Search

Your search keyword '"Laura, Clarke"' showing total 278 results
Start Over Author "Laura, Clarke"
278 results on '"Laura, Clarke"'

2. Expression Atlas update: gene and protein expression in multiple species.

Author

Pablo A. Moreno, Silvie Fexova, Nancy George, Jonathan R. Manning, Zhichao Miao, Suhaib Mohammed, Alfonso Muñoz-Pomer Fuentes, Anja Füllgrabe, Yalan Bi, Natassja Bush, Haider Iqbal, Upendra Kumbham, Andrey Solovyev, Lingyun Zhao, Ananth Prakash, David García-Seisdedos, Deepti Jaiswal Kundu, Shengbo Wang, Mathias Walzer, Laura Clarke, David Osumi-Sutherland, Marcela Karey Tello-Ruiz, Sunita Kumari, Doreen Ware, Jana Eliasova, Mark J. Arends, Martijn C. Nawijn, Kerstin B. Meyer, Tony Burdett, John C. Marioni, Sarah A. Teichmann, Juan Antonio Vizcaíno, Alvis Brazma, and Irene Papatheodorou

Published
2022
Full Text
View/download PDF

3. RNAget: an API to securely retrieve RNA quantifications.

Author

Sean Upchurch, Emilio Palumbo, Jeremy Adams, David Bujold, Guillaume Bourque, Jared Nedzel, Keenan Graham, Meenakshi S. Kagda, Pedro Assis, Benjamin C. Hitz, Emilio Righi, Roderic Guigó, Barbara J. Wold, Alvis Brazma, Julia Burchard, Joe Capka, Michael Cherry, Laura Clarke, Brian Craft, Manolis Dermitzakis, Mark Diekhans, John Dursi, Michael Sean Fitzsimons, Zac Flaming, Romina Garrido, Alfred Gil, Paul Godden, Matt Green, Mitch Guttman, Brian Haas, Max Haeussler, Bo Li, Sten Linnarsson, Adam Lipski, David Liu, Simonne Longerich, David Lougheed, Jonathan Manning, John C. Marioni, Christopher Meyer, Stephen B. Montgomery, Alyssa Morrow, Alfonso Muñoz-Pomer Fuentes, Jared L. Nedzel, David Nguyen, Kevin Osborn, Francis Ouellette, Irene Papatheodorou, Dmitri D. Pervouchine, Arun K. Ramani, Jordi Rambla, Bashir Sadjad, David Steinberg, Jeremiah Talkar, Timothy Tickle, Kathy Tzeng, Saman Vaisipour, Sean Watford, Barbara Wold, Zhenyu Zhang, and Jing Zhu

Published
2023
Full Text
View/download PDF

4. Genetic perturbation of PU.1 binding and chromatin looping at neutrophil enhancers associates with autoimmune disease

Author

Stephen Watt, Louella Vasquez, Klaudia Walter, Alice L. Mann, Kousik Kundu, Lu Chen, Ying Sims, Simone Ecker, Frances Burden, Samantha Farrow, Ben Farr, Valentina Iotchkova, Heather Elding, Daniel Mead, Manuel Tardaguila, Hannes Ponstingl, David Richardson, Avik Datta, Paul Flicek, Laura Clarke, Kate Downes, Tomi Pastinen, Peter Fraser, Mattia Frontini, Biola-Maria Javierre, Mikhail Spivakov, and Nicole Soranzo

Subjects
Science
Abstract

PU.1 is a master regulator of myeloid development but its role in disease-relevant neutrophils is not well known. Here, the authors look at primary neutrophils from a human population and find that genetic variants affecting binding of PU.1 are associated with cell count and disease susceptibility.

Published
2021
Full Text
View/download PDF

5. MRI Patterns Distinguish AQP4 Antibody Positive Neuromyelitis Optica Spectrum Disorder From Multiple Sclerosis

Author

Laura Clarke, Simon Arnett, Wajih Bukhari, Elham Khalilidehkordi, Sofia Jimenez Sanchez, Cullen O'Gorman, Jing Sun, Kerri M. Prain, Mark Woodhall, Roger Silvestrini, Christine S. Bundell, David A. Abernethy, Sandeep Bhuta, Stefan Blum, Mike Boggild, Karyn Boundy, Bruce J. Brew, Wallace Brownlee, Helmut Butzkueven, William M. Carroll, Cella Chen, Alan Coulthard, Russell C. Dale, Chandi Das, Marzena J. Fabis-Pedrini, David Gillis, Simon Hawke, Robert Heard, Andrew P. D. Henderson, Saman Heshmat, Suzanne Hodgkinson, Trevor J. Kilpatrick, John King, Christopher Kneebone, Andrew J. Kornberg, Jeannette Lechner-Scott, Ming-Wei Lin, Christopher Lynch, Richard A. L. Macdonell, Deborah F. Mason, Pamela A. McCombe, Jennifer Pereira, John D. Pollard, Sudarshini Ramanathan, Stephen W. Reddel, Cameron P. Shaw, Judith M. Spies, James Stankovich, Ian Sutton, Steve Vucic, Michael Walsh, Richard C. Wong, Eppie M. Yiu, Michael H. Barnett, Allan G. K. Kermode, Mark P. Marriott, John D. E. Parratt, Mark Slee, Bruce V. Taylor, Ernest Willoughby, Fabienne Brilot, Angela Vincent, Patrick Waters, and Simon A. Broadley

Subjects
neuromyelitis optica, multiple sclerosis, magnetic resonance imaging, diagnosis, NMOSD, Neurology. Diseases of the nervous system, RC346-429
Abstract

Neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS) are inflammatory diseases of the CNS. Overlap in the clinical and MRI features of NMOSD and MS means that distinguishing these conditions can be difficult. With the aim of evaluating the diagnostic utility of MRI features in distinguishing NMOSD from MS, we have conducted a cross-sectional analysis of imaging data and developed predictive models to distinguish the two conditions. NMOSD and MS MRI lesions were identified and defined through a literature search. Aquaporin-4 (AQP4) antibody positive NMOSD cases and age- and sex-matched MS cases were collected. MRI of orbits, brain and spine were reported by at least two blinded reviewers. MRI brain or spine was available for 166/168 (99%) of cases. Longitudinally extensive (OR = 203), “bright spotty” (OR = 93.8), whole (axial; OR = 57.8) or gadolinium (Gd) enhancing (OR = 28.6) spinal cord lesions, bilateral (OR = 31.3) or Gd-enhancing (OR = 15.4) optic nerve lesions, and nucleus tractus solitarius (OR = 19.2), periaqueductal (OR = 16.8) or hypothalamic (OR = 7.2) brain lesions were associated with NMOSD. Ovoid (OR = 0.029), Dawson's fingers (OR = 0.031), pyramidal corpus callosum (OR = 0.058), periventricular (OR = 0.136), temporal lobe (OR = 0.137) and T1 black holes (OR = 0.154) brain lesions were associated with MS. A score-based algorithm and a decision tree determined by machine learning accurately predicted more than 85% of both diagnoses using first available imaging alone. We have confirmed NMOSD and MS specific MRI features and combined these in predictive models that can accurately identify more than 85% of cases as either AQP4 seropositive NMOSD or MS.

Published
2021
Full Text
View/download PDF

6. Multi-platform discovery of haplotype-resolved structural variation in human genomes

Author

Mark J. P. Chaisson, Ashley D. Sanders, Xuefang Zhao, Ankit Malhotra, David Porubsky, Tobias Rausch, Eugene J. Gardner, Oscar L. Rodriguez, Li Guo, Ryan L. Collins, Xian Fan, Jia Wen, Robert E. Handsaker, Susan Fairley, Zev N. Kronenberg, Xiangmeng Kong, Fereydoun Hormozdiari, Dillon Lee, Aaron M. Wenger, Alex R. Hastie, Danny Antaki, Thomas Anantharaman, Peter A. Audano, Harrison Brand, Stuart Cantsilieris, Han Cao, Eliza Cerveira, Chong Chen, Xintong Chen, Chen-Shan Chin, Zechen Chong, Nelson T. Chuang, Christine C. Lambert, Deanna M. Church, Laura Clarke, Andrew Farrell, Joey Flores, Timur Galeev, David U. Gorkin, Madhusudan Gujral, Victor Guryev, William Haynes Heaton, Jonas Korlach, Sushant Kumar, Jee Young Kwon, Ernest T. Lam, Jong Eun Lee, Joyce Lee, Wan-Ping Lee, Sau Peng Lee, Shantao Li, Patrick Marks, Karine Viaud-Martinez, Sascha Meiers, Katherine M. Munson, Fabio C. P. Navarro, Bradley J. Nelson, Conor Nodzak, Amina Noor, Sofia Kyriazopoulou-Panagiotopoulou, Andy W. C. Pang, Yunjiang Qiu, Gabriel Rosanio, Mallory Ryan, Adrian Stütz, Diana C. J. Spierings, Alistair Ward, AnneMarie E. Welch, Ming Xiao, Wei Xu, Chengsheng Zhang, Qihui Zhu, Xiangqun Zheng-Bradley, Ernesto Lowy, Sergei Yakneen, Steven McCarroll, Goo Jun, Li Ding, Chong Lek Koh, Bing Ren, Paul Flicek, Ken Chen, Mark B. Gerstein, Pui-Yan Kwok, Peter M. Lansdorp, Gabor T. Marth, Jonathan Sebat, Xinghua Shi, Ali Bashir, Kai Ye, Scott E. Devine, Michael E. Talkowski, Ryan E. Mills, Tobias Marschall, Jan O. Korbel, Evan E. Eichler, and Charles Lee

Subjects
Science
Abstract

Structural variants (SVs) in human genomes contribute diversity and diseases. Here, the authors use a multi-platform strategy to generate haplotype-resolved SVs for three human parent–child trios.

