie L., Braden Maduro, Valerie V., Bouffard, Gerard G., ...

The identification of the cystic fibrosis transmembrane conductance regulator gene (CFTR) in 1989 represents a landmark accomplishment in human genetics. Since that time, there have been numerous...

Hox cluster genomics in the horn shark, Heterodontus francisci

Kim, Chang-Bae, Amemiya, Chris, Bailey, Wendy, Kawasaki, Kazuhiko, Mezey, Jason, Miller, Webb, ...

Reconstructing the evolutionary history of Hox cluster origins will lead to insights into the developmental and evolutionary significance of Hox gene clusters in vertebrate phylogeny and to their...

Comparative analysis of the gene-dense ACHE/TFR2 region on human chromosome 7q22 with the orthologous region on mouse chromosome 5

Wilson, Michael D., Riemer, Cathy, Martindale, Duane W., Schnupf, Pamela, Boright, Andrew P., Cheung, Tony L., ...

Chromosome 7q22 has been the focus of many cytogenetic and molecular studies aimed at delineating regions commonly deleted in myeloid leukemias and myelodysplastic syndromes. We have compared a...

Sequence conservation at human and mouse orthologous common fragile regions, FRA3B/FHIT and Fra14A2/Fhit

Shiraishi, Takeshi, Druck, Teresa, Mimori, Koshi, Flomenberg, Jacob, Berk, Lori, Alder, Hansjuerg, ...

It has been suggested that delayed DNA replication underlies fragility at common human fragile sites, but specific sequences responsible for expression of these inducible fragile sites have not been...

Association between divergence and interspersed repeats in mammalian noncoding genomic DNA

Chiaromonte, Francesca, Yang, Shan, Elnitski, Laura, Yap, Von Bing, Miller, Webb, Hardison, Ross C.

The amount of noncoding genomic DNA sequence that aligns between human and mouse varies substantially in different regions of their genomes, and the amount of repetitive DNA also varies. In this...

Sequences Flanking Hypersensitive Sites of the β-Globin Locus Control Region Are Required for Synergistic Enhancement

Molete, Joseph M., Petrykowska, Hanna, Bouhassira, Eric E., Feng, Yong-Qing, Miller, Webb, Hardison, Ross C.

The major distal regulatory sequence for the β-globin gene locus, the locus control region (LCR), is composed of multiple hypersensitive sites (HSs). Different models for LCR function postulate that...

Web-based visualization tools for bacterial genome alignments

Florea, Liliana, Riemer, Cathy, Schwartz, Scott, Zhang, Zheng, Stojanovic, Nikola, Miller, Webb, ...

With the increase in the flow of sequence data, both in contigs and whole genomes, visual aids for comparison and analysis studies are becoming imperative. We describe three web-based tools for...

Comparison of the Escherichia coli K-12 genome with sampled genomes of a Klebsiella pneumoniae and three Salmonella enterica serovars, Typhimurium, Typhi and Paratyphi

McClelland, Michael, Florea, Liliana, Sanderson, Ken, Clifton, Sandra W., Parkhill, Julian, Churcher, Carol, ...

The Escherichia coli K-12 genome (ECO) was compared with the sampled genomes of the sibling species Salmonella enterica serovars Typhimurium, Typhi and Paratyphi A (collectively referred to as SAL)...

Genomic structure and functional control of the Dlx3-7 bigene cluster

Sumiyama, Kenta, Irvine, Steven Q., Stock, David W., Weiss, Kenneth M., Kawasaki, Kazuhiko, Shimizu, Nobuyoshi, ...

The Dlx genes are involved in early vertebrate morphogenesis, notably of the head. The six Dlx genes of mammals are arranged in three convergently transcribed bigene clusters. In this study, we...

The Chlamydomonas reinhardtii Plastid Chromosome: Islands of Genes in a Sea of RepeatsW⃞

Maul, Jude E., Lilly, Jason W., Cui, Liying, DePamphilis, Claude W., Miller, Webb, Harris, Elizabeth H., ...

Chlamydomonas reinhardtii is a unicellular eukaryotic alga possessing a single chloroplast that is widely used as a model system for the study of photosynthetic processes. This report analyzes the...

EnteriX 2003: visualization tools for genome alignments of Enterobacteriaceae

Florea, Liliana, McClelland, Michael, Riemer, Cathy, Schwartz, Scott, Miller, Webb

We describe EnteriX, a suite of three web-based visualization tools for graphically portraying alignment information from comparisons among several fixed and user-supplied sequences from related...

