Analyses of Deep Mammalian Sequence Alignments and Constraint Predictions for 1% of the Human Genome
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A Bivalent Chromatin Structure Marks Key Developmental Genes in Embryonic Stem Cells
A Bivalent Chromatin Structure Marks Key Developmental Genes in Embryonic Stem Cells Bradley E. Bernstein,1,2,3,* Tarjei S. Mikkelsen,3,4 Xiaohui Xie,3 Michael Kamal,3 Dana J. Huebert,1 James Cuff,3 Ben Fry,3 Alex Meissner,5 Marius Wernig,5 Kathrin Plath,5 Rudolf Jaenisch,5 Alexandre Wagschal,6 Robert Feil,6 Stuart L. Schreiber,3,7 and Eric S. Lander3,5 1 Molecular Pathology Unit and Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA 02129, USA 2 Department of Pathology, Harvard Medical School, Boston, MA 02115, USA 3 Broad Institute of Harvard and MIT, Cambridge, MA 02139, USA 4 Division of Health Sciences and Technology, MIT, Cambridge, MA 02139, USA 5 Whitehead Institute for Biomedical Research, MIT, Cambridge, MA 02139, USA 6 Institute of Molecular Genetics, CNRS UMR-5535 and University of Montpellier-II, Montpellier, France 7 Howard Hughes Medical Institute at the Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA *Contact: [email protected] DOI 10.1016/j.cell.2006.02.041 SUMMARY which in turn modulate chromatin structure (Jenuwein and Allis, 2001; Margueron et al., 2005). The core histones The most highly conserved noncoding ele- H2A, H2B, H3, and H4 are subject to dozens of different ments (HCNEs) in mammalian genomes cluster modifications, including acetylation, methylation, and within regions enriched for genes encoding de- phosphorylation. Histone H3 lysine 4 (Lys4) and lysine velopmentally important transcription factors 27 (Lys27) methylation are of particular interest as these (TFs). This suggests that HCNE-rich regions modifications are catalyzed, respectively, by trithorax- may contain key regulatory controls involved and Polycomb-group proteins, which mediate mitotic in- heritance of lineage-specific gene expression programs in development. -
Classifying Transport Proteins Using Profile Hidden Markov Models And
Classifying Transport Proteins Using Profile Hidden Markov Models and Specificity Determining Sites Qing Ye A Thesis in The Department of Computer Science and Software Engineering Presented in Partial Fulfillment of the Requirements for the Degree of Master of Computer Science (MCompSc) at Concordia University Montréal, Québec, Canada April 2019 ⃝c Qing Ye, 2019 CONCORDIA UNIVERSITY School of Graduate Studies This is to certify that the thesis prepared By: Qing Ye Entitled: Classifying Transport Proteins Using Profile Hidden Markov Models and Specificity Determining Sites and submitted in partial fulfillment of the requirements for the degree of Master of Computer Science (MCompSc) complies with the regulations of this University and meets the accepted standards with respect to originality and quality. Signed by the Final Examining Committee: Chair Dr. T.-H. Chen Examiner Dr. T. Glatard Examiner Dr. A. Krzyzak Supervisor Dr. G. Butler Approved by Martin D. Pugh, Chair Department of Computer Science and Software Engineering 2019 Amir Asif, Dean Faculty of Engineering and Computer Science Abstract Classifying Transport Proteins Using Profile Hidden Markov Models and Specificity Determining Sites Qing Ye This thesis develops methods to classifiy the substrates transported across a membrane by a given transmembrane protein. Our methods use tools that predict specificity determining sites (SDS) after computing a multiple sequence alignment (MSA), and then building a profile Hidden Markov Model (HMM) using HMMER. In bioinformatics, HMMER is a set of widely used applications for sequence analysis based on profile HMM. Specificity determining sites (SDS) are the key positions in a protein sequence that play a crucial role in functional variation within the protein family during the course of evolution. -
BIOGRAPHICAL SKETCH NAME: Berger
