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Analysis of Gene Expression Data for Gene Ontology
ANALYSIS OF GENE EXPRESSION DATA FOR GENE ONTOLOGY BASED PROTEIN FUNCTION PREDICTION A Thesis Presented to The Graduate Faculty of The University of Akron In Partial Fulfillment of the Requirements for the Degree Master of Science Robert Daniel Macholan May 2011 ANALYSIS OF GENE EXPRESSION DATA FOR GENE ONTOLOGY BASED PROTEIN FUNCTION PREDICTION Robert Daniel Macholan Thesis Approved: Accepted: _______________________________ _______________________________ Advisor Department Chair Dr. Zhong-Hui Duan Dr. Chien-Chung Chan _______________________________ _______________________________ Committee Member Dean of the College Dr. Chien-Chung Chan Dr. Chand K. Midha _______________________________ _______________________________ Committee Member Dean of the Graduate School Dr. Yingcai Xiao Dr. George R. Newkome _______________________________ Date ii ABSTRACT A tremendous increase in genomic data has encouraged biologists to turn to bioinformatics in order to assist in its interpretation and processing. One of the present challenges that need to be overcome in order to understand this data more completely is the development of a reliable method to accurately predict the function of a protein from its genomic information. This study focuses on developing an effective algorithm for protein function prediction. The algorithm is based on proteins that have similar expression patterns. The similarity of the expression data is determined using a novel measure, the slope matrix. The slope matrix introduces a normalized method for the comparison of expression levels throughout a proteome. The algorithm is tested using real microarray gene expression data. Their functions are characterized using gene ontology annotations. The results of the case study indicate the protein function prediction algorithm developed is comparable to the prediction algorithms that are based on the annotations of homologous proteins. -
The EMBL-European Bioinformatics Institute the Hub for Bioinformatics in Europe
The EMBL-European Bioinformatics Institute The hub for bioinformatics in Europe Blaise T.F. Alako, PhD [email protected] www.ebi.ac.uk What is EMBL-EBI? • Part of the European Molecular Biology Laboratory • International, non-profit research institute • Europe’s hub for biological data, services and research The European Molecular Biology Laboratory Heidelberg Hamburg Hinxton, Cambridge Basic research Structural biology Bioinformatics Administration Grenoble Monterotondo, Rome EMBO EMBL staff: 1500 people Structural biology Mouse biology >60 nationalities EMBL member states Austria, Belgium, Croatia, Denmark, Finland, France, Germany, Greece, Iceland, Ireland, Israel, Italy, Luxembourg, the Netherlands, Norway, Portugal, Spain, Sweden, Switzerland and the United Kingdom Associate member state: Australia Who we are ~500 members of staff ~400 work in services & support >53 nationalities ~120 focus on basic research EMBL-EBI’s mission • Provide freely available data and bioinformatics services to all facets of the scientific community in ways that promote scientific progress • Contribute to the advancement of biology through basic investigator-driven research in bioinformatics • Provide advanced bioinformatics training to scientists at all levels, from PhD students to independent investigators • Help disseminate cutting-edge technologies to industry • Coordinate biological data provision throughout Europe Services Data and tools for molecular life science www.ebi.ac.uk/services Browse our services 9 What services do we provide? Labs around the -
Functional Effects Detailed Research Plan
GeCIP Detailed Research Plan Form Background The Genomics England Clinical Interpretation Partnership (GeCIP) brings together researchers, clinicians and trainees from both academia and the NHS to analyse, refine and make new discoveries from the data from the 100,000 Genomes Project. The aims of the partnerships are: 1. To optimise: • clinical data and sample collection • clinical reporting • data validation and interpretation. 2. To improve understanding of the implications of genomic findings and improve the accuracy and reliability of information fed back to patients. To add to knowledge of the genetic basis of disease. 