MultiPipMaker and supporting tools: alignments and analysis of multiple genomic DNA sequences

Schwartz, Scott, Elnitski, Laura, Li, Mei, Weirauch, Matt, Riemer, Cathy, Smit, Arian, ...

Analysis of multiple sequence alignments can generate important, testable hypotheses about the phylogenetic history and cellular function of genomic sequences. We describe the MultiPipMaker server,...

Evolution's cauldron: Duplication, deletion, and rearrangement in the mouse and human genomes

Kent, W. James, Baertsch, Robert, Hinrichs, Angie, Miller, Webb, Haussler, David

This study examines genomic duplications, deletions, and rearrangements that have happened at scales ranging from a single base to complete chromosomes by comparing the mouse and human genomes. From...

Improvements in the HbVar database of human hemoglobin variants and thalassemia mutations for population and sequence variation studies

Patrinos, George P., Giardine, Belinda, Riemer, Cathy, Miller, Webb, Chui, David H. K., Anagnou, Nicholas P., ...

HbVar (http://globin.cse.psu.edu/globin/hbvar/) is a relational database developed by a multi-center academic effort to provide up-to-date and high quality information on the genomic sequence changes...

Comparative Sequence of Human and Mouse BAC Clones from the mnd2 Region of Chromosome 2p13

Jang, Wonhee, Hua, Axin, Spilson, Sandra V., Miller, Webb, Roe, Bruce A., Meisler, Miriam H.

The mnd2 mutation on mouse chromosome 6 produces a progressive neuromuscular disorder. To determine the gene content of the 400-kb mnd2 nonrecombinant region, we sequenced 108 kb of mouse genomic DNA...

A Computer Program for Aligning a cDNA Sequence with a Genomic DNA Sequence

Florea, Liliana, Hartzell, George, Zhang, Zheng, Rubin, Gerald M., Miller, Webb

We address the problem of efficiently aligning a transcribed and spliced DNA sequence with a genomic sequence containing that gene, allowing for introns in the genomic sequence and a relatively small...

Analysis of the Quality and Utility of Random Shotgun Sequencing at Low Redundancies

Bouck, John, Miller, Webb, Gorrell, James H., Muzny, Donna, Gibbs, Richard A.

The currently favored approach for sequencing the human genome involves selecting representative large-insert clones (100–200 kb), randomly shearing this DNA to construct shotgun libraries, and...

PipMaker—A Web Server for Aligning Two Genomic DNA Sequences

Schwartz, Scott, Zhang, Zheng, Frazer, Kelly A., Smit, Arian, Riemer, Cathy, Bouck, John, ...

PipMaker (http://bio.cse.psu.edu) is a World-Wide Web site for comparing two long DNA sequences to identify conserved segments and for producing informative, high-resolution displays of the resulting...

Genomic Sequence Analysis of the Mouse Naip Gene Array

Endrizzi, Matthew G., Hadinoto, Vey, Growney, Joseph D., Miller, Webb, Dietrich, William F.

A mouse locus called Lgn1 determines differences in macrophage permissiveness for the intracellular replication of Legionella pneumophila. The only regional candidate genes for this phenotype...

zPicture: Dynamic Alignment and Visualization Tool for Analyzing Conservation Profiles

Ovcharenko, Ivan, Loots, Gabriela G., Hardison, Ross C., Miller, Webb, Stubbs, Lisa

Comparative sequence analysis has evolved as an essential technique for identifying functional coding and noncoding elements conserved throughout evolution. Here, we introduce zPicture, an...

Patterns of Insertions and Their Covariation With Substitutions in the Rat, Mouse, and Human Genomes

Yang, Shan, Smit, Arian F., Schwartz, Scott, Chiaromonte, Francesca, Roskin, Krishna M., Haussler, David, ...

The rates at which human genomic DNA changes by neutral substitution and insertion of certain families of transposable elements covary in large, megabase-sized segments. We used the rat, mouse, and...

Comparative Analysis of the α-Like Globin Clusters in Mouse, Rat, and Human Chromosomes Indicates a Mechanism Underlying Breaks in Conserved Synteny

Tufarelli, Cristina, Hardison, Ross, Miller, Webb, Hughes, Jim, Clark, Kevin, Ventress, Nicki, ...