BIOGRAPHICAL SKETCH NAME: Berger, Bonnie eRA COMMONS USER NAME (credential, e.g., agency login): BABERGER POSITION TITLE: Simons Professor of Mathematics and Professor of Electrical Engineering and Computer Science EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and residency training if applicable. Add/delete rows as necessary.) EDUCATION/TRAINING DEGREE Completion (if Date FIELD OF STUDY INSTITUTION AND LOCATION applicable) MM/YYYY Brandeis University, Waltham, MA AB 06/1983 Computer Science Massachusetts Institute of Technology SM 01/1986 Computer Science Massachusetts Institute of Technology Ph.D. 06/1990 Computer Science Massachusetts Institute of Technology Postdoc 06/1992 Applied Mathematics A. Personal Statement Advances in modern biology revolve around automated data collection and sharing of the large resulting datasets. I am considered a pioneer in the area of bringing computer algorithms to the study of biological data, and a founder in this community that I have witnessed grow so profoundly over the last 26 years. I have made major contributions to many areas of computational biology and biomedicine, largely, though not exclusively through algorithmic innovations, as demonstrated by nearly twenty thousand citations to my scientific papers and widely-used software. In recognition of my success, I have just been elected to the National Academy of Sciences and in 2019 received the ISCB Senior Scientist Award, the pinnacle award in computational biology. My research group works on diverse challenges, including Computational Genomics, High-throughput Technology Analysis and Design, Biological Networks, Structural Bioinformatics, Population Genetics and Biomedical Privacy. I spearheaded research on analyzing large and complex biological data sets through topological and machine learning approaches; e.g. -
The Bioperl Toolkit: Perl Modules for the Life Sciences
Downloaded from genome.cshlp.org on January 25, 2012 - Published by Cold Spring Harbor Laboratory Press The Bioperl Toolkit: Perl Modules for the Life Sciences Jason E. Stajich, David Block, Kris Boulez, et al. Genome Res. 2002 12: 1611-1618 Access the most recent version at doi:10.1101/gr.361602 Supplemental http://genome.cshlp.org/content/suppl/2002/10/20/12.10.1611.DC1.html Material References This article cites 14 articles, 9 of which can be accessed free at: http://genome.cshlp.org/content/12/10/1611.full.html#ref-list-1 Article cited in: http://genome.cshlp.org/content/12/10/1611.full.html#related-urls Email alerting Receive free email alerts when new articles cite this article - sign up in the box at the service top right corner of the article or click here To subscribe to Genome Research go to: http://genome.cshlp.org/subscriptions Cold Spring Harbor Laboratory Press Downloaded from genome.cshlp.org on January 25, 2012 - Published by Cold Spring Harbor Laboratory Press Resource The Bioperl Toolkit: Perl Modules for the Life Sciences Jason E. Stajich,1,18,19 David Block,2,18 Kris Boulez,3 Steven E. Brenner,4 Stephen A. Chervitz,5 Chris Dagdigian,6 Georg Fuellen,7 James G.R. Gilbert,8 Ian Korf,9 Hilmar Lapp,10 Heikki Lehva¨slaiho,11 Chad Matsalla,12 Chris J. Mungall,13 Brian I. Osborne,14 Matthew R. Pocock,8 Peter Schattner,15 Martin Senger,11 Lincoln D. Stein,16 Elia Stupka,17 Mark D. Wilkinson,2 and Ewan Birney11 1University Program in Genetics, Duke University, Durham, North Carolina 27710, USA; 2National Research Council of -
Lior Pachter Genome Informatics 2013 Keynote
Stories from the Supplement Lior Pachter! Department of Mathematics and Molecular & Cell Biology! UC Berkeley! ! November 1, 2013! Genome Informatics, CSHL The Cufflinks supplements • C. Trapnell, B.A. Williams, G. Pertea, A. Mortazavi, G. Kwan, M.J. van Baren, S.L. Salzberg, B.J. Wold and L. Pachter, Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation, Nature Biotechnology 28, (2010), p 511–515. Supplementary Material: 42 pages. • C. Trapnell, D.G. Hendrickson, M. Sauvageau, L. Goff, J.L. Rinn and L. Pachter, Differential analysis of gene regulation at transcript resolution with RNA-seq, Nature Biotechnology, 31 (2012), p 46–53. Supplementary Material: 70 pages. A supplementary arithmetic progression? • C. Trapnell, B.A. Williams, G. Pertea, A. Mortazavi, G. Kwan, M.J. van Baren, S.L. Salzberg, B.J. Wold and L. Pachter, Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation, Nature Biotechnology 28, (2010), p 511–515. Supplementary Material: 42 pages. • C. Trapnell, D.G. Hendrickson, M. Sauvageau, L. Goff, J.L. Rinn and L. Pachter, Differential analysis of gene regulation at transcript resolution with RNA- seq, Nature Biotechnology, 31 (2012), p 46–53. Supplementary Material: 70 pages. • A. Roberts and L. Pachter, Streaming algorithms for fragment assignment, Nature Methods 10 (2013), p 71—73. Supplementary Material: 98 pages? The nature methods manuscript checklist The nature methods manuscript checklist Emperor Joseph II: My dear young man, don't take it too hard. Your work is ingenious. It's quality work. And there are simply too many notes, that's all. -
