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396 results on '"Gunawardena, Harsha"'

3. Safety, tolerability, and efficacy of pirfenidone in patients with rheumatoid arthritis-associated interstitial lung disease: a randomised, double-blind, placebo-controlled, phase 2 study

Author

Haynes-Harp, Shana, Poli, Fernando, Vidya, Coimbatore Sree, Baron, Rebecca R., Clouser, Timothy, Doyle, Tracy, Maeda, Anthony, Highland, Kristin B., Albayda, Jemima F., Collins, Sarah E., Suresh, Karthik S., Davis, John M., Limper, Andrew H., Amigues, Isabel, Eliopoulos, Kristina, Swigris, Jeffery J., Humphries, Stephen, Huntwork, John C., Glynn, Chris, Duncan, Steve R., Danila, Maria I., Glassberg, Marilyn K., Oberstein, Elana M., Belloli, Elizabeth A., Briggs, Linda, Nagaraja, Vivek, Cholewa, Linda, DiFranco, Donna, Green, Edward, Liffick, Christie, Naik, Tanvi, Montas, Genevieve, Lebiedz-Odrobina, Dorota, Bissell, Reba, Wener, Mark, Lancaster, Lisa H., Crawford, Leslie J., Chan, Karmela, Kaner, Robert J., Morris, Alicia, Wu, Xiaoping, Khalidi, Nader A., Ryerson, Christopher J., Wong, Alyson W., Fell, Charlene D., LeClercq, Sharon A., Hyman, Mark, Shapera, Shane, Mittoo, Shikha, Shaffu, Shireen, Gaffney, Karl, Wilson, Andrew M., Barratt, Shaney, Gunawardena, Harsha, Hoyles, Rachel K., David, Joel, Kewalramani, Namrata, Maher, Toby M., Molyneaux, Philip L., Kokosi, Maria A., Cates, Matthew J., Mandizha, Mandizha, Ashish, Abdul, Chelliah, Gladstone, Parfrey, Helen, Thillai, Muhunthan, Vila, Josephine, Fletcher, Sophie V., Beirne, Paul, Favager, Clair, Brown, Jo, Dawson, Julie K., Ortega, Pilar Rivera, Haque, Sahena, Watson, Pippa, Khoo, Jun K., Symons, Karen, Youssef, Peter, Mackintosh, John A., Solomon, Joshua J, Danoff, Sonye K, Woodhead, Felix A, Hurwitz, Shelley, Maurer, Rie, Glaspole, Ian, Dellaripa, Paul F, Gooptu, Bibek, Vassallo, Robert, Cox, P Gerard, Flaherty, Kevin R, Adamali, Huzaifa I, Gibbons, Michael A, Troy, Lauren, Forrest, Ian A, Lasky, Joseph A, Spencer, Lisa G, Golden, Jeffrey, Scholand, Mary Beth, Chaudhuri, Nazia, Perrella, Mark A, Lynch, David A, Chambers, Daniel C, Kolb, Martin, Spino, Cathie, Raghu, Ganesh, Goldberg, Hilary J, and Rosas, Ivan O

Published
2023
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5. The Midpoint Mixed Model with a Missingness Mechanism (M5): A Likelihood-Based Framework for Quantification of Mass Spectrometry Proteomics Data (Preprint)

Author

O'Brien, Jonathon, Gunawardena, Harsha, Chen, Xian, Ibrahim, Joseph, and Qaqish, Bahjat

Subjects
Statistics - Applications
Abstract

Statistical models for proteomics data often estimate protein fold changes between two samples, A and B, as the average peptide intensity from sample A divided by the average peptide intensity from sample B. Such average intensity ratios fail to take full advantage of the experimental design which eliminates unseen confounding variables by processing peptides from both samples under identical conditions. Typically this structure is exploited through the estimation of a protein ratio as the median ratio of matched peptide intensities. This simple solution fails to account for a substantial missing data bias which has led to the development of more sophisticated average intensity models. Here we develop the first statistical model that accounts for nonignorable missingness while utilizing peptide level matched pairs across samples. Our simulation analysis shows that models which fail to utilize peptide level ratios, su.er astonishing losses to accuracy with basic ANOVA estimates having an average MSE 371% higher than median ratio estimates. In turn, median ratio estimates have an average MSE 35% higher than our model estimates. An analysis of breast cancer data reinforces these relationships and shows that our model is capable of increasing the number of proteins estimated by 22%.

Published
2015

8. The diagnosis and management of systemic autoimmune rheumatic disease-related interstitial lung disease: British Society for Rheumatology guideline scope.

Author

Hannah, Jennifer, Rodziewicz, Mia, Mehta, Puja, Heenan, Kerri-Marie, Ball, Elizabeth, Barratt, Shaney, Carty, Sara, Conway, Richard, Cotton, Caroline V, Cox, Sarah, Crawshaw, Anjali, Dawson, Julie, Desai, Sujal, Fahim, Ahmed, Fielding, Carol, Garton, Mark, George, Peter, Gunawardena, Harsha, Kelly, Clive, and Khan, Fasihul

Subjects
INTERSTITIAL lung diseases, RHEUMATISM, CONNECTIVE tissue diseases
Abstract

Interstitial lung disease (ILD) is a significant complication of many systemic autoimmune rheumatic diseases (SARDs), although the clinical presentation, severity and outlook may vary widely between individuals. Despite the prevalence, there are no specific guidelines addressing the issue of screening, diagnosis and management of ILD across this diverse group. Guidelines from the ACR and EULAR are expected, but there is a need for UK-specific guidelines that consider the framework of the UK National Health Service, local licensing and funding strategies. This article outlines the intended scope for the British Society for Rheumatology guideline on the diagnosis and management of SARD-ILD developed by the guideline working group. It specifically identifies the SARDs for consideration, alongside the overarching principles for which systematic review will be conducted. Expert consensus will be produced based on the most up-to-date available evidence for inclusion within the final guideline. Key issues to be addressed include recommendations for screening of ILD, identifying the methodology and frequency of monitoring and pharmacological and non-pharmacological management. The guideline will be developed according to methods and processes outlined in Creating Clinical Guidelines: British Society for Rheumatology Protocol version 5.1. [ABSTRACT FROM AUTHOR]