Published
2019
Full Text
View/download PDF

8. 077 Acute monoplegia

Author

Andrew Swayne, Daniel Schweitzer, Jared Eisemann, Kristen Lefever, Laura Clarke, Cullen O’Gorman, and Letitia Gore

Subjects
Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Published
2021
Full Text
View/download PDF

9. Cell type-specific novel long non-coding RNA and circular RNA in the BLUEPRINT hematopoietic transcriptomes atlas

Author

Luigi Grassi, Osagie G. Izuogu, Natasha A.N. Jorge, Denis Seyres, Mariona Bustamante, Frances Burden, Samantha Farrow, Neda Farahi, Fergal J. Martin, Adam Frankish, Jonathan M. Mudge, Myrto Kostadima, Romina Petersen, John J. Lambourne, Sophia Rowlston, Enca Martin-Rendon, Laura Clarke, Kate Downes, Xavier Estivill, Paul Flicek, Joost H.A. Martens, Marie-Laure Yaspo, Hendrik G. Stunnenberg, Willem H. Ouwehand, Fabio Passetti, Ernest Turro, and Mattia Frontini

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

Transcriptional profiling of hematopoietic cell subpopulations has helped to characterize the developmental stages of the hematopoietic system and the molecular bases of malignant and non-malignant blood diseases. Previously, only the genes targeted by expression microarrays could be profiled genome-wide. High-throughput RNA sequencing, however, encompasses a broader repertoire of RNA molecules, without restriction to previously annotated genes. We analyzed the BLUEPRINT consortium RNA-sequencing data for mature hematopoietic cell types. The data comprised 90 total RNA-sequencing samples, each composed of one of 27 cell types, and 32 small RNA-sequencing samples, each composed of one of 11 cell types. We estimated gene and isoform expression levels for each cell type using existing annotations from Ensembl. We then used guided transcriptome assembly to discover unannotated transcripts. We identified hundreds of novel non-coding RNA genes and showed that the majority have cell type-dependent expression. We also characterized the expression of circular RNA and found that these are also cell type-specific. These analyses refine the active transcriptional landscape of mature hematopoietic cells, highlight abundant genes and transcriptional isoforms for each blood cell type, and provide a valuable resource for researchers of hematologic development and diseases. Finally, we made the data accessible via a web-based interface: https://blueprint.haem.cam.ac.uk/bloodatlas/.

Published
2020
Full Text
View/download PDF

10. Relapse Patterns in NMOSD: Evidence for Earlier Occurrence of Optic Neuritis and Possible Seasonal Variation

Author

Elham Khalilidehkordi, Laura Clarke, Simon Arnett, Wajih Bukhari, Sofia Jimenez Sanchez, Cullen O'Gorman, Jing Sun, Kerri M. Prain, Mark Woodhall, Roger Silvestrini, Christine S. Bundell, David Abernethy, Sandeep Bhuta, Stefan Blum, Mike Boggild, Karyn Boundy, Bruce J. Brew, Matthew Brown, Wallace Brownlee, Helmut Butzkueven, William M. Carroll, Celia Chen, Alan Coulthard, Russell C. Dale, Chandi Das, Marzena J. Fabis-Pedrini, David Fulcher, David Gillis, Simon Hawke, Robert Heard, Andrew P. D. Henderson, Saman Heshmat, Suzanne Hodgkinson, Trevor J. Kilpatrick, John King, Chris Kneebone, Andrew J. Kornberg, Jeannette Lechner-Scott, Ming-Wei Lin, Christopher Lynch, Richard A. L. Macdonell, Deborah F. Mason, Pamela A. McCombe, Jennifer Pereira, John D. Pollard, Sudarshini Ramanathan, Stephen W. Reddel, Cameron Shaw, Judith Spies, James Stankovich, Ian Sutton, Steve Vucic, Michael Walsh, Richard C. Wong, Eppie M. Yiu, Michael H. Barnett, Allan G. Kermode, Mark P. Marriott, John Parratt, Mark Slee, Bruce V. Taylor, Ernest Willoughby, Fabienne Brilot, Angela Vincent, Patrick Waters, and Simon A. Broadley

Subjects
neuromyelitis optica, multiple sclerosis, aquaporin, epidemiology, relapse, seasonality, Neurology. Diseases of the nervous system, RC346-429
Abstract

Neuromyelitis optica spectrum disorders (NMOSD) and multiple sclerosis (MS) show overlap in their clinical features. We performed an analysis of relapses with the aim of determining differences between the two conditions. Cases of NMOSD and age- and sex-matched MS controls were collected from across Australia and New Zealand. Demographic and clinical information, including relapse histories, were recorded using a standard questionnaire. There were 75 cases of NMOSD and 101 MS controls. There were 328 relapses in the NMOSD cases and 375 in MS controls. Spinal cord and optic neuritis attacks were the most common relapses in both NMOSD and MS. Optic neuritis (p < 0.001) and area postrema relapses (P = 0.002) were more common in NMOSD and other brainstem attacks were more common in MS (p < 0.001). Prior to age 30 years, attacks of optic neuritis were more common in NMOSD than transverse myelitis. After 30 this pattern was reversed. Relapses in NMOSD were more likely to be treated with acute immunotherapies and were less likely to recover completely. Analysis by month of relapse in NMOSD showed a trend toward reduced risk of relapse in February to April compared to a peak in November to January (P = 0.065). Optic neuritis and transverse myelitis are the most common types of relapse in NMOSD and MS. Optic neuritis tends to occur more frequently in NMOSD prior to the age of 30, with transverse myelitis being more common thereafter. Relapses in NMOSD were more severe. A seasonal bias for relapses in spring-summer may exist in NMOSD.

Published
2020
Full Text
View/download PDF

11. Dynamics of Transcription Regulation in Human Bone Marrow Myeloid Differentiation to Mature Blood Neutrophils

Author

Luigi Grassi, Farzin Pourfarzad, Sebastian Ullrich, Angelika Merkel, Felipe Were, Enrique Carrillo-de-Santa-Pau, Guoqiang Yi, Ida H. Hiemstra, Anton T.J. Tool, Erik Mul, Juliane Perner, Eva Janssen-Megens, Kim Berentsen, Hinri Kerstens, Ehsan Habibi, Marta Gut, Marie Laure Yaspo, Matthias Linser, Ernesto Lowy, Avik Datta, Laura Clarke, Paul Flicek, Martin Vingron, Dirk Roos, Timo K. van den Berg, Simon Heath, Daniel Rico, Mattia Frontini, Myrto Kostadima, Ivo Gut, Alfonso Valencia, Willem H. Ouwehand, Hendrik G. Stunnenberg, Joost H.A. Martens, and Taco W. Kuijpers

Subjects
Biology (General), QH301-705.5
Abstract

Summary: Neutrophils are short-lived blood cells that play a critical role in host defense against infections. To better comprehend neutrophil functions and their regulation, we provide a complete epigenetic overview, assessing important functional features of their differentiation stages from bone marrow-residing progenitors to mature circulating cells. Integration of chromatin modifications, methylation, and transcriptome dynamics reveals an enforced regulation of differentiation, for cellular functions such as release of proteases, respiratory burst, cell cycle regulation, and apoptosis. We observe an early establishment of the cytotoxic capability, while the signaling components that activate these antimicrobial mechanisms are transcribed at later stages, outside the bone marrow, thus preventing toxic effects in the bone marrow niche. Altogether, these data reveal how the developmental dynamics of the chromatin landscape orchestrate the daily production of a large number of neutrophils required for innate host defense and provide a comprehensive overview of differentiating human neutrophils. : Grassi et al. report that the establishment of transcriptional enhancers drives neutrophil differentiation. Coordinated waves of gene expression establish the cytotoxic capability of these cells at early stages of maturation. A set of super-enhancers is specifically opened at the end of the differentiation process to control neutrophil activation. Keywords: neutrophil, epigenome, transcriptome, myeloid differentiation

Published
2018
Full Text
View/download PDF

12. Convergent genomic signatures of domestication in sheep and goats

Author

Florian J. Alberto, Frédéric Boyer, Pablo Orozco-terWengel, Ian Streeter, Bertrand Servin, Pierre de Villemereuil, Badr Benjelloun, Pablo Librado, Filippo Biscarini, Licia Colli, Mario Barbato, Wahid Zamani, Adriana Alberti, Stefan Engelen, Alessandra Stella, Stéphane Joost, Paolo Ajmone-Marsan, Riccardo Negrini, Ludovic Orlando, Hamid Reza Rezaei, Saeid Naderi, Laura Clarke, Paul Flicek, Patrick Wincker, Eric Coissac, James Kijas, Gwenola Tosser-Klopp, Abdelkader Chikhi, Michael W. Bruford, Pierre Taberlet, and François Pompanon

Subjects
Science
Abstract

The sheep and goat were domesticated ~10,500 years ago in the same region of the Middle-East. Here, Alberto et al compare the genomes of wild Asiatic mouflon and Bezoar ibex with that of domestics from local, traditional and improved breeds and find common targets of selection related to domestication and improvement in sheep and goats.