We have sequenced and fully annotated a 65,871-bp region of mouse Chromosome 17 including the Hba-ps4 α-globin pseudogene. Comparative sequence analysis with the functional α-globin loci at human...

Regulatory Potential Scores From Genome-Wide Three-Way Alignments of Human, Mouse, and Rat

Kolbe, Diana, Taylor, James, Elnitski, Laura, Eswara, Pallavi, Li, Jia, Miller, Webb, ...

We generalize the computation of the Regulatory Potential (RP) score from two-way alignments of human and mouse to three-way alignments of human, mouse, and rat. This requires overcoming technical...

Aligning Multiple Genomic Sequences With the Threaded Blockset Aligner

Blanchette, Mathieu, Kent, W. James, Riemer, Cathy, Elnitski, Laura, Smit, Arian F.A., Roskin, Krishna M., ...

We define a “threaded blockset,” which is a novel generalization of the classic notion of a multiple alignment. A new computer program called TBA (for “threaded blockset aligner”) builds a...

Gene Length and Proximity to Neighbors Affect Genome-Wide Expression Levels

Chiaromonte, Francesca, Miller, Webb

Steady-state levels of mRNA in cells theoretically depend on the rate and efficiency of transcription and posttranscriptional processing, on mRNA stability, on transcriptional interference from other...

GALA, a Database for Genomic Sequence Alignments and Annotations

Giardine, Belinda, Elnitski, Laura, Riemer, Cathy, Makalowska, Izabela, Schwartz, Scott, Miller, Webb, ...

We have developed a relational database to contain whole genome sequence alignments between human and mouse with extensive annotations of the human sequence. Complex queries are supported on recorded...

Human–Mouse Alignments with BLASTZ

Schwartz, Scott, Kent, W. James, Smit, Arian, Zhang, Zheng, Baertsch, Robert, Hardison, Ross C., ...

The Mouse Genome Analysis Consortium aligned the human and mouse genome sequences for a variety of purposes, using alignment programs that suited the various needs. For investigating issues regarding...

Covariation in Frequencies of Substitution, Deletion, Transposition, and Recombination During Eutherian Evolution

Hardison, Ross C., Roskin, Krishna M., Yang, Shan, Diekhans, Mark, Kent, W. James, Weber, Ryan, ...

Six measures of evolutionary change in the human genome were studied, three derived from the aligned human and mouse genomes in conjunction with the Mouse Genome Sequencing Consortium, consisting of...

Distinguishing Regulatory DNA From Neutral Sites

Elnitski, Laura, Hardison, Ross C., Li, Jia, Yang, Shan, Kolbe, Diana, Eswara, Pallavi, ...

We explore several computational approaches to analyzing interspecies genomic sequence alignments, aiming to distinguish regulatory regions from neutrally evolving DNA. Human–mouse genomic...

Reconstructing large regions of an ancestral mammalian genome in silico

Blanchette, Mathieu, Green, Eric D., Miller, Webb, Haussler, David

It is believed that most modern mammalian lineages arose from a series of rapid speciation events near the Cretaceous-Tertiary boundary. It is shown that such a phylogeny makes the common ancestral...

Improvements to GALA and dbERGE II: databases featuring genomic sequence alignment, annotation and experimental results

Elnitski, Laura, Giardine, Belinda, Shah, Prachi, Zhang, Yi, Riemer, Cathy, Weirauch, Matthew, ...

We describe improvements to two databases that give access to information on genomic sequence similarities, functional elements in DNA and experimental results that demonstrate those functions. GALA,...

Evolution and functional classification of vertebrate gene deserts

Ovcharenko, Ivan, Loots, Gabriela G., Nobrega, Marcelo A., Hardison, Ross C., Miller, Webb, Stubbs, Lisa

Large tracts of the human genome, known as gene deserts, are devoid of protein-coding genes. Dichotomy in their level of conservation with chicken separates these regions into two distinct...

Mulan: Multiple-sequence local alignment and visualization for studying function and evolution

Ovcharenko, Ivan, Loots, Gabriela G., Giardine, Belinda M., Hou, Minmei, Ma, Jian, Hardison, Ross C., ...

Multiple-sequence alignment analysis is a powerful approach for understanding phylogenetic relationships, annotating genes, and detecting functional regulatory elements. With a growing number of...