Published
2024
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11. A clinical and serological study of adult and juvenile idiopathic inflammatory myopathy

Author

Gunawardena, Harsha, Stevens, Clifford, and McHugh, Neil

Subjects
616.079, myositis, autoantibodies
Abstract

Introduction: The idiopathic inflammatory myopathies (IIM): dermatomyositis (DM) and polymyositis (PM) have been historically defined by broad clinical and pathological criteria. These conditions affect both adults and children with clinical features including muscle weakness, skin disease and internal organ involvement. Using a clinico-serological approach DM and PM can be defined into more homogeneous subsets. Myositis-specific autoantibodies (MSAs) are directed against cytoplasmic or nuclear components involved in key regulatory intra-cellular processes including protein synthesis, translocation and gene transcription. Over the last few years MSAs have been better characterised including autoantibodies directed against the aminoacyl tRNA-synthetase (ARS) enzymes, the signal recognition particle and the Mi-2 protein. Aim: The overall aim of this thesis is to describe a comprehensive clinical and serological study of adult and juvenile IIM. Autoantigen targets including novel specificities were identified using protein immunoprecipitation. Results: The first part of this thesis is a descriptive study on known myositis autoantibodies in adult IIM, confirming the significant association of interstitial pneumonia with anti-ARS, severe myopathy with anti-SRP, and classic DM with anti-Mi-2 serotype. In the next section, new autoantigen systems in adult IIM are described including a new anti-ARS (anti-Zo) in the anti-synthetase syndrome. Further autoantibodies directed against small ubiquitin-like modifier enzyme and a p155/140 autoantigen are major serological subsets in adult DM, the latter significantly associated with malignancy. The final section outlines a large serological study of juvenile DM (JDM) and JDM-overlap showing the frequency and clinical associations of MSAs and myositis-associated autoantibodies, including work on two new major subsets anti-p155/140 and anti-p140, which appear to define more severe disease. Conclusion: The work in this thesis highlights the importance of autoimmunity in IIM and suggests a new approach where MSAs can classify patients into clinical syndromes, which predict outcomes and may as a result influence treatment strategies.

Published
2010

12. Landscape of transcription in human cells

Author

Djebali, Sarah, Davis, Carrie A, Merkel, Angelika, Dobin, Alex, Lassmann, Timo, Mortazavi, Ali, Tanzer, Andrea, Lagarde, Julien, Lin, Wei, Schlesinger, Felix, Xue, Chenghai, Marinov, Georgi K, Khatun, Jainab, Williams, Brian A, Zaleski, Chris, Rozowsky, Joel, Röder, Maik, Kokocinski, Felix, Abdelhamid, Rehab F, Alioto, Tyler, Antoshechkin, Igor, Baer, Michael T, Bar, Nadav S, Batut, Philippe, Bell, Kimberly, Bell, Ian, Chakrabortty, Sudipto, Chen, Xian, Chrast, Jacqueline, Curado, Joao, Derrien, Thomas, Drenkow, Jorg, Dumais, Erica, Dumais, Jacqueline, Duttagupta, Radha, Falconnet, Emilie, Fastuca, Meagan, Fejes-Toth, Kata, Ferreira, Pedro, Foissac, Sylvain, Fullwood, Melissa J, Gao, Hui, Gonzalez, David, Gordon, Assaf, Gunawardena, Harsha, Howald, Cedric, Jha, Sonali, Johnson, Rory, Kapranov, Philipp, King, Brandon, Kingswood, Colin, Luo, Oscar J, Park, Eddie, Persaud, Kimberly, Preall, Jonathan B, Ribeca, Paolo, Risk, Brian, Robyr, Daniel, Sammeth, Michael, Schaffer, Lorian, See, Lei-Hoon, Shahab, Atif, Skancke, Jorgen, Suzuki, Ana Maria, Takahashi, Hazuki, Tilgner, Hagen, Trout, Diane, Walters, Nathalie, Wang, Huaien, Wrobel, John, Yu, Yanbao, Ruan, Xiaoan, Hayashizaki, Yoshihide, Harrow, Jennifer, Gerstein, Mark, Hubbard, Tim, Reymond, Alexandre, Antonarakis, Stylianos E, Hannon, Gregory, Giddings, Morgan C, Ruan, Yijun, Wold, Barbara, Carninci, Piero, Guigó, Roderic, and Gingeras, Thomas R

Subjects
Genetics, Human Genome, Underpinning research, 1.1 Normal biological development and functioning, Generic health relevance, Alleles, Cell Line, DNA, DNA, Intergenic, Encyclopedias as Topic, Enhancer Elements, Genetic, Exons, Gene Expression Profiling, Genes, Genome, Human, Genomics, Humans, Molecular Sequence Annotation, Polyadenylation, Protein Isoforms, RNA, RNA Editing, RNA Splicing, Regulatory Sequences, Nucleic Acid, Repetitive Sequences, Nucleic Acid, Sequence Analysis, RNA, Transcription, Genetic, Transcriptome, General Science & Technology
Abstract

Eukaryotic cells make many types of primary and processed RNAs that are found either in specific subcellular compartments or throughout the cells. A complete catalogue of these RNAs is not yet available and their characteristic subcellular localizations are also poorly understood. Because RNA represents the direct output of the genetic information encoded by genomes and a significant proportion of a cell's regulatory capabilities are focused on its synthesis, processing, transport, modification and translation, the generation of such a catalogue is crucial for understanding genome function. Here we report evidence that three-quarters of the human genome is capable of being transcribed, as well as observations about the range and levels of expression, localization, processing fates, regulatory regions and modifications of almost all currently annotated and thousands of previously unannotated RNAs. These observations, taken together, prompt a redefinition of the concept of a gene.