Published
2018
Full Text
View/download PDF

13. The European Nucleotide Archive in 2017.

Author

Nicole Silvester, Blaise T. F. Alako, Clara Amid, Ana Cerdeño-Tárraga, Laura Clarke, Iain Cleland, Peter W. Harrison, Suran Jayathilaka, Simon Kay, Thomas M. Keane, Rasko Leinonen, Xin Liu 0006, Josué Martínez-Villacorta, Manuela Menchi, Kethi Reddy, Nima Pakseresht, Jeena Rajan, Marc Rossello, Dmitriy Smirnov 0002, Ana Luisa Toribio, Daniel Vaughan, Vadim Zalunin, and Guy Cochrane

Published
2018
Full Text
View/download PDF

14. A Standard Nomenclature for Referencing and Authentication of Pluripotent Stem Cells

Author

Andreas Kurtz, Stefanie Seltmann, Amos Bairoch, Marie-Sophie Bittner, Kevin Bruce, Amanda Capes-Davis, Laura Clarke, Jeremy M. Crook, Laurence Daheron, Johannes Dewender, Adam Faulconbridge, Wataru Fujibuchi, Alexander Gutteridge, Derek J. Hei, Yong-Ou Kim, Jung-Hyun Kim, Anja Kolb- Kokocinski, Fritz Lekschas, Geoffrey P. Lomax, Jeanne F. Loring, Tenneille Ludwig, Nancy Mah, Tohru Matsui, Robert Müller, Helen Parkinson, Michael Sheldon, Kelly Smith, Harald Stachelscheid, Glyn Stacey, Ian Streeter, Anna Veiga, and Ren-He Xu

Subjects
human pluripotent stem cells, cell line nomenclature, cell data referencing, cell line authentication, cell databases, stem cell registry, Medicine (General), R5-920, Biology (General), QH301-705.5
Abstract

Unambiguous cell line authentication is essential to avoid loss of association between data and cells. The risk for loss of references increases with the rapidity that new human pluripotent stem cell (hPSC) lines are generated, exchanged, and implemented. Ideally, a single name should be used as a generally applied reference for each cell line to access and unify cell-related information across publications, cell banks, cell registries, and databases and to ensure scientific reproducibility. We discuss the needs and requirements for such a unique identifier and implement a standard nomenclature for hPSCs, which can be automatically generated and registered by the human pluripotent stem cell registry (hPSCreg). To avoid ambiguities in PSC-line referencing, we strongly urge publishers to demand registration and use of the standard name when publishing research based on hPSC lines.

Published
2018
Full Text
View/download PDF

15. Platelet function is modified by common sequence variation in megakaryocyte super enhancers

Author

Romina Petersen, John J. Lambourne, Biola M. Javierre, Luigi Grassi, Roman Kreuzhuber, Dace Ruklisa, Isabel M. Rosa, Ana R. Tomé, Heather Elding, Johanna P. van Geffen, Tao Jiang, Samantha Farrow, Jonathan Cairns, Abeer M. Al-Subaie, Sofie Ashford, Antony Attwood, Joana Batista, Heleen Bouman, Frances Burden, Fizzah A. Choudry, Laura Clarke, Paul Flicek, Stephen F. Garner, Matthias Haimel, Carly Kempster, Vasileios Ladopoulos, An-Sofie Lenaerts, Paulina M. Materek, Harriet McKinney, Stuart Meacham, Daniel Mead, Magdolna Nagy, Christopher J. Penkett, Augusto Rendon, Denis Seyres, Benjamin Sun, Salih Tuna, Marie-Elise van der Weide, Steven W. Wingett, Joost H. Martens, Oliver Stegle, Sylvia Richardson, Ludovic Vallier, David J. Roberts, Kathleen Freson, Lorenz Wernisch, Hendrik G. Stunnenberg, John Danesh, Peter Fraser, Nicole Soranzo, Adam S. Butterworth, Johan W. Heemskerk, Ernest Turro, Mikhail Spivakov, Willem H. Ouwehand, William J. Astle, Kate Downes, Myrto Kostadima, and Mattia Frontini

Subjects
Science
Abstract

Numerous genetic variants, including those located in the non-coding regions of the genome, are known to be associated with blood cells traits. Here, Frontini and colleagues investigate their potential regulatory functions using epigenomic data and promoter long-range interactions.

Published
2017
Full Text
View/download PDF

16. Rapid establishment of the European Bank for induced Pluripotent Stem Cells (EBiSC) - the Hot Start experience

Author

Paul A. De Sousa, Rachel Steeg, Elisabeth Wachter, Kevin Bruce, Jason King, Marieke Hoeve, Shalinee Khadun, George McConnachie, Julie Holder, Andreas Kurtz, Stefanie Seltmann, Johannes Dewender, Sascha Reimann, Glyn Stacey, Orla O'Shea, Charlotte Chapman, Lyn Healy, Heiko Zimmermann, Bryan Bolton, Trisha Rawat, Isobel Atkin, Anna Veiga, Bernd Kuebler, Blanca Miranda Serano, Tomo Saric, Jürgen Hescheler, Oliver Brüstle, Michael Peitz, Cornelia Thiele, Niels Geijsen, Bjørn Holst, Christian Clausen, Majlinda Lako, Lyle Armstrong, Shailesh K. Gupta, Alexander J. Kvist, Ryan Hicks, Anna Jonebring, Gabriella Brolén, Andreas Ebneth, Alfredo Cabrera-Socorro, Patrik Foerch, Martine Geraerts, Tina C. Stummann, Shawn Harmon, Carol George, Ian Streeter, Laura Clarke, Helen Parkinson, Peter W. Harrison, Adam Faulconbridge, Luca Cherubin, Tony Burdett, Cesar Trigueros, Minal J Patel, Christa Lucas, Barry Hardy, Rok Predan, Joh Dokler, Maja Brajnik, Oliver Keminer, Ole Pless, Philip Gribbon, Carsten Claussen, Annette Ringwald, Beate Kreisel, Aidan Courtney, and Timothy E. Allsopp

Subjects
Biology (General), QH301-705.5
Abstract

A fast track “Hot Start” process was implemented to launch the European Bank for Induced Pluripotent Stem Cells (EBiSC) to provide early release of a range of established control and disease linked human induced pluripotent stem cell (hiPSC) lines. Established practice amongst consortium members was surveyed to arrive at harmonised and publically accessible Standard Operations Procedures (SOPs) for tissue procurement, bio-sample tracking, iPSC expansion, cryopreservation, qualification and distribution to the research community. These were implemented to create a quality managed foundational collection of lines and associated data made available for distribution. Here we report on the successful outcome of this experience and work flow for banking and facilitating access to an otherwise disparate European resource, with lessons to benefit the international research community. eTOC: The report focuses on the EBiSC experience of rapidly establishing an operational capacity to procure, bank and distribute a foundational collection of established hiPSC lines. It validates the feasibility and defines the challenges of harnessing and integrating the capability and productivity of centres across Europe using commonly available resources currently in the field.

Published
2017
Full Text
View/download PDF

17. Variant calling on the GRCh38 assembly with the data from phase three of the 1000 Genomes Project [version 2; peer review: 2 approved]

Author

Ernesto Lowy-Gallego, Susan Fairley, Xiangqun Zheng-Bradley, Magali Ruffier, Laura Clarke, Paul Flicek, and The 1000 Genomes Project Consortium

Subjects
Medicine, Science
Abstract

We present a set of biallelic SNVs and INDELs, from 2,548 samples spanning 26 populations from the 1000 Genomes Project, called de novo on GRCh38. We believe this will be a useful reference resource for those using GRCh38. It represents an improvement over the “lift-overs” of the 1000 Genomes Project data that have been available to date by encompassing all of the GRCh38 primary assembly autosomes and pseudo-autosomal regions, including novel, medically relevant loci. Here, we describe how the data set was created and benchmark our call set against that produced by the final phase of the 1000 Genomes Project on GRCh37 and the lift-over of that data to GRCh38.