Modeling and Analysis of RNA-Seq Data: a Review from a Statistical Perspective
Modeling and analysis of RNA-seq data: a review from a statistical perspective Wei Vivian Li 1 and Jingyi Jessica Li 1;2;∗ Abstract Background: Since the invention of next-generation RNA sequencing (RNA-seq) technolo- gies, they have become a powerful tool to study the presence and quantity of RNA molecules in biological samples and have revolutionized transcriptomic studies. The analysis of RNA-seq data at four different levels (samples, genes, transcripts, and exons) involve multiple statistical and computational questions, some of which remain challenging up to date. Results: We review RNA-seq analysis tools at the sample, gene, transcript, and exon levels from a statistical perspective. We also highlight the biological and statistical questions of most practical considerations. Conclusion: The development of statistical and computational methods for analyzing RNA- seq data has made significant advances in the past decade. However, methods developed to answer the same biological question often rely on diverse statical models and exhibit dif- ferent performance under different scenarios. This review discusses and compares multiple commonly used statistical models regarding their assumptions, in the hope of helping users select appropriate methods as needed, as well as assisting developers for future method development. 1 Introduction RNA sequencing (RNA-seq) uses the next generation sequencing (NGS) technologies to reveal arXiv:1804.06050v3 [q-bio.GN] 1 May 2018 the presence and quantity of RNA molecules in biological samples. Since its invention, RNA- seq has revolutionized transcriptome analysis in biological research. RNA-seq does not require any prior knowledge on RNA sequences, and its high-throughput manner allows for genome-wide profiling of transcriptome landscapes [1,2]. -
Research Computing Facility an Update from Dr
Research Computing Facility An Update from Dr. Francesca Dominici June 20, 2013 Dear all, We are very excited to provide you some important updates regarding the research computing facility at the Faculty of Arts and Science (FASRC) http://rc.fas.harvard.edu. Please note that we are phasing out the HSPH cluster, and if you are currently leasing nodes on the HSPH cluster we will be working with you to migrate to FASRC. We have developed a FAQ document, which is available at the web link https://rc.fas.harvard.edu/hsph-at-fas-rc-frequently- asked-questions/ and also included in this message. Updates: 1. 158 HSPH accounts have been opened on FASRC, enabling users to run computing jobs on the FAS High Performance Computing Cluster (HPCC), also known as Odyssey 2. Several HSPH faculty have worked with the FASRC team to purchase data storage equipment and hardware that have been deployed at FASRC in Cambridge and linked to Odyssey via a secured network 3. FASRC has developed personalized solutions for our faculty to transfer secure data from HSPH to FAS in accordance with data user agreements. 4. FASRC has been mentioned as a key strength in training and research grant applications from HSPH, and high impact papers have been published that previously were delayed for lack of computing power 5. Please bookmark the web site http://rc.fas.harvard.edu/hsph- overview/ for additional and up to date information To access FASRC you will be charged approximately $3000 per year per account. Access for PhD and ScD students is free. -
Human and Mouse Gene Structure: Comparative Analysis and Application to Exon Prediction