Published
2012

14. “Lab of the Future”─Today: Fully Automated System for High-Throughput Mass Spectrometry Analysis of Biotherapeutics

Author

Waldenmaier, Hans E., primary, Gorre, Elsa, additional, Poltash, Michael L., additional, Gunawardena, Harsha P., additional, Zhai, Xianglin Alex, additional, Li, Jing, additional, Zhai, Bo, additional, Beil, Eric J., additional, Terzo, Joseph C., additional, Lawler, Rose, additional, English, A. Michelle, additional, Bern, Marshall, additional, Mahan, Andrew D., additional, Carlson, Eric, additional, and Nanda, Hirsh, additional

Published
2023
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15. “Stapling” scFv for multispecific biotherapeutics of superior properties

Author

Boucher, Lauren E., primary, Prinslow, Elisabeth Geyer, additional, Feldkamp, Michael, additional, Yi, Fang, additional, Nanjunda, Rupesh, additional, Wu, Sheng-Jiun, additional, Liu, Tun, additional, Lacy, Eilyn R., additional, Jacobs, Steven, additional, Kozlyuk, Natalia, additional, Del Rosario, Brian, additional, Wu, Bingyuan, additional, Aquino, Patricia, additional, Davidson, Robert C., additional, Heyne, Samantha, additional, Mazzanti, Nicholas, additional, Testa, James, additional, Diem, Michael D., additional, Gorre, Elsa, additional, Mahan, Andrew, additional, Nanda, Hirsh, additional, Gunawardena, Harsha P., additional, Gervais, Alexis, additional, Armstrong, Anthony A., additional, Teplyakov, Alexey, additional, Huang, Chichi, additional, Zwolak, Adam, additional, Chowdhury, Partha, additional, Cheung, Wan Cheung, additional, and Luo, Jinquan, additional

Published
2023
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16. A Phase II randomised controlled trial of oral prednisolone in early diffuse cutaneous systemic sclerosis (PRedSS)

Author

Griffiths-Jones, Deborah J, Garcia, Yvonne Sylvestre, Ryder, W David, Pauling, John D, Hall, Frances, Lanyon, Peter, Bhat, Smita, Douglas, Karen, Gunawardena, Harsha, Akil, Mohammed, Anderson, Marina, Griffiths, Bridget, Del Galdo, Francesco, Youssef, Hazem, Madhok, Rajan, Arthurs, Barbara, Buch, Maya, Fligelstone, Kim, Zubair, Mohammed, Mason, Justin C, Denton, Christopher P, Herrick, Ariane L, Griffiths-Jones, Deborah J, Garcia, Yvonne Sylvestre, Ryder, W David, Pauling, John D, Hall, Frances, Lanyon, Peter, Bhat, Smita, Douglas, Karen, Gunawardena, Harsha, Akil, Mohammed, Anderson, Marina, Griffiths, Bridget, Del Galdo, Francesco, Youssef, Hazem, Madhok, Rajan, Arthurs, Barbara, Buch, Maya, Fligelstone, Kim, Zubair, Mohammed, Mason, Justin C, Denton, Christopher P, and Herrick, Ariane L

Abstract

Objectives Although the painful and disabling features of early diffuse cutaneous systemic sclerosis (dcSSc) have an inflammatory basis and could respond to corticosteroids, corticosteroids are a risk factor for scleroderma renal crisis. Whether or not they should be prescribed is therefore highly contentious. Our aim was to examine safety and efficacy of moderate dose prednisolone in early dcSSc. Methods PRedSS set out as a Phase II, multicentre, double-blind randomised controlled trial, converted to open-label during the Covid-19 pandemic. Patients were randomised to receive either prednisolone (∼0.3 mg/kg) or matching placebo (or no treatment during open-label) for 6 months. Co-primary endpoints were the Health Assessment Questionnaire Disability Index (HAQ-DI) and modified Rodnan skin core (mRSS) at 3 months. Over 20 secondary endpoints included patient reported outcome measures reflecting pain, itch, fatigue, anxiety and depression, and helplessness. Target recruitment was 72 patients. Results Thirty-five patients were randomised (17 prednisolone, 18 placebo/control). The adjusted mean difference between treatment groups at 3 months in HAQ-DI score was -0.10 (97.5% CI -0.29–0.10), p= 0.254, and in mRSS -3.90 (97.5% CI -8.83–1.03), p= 0.070, both favouring prednisolone but not significantly. Patients in the prednisolone group experienced significantly less pain (p= 0.027), anxiety (p= 0.018) and helplessness (p= 0.040) than control patients at 3 months. There were no renal crises, but sample size was small. Conclusion PRedSS was terminated early primarily due to the Covid-19 pandemic, and so was underpowered. Therefore, interpretation must be cautious and results considered inconclusive, indicating the need for a further randomised trial. Trial registration ClinicalTrials.gov, https://clinicaltrials.gov, NCT03708718

Published
2023

18. A Phase II randomized controlled trial of oral prednisolone in early diffuse cutaneous systemic sclerosis (PRedSS)

Author

Griffiths-Jones, Deborah J, primary, Garcia, Yvonne Sylvestre, additional, Ryder, W David, additional, Pauling, John D, additional, Hall, Frances, additional, Lanyon, Peter, additional, Bhat, Smita, additional, Douglas, Karen, additional, Gunawardena, Harsha, additional, Akil, Mohammed, additional, Anderson, Marina, additional, Griffiths, Bridget, additional, Del Galdo, Francesco, additional, Youssef, Hazem, additional, Madhok, Rajan, additional, Arthurs, Barbara, additional, Buch, Maya, additional, Fligelstone, Kim, additional, Zubair, Mohammed, additional, Mason, Justin C, additional, Denton, Christopher P, additional, and Herrick, Ariane L, additional