3. To provide a sustainable thriving training environment. The initial wave of GeCIP domains was announced in June 2015 following a first round of applications in January 2015. On the 18th June 2015 we invited the inaugurated GeCIP domains to develop more detailed research plans working closely with Genomics England. These will be used to ensure that the plans are complimentary and add real value across the GeCIP portfolio and address the aims and objectives of the 100,000 Genomes Project. They will be shared with the MRC, Wellcome Trust, NIHR and Cancer Research UK as existing members of the GeCIP Board to give advance warning and manage funding requests to maximise the funds available to each domain. However, formal applications will then be required to be submitted to individual funders. They will allow Genomics England to plan shared core analyses and the required research and computing infrastructure to support the proposed research. They will also form the basis of assessment by the Project’s Access Review Committee, to permit access to data. -
A Molecular and Genetic Analysis of Otosclerosis
A molecular and genetic analysis of otosclerosis Joanna Lauren Ziff Submitted for the degree of PhD University College London January 2014 1 Declaration I, Joanna Ziff, confirm that the work presented in this thesis is my own. Where information has been derived from other sources, I confirm that this has been indicated in the thesis. Where work has been conducted by other members of our laboratory, this has been indicated by an appropriate reference. 2 Abstract Otosclerosis is a common form of conductive hearing loss. It is characterised by abnormal bone remodelling within the otic capsule, leading to formation of sclerotic lesions of the temporal bone. Encroachment of these lesions on to the footplate of the stapes in the middle ear leads to stapes fixation and subsequent conductive hearing loss. The hereditary nature of otosclerosis has long been recognised due to its recurrence within families, but its genetic aetiology is yet to be characterised. Although many familial linkage studies and candidate gene association studies to investigate the genetic nature of otosclerosis have been performed in recent years, progress in identifying disease causing genes has been slow. This is largely due to the highly heterogeneous nature of this condition. The research presented in this thesis examines the molecular and genetic basis of otosclerosis using two next generation sequencing technologies; RNA-sequencing and Whole Exome Sequencing. RNA–sequencing has provided human stapes transcriptomes for healthy and diseased stapes, and in combination with pathway analysis has helped identify genes and molecular processes dysregulated in otosclerotic tissue. Whole Exome Sequencing has been employed to investigate rare variants that segregate with otosclerosis in affected families, and has been followed by a variant filtering strategy, which has prioritised genes found to be dysregulated during RNA-sequencing. -
Regulation of Neuronal Gene Expression and Survival by Basal NMDA Receptor Activity: a Role for Histone Deacetylase 4
The Journal of Neuroscience, November 12, 2014 • 34(46):15327–15339 • 15327 Cellular/Molecular Regulation of Neuronal Gene Expression and Survival by Basal NMDA Receptor Activity: A Role for Histone Deacetylase 4 Yelin Chen,1 Yuanyuan Wang,1 Zora Modrusan,3 Morgan Sheng,1 and Joshua S. Kaminker1,2 Departments of 1Neuroscience, 2Bioinformatics and Computational Biology, and 3Molecular Biology, Genentech Inc., South San Francisco, California 94080 Neuronal gene expression is modulated by activity via calcium-permeable receptors such as NMDA receptors (NMDARs). While gene expression changes downstream of evoked NMDAR activity have been well studied, much less is known about gene expression changes that occur under conditions of basal neuronal activity. In mouse dissociated hippocampal neuronal cultures, we found that a broad NMDAR antagonist, AP5, induced robust gene expression changes under basal activity, but subtype-specific antagonists did not. While some of the gene expression changes are also known to be downstream of stimulated NMDAR activity, others appear specific to basal NMDARactivity.ThegenesalteredbyAP5treatmentofbasalcultureswereenrichedforpathwaysrelatedtoclassIIahistonedeacetylases (HDACs), apoptosis, and synapse-related signaling. Specifically, AP5 altered the expression of all three class IIa HDACs that are highly expressed in the brain, HDAC4, HDAC5, and HDAC9, and also induced nuclear accumulation of HDAC4. HDAC4 knockdown abolished a subset of the gene expression changes induced by AP5, and led to neuronal death under -