Downloaded from genome.cshlp.org on October 4, 2021 - Published by Cold Spring Harbor Laboratory Press Letter Human and Mouse Gene Structure: Comparative Analysis and Application to Exon Prediction Serafim Batzoglou,1,4,7 Lior Pachter,2,7 Jill P. Mesirov,3 Bonnie Berger,1,4,6 and Eric S. Lander3,5,6 1Laboratory for Computer Science, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 USA; 2Department of Mathematics, University of California Berkeley, Berkeley, California 94720 USA; 3Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142 USA; 4Department of Mathematics, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 USA; 5Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 USA 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 similarity in the number, size and sequence of exons and introns. We then developed an approach for recognizing genes within such orthologous regions by first aligning the regions using an iterative global alignment system and then identifying genes based on conservation of exonic features at aligned positions in both species. The alignment and gene recognition are performed by new programs called GLASS and ROSETTA, respectively. ROSETTA performed well at exact identification of coding exons in 117 orthologous pairs tested. A fundamental task in analyzing genomes is to identify by comparison of syntenic human and mouse genomic the genes. This is relatively straightforward for organ- sequences. isms with compact genomes (such as bacteria, yeast, It is well known that cross-species sequence com- flies and worms) because exons tend to be large and the parison can help highlight important functional ele- introns are either non-existent or tend to be short. -
Eric S. Lander
Chancellor's Distinguished Fellows Program 2004-2005 Selective Bibliography UC Irvine Libraries Eric S. Lander February 25, 2005 Prepared by: John E. Sisson Biological Sciences Librarian [email protected] Journal Articles (Selected from over 220 articles he has authored or co-authored) Poirier, C., Y. J. Qin, C.P. Adams, Y. Anaya, J. B. Singer, A. E. Hill, Eric S. Lander, J.H. Nadeau, and C. E. Bishop. "A complex interaction of imprinted and maternal-effect genes modifies sex determination in odd sex (Ods) mice." Genetics 168, no. 3 (2004): 1557-1562. Skuse, D. H., S. Purcell, M. J. Daly, R. J. Dolan, J. S. Morris, K. Lawrence, Eric S. Lander, and P. Sklar. "What can studies on Turner syndrome tell us about the role of X- linked genes in social cognition?." American Journal of Medical Genetics Part B- Neuropsychiatric Genetics 130B, no. 1 (2004): 8-9. Rioux, J. D., H. Karinen, K. Kocher, S. G. McMahon, P. Karkkainen, E. Janatuinen, M. Heikkinen, R. Julkunen, J. Pihlajamaki, A. Naukkarinen, V. M. Kosma, M. J. Daly, Eric S. Lander, and M. Laakso. "Genomewide search and association studies in a Finnish celiac disease population: Identification of a novel locus and replication of the HLA and CTLA4 loci." American Journal of Medical Genetics Part A 130A, no. 4 (2004): 345- 350. Michalkiewicz, M., T. Michalkiewicz, R. A. Ettinger, E. A. Rutledge, J. M. Fuller, D. H. Moralejo, B. Van Yserloo, A. J. MacMurray, A. E. Kwitek, H. J. Jacob, Eric S. Lander, and A. Lernmark. "Transgenic rescue demonstrates involvement of the Ian5 gene in T cell development in the rat." Physiological Genomics 19, no. -
Convergent Regulatory Evolution and Loss of Flight in Paleognathous Birds
Convergent regulatory evolution and loss of flight in paleognathous birds The Harvard community has made this article openly available. Please share how this access benefits you. Your story matters Citation Sackton, Timothy B., Phil Grayson, Alison Cloutier, Zhirui Hu, Jun S. Liu, Nicole E. Wheeler, Paul P. Gardner, et al. 2019. Convergent Regulatory Evolution and Loss of Flight in Paleognathous Birds. Science 364 (6435): 74–78. Citable link http://nrs.harvard.edu/urn-3:HUL.InstRepos:39865637 Terms of Use This article was downloaded from Harvard University’s DASH repository, and is made available under the terms and conditions applicable to Open Access Policy Articles, as set forth at http:// nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of- use#OAP Convergent regulatory evolution and loss of flight in palaeognathous birds Timothy B. Sackton* (1,2), Phil Grayson (2,3), Alison Cloutier (2,3), Zhirui Hu (4), Jun S. Liu (4), Nicole E. Wheeler (5,6), Paul P. Gardner (5,7), Julia A. Clarke (8), Allan J. Baker (9,10), Michele Clamp (1), Scott V. Edwards* (2,3) Affiliations: 1) Informatics Group, Harvard University, Cambridge, USA 2) Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, USA 3) Museum of Comparative Zoology, Harvard University, Cambridge, USA 4) Department of Statistics, Harvard