Published
2019
Full Text
View/download PDF

18. Induction of Neural Crest Stem Cells From Bardet–Biedl Syndrome Patient Derived hiPSCs

Author

William B. Barrell, John N. Griffin, Jessica-Lily Harvey, HipSci Consortium, Davide Danovi, Philip Beales, Agamemnon E. Grigoriadis, Karen J. Liu, Richard Durbin, Daniel Gaffney, Chukwuma Agu, Alex Alderton, Shrada Amatya, Petr Danecek, Rachel Denton, Angela Goncalves, Reena Halai, Sarah Harper, Chris Kirton, Andrew Knights, Anja Kolb-Kokocinski, Andreas Leha, Shane McCarthy, Yasin Memari, Minal Patel, Ewan Birney, Oliver Stegle, Francesco Paolo Casale, Laura Clarke, Peter Harrison, Helena Kilpinen, Davis McCarthy, Ian Streeter, Fiona Watt, Davide Denovi, Ruta Meleckyte, Natalie Moens, Willem Ouwehand, Ludovic Vallier, Angus Lamond, and Dalila Bensaddek

Subjects
neural crest, human induced pluripotent stem cells, hiPSCs, Bardet–Biedl Syndrome, BBS, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Neural crest cells arise in the embryo from the neural plate border and migrate throughout the body, giving rise to many different tissue types such as bones and cartilage of the face, smooth muscles, neurons, and melanocytes. While studied extensively in animal models, neural crest development and disease have been poorly described in humans due to the challenges in accessing embryonic tissues. In recent years, patient-derived human induced pluripotent stem cells (hiPSCs) have become easier to generate, and several streamlined protocols have enabled robust differentiation of hiPSCs to the neural crest lineage. Thus, a unique opportunity is offered for modeling neurocristopathies using patient specific stem cell lines. In this work, we make use of hiPSCs derived from patients affected by the Bardet–Biedl Syndrome (BBS) ciliopathy. BBS patients often exhibit subclinical craniofacial dysmorphisms that are likely to be associated with the neural crest-derived facial skeleton. We focus on hiPSCs carrying variants in the BBS10 gene, which encodes a protein forming part of a chaperonin-like complex associated with the cilium. Here, we establish a pipeline for profiling hiPSCs during differentiation toward the neural crest stem cell fate. This can be used to characterize the differentiation properties of the neural crest-like cells. Two different BBS10 mutant lines showed a reduction in expression of the characteristic neural crest gene expression profile. Further analysis of both BBS10 mutant lines highlighted the inability of these mutant lines to differentiate toward a neural crest fate, which was also characterized by a decreased WNT and BMP response. Altogether, our study suggests a requirement for wild-type BBS10 in human neural crest development. In the long term, approaches such as the one we describe will allow direct comparison of disease-specific cell lines. This will provide valuable insights into the relationships between genetic background and heterogeneity in cellular models. The possibility of integrating laboratory data with clinical phenotypes will move us toward precision medicine approaches.

Published
2019
Full Text
View/download PDF

20. European Nucleotide Archive in 2016.

Author

Ana Luisa Toribio, Blaise T. F. Alako, Clara Amid, Ana Cerdeño-Tárraga, Laura Clarke, Iain Cleland, Susan Fairley, Richard Gibson, Neil Goodgame, Petra ten Hoopen, Suran Jayathilaka, Simon Kay, Rasko Leinonen, Xin Liu 0006, Josué Martínez-Villacorta, Nima Pakseresht, Jeena Rajan, Kethi Reddy, Marc Rossello, Nicole Silvester, Dimitriy Smirnov, Daniel Vaughan, Vadim Zalunin, and Guy Cochrane

Published
2017
Full Text
View/download PDF

22. Increased DNA methylation variability in type 1 diabetes across three immune effector cell types

Author

Dirk S. Paul, Andrew E. Teschendorff, Mary A.N. Dang, Robert Lowe, Mohammed I. Hawa, Simone Ecker, Huriya Beyan, Stephanie Cunningham, Alexandra R. Fouts, Anita Ramelius, Frances Burden, Samantha Farrow, Sophia Rowlston, Karola Rehnstrom, Mattia Frontini, Kate Downes, Stephan Busche, Warren A. Cheung, Bing Ge, Marie-Michelle Simon, David Bujold, Tony Kwan, Guillaume Bourque, Avik Datta, Ernesto Lowy, Laura Clarke, Paul Flicek, Emanuele Libertini, Simon Heath, Marta Gut, Ivo G Gut, Willem H. Ouwehand, Tomi Pastinen, Nicole Soranzo, Sabine E. Hofer, Beate Karges, Thomas Meissner, Bernhard O. Boehm, Corrado Cilio, Helena Elding Larsson, Åke Lernmark, Andrea K. Steck, Vardhman K. Rakyan, Stephan Beck, and R. David Leslie

Subjects
Science
Abstract

The incidence of type 1 diabetes is increasing, potentially implicating non-genetic factors. Here the authors conduct an epigenome-wide association study in disease-discordant twins and find increased DNA methylation variability at genes associated with immune cell metabolism and the cell cycle.

Published
2016
Full Text
View/download PDF

23. Neuromyelitis optica spectrum disorder

Author

Simon Broadley, Elham Khalili, Saman Heshmat, and Laura Clarke

Subjects
Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Over the past 13 years neuromyelitis optica spectrum disorder (NMOSD) has emerged as a discrete form of demyelinating disease of the central nervous system in which antibodies against a water channel found in high concentration on astrocytes are frequently found. Following the discovery of this pathogenic antibody the phenotype of this condition, previously known as Devic’s disease, has broadened from one of monophasic or recurrent, optic neuritis and transverse myelitis, to include area postrema lesions, hypothalamic lesions and a fulminant encephalopathic presentation. Clues to the diagnosis include clinical presentations related to the above locations of pathology and imaging changes including longitudinally extensive spinal cord lesions, extensive optic nerve lesions, particularly lesions posterior to or involving the chiasm, and reactive cerebrospinal fluid. Early identification of this disorder is important as the prognosis without treatment is poor and generally worse than is seen in multiple sclerosis (MS). In addition, the approach to treatment (immunosuppression and anti-B-cell therapy) is different to MS and there is a concern that some disease modifying therapies that are helpful in MS may be harmful in NMOSD.

Published
2017
Full Text
View/download PDF

24. Magnetic resonance imaging in neuromyelitis optica spectrum disorder

Author

Sandeep Bhuta, Jacky Liao, Laura Clarke, Simon Arnett, Kate Lilley, and Simon Broadley

Subjects
Pathology, medicine.medical_specialty, Immunology, Optic chiasm, White matter, medicine, Humans, Immunology and Allergy, Autoantibodies, Aquaporin 4, Neuromyelitis optica, medicine.diagnostic_test, business.industry, Multiple sclerosis, Neuromyelitis Optica, REVIEW SERIES: IMAGING IMMUNOLOGICAL PROCESSES IN NEUROINFLAMMATORY DISEASES, Optic Nerve, Magnetic resonance imaging, medicine.disease, Spinal cord, Magnetic Resonance Imaging, White Matter, Hyperintensity, medicine.anatomical_structure, Spinal Cord, Immunoglobulin G, Optic nerve, sense organs, business
Abstract

Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory disease of the central nervous system (CNS) associated with antibodies to aquaporin-4 (AQP4), which has distinct clinical, radiological and pathological features, but also has some overlap with multiple sclerosis and myelin oligodendrocyte glycoprotein (MOG) antibody associated disease. Early recognition of NMOSD is important because of differing responses to both acute and preventive therapy. Magnetic resonance (MR) imaging has proved essential in this process. Key MR imaging clues to the diagnosis of NMOSD are longitudinally extensive lesions of the optic nerve (more than half the length) and spinal cord (three or more vertebral segments), bilateral optic nerve lesions and lesions of the optic chiasm, area postrema, floor of the IV ventricle, periaqueductal grey matter, hypothalamus and walls of the III ventricle. Other NMOSD-specific lesions are denoted by their unique morphology: heterogeneous lesions of the corpus callosum, ‘cloud-like’ gadolinium (Gd)-enhancing white matter lesions and ‘bright spotty’ lesions of the spinal cord. Other lesions described in NMOSD, including linear periventricular peri-ependymal lesions and patch subcortical white matter lesions, may be less specific. The use of advanced MR imaging techniques is yielding further useful information regarding focal degeneration of the thalamus and optic radiation in NMOSD and suggests that paramagnetic rim patterns and changes in normal appearing white matter are specific to MS. MR imaging is crucial in the early recognition of NMOSD and in directing testing for AQP4 antibodies and guiding immediate acute treatment decisions. Increasingly, MR imaging is playing a role in diagnosing seronegative cases of NMOSD.

Published
2021
Full Text
View/download PDF

25. Correction to: Functional variation in allelic methylomes underscores a strong genetic contribution and reveals novel epigenetic alterations in the human epigenome

Author

Warren A. Cheung, Xiaojian Shao, Andréanne Morin, Valérie Siroux, Tony Kwan, Bing Ge, Dylan Aïssi, Lu Chen, Louella Vasquez, Fiona Allum, Frédéric Guénard, Emmanuelle Bouzigon, Marie-Michelle Simon, Elodie Boulier, Adriana Redensek, Stephen Watt, Avik Datta, Laura Clarke, Paul Flicek, Daniel Mead, Dirk S. Paul, Stephan Beck, Guillaume Bourque, Mark Lathrop, André Tchernof, Marie-Claude Vohl, Florence Demenais, Isabelle Pin, Kate Downes, Hendrick G. Stunnenberg, Nicole Soranzo, Tomi Pastinen, and Elin Grundberg

Subjects
Biology (General), QH301-705.5, Genetics, QH426-470
Abstract

Following publication of the original article [1], the authors reported an error in Additional file 1.