Published
2023
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19. Safety, tolerability, and efficacy of pirfenidone in patients with rheumatoid arthritis-associated interstitial lung disease: a randomised, double-blind, placebo-controlled, phase 2 study

Author

Solomon, Joshua J, primary, Danoff, Sonye K, additional, Woodhead, Felix A, additional, Hurwitz, Shelley, additional, Maurer, Rie, additional, Glaspole, Ian, additional, Dellaripa, Paul F, additional, Gooptu, Bibek, additional, Vassallo, Robert, additional, Cox, P Gerard, additional, Flaherty, Kevin R, additional, Adamali, Huzaifa I, additional, Gibbons, Michael A, additional, Troy, Lauren, additional, Forrest, Ian A, additional, Lasky, Joseph A, additional, Spencer, Lisa G, additional, Golden, Jeffrey, additional, Scholand, Mary Beth, additional, Chaudhuri, Nazia, additional, Perrella, Mark A, additional, Lynch, David A, additional, Chambers, Daniel C, additional, Kolb, Martin, additional, Spino, Cathie, additional, Raghu, Ganesh, additional, Goldberg, Hilary J, additional, Rosas, Ivan O, additional, Haynes-Harp, Shana, additional, Poli, Fernando, additional, Vidya, Coimbatore Sree, additional, Baron, Rebecca R., additional, Clouser, Timothy, additional, Doyle, Tracy, additional, Maeda, Anthony, additional, Highland, Kristin B., additional, Albayda, Jemima F., additional, Collins, Sarah E., additional, Suresh, Karthik S., additional, Davis, John M., additional, Limper, Andrew H., additional, Amigues, Isabel, additional, Eliopoulos, Kristina, additional, Swigris, Jeffery J., additional, Humphries, Stephen, additional, Huntwork, John C., additional, Glynn, Chris, additional, Duncan, Steve R., additional, Danila, Maria I., additional, Glassberg, Marilyn K., additional, Oberstein, Elana M., additional, Belloli, Elizabeth A., additional, Briggs, Linda, additional, Nagaraja, Vivek, additional, Cholewa, Linda, additional, DiFranco, Donna, additional, Green, Edward, additional, Liffick, Christie, additional, Naik, Tanvi, additional, Montas, Genevieve, additional, Lebiedz-Odrobina, Dorota, additional, Bissell, Reba, additional, Wener, Mark, additional, Lancaster, Lisa H., additional, Crawford, Leslie J., additional, Chan, Karmela, additional, Kaner, Robert J., additional, Morris, Alicia, additional, Wu, Xiaoping, additional, Khalidi, Nader A., additional, Ryerson, Christopher J., additional, Wong, Alyson W., additional, Fell, Charlene D., additional, LeClercq, Sharon A., additional, Hyman, Mark, additional, Shapera, Shane, additional, Mittoo, Shikha, additional, Shaffu, Shireen, additional, Gaffney, Karl, additional, Wilson, Andrew M., additional, Barratt, Shaney, additional, Gunawardena, Harsha, additional, Hoyles, Rachel K., additional, David, Joel, additional, Kewalramani, Namrata, additional, Maher, Toby M., additional, Molyneaux, Philip L., additional, Kokosi, Maria A., additional, Cates, Matthew J., additional, Mandizha, Mandizha, additional, Ashish, Abdul, additional, Chelliah, Gladstone, additional, Parfrey, Helen, additional, Thillai, Muhunthan, additional, Vila, Josephine, additional, Fletcher, Sophie V., additional, Beirne, Paul, additional, Favager, Clair, additional, Brown, Jo, additional, Dawson, Julie K., additional, Ortega, Pilar Rivera, additional, Haque, Sahena, additional, Watson, Pippa, additional, Khoo, Jun K., additional, Symons, Karen, additional, Youssef, Peter, additional, and Mackintosh, John A., additional

Published
2023
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24. The EuroMyositis registry: an international collaborative tool to facilitate myositis research

Author

Lilleker, James B, Vencovsky, Jiri, Wang, Guochun, Wedderburn, Lucy R, Diederichsen, Louise Pyndt, Schmidt, Jens, Oakley, Paula, Benveniste, Olivier, Danieli, Maria Giovanna, Danko, Katalin, Thuy, Nguyen Thi Phuong, Vazquez-Del Mercado, Monica, Andersson, Helena, De Paepe, Boel, deBleecker, Jan L, Maurer, Britta, McCann, Liza J, Pipitone, Nicolo, McHugh, Neil, Betteridge, Zoe E, New, Paul, Cooper, Robert G, Ollier, William E, Lamb, Janine A, Krogh, Niels Steen, Lundberg, Ingrid E, Chinoy, Hector, D’hose, Sophie, Tian, Xin Lu,xiaolan, Mann, Herman, Kryštufková, Olga, Pleštilová, Lenka, Barochová,katerina kubínová, Martin Klein,tereza, Gelardi, Chiara, Pedini, Veronica, Cardinaletti, Paolo, Jara, Luis J, Saavedra, Miguel A, Cruz-reyes, Claudia V, Vera-lastra, Olga, Andrade-ortega, Lilia, Medrano-ramírez, Gabriel, Satoh, Minoru, Salazar-páramo, Mario, Gomez-bañuelos, Eduardo, Aguilar-arreola, Jorge, Durán-barragán, Sergio, Navarro-hernandez, Rosa Elena, Petri, Marcelo H, Molberg, Øyvind, Dastmalchi, Maryam, Notarnicola, Antonella, Gheorghe, Karina, Rönnelid, Johan, Liden, Maria, Hanna, Balsam, Jalal, Awat, Hellström, Helena, Martineus, Jehns Christian, Ngoc lan, Nguyen Thi, Padyukov, Leonid, New, Paul, Platt, Hazel, Rothwell, Simon, Ahmed, Yasmeen, Armstrong, Raymond, Bernstein, Robert, Black, Carol, Bowman, Simon, Bruce, Ian, Butler, Robin, Carty, John, Chattopadhyay, Chandra, Chelliah, Easwaradhas, Clarke, Fiona, Dawes, Peter, Denton, Christopher, Devlin, Joseph, Edwards, Christopher, Emery, Paul, Fordham, John, Fraser, Alexander, Gaston, Hill, Gordon, Patrick, Griffiths, Bridget, Gunawardena, Harsha, Hall, Frances, Hanna, Michael, Harrison, Beverley, Hay, Elaine, Hilton-jones, David, Horden, Lesley, Isaacs, John, Isenberg, David, Jones, Adrian, Kamath, Sanjeet, Kennedy, Thomas, Kitas, George, Klimiuk, Peter, Knights, Sally, Lambert, John, Lanyon, Peter, Laxminarayan, Ramasharan, Lecky, Bryan, Luqmani, Raashid, Machado, Pedro, Marks, Jeffrey, Martin, Michael, Mcgonagle, Dennis, Mchugh, Neil, Mckenna, Francis, Mclaren, John, Mcmahon, Michael, Mcrorie, Euan, Merry, Peter, Miles, Sarah, Miller, James, Nicholls, Anne, Nixon, Jennifer, Ong, Voon, Over, Katherine, Packham, John, Pipitone, Nicolo, Plant, Michael, Pountain, Gillian, Pullar, Thomas, Roberts, Mark, Sanders, Paul, Scott, David, Scott, David, Shadforth, Michael, Sheeran, Thomas, Srinivasan, Arul, Swinson, David, Teh, Lee-suan, Webley, Michael, Williams, Brian, and Winer, Jonathan