Exploring the Structure and Function Paradigm Oliver C Redfern, Benoit Dessailly and Christine a Orengo
Available online at www.sciencedirect.com Exploring the structure and function paradigm Oliver C Redfern, Benoit Dessailly and Christine A Orengo Advances in protein structure determination, led by the Figure 1 shows that as the international genomics initiat- structural genomics initiatives have increased the proportion of ives gather pace, both the number of sequences and novel folds deposited in the Protein Data Bank. However, these protein families are still growing at an exponential rate, structures are often not accompanied by functional annotations although the rate of expansion of protein families is with experimental confirmation. In this review, we reassess the substantially less. This trend is also observed among meaning of structural novelty and examine its relevance domain families, which are 10-fold fewer (<10 000) than to the complexity of the structure-function paradigm. the number of protein families. By targeting these, the Recent advances in the prediction of protein function from structural genomics initiatives can aim to characterise the structure are discussed, as well as new sequence-based major building blocks of whole proteins and since these methods for partitioning large, diverse superfamilies into domains recur in different combination in the genomes, it biologically meaningful clusters. Obtaining structural data for will be an important step towards understanding the these functionally coherent groups of proteins will allow us to complete structural repertoire in nature. Furthermore, better understand the relationship between structure and the complement of molecular functions found within function. an organism is likely to be even fewer. For example, 97% of proteins in yeast can be assigned one or more of Address 4000 unique GO terms. -
EMBO Facts & Figures
excellence in life sciences Reykjavik Helsinki Oslo Stockholm Tallinn EMBO facts & figures & EMBO facts Copenhagen Dublin Amsterdam Berlin Warsaw London Brussels Prague Luxembourg Paris Vienna Bratislava Budapest Bern Ljubljana Zagreb Rome Madrid Ankara Lisbon Athens Jerusalem EMBO facts & figures HIGHLIGHTS CONTACT EMBO & EMBC EMBO Long-Term Fellowships Five Advanced Fellows are selected (page ). Long-Term and Short-Term Fellowships are awarded. The Fellows’ EMBO Young Investigators Meeting is held in Heidelberg in June . EMBO Installation Grants New EMBO Members & EMBO elects new members (page ), selects Young EMBO Women in Science Young Investigators Investigators (page ) and eight Installation Grantees Gerlind Wallon EMBO Scientific Publications (page ). Programme Manager Bernd Pulverer S Maria Leptin Deputy Director Head A EMBO Science Policy Issues report on quotas in academia to assure gender balance. R EMBO Director + + A Conducts workshops on emerging biotechnologies and on H T cognitive genomics. Gives invited talks at US National Academy E IC of Sciences, International Summit on Human Genome Editing, I H 5 D MAN 201 O N Washington, DC.; World Congress on Research Integrity, Rio de A M Janeiro; International Scienti c Advisory Board for the Centre for Eilish Craddock IT 2 015 Mammalian Synthetic Biology, Edinburgh. Personal Assistant to EMBO Fellowships EMBO Scientific Publications EMBO Gold Medal Sarah Teichmann and Ido Amit receive the EMBO Gold the EMBO Director David del Álamo Thomas Lemberger Medal (page ). + Programme Manager Deputy Head EMBO Global Activities India and Singapore sign agreements to become EMBC Associate + + Member States. EMBO Courses & Workshops More than , participants from countries attend 6th scienti c events (page ); participants attend EMBO Laboratory Management Courses (page ); rst online course EMBO Courses & Workshops recorded in collaboration with iBiology. -
A Genome-Wide Rnai Screen for Modifiers of Polyglutamine-Induced Neurotoxicity in Drosophila