Published
2019
Full Text
View/download PDF

26. Increasing ionic conductivity within thermoplastics via commercial additives results in a dramatic decrease in fiber diameter from melt electrospinning

Author

Neelam Sheoran, Laura Clarke, Samuel Thornton, Brent Boland, and Jason R. Bochinski

Subjects
Physics::Fluid Dynamics, Viscosity, Jet (fluid), Materials science, Fluid mechanics, General Chemistry, Fiber, Composite material, Conductivity, Condensed Matter Physics, Melt electrospinning, Electrospinning, Volumetric flow rate
Abstract

Polyethylene melt conductivity was increased by adding a commercial anti-static agent, which resulted in a 20× decrease in electrospun fiber diameter and formation of a significant fraction of sub-micron diameter fibers. Two polyethylene formulations and varying additive concentrations were utilized to span the parameter space of conductivity and viscosity. The key role of conductivity in determining the jet radius (which sets the upper limit on the fiber size) is discussed in the context of fluid mechanics theory and previous simulations. Parameters which affect the conversion of the liquid jet to a solid fiber and the pertinent theory are outlined. An “unconfined” experimental configuration is utilized to both avoid potential needle clogging and enable direct observation of important characteristic length scales related to the interaction of the fluid and the applied electric field. In this approach, the fluid spontaneously forms an array of cone perturbations which act as stationary “nozzles” through which the mobile fluid flows to form the jet. The experimental data and theory considerations allow for a holistic discussion of the interaction between flow rate, viscosity, conductivity, and the resultant jet and fiber size. Information about the fluid viscosity and conductivity gained by observing the electrospinning process is highlighted. Schemes for theoretically predicting the cone-jet density, cone size, and flow rate are compared to experimental results.

Published
2021
Full Text
View/download PDF

27. Ensembl 2009.

Author

Tim J. P. Hubbard, Bronwen L. Aken, Sarah C. Ayling, Benoît Ballester, Kathryn Beal, Eugene Bragin, Simon Brent, Yuan Chen 0007, Peter Clapham, Laura Clarke, Guy Coates, Susan Fairley, Stephen Fitzgerald, Julio Fernandez-Banet, Leo Gordon, Stefan Gräf, Syed Haider, Martin Hammond, Richard C. G. Holland, Kevin L. Howe, Andrew M. Jenkinson, Nathan Johnson, Andreas Kähäri, Damian Keefe, Stephen Keenan, Rhoda Kinsella, Felix Kokocinski, Eugene Kulesha, Daniel Lawson, Ian Longden, Karine Megy, Patrick Meidl, Bert Overduin, Anne Parker, Bethan Pritchard, Daniel Rios, Michael Schuster, Guy Slater, Damian Smedley, William Spooner, Giulietta Spudich, Stephen J. Trevanion, Albert J. Vilella, Jan Vogel, Simon White, Steven P. Wilder, Arek Zadissa, Ewan Birney, Fiona Cunningham, Val Curwen, Richard Durbin, Xosé M. Fernández-Suárez, Javier Herrero, Arek Kasprzyk, Glenn Proctor, James A. Smith, Stephen M. J. Searle, and Paul Flicek

Published
2009
Full Text
View/download PDF

28. The adult retinal stem cell is a rare cell in the ciliary epithelium whose progeny can differentiate into photoreceptors

Author

Brian G. Ballios, Laura Clarke, Brenda L. K. Coles, Molly S. Shoichet, and Derek Van Der Kooy

Subjects
retina, stem cells, photoreceptor differentiation, Science, Biology (General), QH301-705.5
Abstract

Summary Self-renewing, multipotential retinal stem cells (RSCs) reside in the pigmented ciliary epithelium of the peripheral retina in adult mammals. RSCs can give rise to rhodopsin positive-cells, which can integrate into early postnatal retina, and represent a potentially useful option for cellular therapy. The ability to purify a stem cell population and direct the differentiation toward a particular cell lineage is a challenge facing the application of stem cells in regenerative medicine. Here we use cell sorting to prospectively enrich mouse RSCs based on size, granularity and low expression of P-cadherin and demonstrate that only rare cells with defined properties proliferate to form colonies. We show that clonally-derived mouse and human RSC progeny are multipotent and can differentiate into mature rhodopsin-positive cells with high efficiency using combinations of exogenous culture additives known to influence neural retinal development, including taurine and retinoic acid. This directed RSC differentiation follows the temporal sequence of photoreceptor differentiation in vivo, and the cells exhibit morphology, protein and gene expression consistent with primary cultures of rods in vitro. These results demonstrate that the RSC, an adult stem cell, can be enriched and directed to produce photoreceptors as a first step toward a targeted cell replacement strategy to treat retinal degenerative disease.

Published
2012
Full Text
View/download PDF

29. Ensembl 2008.

Author

Paul Flicek, Bronwen L. Aken, Kathryn Beal, Benoît Ballester, Mario Cáccamo, Yuan Chen 0007, Laura Clarke, Guy Coates, Fiona Cunningham, Tim Cutts, Thomas A. Down, S. C. Dyer, T. Eyre, Stephen Fitzgerald, Julio Fernandez-Banet, Stefan Gräf, Syed Haider, Martin Hammond, Richard C. G. Holland, Kevin L. Howe, Kerstin Howe, Nathan Johnson, Andrew M. Jenkinson, Andreas Kähäri, Damian Keefe, Felix Kokocinski, Eugene Kulesha, Daniel Lawson, Ian Longden, Karine Megy, Patrick Meidl, Bert Overduin, Anne Parker, Bethan Pritchard, Andreas Prlic, S. Rice, Daniel Rios, Michael Schuster, Ian Sealy, Guy Slater, Damian Smedley, Giulietta Spudich, Stephen J. Trevanion, Albert J. Vilella, Jan Vogel, Simon White, M. Wood, Ewan Birney, Tony Cox 0001, Val Curwen, Richard Durbin, Xosé M. Fernández-Suárez, Javier Herrero, Tim J. P. Hubbard, Arek Kasprzyk, Glenn Proctor, James A. Smith, Abel Ureta-Vidal, and Stephen M. J. Searle

Published
2008
Full Text
View/download PDF

30. The Ensembl gene annotation system.

Author

Bronwen L. Aken, Sarah C. Ayling, Daniel Barrell, Laura Clarke, Valery Curwen, Susan Fairley, Julio Fernandez-Banet, Konstantinos Billis, Carlos García-Girón, Thibaut Hourlier, Kevin Lee Howe, Andreas Kähäri, Felix Kokocinski, Fergal J. Martin, Daniel N. Murphy, Rishi Nag, Magali Ruffier, Michael Schuster, Y. Amy Tang, Jan Vogel, Simon White, Amonida Zadissa, Paul Flicek, and Stephen M. J. Searle

Published
2016
Full Text
View/download PDF

31. Ensembl 2007.

Author

Tim J. P. Hubbard, Bronwen L. Aken, Kathryn Beal, Benoît Ballester, Mario Cáccamo, Yuan Chen 0007, Laura Clarke, Guy Coates, Fiona Cunningham, Tim Cutts, Thomas A. Down, S. C. Dyer, Stephen Fitzgerald, Julio Fernandez-Banet, Stefan Gräf, Syed Haider, Martin Hammond, Javier Herrero, Richard C. G. Holland, Kevin L. Howe, Kerstin Howe, Nathan Johnson, Andreas Kähäri, Damian Keefe, Felix Kokocinski, Eugene Kulesha, Daniel Lawson, Ian Longden, Craig Melsopp, Karine Megy, Patrick Meidl, Bert Overduin, Anne Parker, Andreas Prlic, S. Rice, Daniel Rios, Michael Schuster, Ian Sealy, Jessica Severin, Guy Slater, Damian Smedley, Giulietta Spudich, Stephen J. Trevanion, Albert J. Vilella, Jan Vogel, Simon White, M. Wood, Tony Cox 0001, Val Curwen, Richard Durbin, Xosé M. Fernández-Suárez, Paul Flicek, Arek Kasprzyk, Glenn Proctor, Stephen M. J. Searle, James A. Smith, Abel Ureta-Vidal, and Ewan Birney

Published
2007
Full Text
View/download PDF

32. Ensembl 2006.

Author

Ewan Birney, T. Daniel Andrews, Mario Cáccamo, Yuan Chen 0007, Laura Clarke, Guy Coates, Tony Cox 0001, Fiona Cunningham, Val Curwen, Tim Cutts, Thomas A. Down, Richard Durbin, Xosé M. Fernández-Suárez, Paul Flicek, Stefan Gräf, Martin Hammond, Javier Herrero, Kevin L. Howe, Vivek Iyer, Kerstin Jekosch, Andreas Kähäri, Arek Kasprzyk, Damian Keefe, Felix Kokocinski, Eugene Kulesha, D. London, Ian Longden, Craig Melsopp, Patrick Meidl, Bert Overduin, Anne Parker, Glenn Proctor, Andreas Prlic, Mark Rae, Daniel Rios, Seth Redmond, Michael Schuster, Ian Sealy, Stephen M. J. Searle, Jessica Severin, Guy Slater, Damian Smedley, James A. Smith, Arne Stabenau, Jim Stalker, Stephen J. Trevanion, Abel Ureta-Vidal, Jan Vogel, Simon White, Cara Woodwark, and Tim J. P. Hubbard