An initial strategy for the systematic identification of functional elements in the human genome by low-redundancy comparative sequencing

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...

Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes

Siepel, Adam, Bejerano, Gill, Pedersen, Jakob S., Hinrichs, Angie S., Hou, Minmei, Rosenbloom, Kate, ...

We have conducted a comprehensive search for conserved elements in vertebrate genomes, using genome-wide multiple alignments of five vertebrate species (human, mouse, rat, chicken, and Fugu...

Evaluation of regulatory potential and conservation scores for detecting cis-regulatory modules in aligned mammalian genome sequences

King, David C., Taylor, James, Elnitski, Laura, Chiaromonte, Francesca, Miller, Webb, Hardison, Ross C.

Techniques of comparative genomics are being used to identify candidate functional DNA sequences, and objective evaluations are needed to assess their effectiveness. Different analytical methods...

Generation and Comparative Analysis of ∼3.3 Mb of Mouse Genomic Sequence Orthologous to the Region of Human Chromosome 7q11.23 Implicated in Williams Syndrome

DeSilva, Udaya, Elnitski, Laura, Idol, Jacquelyn R., Doyle, Johannah L., Gan, Weiniu, Thomas, James W., ...

Williams syndrome is a complex developmental disorder that results from the heterozygous deletion of a ∼1.6-Mb segment of human chromosome 7q11.23. These deletions are mediated by large (∼300 kb)...

Galaxy: A platform for interactive large-scale genome analysis

Giardine, Belinda, Riemer, Cathy, Hardison, Ross C., Burhans, Richard, Elnitski, Laura, Shah, Prachi, ...

Accessing and analyzing the exponentially expanding genomic sequence and functional data pose a challenge for biomedical researchers. Here we describe an interactive system, Galaxy, that combines the...

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...

Comparative genomic sequence analysis of the human and mouse cystic fibrosis transmembrane conductance regulator genes

Ellsworth, Rachel E., Jamison, D. Curtis, Touchman, Jeffrey W., Chissoe, Stephanie L., Braden Maduro, Valerie V., Bouffard, Gerard G., ...

The identification of the cystic fibrosis transmembrane conductance regulator gene (CFTR) in 1989 represents a landmark accomplishment in human genetics. Since that time, there have been numerous...

Hox cluster genomics in the horn shark, Heterodontus francisci

Kim, Chang-Bae, Amemiya, Chris, Bailey, Wendy, Kawasaki, Kazuhiko, Mezey, Jason, Miller, Webb, ...

Reconstructing the evolutionary history of Hox cluster origins will lead to insights into the developmental and evolutionary significance of Hox gene clusters in vertebrate phylogeny and to their...

Comparative analysis of the gene-dense ACHE/TFR2 region on human chromosome 7q22 with the orthologous region on mouse chromosome 5

Wilson, Michael D., Riemer, Cathy, Martindale, Duane W., Schnupf, Pamela, Boright, Andrew P., Cheung, Tony L., ...

Chromosome 7q22 has been the focus of many cytogenetic and molecular studies aimed at delineating regions commonly deleted in myeloid leukemias and myelodysplastic syndromes. We have compared a...

Sequence conservation at human and mouse orthologous common fragile regions, FRA3B/FHIT and Fra14A2/Fhit

Shiraishi, Takeshi, Druck, Teresa, Mimori, Koshi, Flomenberg, Jacob, Berk, Lori, Alder, Hansjuerg, ...

It has been suggested that delayed DNA replication underlies fragility at common human fragile sites, but specific sequences responsible for expression of these inducible fragile sites have not been...

Association between divergence and interspersed repeats in mammalian noncoding genomic DNA

Chiaromonte, Francesca, Yang, Shan, Elnitski, Laura, Yap, Von Bing, Miller, Webb, Hardison, Ross C.

The amount of noncoding genomic DNA sequence that aligns between human and mouse varies substantially in different regions of their genomes, and the amount of repetitive DNA also varies. In this...

Sequences Flanking Hypersensitive Sites of the β-Globin Locus Control Region Are Required for Synergistic Enhancement

Molete, Joseph M., Petrykowska, Hanna, Bouhassira, Eric E., Feng, Yong-Qing, Miller, Webb, Hardison, Ross C.

The major distal regulatory sequence for the β-globin gene locus, the locus control region (LCR), is composed of multiple hypersensitive sites (HSs). Different models for LCR function postulate that...