University, Cambridge, USA 5) School of Biological Sciences, University of Canterbury, New Zealand 6) Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, UK 7) Department of Biochemistry, University of Otago, New Zealand 8) Jackson School of Geosciences, The University of Texas at Austin, Austin, USA 9) Department of Natural History, Royal Ontario Museum, Toronto, Canada 10) Department of Ecology and Evolutionary Biology, University of Toronto, Toronto, Canada *correspondence to: TBS ([email protected]) or SVE ([email protected]) 1 Whether convergent phenotypic evolution is driven by convergent molecular changes, in proteins or regulatory regions, are core questions in evolutionary biology. -
Motif Selection Using Simulated Annealing Algorithm with Application to Identify Regulatory Elements
Motif Selection Using Simulated Annealing Algorithm with Application to Identify Regulatory Elements A thesis presented to the faculty of the Russ College of Engineering and Technology of Ohio University In partial fulfillment of the requirements for the degree Master of Science Liang Chen August 2018 © 2018 Liang Chen. All Rights Reserved. 2 This thesis titled Motif Selection Using Simulated Annealing Algorithm with Application to Identify Regulatory Elements by LIANG CHEN has been approved for the Department of Electrical Engineering and Computer Science and the Russ College of Engineering and Technology by Lonnie Welch Professor of Electrical Engineering and Computer Science Dennis Irwin Dean, Russ College of Engineering and Technology 3 Abstract CHEN, LIANG, M.S., August 2018, Computer Science Master Program Motif Selection Using Simulated Annealing Algorithm with Application to Identify Regulatory Elements (106 pp.) Director of Thesis: Lonnie Welch Modern research on gene regulation and disorder-related pathways utilize the tools such as microarray and RNA-Seq to analyze the changes in the expression levels of large sets of genes. In silico motif discovery was performed based on the gene expression profile data, which generated a large set of candidate motifs (usually hundreds or thousands of motifs). How to pick a set of biologically meaningful motifs from the candidate motif set is a challenging biological and computational problem. As a computational problem it can be modeled as motif selection problem (MSP). Building solutions for motif selection problem will give biologists direct help in finding transcription factors (TF) that are strongly related to specific pathways and gaining insights of the relationships between genes. -
The Anatomy of Successful Computational Biology Software
FEATURE The anatomy of successful computational biology software Stephen Altschul1, Barry Demchak2, Richard Durbin3, Robert Gentleman4, Martin Krzywinski5, Heng Li6, Anton Nekrutenko7, James Robinson6, Wayne Rasband8, James Taylor9 & Cole Trapnell10 Creators of software widely used in computational biology discuss the factors that contributed to their success he year was 1989 and Stephen Altschul What factors determine whether scientific tant thing is that Thad a problem. Sam Karlin, the brilliant software is successful? Cufflinks, Bowtie mathematician whose help he needed, was Stephen Altschul: BLAST was the first program (which is mainly Ben so convinced of the power of a mathemati- to assign rigorous statistics to useful scores of Langmead’s work) cally tractable but biologically constrained local sequence alignments. Before then people and TopHat were in measure of protein sequence similarity that had derived many large part at the right he would not listen to Altschul (or anyone different scoring sys- place at the right time. else for that matter). So Altschul essentially tems, and it wasn’t We were stepping into tricked him into solving the problem sty- clear why any should Cole Trapnell fields that were poised mying the field of computational biology have a particular developed the Tophat/ to explode, but which by posing it in terms of pure mathematics, advantage. I had made Cufflinks suite of short- really had a vacuum in devoid of any reference to biology. The treat a conjecture that read analysis tools. terms of usable tools. from that trick became known as the Karlin- every scoring system You get two things Altschul statistics that are a key part of that people proposed from being first.