Published
2018
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31. P293 Tocilizumab for refractory or relapsing giant cell arteritis: audit data from the Bristol and Bath regional multidisciplinary meetings 2018-2021

Author

Jayatilleke, Chandrin, primary, Janagan, Shalini, additional, Marshall, Robert, additional, Skeoch, Sarah, additional, Guly, Catherine M, additional, Sin, Fang En, additional, Sweedan, Laith AL, additional, Anilkumar, Aishwarya, additional, Austin, Keziah, additional, Bourn, Alexandra, additional, Clarke, Lynsey, additional, Gunawardena, Harsha, additional, Johnson, Ah, additional, Knights, Sally, additional, Pauling, John D, additional, Reilly, Elizabeth, additional, Reynolds, Timothy D, additional, Villar, Sarah, additional, and Robson, Joanna C, additional

Published
2022
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33. Correction: Corrigendum: Proteogenomic integration reveals therapeutic targets in breast cancer xenografts

Author

Huang, Kuan-lin, Li, Shunqiang, Mertins, Philipp, Cao, Song, Gunawardena, Harsha P., Ruggles, Kelly V., Mani, D. R., Clauser, Karl R., Tanioka, Maki, Usary, Jerry, Kavuri, Shyam M., Xie, Ling, Yoon, Christopher, Qiao, Jana W., Wrobel, John, Wyczalkowski, Matthew A., Erdmann-Gilmore, Petra, Snider, Jacqueline E., Hoog, Jeremy, Singh, Purba, Niu, Beifang, Guo, Zhanfang, Sun, Sam Qiancheng, Sanati, Souzan, Kawaler, Emily, Wang, Xuya, Scott, Adam, Ye, Kai, McLellan, Michael D., Wendl, Michael C., Malovannaya, Anna, Held, Jason M., Gillette, Michael A., Fenyö, David, Kinsinger, Christopher R., Mesri, Mehdi, Rodriguez, Henry, Davies, Sherri R., Perou, Charles M., Ma, Cynthia, Townsend, R. Reid, Chen, Xian, Carr, Steven A., Ellis, Matthew J., and Ding, Li

Published
2017
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34. Rheumatologists have an important role in the management of interstitial lung disease (ILD): a cross-speciality, multi-centre, UK perspective

Author

Mehta, Puja, primary, Hoyles, Rachel K, additional, Gunawardena, Harsha, additional, Gooptu, Bibek, additional, Chaudhuri, Nazia, additional, Heightmann, Melissa J, additional, Garthwaite, Helen, additional, Penn, Henry, additional, Datta, Arnab, additional, Hamdulay, Shahir, additional, Lams, Boris, additional, Agarwal, Sangita, additional, Wickremesinghe, Melissa, additional, Jenkins, Gisli, additional, Porter, Joanna C, additional, and Denton, Christopher P, additional

Published
2022
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39. An integrated encyclopedia of DNA elements in the human genome