Web-based visualization tools for bacterial genome alignments

Florea, Liliana, Riemer, Cathy, Schwartz, Scott, Zhang, Zheng, Stojanovic, Nikola, Miller, Webb, ...

With the increase in the flow of sequence data, both in contigs and whole genomes, visual aids for comparison and analysis studies are becoming imperative. We describe three web-based tools for...

Comparison of the Escherichia coli K-12 genome with sampled genomes of a Klebsiella pneumoniae and three Salmonella enterica serovars, Typhimurium, Typhi and Paratyphi

McClelland, Michael, Florea, Liliana, Sanderson, Ken, Clifton, Sandra W., Parkhill, Julian, Churcher, Carol, ...

The Escherichia coli K-12 genome (ECO) was compared with the sampled genomes of the sibling species Salmonella enterica serovars Typhimurium, Typhi and Paratyphi A (collectively referred to as SAL)...

Genomic structure and functional control of the Dlx3-7 bigene cluster

Sumiyama, Kenta, Irvine, Steven Q., Stock, David W., Weiss, Kenneth M., Kawasaki, Kazuhiko, Shimizu, Nobuyoshi, ...

The Dlx genes are involved in early vertebrate morphogenesis, notably of the head. The six Dlx genes of mammals are arranged in three convergently transcribed bigene clusters. In this study, we...

The Chlamydomonas reinhardtii Plastid Chromosome: Islands of Genes in a Sea of RepeatsW⃞

Maul, Jude E., Lilly, Jason W., Cui, Liying, DePamphilis, Claude W., Miller, Webb, Harris, Elizabeth H., ...

Chlamydomonas reinhardtii is a unicellular eukaryotic alga possessing a single chloroplast that is widely used as a model system for the study of photosynthetic processes. This report analyzes the...

Generation and Comparative Analysis of ∼3.3 Mb of Mouse Genomic Sequence Orthologous to the Region of Human Chromosome 7q11.23 Implicated in Williams Syndrome

DeSilva, Udaya, Elnitski, Laura, Idol, Jacquelyn R., Doyle, Johannah L., Gan, Weiniu, Thomas, James W., ...

Williams syndrome is a complex developmental disorder that results from the heterozygous deletion of a ∼1.6-Mb segment of human chromosome 7q11.23. These deletions are mediated by large (∼300 kb)...

EnteriX 2003: visualization tools for genome alignments of Enterobacteriaceae

Florea, Liliana, McClelland, Michael, Riemer, Cathy, Schwartz, Scott, Miller, Webb

We describe EnteriX, a suite of three web-based visualization tools for graphically portraying alignment information from comparisons among several fixed and user-supplied sequences from related...

MultiPipMaker and supporting tools: alignments and analysis of multiple genomic DNA sequences

Schwartz, Scott, Elnitski, Laura, Li, Mei, Weirauch, Matt, Riemer, Cathy, Smit, Arian, ...

Analysis of multiple sequence alignments can generate important, testable hypotheses about the phylogenetic history and cellular function of genomic sequences. We describe the MultiPipMaker server,...

Evolution's cauldron: Duplication, deletion, and rearrangement in the mouse and human genomes

Kent, W. James, Baertsch, Robert, Hinrichs, Angie, Miller, Webb, Haussler, David

This study examines genomic duplications, deletions, and rearrangements that have happened at scales ranging from a single base to complete chromosomes by comparing the mouse and human genomes. From...

Improvements in the HbVar database of human hemoglobin variants and thalassemia mutations for population and sequence variation studies

Patrinos, George P., Giardine, Belinda, Riemer, Cathy, Miller, Webb, Chui, David H. K., Anagnou, Nicholas P., ...

HbVar (http://globin.cse.psu.edu/globin/hbvar/) is a relational database developed by a multi-center academic effort to provide up-to-date and high quality information on the genomic sequence changes...

Comparative Sequence of Human and Mouse BAC Clones from the mnd2 Region of Chromosome 2p13

Jang, Wonhee, Hua, Axin, Spilson, Sandra V., Miller, Webb, Roe, Bruce A., Meisler, Miriam H.

The mnd2 mutation on mouse chromosome 6 produces a progressive neuromuscular disorder. To determine the gene content of the 400-kb mnd2 nonrecombinant region, we sequenced 108 kb of mouse genomic DNA...