Published
2006
Full Text
View/download PDF

33. Ensembl 2005.

Author

Tim J. P. Hubbard, D. Andrews, Mario Cáccamo, Graham Cameron, Yuan Chen 0007, Michele E. Clamp, Laura Clarke, Guy Coates, Tony Cox 0001, Fiona Cunningham, Val Curwen, Tim Cutts, Thomas A. Down, Richard Durbin, Xosé M. Fernández-Suárez, James G. R. Gilbert, Martin Hammond, Javier Herrero, H. Hotz, Kevin L. Howe, Vivek Iyer, Kerstin Jekosch, Andreas Kähäri, Arek Kasprzyk, Damian Keefe, Stephen Keenan, Felix Kokocinski, D. London, Ian Longden, Graham P. McVicker, Craig Melsopp, Patrick Meidl, Simon C. Potter, Glenn Proctor, Mark Rae, Daniel Rios, Michael Schuster, Stephen M. J. Searle, Jessica Severin, Guy Slater, Damian Smedley, James A. Smith, William Spooner, Arne Stabenau, Jim Stalker, R. Storey, Stephen J. Trevanion, Abel Ureta-Vidal, Jan Vogel, Simon White, Cara Woodwark, and Ewan Birney

Published
2005
Full Text
View/download PDF

34. Ensembl 2002: accommodating comparative genomics.

Author

Michele E. Clamp, T. Daniel Andrews, Daniel Barker, Paul Bevan 0001, Graham Cameron, Yuan Chen 0007, Laura Clarke, Tony Cox 0001, James A. Cuff, Val Curwen, Thomas A. Down, Richard Durbin, Eduardo Eyras, James G. R. Gilbert, Martin Hammond, Tim J. P. Hubbard, Arek Kasprzyk, Damian Keefe, Heikki Lehväslaiho, Vivek Iyer, Craig Melsopp, Emmanuel Mongin, Roger Pettett, Simon C. Potter, Alistair G. Rust, Esther Schmidt, Stephen M. J. Searle, Guy Slater, James A. Smith, William Spooner, Arne Stabenau, Jim Stalker, Elia Stupka, Abel Ureta-Vidal, Imre Vastrik, and Ewan Birney

Published
2003
Full Text
View/download PDF

35. The Ensembl genome database project.

Author

Tim J. P. Hubbard, Daniel Barker, Ewan Birney, Graham Cameron, Yuan Chen 0007, Laura Clarke, Tony Cox 0001, James A. Cuff, Val Curwen, Thomas A. Down, Richard Durbin, Eduardo Eyras, James G. R. Gilbert, Martin Hammond, Lukasz Huminiecki, Arek Kasprzyk, Heikki Lehväslaiho, Philip Lijnzaad, Craig Melsopp, Emmanuel Mongin, Roger Pettett, Matthew R. Pocock, Simon C. Potter, Alistair G. Rust, Esther Schmidt, Stephen M. J. Searle, Guy Slater, James A. Smith, William Spooner, Arne Stabenau, Jim Stalker, Elia Stupka, Abel Ureta-Vidal, Imre Vastrik, and Michele E. Clamp

Published
2002
Full Text
View/download PDF

36. Multiple adaptive solutions to face climatic constraints: novel insights in the debate over the role of convergence in local adaptation

Author

Filippo Biscarini, Badr Benjelloun, Pierre Taberlet, Stéphane Joost, Kevin Leempoel, Florian J. Alberto, Frédéric Boyer, Paul Flicek, Paolo Ajmone-Marsan, Riccardo Negrini, François Pompanon, Stefan Engelen, Ian Streeter, Licia Colli, Sylvie Stucki, Bertrand Servin, Alessandra Stella, Pablo Orozco-terWengel, Laura Clarke, Abdelkader Chikhi, Eric Coissac, Adriana Alberti, and Michael William Bruford

Subjects
Evolutionary biology, Face (geometry), Convergence (relationship), Biology, Adaptation, Set (psychology), Domestication, Determinism, Local adaptation
Abstract

The extent to which genomic convergence shapes locally adapted phenotypes in different species remains a fundamental question in evolutionary biology. It would help assessing the relative role of historical contingencies versus determinism in evolution. To bring new insights to this debate we set up a framework which aimed to compare the adaptive trajectories of two domesticated mammal species co-distributed in diversified landscapes. We sequenced the genomes of 160 sheep and 161 goats extensively managed along environmental gradients, including temperature, rainfall, seasonality and altitude, to identify genes and biological processes shaping local adaptation. Allele frequencies at adaptive loci were rarely found to vary gradually along environmental gradients, but rather displayed a discontinuous shift at the extremities of environmental clines. Of the more than 430 adaptive genes identified, only 6 were orthologous between sheep and goats and those responded differently to environmental pressures, suggesting different adaptive mechanisms in these two closely related species. Such diversity of adaptive pathways may result from a high number of biological functions involved in adaptation to multiple eco-climatic gradients, and provides more arguments for the role of contingency and stochasticity in adaptation rather than repeatability and determinism.

Published
2021
Full Text
View/download PDF

37. Guidelines for reporting single-cell RNA-seq experiments

Author

Anja Füllgrabe, Deanne Taylor, John C. Marioni, Nancy George, Irene Papatheodorou, Silvie Fexova, Matthew Green, Jim Kent, Norman Morrison, Nils Gehlenborg, Alvis Brazma, Sarah A. Teichmann, Parisa Nejad, Mallory A. Freeberg, Richard H. Scheuermann, Bruce J. Aronow, Laura Clarke, Nicole Vasilevsky, Clay Fischer, and Laura Huerta

Subjects
Computer science, Cell, Biomedical Engineering, MEDLINE, Guidelines as Topic, Bioengineering, RNA-Seq, Computational biology, Applied Microbiology and Biotechnology, Article, 03 medical and health sciences, 0302 clinical medicine, Text mining, medicine, Quantitative Biology - Genomics, 030304 developmental biology, Genomics (q-bio.GN), 0303 health sciences, business.industry, medicine.anatomical_structure, FOS: Biological sciences, Molecular Medicine, Periodicals as Topic, Single-Cell Analysis, Transcriptome, business, 030217 neurology & neurosurgery, Biotechnology
Abstract

Single-cell RNA-Sequencing (scRNA-Seq) has undergone major technological advances in recent years, enabling the conception of various organism-level cell atlassing projects. With increasing numbers of datasets being deposited in public archives, there is a need to address the challenges of enabling the reproducibility of such data sets. Here, we describe guidelines for a minimum set of metadata to sufficiently describe scRNA-Seq experiments, ensuring reproducibility of data analyses.

Published
2020
Full Text
View/download PDF

40. 078 A case of non-convulsive status epilepticus (NCSE) as first presentation of sporadic creutzfeldt-jakob Disease (sCJD)

Author

Luke Gagen, Laura Clarke, Kristen Lefever, Cullen O’Gorman, Daniel Schweitzer, and Andrew Swayne

Subjects
Pediatrics, medicine.medical_specialty, Palliative care, medicine.diagnostic_test, business.industry, Brain biopsy, Neurosciences. Biological psychiatry. Neuropsychiatry, Context (language use), Status epilepticus, medicine.disease, Apraxia, medicine, Infectious encephalitis, Neurosurgery, Differential diagnosis, medicine.symptom, business, RC321-571
Abstract

Objectives sCJD is a neurodegenerative prion disease characterised by rapidly progressive neuropsychiatric symptoms and movement disorder. Seizures are an uncommon first presentation of sCJD. We present a case of a 71 year-old female in whom presented in NCSE. Methods Single Case Report. Results A 71-year-old female initially presented with higher cortical impairment characterised by visuospatial deficits and apraxia suggestive of parietal lobe dysfunction. Subsequent MRI showed multifocal patches of gyriform diffusion restriction – cortical ribboning – predominantly in the right parietal cortex. Autoimmune and metabolic cerebrospinal fluid (CSF) testing were unremarkable for markers of autoimmune or infectious encephalitis. EEG demonstrated NCSE arising from this right hemisphere lesion, with severe diffuse encephalopathy. A ward-based anti-epileptic drug regime was instituted without success. ICU management with midazolam infusion and intubation for NCSE was required. Clinically and electrographically the patient improved over a two-week period, with resolution of NCSE on repeat EEG. Unfortunately however a repeat MRI on Day 17 of admission demonstrated progression of cortical ribboning beyond the initial focus across hemispheres. This in combination with a positive 14-3-3 and tau protein on CSF, raised the likelihood of sCJD. Marked clinical deterioration followed extubation, with palliative care involvement and end of life planning. The diagnosis of sCJD was confirmed with brain biopsy at autopsy. Conclusion The case is notable as it is rare for sCJD to present early with NCSE1 and reinforces the need for atypical presentations to prompt exploration of a broader differential diagnosis in the context of unexpected investigation findings. Reference Espinosa PS, Bensalem-Owen MK, Fee DB. Sporadic creutzfeldt–jakob disease presenting as nonconvulsive status epilepticus case report and review of the literature. Clinical Neurology and Neurosurgery 2010 July 1;112(6):537–40.