Author

Dunham, Ian, Kundaje, Anshul, Aldred, Shelley F., Collins, Patrick J., Davis, Carrie A., Doyle, Francis, Epstein, Charles B., Frietze, Seth, Harrow, Jennifer, Kaul, Rajinder, Khatun, Jainab, Lajoie, Bryan R., Landt, Stephen G., Lee, Bum-Kyu, Pauli, Florencia, Rosenbloom, Kate R., Sabo, Peter, Safi, Alexias, Sanyal, Amartya, Shoresh, Noam, Simon, Jeremy M., Song, Lingyun, Trinklein, Nathan D., Altshuler, Robert C., Birney, Ewan, Brown, James B., Cheng, Chao, Djebali, Sarah, Dong, Xianjun, Ernst, Jason, Furey, Terrence S., Gerstein, Mark, Giardine, Belinda, Greven, Melissa, Hardison, Ross C., Harris, Robert S., Herrero, Javier, Hoffman, Michael M., Iyer, Sowmya, Kellis, Manolis, Kheradpour, Pouya, Lassmann, Timo, Li, Qunhua, Lin, Xinying, Marinov, Georgi K., Merkel, Angelika, Mortazavi, Ali, Parker, Stephen C. J., Reddy, Timothy E., Rozowsky, Joel, Schlesinger, Felix, Thurman, Robert E., Wang, Jie, Ward, Lucas D., Whitfield, Troy W., Wilder, Steven P., Wu, Weisheng, Xi, Hualin S., Yip, Kevin Y., Zhuang, Jiali, Bernstein, Bradley E., Green, Eric D., Gunter, Chris, Snyder, Michael, Pazin, Michael J., Lowdon, Rebecca F., Dillon, Laura A. L., Adams, Leslie B., Kelly, Caroline J., Zhang, Julia, Wexler, Judith R., Good, Peter J., Feingold, Elise A., Crawford, Gregory E., Dekker, Job, Elnitski, Laura, Farnham, Peggy J., Giddings, Morgan C., Gingeras, Thomas R., Guigo, Roderic, Hubbard, Timothy J., Kent, W. James, Lieb, Jason D., Margulies, Elliott H., Myers, Richard M., Stamatoyannopoulos, John A., Tenenbaum, Scott A., Weng, Zhiping, White, Kevin P., Wold, Barbara, Yu, Yanbao, Wrobel, John, Risk, Brian A., Gunawardena, Harsha P., Kuiper, Heather C., Maier, Christopher W., Xie, Ling, Chen, Xian, Mikkelsen, Tarjei S., Gillespie, Shawn, Goren, Alon, Ram, Oren, Zhang, Xiaolan, Wang, Li, Issner, Robbyn, Coyne, Michael J., Durham, Timothy, Ku, Manching, Truong, Thanh, Eaton, Matthew L., Dobin, Alex, Tanzer, Andrea, Lagarde, Julien, Lin, Wei, Xue, Chenghai, Williams, Brian A., Zaleski, Chris, Roder, Maik, Kokocinski, Felix, Abdelhamid, Rehab F., Alioto, Tyler, Antoshechkin, Igor, Baer, Michael T., Batut, Philippe, Bell, Ian, Bell, Kimberly, Chakrabortty, Sudipto, Chrast, Jacqueline, Curado, Joao, Derrien, Thomas, Drenkow, Jorg, Dumais, Erica, Dumais, Jackie, Duttagupta, Radha, Fastuca, Megan, Fejes-Toth, Kata, Ferreira, Pedro, Foissac, Sylvain, Fullwood, Melissa J., Gao, Hui, Gonzalez, David, Gordon, Assaf, Howald, Cedric, Jha, Sonali, Johnson, Rory, Kapranov, Philipp, King, Brandon, Kingswood, Colin, Li, Guoliang, Luo, Oscar J., Park, Eddie, Preall, Jonathan B., Presaud, Kimberly, Ribeca, Paolo, Robyr, Daniel, Ruan, Xiaoan, Sammeth, Michael, Sandhu, Kuljeet Singh, Schaeffer, Lorain, See, Lei-Hoon, Shahab, Atif, Skancke, Jorgen, Suzuki, Ana Maria, Takahashi, Hazuki, Tilgner, Hagen, Trout, Diane, Walters, Nathalie, Wang, Huaien, Hayashizaki, Yoshihide, Reymond, Alexandre, Antonarakis, Stylianos E., Hannon, Gregory J., Ruan, Yijun, Carninci, Piero, Sloan, Cricket A., Learned, Katrina, Malladi, Venkat S., Wong, Matthew C., Barber, Galt P., Cline, Melissa S., Dreszer, Timothy R., Heitner, Steven G., Karolchik, Donna, Kirkup, Vanessa M., Meyer, Laurence R., Long, Jeffrey C., Maddren, Morgan, Raney, Brian J., Grasfeder, Linda L., Giresi, Paul G., Battenhouse, Anna, Sheffield, Nathan C., Showers, Kimberly A., London, Darin, Bhinge, Akshay A., Shestak, Christopher, Schaner, Matthew R., Ki Kim, Seul, Zhang, Zhuzhu Z., Mieczkowski, Piotr A., Mieczkowska, Joanna O., Liu, Zheng, McDaniell, Ryan M., Ni, Yunyun, Rashid, Naim U., Kim, Min Jae, Adar, Sheera, Zhang, Zhancheng, Wang, Tianyuan, Winter, Deborah, Keefe, Damian, Iyer, Vishwanath R., Zheng, Meizhen, Wang, Ping, Gertz, Jason, Vielmetter, Jost, Partridge, E., Varley, Katherine E., Gasper, Clarke, Bansal, Anita, Pepke, Shirley, Jain, Preti, Amrhein, Henry, Bowling, Kevin