A Computer Program for Aligning a cDNA Sequence with a Genomic DNA Sequence

Florea, Liliana, Hartzell, George, Zhang, Zheng, Rubin, Gerald M., Miller, Webb

We address the problem of efficiently aligning a transcribed and spliced DNA sequence with a genomic sequence containing that gene, allowing for introns in the genomic sequence and a relatively small...

Analysis of the Quality and Utility of Random Shotgun Sequencing at Low Redundancies

Bouck, John, Miller, Webb, Gorrell, James H., Muzny, Donna, Gibbs, Richard A.

The currently favored approach for sequencing the human genome involves selecting representative large-insert clones (100–200 kb), randomly shearing this DNA to construct shotgun libraries, and...

PipMaker—A Web Server for Aligning Two Genomic DNA Sequences

Schwartz, Scott, Zhang, Zheng, Frazer, Kelly A., Smit, Arian, Riemer, Cathy, Bouck, John, ...

PipMaker (http://bio.cse.psu.edu) is a World-Wide Web site for comparing two long DNA sequences to identify conserved segments and for producing informative, high-resolution displays of the resulting...

Genomic Sequence Analysis of the Mouse Naip Gene Array

Endrizzi, Matthew G., Hadinoto, Vey, Growney, Joseph D., Miller, Webb, Dietrich, William F.

A mouse locus called Lgn1 determines differences in macrophage permissiveness for the intracellular replication of Legionella pneumophila. The only regional candidate genes for this phenotype...

zPicture: Dynamic Alignment and Visualization Tool for Analyzing Conservation Profiles

Ovcharenko, Ivan, Loots, Gabriela G., Hardison, Ross C., Miller, Webb, Stubbs, Lisa

Comparative sequence analysis has evolved as an essential technique for identifying functional coding and noncoding elements conserved throughout evolution. Here, we introduce zPicture, an...

Patterns of Insertions and Their Covariation With Substitutions in the Rat, Mouse, and Human Genomes

Yang, Shan, Smit, Arian F., Schwartz, Scott, Chiaromonte, Francesca, Roskin, Krishna M., Haussler, David, ...

The rates at which human genomic DNA changes by neutral substitution and insertion of certain families of transposable elements covary in large, megabase-sized segments. We used the rat, mouse, and...

Comparative Analysis of the α-Like Globin Clusters in Mouse, Rat, and Human Chromosomes Indicates a Mechanism Underlying Breaks in Conserved Synteny

Tufarelli, Cristina, Hardison, Ross, Miller, Webb, Hughes, Jim, Clark, Kevin, Ventress, Nicki, ...

We have sequenced and fully annotated a 65,871-bp region of mouse Chromosome 17 including the Hba-ps4 α-globin pseudogene. Comparative sequence analysis with the functional α-globin loci at human...

Regulatory Potential Scores From Genome-Wide Three-Way Alignments of Human, Mouse, and Rat

Kolbe, Diana, Taylor, James, Elnitski, Laura, Eswara, Pallavi, Li, Jia, Miller, Webb, ...

We generalize the computation of the Regulatory Potential (RP) score from two-way alignments of human and mouse to three-way alignments of human, mouse, and rat. This requires overcoming technical...

Aligning Multiple Genomic Sequences With the Threaded Blockset Aligner

Blanchette, Mathieu, Kent, W. James, Riemer, Cathy, Elnitski, Laura, Smit, Arian F.A., Roskin, Krishna M., ...

We define a “threaded blockset,” which is a novel generalization of the classic notion of a multiple alignment. A new computer program called TBA (for “threaded blockset aligner”) builds a...

Gene Length and Proximity to Neighbors Affect Genome-Wide Expression Levels

Chiaromonte, Francesca, Miller, Webb

Steady-state levels of mRNA in cells theoretically depend on the rate and efficiency of transcription and posttranscriptional processing, on mRNA stability, on transcriptional interference from other...

GALA, a Database for Genomic Sequence Alignments and Annotations

Giardine, Belinda, Elnitski, Laura, Riemer, Cathy, Makalowska, Izabela, Schwartz, Scott, Miller, Webb, ...

We have developed a relational database to contain whole genome sequence alignments between human and mouse with extensive annotations of the human sequence. Complex queries are supported on recorded...

Human–Mouse Alignments with BLASTZ

Schwartz, Scott, Kent, W. James, Smit, Arian, Zhang, Zheng, Baertsch, Robert, Hardison, Ross C., ...