Published
2021
Full Text
View/download PDF

41. 077 Acute monoplegia

Author

Kristen Lefever, Laura Clarke, Daniel Schweitzer, Andrew Swayne, Cullen O’Gorman, Jared Eisemann, and Letitia Gore

Subjects
medicine.medical_specialty, Weakness, medicine.diagnostic_test, Pyomyositis, business.industry, Monoplegia, Physical examination, Neurosciences. Biological psychiatry. Neuropsychiatry, medicine.disease, Surgery, Infective endocarditis, medicine, Back pain, Flucloxacillin, medicine.symptom, Differential diagnosis, business, medicine.drug, RC321-571
Abstract

Objectives Pyomyositis is a purulent infection of skeletal muscle, most commonly resulting from haematogenous spread of Staphylococcus aureus infection in immunocompromised individuals1. Early recognition and management is important to prevent dissemination of infection and associated complications, including death. Methods Single case report. Results 63year old female represented to the emergency department with a three day history of a painful left arm, radiating from the neck. More recently, she had developed proximal left arm weakness and paraesthesia. She had suffered from a self-resolving diarrhoeal illness in the 48hours prior. Clinical examination confirmed a proximal left arm weakness of lower motor neuron pattern. Initial investigations demonstrated a normal creatinine kinase (CK) and white cell count, but elevated inflammatory markers. MRI cervical spine imaging excluded degenerative disease but raised suspicion of oedema within the left sided posterior cervical musculature. Subsequent blood cultures isolated methicillin sensitive Staphylococcus aureus. The patient developed lower back pain and fevers prompting further imaging, demonstrating multifocal epidural abscesses. There was no evidence of infective endocarditis. She received six weeks of intravenous flucloxacillin, followed by oral therapy, resulting in normalization of her inflammatory markers. Delayed repeat MRI imaging confirmed resolution of the epidural infection and improvement in left shoulder musculature oedema and hyperenhancement, which correlated with marked clinical improvement. Conclusion Pyomyositis is increasingly recognised in temperate climates and immunocompetent individuals. Pain is an early feature, with CK often remaining normal throughout the disease.1 2 Pyomyositis should be considered as a differential diagnosis in all patients with new onset painful weakness. References Crum. Bacterial pyomyositis in the United States. The American Journal of Medicine 2004;117:420–428. Bickels, Ben-Sira, Kessler, Wientroub. Primary pyomyositis. The Journal of Bone and Joint Surgery 2002;84:2277–2286.

Published
2021

42. The Christmas Story - In Rhyme!

Author

Laura Clarke and Laura Clarke

Abstract

Children will delight in this beautifully written retelling of the Christmas nativity story. Filled with stunning illustrations and written in engaging rhyming text, this book will become a cherished favourite, perfect for bedtime or sharing with others. Bringing the story of Jesus'birth to life, it's ideal for reading at churches, community gatherings, nursing homes, and Sunday school performances. From the divine visit of the angel Gabriel to Mary, to the birth of Jesus, the journey of the shepherds and the wise men, King Herod's fury upon discovering that the ‘King of the Jews'had been born, and the final exodus of Joseph, Mary, and Jesus to Egypt. This timeless story will captivate the imagination of any child.

Published
2024

44. Ensembl 2004.

Author

Ewan Birney, T. Daniel Andrews, Paul Bevan 0001, Mario Cáccamo, Graham Cameron, Yuan Chen 0007, Laura Clarke, Guy Coates, Tony Cox 0001, James A. Cuff, Val Curwen, Tim Cutts, Thomas A. Down, Richard Durbin, Eduardo Eyras, Xosé M. Fernández-Suárez, Paul J. Gane, B. Gibbins, James G. R. Gilbert, Martin Hammond, H. Hotz, Vivek Iyer, Andreas Kähäri, Kerstin Jekosch, Arek Kasprzyk, Damian Keefe, Stephen Keenan, Heikki Lehväslaiho, Graham P. McVicker, Craig Melsopp, Patrick Meidl, Emmanuel Mongin, Roger Pettett, Simon C. Potter, Glenn Proctor, Mark Rae, Stephen M. J. Searle, Guy Slater, Damian Smedley, James A. Smith, William Spooner, Arne Stabenau, Jim Stalker, R. Storey, Abel Ureta-Vidal, Cara Woodwark, Michele E. Clamp, and Tim J. P. Hubbard

Published
2004
Full Text
View/download PDF

45. Genetic perturbation of PU.1 binding and chromatin looping at neutrophil enhancers associates with autoimmune disease

Author

Hannes Ponstingl, Simone Ecker, Manuel Tardaguila, Samantha Farrow, Paul Flicek, Valentina Iotchkova, Ben Farr, Mattia Frontini, Lu Chen, Nicole Soranzo, Louella Vasquez, Peter Fraser, David J. Richardson, Alice L. Mann, Avik Datta, Daniel Mead, Heather Elding, Kate Downes, Klaudia Walter, Tomi Pastinen, Kousik Kundu, Biola-Maria Javierre, Mikhail Spivakov, Ying Sims, Stephen Watt, Frances Burden, Laura Clarke, Walter, Klaudia [0000-0003-4448-0301], Kundu, Kousik [0000-0002-1019-8351], Ecker, Simone [0000-0001-5648-1710], Iotchkova, Valentina [0000-0001-5057-0210], Mead, Daniel [0000-0001-7717-4330], Ponstingl, Hannes [0000-0001-7573-1703], Richardson, David [0000-0003-0247-9118], Flicek, Paul [0000-0002-3897-7955], Clarke, Laura [0000-0002-5989-6898], Fraser, Peter [0000-0002-0041-1227], Javierre, Biola-Maria [0000-0002-8682-6748], Spivakov, Mikhail [0000-0002-0383-3943], Soranzo, Nicole [0000-0003-1095-3852], and Apollo - University of Cambridge Repository

Subjects
0301 basic medicine, Male, Neutrophils, 45/43, General Physics and Astronomy, 631/250/262, 0302 clinical medicine, Transcriptional regulation, Promoter Regions, Genetic, Innate immunity, Multidisciplinary, article, 49/39, Middle Aged, Acquired immune system, Chromatin, Cell biology, Enhancer Elements, Genetic, Chromatin Immunoprecipitation Sequencing, Female, Adult, Science, Quantitative Trait Loci, Biology, Chromatin structure, General Biochemistry, Genetics and Molecular Biology, Autoimmune Diseases, 03 medical and health sciences, Young Adult, Immune system, Proto-Oncogene Proteins, 631/208/200, medicine, Humans, Enhancer, Gene, Aged, 45/91, Autoimmune disease, Innate immune system, General Chemistry, 631/337/100/101, medicine.disease, Gene regulation, 631/208/199, 030104 developmental biology, Gene Expression Regulation, Trans-Activators, Gene expression, 38/15, 030217 neurology & neurosurgery
Abstract

Funder: MS is funded by Medical Research Council (MC-A652-5QA20), Funder: This work was supported by the Wellcome Trust grant (206194) and EU FP7 High Impact Project BLUEPRINT (HEALTH-F5-2011-282510), Neutrophils play fundamental roles in innate immune response, shape adaptive immunity, and are a potentially causal cell type underpinning genetic associations with immune system traits and diseases. Here, we profile the binding of myeloid master regulator PU.1 in primary neutrophils across nearly a hundred volunteers. We show that variants associated with differential PU.1 binding underlie genetically-driven differences in cell count and susceptibility to autoimmune and inflammatory diseases. We integrate these results with other multi-individual genomic readouts, revealing coordinated effects of PU.1 binding variants on the local chromatin state, enhancer-promoter contacts and downstream gene expression, and providing a functional interpretation for 27 genes underlying immune traits. Collectively, these results demonstrate the functional role of PU.1 and its target enhancers in neutrophil transcriptional control and immune disease susceptibility.

Published
2021

46. Sustainable personal protective clothing for healthcare applications: a review

Author

Kate Lloyd, Shaila Afroj, Kostya S. Novoselov, Nazmul Karim, Andrew D. Farmery, Il-Doo Kim, Laura Clarke Oaten, Chris Carr, and Daria V. Andreeva

Subjects
single-use PPE, Coronavirus disease 2019 (COVID-19), Supply chain, media_common.quotation_subject, Health Personnel, General Physics and Astronomy, medical textiles, 02 engineering and technology, Review, 010402 general chemistry, 01 natural sciences, environmental impact, Health care, parasitic diseases, Disease Transmission, Infectious, Humans, Environmental impact assessment, Quality (business), General Materials Science, Personal protective equipment, Personal Protective Equipment, media_common, protective clothing, business.industry, Textiles, General Engineering, COVID-19, 021001 nanoscience & nanotechnology, Clothing, sustainability, antiviral, 0104 chemical sciences, Risk analysis (engineering), Sustainability, Practice Guidelines as Topic, PPE, antimicrobial, Business, 0210 nano-technology
Abstract

Personal protective equipment (PPE) is critical to protect healthcare workers (HCWs) from highly infectious diseases such as COVID-19. However, hospitals have been at risk of running out of the safe and effective PPE including personal protective clothing needed to treat patients with COVID-19, due to unprecedented global demand. In addition, there are only limited manufacturing facilities of such clothing available worldwide, due to a lack of available knowledge about relevant technologies, ineffective supply chains, and stringent regulatory requirements. Therefore, there remains a clear unmet need for coordinating the actions and efforts from scientists, engineers, manufacturers, suppliers, and regulatory bodies to develop and produce safe and effective protective clothing using the technologies that are locally available around the world. In this review, we discuss currently used PPE, their quality, and the associated regulatory standards. We survey the current state-of-the-art antimicrobial functional finishes on fabrics to protect the wearer against viruses and bacteria and provide an overview of protective medical fabric manufacturing techniques, their supply chains, and the environmental impacts of current single-use synthetic fiber-based protective clothing. Finally, we discuss future research directions, which include increasing efficiency, safety, and availability of personal protective clothing worldwide without conferring environmental problems.