A Genome-Wide RNAi Screen for Modifiers of Polyglutamine-Induced Neurotoxicity in Drosophila Doctoral Thesis In partial fulfilment of the requirements for the degree “Doctor rerum naturalium (Dr. rer. nat.)” in the Molecular Medicine Study Programme at the Georg-August University Göttingen submitted by Hannes Voßfeldt born in Zerbst/Anhalt, Germany Göttingen, January 2012 FÜR MEINE FAMILIE - IM GEDENKEN AN NADINE DU FEHLST. … IT MATTERS NOT HOW STRAIT THE GATE, HOW CHARGED WITH PUNISHMENTS THE SCROLL, I AM THE MASTER OF MY FATE: I AM THE CAPTAIN OF MY SOUL. … Invictus – William Ernest Henley Members of the Thesis Committee: Supervisor Prof. Dr. med. Jörg B. Schulz Head of Department of Neurology University Medical Centre RWTH Aachen University Pauwelsstrasse 30 52074 Aachen Second member of the Thesis Committee Prof. Dr. rer. nat. Ernst A. Wimmer Head of Department of Developmental Biology Johann Friedrich Blumenbach Institute of Zoology and Anthropology Georg-August University Göttingen Justus-von-Liebig-Weg 11 37077 Göttingen Third member of the Thesis Committee Dr. rer. nat. Till Marquardt Research Group Developmental Neurobiology European Neuroscience Institute Göttingen Grisebachstrasse 5 37077 Göttingen Date of Disputation: 2 April 2012 Affidavit I hereby declare that my doctoral thesis entitled “A Genome-Wide RNAi Screen for Modifiers of Polyglutamine-Induced Neurotoxicity in Drosophila” has been written independently with no other sources and aids than quoted. Göttingen, January 2012 Hannes Voßfeldt LIST OF PUBLICATIONS IV List of Publications Parts of this work have already been published with authorisation of Prof. Jörg B. Schulz, Head of the Department of Neurology, University Medical Centre of the RWTH Aachen University, on behalf of the thesis committee. -
Statistical and Computational Methods for Analyzing High-Throughout Genomic Data
Statistical and Computational Methods for Analyzing High-Throughout Genomic Data by Jingyi Li A dissertation submitted in partial satisfaction of the requirements for the degree of Doctor of Philosophy in Biostatistics and the Designated Emphasis in Computational and Genomic Biology in the Graduate Division of the University of California, Berkeley Committee in charge: Professor Peter J. Bickel, Chair Professor Haiyan Huang Professor Sandrine Dudoit Professor Steven E. Brenner Spring 2013 Statistical and Computational Methods for Analyzing High-Throughput Genomic Data Copyright 2013 by Jingyi Li 1 Abstract Statistical and Computational Methods for Analyzing High-Throughput Genomic Data by Jingyi Li Doctor of Philosophy in Biostatistics and the Designated Emphasis in Computational and Genomic Biology University of California, Berkeley Professor Peter J. Bickel, Chair In the burgeoning field of genomics, high-throughput technologies (e.g. microarrays, next-generation sequencing and label-free mass spectrometry) have enabled biologists to perform global analysis on thousands of genes, mRNAs and proteins simultaneously. Ex- tracting useful information from enormous amounts of high-throughput genomic data is an increasingly pressing challenge to statistical and computational science. In this thesis, I will address three problems in which statistical and computational methods were used to analyze high-throughput genomic data to answer important biological questions. The first part of this thesis focuses on addressing an important question in genomics: how to identify and quantify mRNA products of gene transcription (i.e., isoforms) from next- generation mRNA sequencing (RNA-Seq) data? We developed a statistical method called Sparse Linear modeling of RNA-Seq data for Isoform Discovery and abundance Estimation (SLIDE) that employs probabilistic modeling and L1 sparse estimation to answer this ques- tion. -
Janet Thornton Ing for Future Research Needs
THIS MONTH are dedicated to developing and maintaining services THE AUTHOR FILE for the scientific community, including databases such as the genome portal Ensembl, the proteomic data- base UniProt and more, all of which requires strategiz- Janet Thornton ing for future research needs. “These resources don’t Finding ways to navigate the reactions happen overnight; they’re big teams and they have to of life and herd tigers are all part of her think carefully,” she says. workday. Fostering collaborative science internally and across organizational and national boundaries such as for The wealth of available sequenced genomes invites sci- the project ELIXIR—the European life sciences infra- entists to explore the molecular basis of life, to