The Mouse Genome Analysis Consortium aligned the human and mouse genome sequences for a variety of purposes, using alignment programs that suited the various needs. For investigating issues regarding...

Covariation in Frequencies of Substitution, Deletion, Transposition, and Recombination During Eutherian Evolution

Hardison, Ross C., Roskin, Krishna M., Yang, Shan, Diekhans, Mark, Kent, W. James, Weber, Ryan, ...

Six measures of evolutionary change in the human genome were studied, three derived from the aligned human and mouse genomes in conjunction with the Mouse Genome Sequencing Consortium, consisting of...

Distinguishing Regulatory DNA From Neutral Sites

Elnitski, Laura, Hardison, Ross C., Li, Jia, Yang, Shan, Kolbe, Diana, Eswara, Pallavi, ...

We explore several computational approaches to analyzing interspecies genomic sequence alignments, aiming to distinguish regulatory regions from neutrally evolving DNA. Human–mouse genomic...

Reconstructing large regions of an ancestral mammalian genome in silico

Blanchette, Mathieu, Green, Eric D., Miller, Webb, Haussler, David

It is believed that most modern mammalian lineages arose from a series of rapid speciation events near the Cretaceous-Tertiary boundary. It is shown that such a phylogeny makes the common ancestral...

Improvements to GALA and dbERGE II: databases featuring genomic sequence alignment, annotation and experimental results

Elnitski, Laura, Giardine, Belinda, Shah, Prachi, Zhang, Yi, Riemer, Cathy, Weirauch, Matthew, ...

We describe improvements to two databases that give access to information on genomic sequence similarities, functional elements in DNA and experimental results that demonstrate those functions. GALA,...

Evolution and functional classification of vertebrate gene deserts

Ovcharenko, Ivan, Loots, Gabriela G., Nobrega, Marcelo A., Hardison, Ross C., Miller, Webb, Stubbs, Lisa

Large tracts of the human genome, known as gene deserts, are devoid of protein-coding genes. Dichotomy in their level of conservation with chicken separates these regions into two distinct...

Mulan: Multiple-sequence local alignment and visualization for studying function and evolution

Ovcharenko, Ivan, Loots, Gabriela G., Giardine, Belinda M., Hou, Minmei, Ma, Jian, Hardison, Ross C., ...

Multiple-sequence alignment analysis is a powerful approach for understanding phylogenetic relationships, annotating genes, and detecting functional regulatory elements. With a growing number of...

An initial strategy for the systematic identification of functional elements in the human genome by low-redundancy comparative sequencing

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...

Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes

Siepel, Adam, Bejerano, Gill, Pedersen, Jakob S., Hinrichs, Angie S., Hou, Minmei, Rosenbloom, Kate, ...

We have conducted a comprehensive search for conserved elements in vertebrate genomes, using genome-wide multiple alignments of five vertebrate species (human, mouse, rat, chicken, and Fugu...

Evaluation of regulatory potential and conservation scores for detecting cis-regulatory modules in aligned mammalian genome sequences

King, David C., Taylor, James, Elnitski, Laura, Chiaromonte, Francesca, Miller, Webb, Hardison, Ross C.

Techniques of comparative genomics are being used to identify candidate functional DNA sequences, and objective evaluations are needed to assess their effectiveness. Different analytical methods...

Galaxy: A platform for interactive large-scale genome analysis

Giardine, Belinda, Riemer, Cathy, Hardison, Ross C., Burhans, Richard, Elnitski, Laura, Shah, Prachi, ...

Accessing and analyzing the exponentially expanding genomic sequence and functional data pose a challenge for biomedical researchers. Here we describe an interactive system, Galaxy, that combines the...

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...

Recharacterization of ancient DNA miscoding lesions: insights in the era of sequencing-by-synthesis

Gilbert, M. Thomas P., Binladen, Jonas, Miller, Webb, Wiuf, Carsten, Willerslev, Eske, Poinar, Hendrik, ...

Although ancient DNA (aDNA) miscoding lesions have been studied since the earliest days of the field, their nature remains a source of debate. A variety of conflicting hypotheses exist about which...

Experimental validation of predicted mammalian erythroid cis-regulatory modules

Wang, Hao, Zhang, Ying, Cheng, Yong, Zhou, Yuepin, King, David C., Taylor, James, ...