Published
2021

47. Author response: Population-scale proteome variation in human induced pluripotent stem cells

Author

Helena Kilpinen, Rachel Denton, Francesco Paolo Casale, Ewan Birney, Laura Clarke, Christopher M. Kirton, Natalie Moens, Daniel D Seaton, Alex Alderton, Alejandro Brenes, Petr Danecek, Angus I. Lamond, Oliver Stegle, Dalila Bensaddek, Chukwuma A. Agu, Minal Patel, Angela Goncalves, Ian Streeter, Anja Kolb-Kokocinski, Peter W. Harrison, Marc Jan Bonder, Shane A. McCarthy, Philip L. Beales, Reena Halai, Bogdan Mirauta, Davide Denovi, Willem H. Ouwehand, Ruta Meleckyte, Sarah Harper, Andreas Leha, Richard Durbin, Fiona M. Watt, Yasin Memari, and Daniel J. Gaffney

Subjects
education.field_of_study, Variation (linguistics), Scale (ratio), Population, Proteome, Computational biology, Human Induced Pluripotent Stem Cells, Biology, education
Published
2020
Full Text
View/download PDF

48. Cell type-specific novel long non-coding RNA and circular RNA in the BLUEPRINT hematopoietic transcriptomes atlas

Author

Natasha Andressa Nogueira Jorge, Jonathan M. Mudge, Mattia Frontini, Myrto Kostadima, Osagie G. Izuogu, Enca Martin-Rendon, Hendrik G. Stunnenberg, Romina Petersen, Denis Seyres, Xavier Estivill, Paul Flicek, Luigi Grassi, Samantha Farrow, Fabio Passetti, John J. Lambourne, Willem H. Ouwehand, Neda Farahi, Frances Burden, Adam Frankish, Sophia Rowlston, Joost H.A. Martens, Marie-Laure Yaspo, Kate Downes, Mariona Bustamante, Laura Clarke, Ernest Turro, Fergal J. Martin, Ouwehand, Willem [0000-0002-7744-1790], and Apollo - University of Cambridge Repository

Subjects
Cell type, Cell, Sang -- Malalties, Computational biology, Biology, Article, Transcriptome, 03 medical and health sciences, 0302 clinical medicine, Circular RNA, medicine, Gene, Sequence Analysis, RNA, Gene Expression Profiling, RNA, High-Throughput Nucleotide Sequencing, Hematology, RNA, Circular, Long non-coding RNA, medicine.anatomical_structure, RNA, Long Noncoding, DNA microarray, Genètica, 030215 immunology
Abstract

Transcriptional profiling of hematopoietic cell subpopulations has helped to characterize the developmental stages of the hematopoietic system and the molecular bases of malignant and non-malignant blood diseases. Previously, only the genes targeted by expression microarrays could be profiled genome-wide. High-throughput RNA sequencing, however, encompasses a broader repertoire of RNA molecules, without restriction to previously annotated genes. We analyzed the BLUEPRINT consortium RNA-sequencing data for mature hematopoietic cell types. The data comprised 90 total RNA-sequencing samples, each composed of one of 27 cell types, and 32 small RNA-sequencing samples, each composed of one of 11 cell types. We estimated gene and isoform expression levels for each cell type using existing annotations from Ensembl. We then used guided transcriptome assembly to discover unannotated transcripts. We identified hundreds of novel non-coding RNA genes and showed that the majority have cell type-dependent expression. We also characterized the expression of circular RNA and found that these are also cell type-specific. These analyses refine the active transcriptional landscape of mature hematopoietic cells, highlight abundant genes and transcriptional isoforms for each blood cell type, and provide a valuable resource for researchers of hematologic development and diseases. Finally, we made the data accessible via a web-based interface: https://blueprint.haem.cam.ac.uk/bloodatlas/. The work was funded by a grant from the European Commission 7th Framework Program (FP7/2007–2013, grant 282510, BLUEPRINT) to XE, PF, JHAM, MY, HGS and WHO. WHO is an NIHR senior investigator and receives funding from Bristol-Myers Squibb, the British Heart Foundation, the Medical Research Council and the NIHR. OGI, FJM, AF, JMM, LC and PF are funded by the Wellcome Trust (WT108749/Z/15/Z) with additional funding for specific project components such as GENCODE from the National Human Genome Research Institute of the National Institutes of Health (2U41HG007234). FP is supported by the Fundação Carlos Chagas Filho de Amparo à Pesquisado Estado do Rio de Janeiro (FAPERJ; E-26/203.229/2016). NANJ is a recipient of a scholarship from the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES; Finance Code 001). MF is supported by the British Heart Foundation (FS/18/53/33863)

Published
2020
Full Text
View/download PDF

49. Vitamin D for the treatment of multiple sclerosis: a meta-analysis

Author

Laura Clarke, Elham Khalilidehkordi, Simon Broadley, Helmut Butzkueven, Bruce V. Taylor, and Laurie Mclaughlin

Subjects
0301 basic medicine, medicine.medical_specialty, Funnel plot, Multiple Sclerosis, Expanded Disability Status Scale, business.industry, Multiple sclerosis, medicine.disease, vitamin D deficiency, Clinical trial, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Neurology, Meta-analysis, Internal medicine, Inclusion and exclusion criteria, Vitamin D and neurology, Humans, Immunologic Factors, Medicine, Neurology (clinical), Vitamin D, business, 030217 neurology & neurosurgery
Abstract

There is an association between latitude, relative vitamin D deficiency and risk of multiple sclerosis (MS), and an association between vitamin D and disease progression. We have performed a meta-analysis with the aim of investigating the role of therapeutic vitamin D in MS. A systematic search of databases was performed to identify clinical trials assessing vitamin D in patients with relapsing–remitting MS. Studies were selected based on inclusion and exclusion criteria. Analysis was performed using RevMan 5.3 software. Twelve studies involving 950 patients were included in the final analysis. Studies were divided into four groups because of heterogeneity in study design. Studies were judged to be at low or unclear risk of bias, except in three studies, and this was confirmed by funnel plots. No statistically significant difference was seen for any of the outcome measures. There were non-significant trends in favour of vitamin D for all outcome measures, particularly when only placebo-controlled studies were included. Dose comparison studies showed a significant increase in annualised relapse rate (mean difference 0.15 [95%CI 0.01–0.30]) and non-significant trends of increased Expanded Disability Status Scale and gadolinium-enhancing lesions for the higher-dose arms. These findings suggest that vitamin D supplementation may have a therapeutic role in the treatment of MS. However, there is uncertainty with regard to the most appropriate dose, with high doses potentially being associated with worse outcomes. There remains the need for further well-performed randomised, dose-ranging, placebo-controlled trials of vitamin D in MS.

Published
2018
Full Text
View/download PDF

50. FAANG, establishing metadata standards, validation and best practices for the farmed and companion animal community

Author

Laura Clarke, David J. Richardson, Daniel R. Zerbino, Guy Cochrane, C. J. Schmidt, Peter W. Harrison, Alan Archibald, Jun Fan, and Paul Flicek

Subjects
0301 basic medicine, Livestock, metadata validation, media_common.quotation_subject, Best practice, Interoperability, community standards, Biology, genome to phenome, 03 medical and health sciences, Animal data, 0302 clinical medicine, Resource (project management), Genetics, Animals, Quality (business), Community standards, Data Curation, media_common, Metadata, FAIR principles, General Medicine, Articles, Genomics, Pets, functional annotation, Data science, farmed animals, Data sharing, 030104 developmental biology, Animal Science and Zoology, Original Article, 030217 neurology & neurosurgery, Software
Abstract

Summary The Functional Annotation of ANimal Genomes (FAANG) project aims, through a coordinated international effort, to provide high quality functional annotation of animal genomes with an initial focus on farmed and companion animals. A key goal of the initiative is to ensure high quality and rich supporting metadata to describe the project's animals, specimens, cell cultures and experimental assays. By defining rich sample and experimental metadata standards and promoting best practices in data descriptions, deposition and openness, FAANG champions higher quality and reusability of published datasets. FAANG has established a Data Coordination Centre, which sits at the heart of the Metadata and Data Sharing Committee. It continues to evolve the metadata standards, support submissions and, crucially, create powerful and accessible tools to support deposition and validation of metadata. FAANG conforms to the findable, accessible, interoperable, and reusable (FAIR) data principles, with high quality, open access and functionally interlinked data. In addition to data generated by FAANG members and specific FAANG projects, existing datasets that meet the main—or more permissive legacy—standards are incorporated into a central, focused, functional data resource portal for the entire farmed and companion animal community. Through clear and effective metadata standards, validation and conversion software, combined with promotion of best practices in metadata implementation, FAANG aims to maximise effectiveness and inter‐comparability of assay data. This supports the community to create a rich genome‐to‐phenotype resource and promotes continuing improvements in animal data standards as a whole.

Published
2018
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results