M., Anaya, Michael, Cross, Marie K., Muratet, Michael A., Newberry, Kimberly M., McCue, Kenneth, Nesmith, Amy S., Fisher-Aylor, Katherine I., Pusey, Barbara, DeSalvo, Gilberto, Parker, Stephanie L., Balasubramanian, Sreeram, Davis, Nicholas S., Meadows, Sarah K., Eggleston, Tracy, Newberry, J. Scott, Levy, Shawn E., Absher, Devin M., Wong, Wing H., Blow, Matthew J., Visel, Axel, Pennachio, Len A., Petrykowska, Hanna M., Abyzov, Alexej, Aken, Bronwen, Barrell, Daniel, Barson, Gemma, Berry, Andrew, Bignell, Alexandra, Boychenko, Veronika, Bussotti, Giovanni, Davidson, Claire, Despacio-Reyes, Gloria, Diekhans, Mark, Ezkurdia, Iakes, Frankish, Adam, Gilbert, James, Gonzalez, Jose Manuel, Griffiths, Ed, Harte, Rachel, Hendrix, David A., Hunt, Toby, Jungreis, Irwin, Kay, Mike, Khurana, Ekta, Leng, Jing, Lin, Michael F., Loveland, Jane, Lu, Zhi, Manthravadi, Deepa, Mariotti, Marco, Mudge, Jonathan, Mukherjee, Gaurab, Notredame, Cedric, Pei, Baikang, Rodriguez, Jose Manuel, Saunders, Gary, Sboner, Andrea, Searle, Stephen, Sisu, Cristina, Snow, Catherine, Steward, Charlie, Tapanari, Electra, Tress, Michael L., van Baren, Marijke J., Washietl, Stefan, Wilming, Laurens, Zadissa, Amonida, Zhang, Zhengdong, Brent, Michael, Haussler, David, Valencia, Alfonso, Addleman, Nick, Alexander, Roger P., Auerbach, Raymond K., Balasubramanian, Suganthi, Bettinger, Keith, Bhardwaj, Nitin, Boyle, Alan P., Cao, Alina R., Cayting, Philip, Charos, Alexandra, Cheng, Yong, Eastman, Catharine, Euskirchen, Ghia, Fleming, Joseph D., Grubert, Fabian, Habegger, Lukas, Hariharan, Manoj, Harmanci, Arif, Iyengar, Sushma, Jin, Victor X., Karczewski, Konrad J., Kasowski, Maya, Lacroute, Phil, Lam, Hugo, Lamarre-Vincent, Nathan, Lian, Jin, Lindahl-Allen, Marianne, Min, Renqiang, Miotto, Benoit, Monahan, Hannah, Moqtaderi, Zarmik, Mu, Xinmeng J., Ouyang, Zhengqing, Patacsil, Dorrelyn, Raha, Debasish, Ramirez, Lucia, Reed, Brian, Shi, Minyi, Slifer, Teri, Witt, Heather, Wu, Linfeng, Xu, Xiaoqin, Yan, Koon-Kiu, Yang, Xinqiong, Struhl, Kevin, Weissman, Sherman M., Penalva, Luiz O., Karmakar, Subhradip, Bhanvadia, Raj R., Choudhury, Alina, Domanus, Marc, Ma, Lijia, Moran, Jennifer, Victorsen, Alec, Auer, Thomas, Centanin, Lazaro, Eichenlaub, Michael, Gruhl, Franziska, Heermann, Stephan, Hoeckendorf, Burkhard, Inoue, Daigo, Kellner, Tanja, Kirchmaier, Stephan, Mueller, Claudia, Reinhardt, Robert, Schertel, Lea, Schneider, Stephanie, Sinn, Rebecca, Wittbrodt, Beate, Wittbrodt, Jochen, Partridge, E. Christopher, Jain, Gaurav, Balasundaram, Gayathri, Bates, Daniel L., Byron, Rachel, Canfield, Theresa K., Diegel, Morgan J., Dunn, Douglas, Ebersol, Abigail K., Frum, Tristan, Garg, Kavita, Gist, Erica, Hansen, R. Scott, Boatman, Lisa, Haugen, Eric, Humbert, Richard, Johnson, Audra K., Johnson, Ericka M., Kutyavin, Tattyana V., Lee, Kristen, Lotakis, Dimitra, Maurano, Matthew T., Neph, Shane J., Neri, Fiedencio V., Nguyen, Eric D., Qu, Hongzhu, Reynolds, Alex P., Roach, Vaughn, Rynes, Eric, Sanchez, Minerva E., Sandstrom, Richard S., Shafer, Anthony O., Stergachis, Andrew B., Thomas, Sean, Vernot, Benjamin, Vierstra, Jeff, Vong, Shinny, Weaver, Molly A., Yan, Yongqi, Zhang, Miaohua, Akey, Joshua M., Bender, Michael, Dorschner, Michael O., Groudine, Mark, MacCoss, Michael J., Navas, Patrick, Stamatoyannopoulos, George, Beal, Kathryn, Brazma, Alvis, Flicek, Paul, Johnson, Nathan, Lukk, Margus, Luscombe, Nicholas M., Sobral, Daniel, Vaquerizas, Juan M., Batzoglou, Serafim, Sidow, Arend, Hussami, Nadine, Kyriazopoulou-Panagiotopoulou, Sofia, Libbrecht, Max W., Schaub, Marc A., Miller, Webb, Bickel, Peter J., Banfai, Balazs, Boley, Nathan P., Huang, Haiyan, Li, Jingyi Jessica, Noble, William Stafford, Bilmes, Jeffrey A., Buske, Orion J., Sahu, Avinash D., Kharchenko, Peter V., Park, Peter J., Baker, Dannon, Taylor, James, and Lochovsky, Lucas