browse structure for biological information, a pan-European and parse the beautiful infrastructure she has spearheaded to help scientists complexity of this now share data—is hard work, especially in times of fiscal “open book,” says Janet belt-tightening. At times, Thornton says, the task can Thornton. feel more like “herding tigers” than cats. A physicist turned Overall she sees the role of computational biology computational shifting, she says. In physics, work by experimentalists biologist, Thornton led to theoretical lines of inquiry. Biology is in its data- directs the European gathering stage, and rapidly moving toward the ability Bioinformatics to model processes such as the effect of a drug on the Institute (EBI), where human body. “We’re only a fraction of the way towards she has cultivated being able to do that,” she says, but she believes the EBI interdisciplinary EBI’s resources help to create the “bedrock” for this teamwork since 2001. -
Protein Family and Fold Occurrence in Genomes: Power-Law Behaviour and Evolutionary Model Jiang Qian, Nicholas M
doi:10.1006/jmbi.2001.5079 available online at http://www.idealibrary.com on J. Mol. Biol. (2001) 313, 673±681 COMMUNICATION Protein Family and Fold Occurrence in Genomes: Power-law Behaviour and Evolutionary Model Jiang Qian, Nicholas M. Luscombe and Mark Gerstein* Department of Molecular Global surveys of genomes measure the usage of essential molecular Biophysics and Biochemistry parts, de®ned here as protein families, superfamilies or folds, in different Yale University, 266 Whitney organisms. Based on surveys of the ®rst 20 completely sequenced gen- Avenue, PO Box 208114, New omes, we observe that the occurrence of these parts follows a power-law Haven, CT 06520-8114, USA distribution. That is, the number of distinct parts (F) with a given geno- mic occurrence (V) decays as F aVb, with a few parts occurring many times and most occurring infrequently. For a given organism, the distri- butions of families, superfamilies and folds are nearly identical, and this is re¯ected in the size of the decay exponent b. Moreover, the exponent varies between different organisms, with those of smaller genomes dis- playing a steeper decay (i.e. larger b). Clearly, the power law indicates a preference to duplicate genes that encode for molecular parts which are already common. Here, we present a minimal, but biologically meaning- ful model that accurately describes the observed power law. Although the model performs equally well for all three protein classes, we focus on the occurrence of folds in preference to families and superfamilies. This is because folds are comparatively insensitive to the effects of point mutations that can cause a family member to diverge beyond detectable similarity. -
Cold Spring Harbor Laboratory 2016 Meetings & Courses
Cold Spring Harbor Laboratory 2016 Meetings & Courses Meetings Gene Expression & Signaling in the Glia in Health & Disease Axon Guidance, Synapse Formation & Regeneration Immune System July 21 - 25 abstracts due May 6 September 20 - 24 abstracts due July 1 Marc Freeman, Kelly Monk Greg Bashaw, Linda Richards, Peter Scheiffele Systems Biology: Global Regulation of April 26 - 30 abstracts due February 5 Gene Expression Diane Mathis, Stephen Nutt, Alexander Rudensky, Art Weiss Genome Engineering: The CRISPR/Cas Revolution August 17 - 20 abstracts due May 27 Mechanisms of Aging March 15 - 19 abstracts due January 8 September 26 - 30 abstracts due July 25 Nuclear Organization & Function Jennifer Doudna, Maria Jasin, Jonathan Weissman Barak Cohen, Christina Leslie, John Stamatoyannopoulos, Sarah Teichmann Vera Gorbunova, Malene Hansen, Scott Pletcher May 3 - 7 abstracts due February 12 Evolutionary Biology of Caenorhabditis & Edith Heard, Martin Hetzer, David Spector Regulatory & Non-Coding RNAs August 23 - 27 abstracts due June 3 Germ Cells October 4 - 8 abstracts due July 15 Other Nematodes The Biology of Genomes Victor Ambros, Elisa Izaurralde, Nicholas Proudfoot Robert Braun, Geraldine Seydoux March 30 - April 2 abstracts due January 15 May 10 - 14 abstracts due February 19 Scott Baird, Marie Delattre, Erik Ragsdale, Adrian Streit Ewan Birney, Michel Georges, Jonathan Pritchard, Molly Przeworski The PI3K-mTOR-PTEN Network in Biological Data Science Neuronal Circuits The Cell Cycle Health & Disease October 25 - 29 abstracts due August 12