Multiple alignments of genome sequences are helpful guides to functional analysis, but predicting cis-regulatory modules (CRMs) accurately from such alignments remains an elusive goal. We predict...

Reconstructing contiguous regions of an ancestral genome

Ma, Jian, Zhang, Louxin, Suh, Bernard B., Raney, Brian J., Burhans, Richard C., Kent, W. James, ...

This article analyzes mammalian genome rearrangements at higher resolution than has been published to date. We identify 3171 intervals, covering ∼92% of the human genome, within which we find no...

ESPERR: Learning strong and weak signals in genomic sequence alignments to identify functional elements

Taylor, James, Tyekucheva, Svitlana, King, David C., Hardison, Ross C., Miller, Webb, Chiaromonte, Francesca

Genomic sequence signals—such as base composition, presence of particular motifs, or evolutionary constraint—have been used effectively to identify functional elements. However, approaches based...

Using genomic data to unravel the root of the placental mammal phylogeny

Murphy, William J., Pringle, Thomas H., Crider, Tess A., Springer, Mark S., Miller, Webb

The phylogeny of placental mammals is a critical framework for choosing future genome sequencing targets and for resolving the ancestral mammalian genome at the nucleotide level. Despite considerable...

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,...

Finding cis-regulatory elements using comparative genomics: Some lessons from ENCODE data

King, David C., Taylor, James, Zhang, Ying, Cheng, Yong, Lawson, Heather A., Martin, Joel, ...

Identification of functional genomic regions using interspecies comparison will be most effective when the full span of relationships between genomic function and evolutionary constraint are...

A framework for collaborative analysis of ENCODE data: Making large-scale analyses biologist-friendly

Blankenberg, Daniel, Taylor, James, Schenck, Ian, He, Jianbin, Zhang, Yi, Ghent, Matthew, ...

The standardization and sharing of data and tools are the biggest challenges of large collaborative projects such as the Encyclopedia of DNA Elements (ENCODE). Here we describe a compact Web...

Fast-evolving noncoding sequences in the human genome

Bird, Christine P, Stranger, Barbara E, Liu, Maureen, Thomas, Daryl J, Ingle, Catherine E, Beazley, Claude, ...

Over 1,300 conserved non-coding sequences were identified that appear to have undergone dramatic human-specific changes in selective pressures; these are enriched in recent segmental duplications,...

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...

Intraspecific phylogenetic analysis of Siberian woolly mammoths using complete mitochondrial genomes

Gilbert, M. Thomas P., Drautz, Daniela I., Lesk, Arthur M., Ho, Simon Y. W., Qi, Ji, Ratan, Aakrosh, ...

We report five new complete mitochondrial DNA (mtDNA) genomes of Siberian woolly mammoth (Mammuthus primigenius), sequenced with up to 73-fold coverage from DNA extracted from hair shaft material....

Human-macaque comparisons illuminate variation in neutral substitution rates

Tyekucheva, Svitlana, Makova, Kateryna D, Karro, John E, Hardison, Ross C, Miller, Webb, Chiaromonte, Francesca

The evolutionary distance between human and macaque is particularly attractive for investigating neutral substitution rates, which were calculated as a function of a number of genomic parameters.

The infinite sites model of genome evolution

Ma, Jian, Ratan, Aakrosh, Raney, Brian J., Suh, Bernard B., Miller, Webb, Haussler, David

We formalize the problem of recovering the evolutionary history of a set of genomes that are related to an unseen common ancestor genome by operations of speciation, deletion, insertion, duplication,...

Transcriptional enhancement by GATA1-occupied DNA segments is strongly associated with evolutionary constraint on the binding site motif

Cheng, Yong, King, David C., Dore, Louis C., Zhang, Xinmin, Zhou, Yuepin, Zhang, Ying, ...

Tissue development and function are exquisitely dependent on proper regulation of gene expression, but it remains controversial whether the genomic signals controlling this process are subject to...

The mitochondrial genome sequence of the Tasmanian tiger (Thylacinus cynocephalus)

Miller, Webb, Drautz, Daniela I., Janecka, Jan E., Lesk, Arthur M., Ratan, Aakrosh, Tomsho, Lynn P., ...

We report the first two complete mitochondrial genome sequences of the thylacine (Thylacinus cynocephalus), or so-called Tasmanian tiger, extinct since 1936. The thylacine's phylogenetic position...