Subjects
Genetic research, Human genome -- Research, Genetic transcription -- Research, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

The human genome encodes the blueprint of life, but the function of the vast majority of its nearly three billion bases is unknown. The Encyclopedia of DNA Elements (ENCODE) project has systematically mapped regions of transcription, transcription factor association, chromatin structure and histone modification. These data enabled us to assign biochemical functions for 80% of the genome, in particular outside of the well-studied protein-coding regions. Many discovered candidate regulatory elements are physically associated with one another and with expressed genes, providing new insights into the mechanisms of gene regulation. The newly identified elements also show a statistical correspondence to sequence variants linked to human disease, and can thereby guide interpretation of this variation. Overall, the project provides new insights into the organization and regulation of our genes and genome, and is an expansive resource of functional annotations for biomedical research., Author(s): The ENCODE Project Consortium; Overall coordination (data analysis coordination); Ian Dunham [2]; Anshul Kundaje [3, 82]; Data production leads (data production); Shelley F. Aldred [4]; Patrick J. Collins [4]; [...]

Published
2012
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42. Denovo Identification of Cross-linked Peptides via Isotope Coded Linkage Tags

Author

Gunawardena, Harsha P.

Subjects
chemistry.chemical_classification, Isotope, chemistry, Stereochemistry, Stable isotope ratio, Tryptic peptide, Database search engine, Peptide, Mass spectrometry, Cleavage (embryo), Peptide sequence
Abstract

An isotope labeled cross-linker (asymmetric d4-DTSSP) was developed to streamline the efforts required for the detection of cross-linked peptides. The cross-linking and mass spectrometry strategy we call Isotope Tagging of Interacting Proteins (iTIP) has improved the specificity of detecting cross-linked peptides and the accurate identification of the interacting peptide sequences via the incorporation of isotopic signatures that are readily observed in the MS/MS spectra. All tryptic peptides derived from the cross-linking reactions of a protein complex are first subjected to ETD-MS2 which results in the facile cleavage of the cross-linker at the disulfide bond and the release of inter-linked polypeptide chains that are detected as a pair of peaks (doublets) in the MS2 spectrum. The constituent peptide halves that are tagged by the heavy/light ends of the cross-linker are easily mass-selected from all other fragment ions, and each polypeptide half is then subjected to CID or HCD-MS3 for identification. The MS3 spectra are subjected to conventional database search strategies available for the sequencing of linear or non-cross-linked peptides. The confident identification of each polypeptide is further assisted by the presence of a stable isotope labeled fragment ions that localizes the cross-linked site on the polypeptide sequence.

Published
2020

44. Phosphopeptide anion characterization via sequential charge inversion and electron-transfer dissociation

Author

Gunawardena, Harsha P., Emory, Joshua F., and McLuckey, Scott A.

Subjects
Electron transport -- Research, Anions -- Properties, Dissociation -- Analysis, Peptides -- Structure, Peptides -- Chemical properties, Peptides -- Properties, Chemistry
Abstract

Sequential ion/ion reactions have been used to characterize phosphopeptides present in relatively simple peptide mixtures, including one generated from the tryptic digestion of [alpha]-casein. The phosphopeptides in these mixtures gave rise to either low or no signals via positive ion electrospray ionization. Strong signals, however, were generated in the negative ion mode. An initial ion/ion reaction that employed multiply protonated amino-terminated dendrimers converted phosphopeptide anions to the doubly protonated species. The doubly charged cations were then subjected to ion/ion electron transfer to induce dissociation. Electron-transfer dissociation of doubly positively charged phosphopeptides yields characteristic c-and z-type fragment ions by dissociation of the N-[C.sub.[alpha]] bond along the peptide backbone while preserving the labile posttranslational modifications. These results illustrate the ability to alter ion charge after ion formation and prior to structural interrogation. Phosphopeptides provide an example where it can be difficult to form strong doubly charged cation signals directly when they are present in mixtures, which, as a result, precludes the use of electron-transfer dissociation as a structural probe. The sequential ion/ion reaction process described here, therefore, can provide a new capability for structural interrogation in phosphoproteomics.

Published
2006

47. Clinicoserological features of antisynthetase syndrome (ASyS)-associated interstitial lung disease presenting to respiratory services: comparison with idiopathic pulmonary fibrosis and ASyS diagnosed in rheumatology services

Author

Barratt, Shaney L, primary, Adamali, Havra H, additional, Cotton, Caroline, additional, Mulhearn, Ben, additional, Iftikhar, Hina, additional, Pauling, John David, additional, Spencer, Lisa, additional, Adamali, Huzaifa I, additional, and Gunawardena, Harsha, additional

Published
2021
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48. Nanoelectrospray ionization of protein mixtures: solution ph and protein pI

Author

Pan, Peng, Gunawardena, Harsha P., Xia, Yu, and McLuckey, Scott A.

Subjects
Chemistry, Analytic -- Research, Proteins -- Research, Chemistry
Abstract

Solutions consisting of single proteins and mixtures of proteins at different pH values have been subjected to both positive ion and negative ion nanoelectrospray ionization to study the influence of solvent pH and protein pl on the ionization responses of proteins. As has been noted previously, it is possible to form protein ions of one polarity despite the fact that the proteins are present as the opposite polarity in solution. However, total response under this condition tends to be at least an order of magnitude less than the condition in which the nanoelectrospray ionization polarity is the same as the net charge of the proteins in solution. Furthermore, maximum signals in positive ion mode were noted when the pH value of the solution was 4-5 units lower than the protein pl. In the negative ion mode, maximum protein anion signals were observed when the pH was roughly 5 units higher than the protein pl. While only small changes in the abundance-weighted average charge were noted as a function of solution conditions, the extent of sodium ion incorporation was seen to depend strongly on the relationship between net protein charge in solution and gas-phase ion polarity. Sodium ion incorporation was minimized under conditions of maximum signal (i.e., low pH positive ion mode and high pH negative ion mode). Sodium ion incorporation was highest when the protein ion polarities in solution and the gas phase were opposite. These observations are consistent with the charged residue model for electrospray ionization and suggest that a degree of selectivity for electrospray ionization applied to protein mixtures can be realized via judicious selection of solution pH and ionization polarity. Furthermore, the relative extent of sodium ion incorporation under a given set of conditions appears to correlate, at least qualitatively, with protein pl.

Published
2004

50. British Society for Rheumatology guideline on management of paediatric, adolescent and adult patients with idiopathic inflammatory myopathy.

Author

Oldroyd, Alexander G S, Lilleker, James B, Amin, Tania, Aragon, Octavio, Bechman, Katie, Cuthbert, Verna, Galloway, James, Gordon, Patrick, Gregory, William J, Gunawardena, Harsha, Hanna, Michael G, Isenberg, David, Jackman, John, Kiely, Patrick D W, Livermore, Polly, Machado, Pedro M, Maillard, Sue, McHugh, Neil, Murphy, Ruth, and Pilkington, Clarissa

Subjects
CARDIOVASCULAR disease treatment, BONE fracture prevention, AUTOIMMUNE disease treatment, AUTOANTIBODY analysis, CARDIOVASCULAR disease diagnosis, GLUCOCORTICOIDS, RITUXIMAB, THERAPEUTICS, WELL-being, COMBINATION drug therapy, DEGLUTITION, RHEUMATOLOGY, SUNSHINE, INTERSTITIAL lung diseases, CUTANEOUS manifestations of general diseases, MEDICAL screening, EARLY detection of cancer, DEGLUTITION disorders, MEDICAL protocols, ANTIRHEUMATIC agents, HEALTH behavior, QUALITY of life, MYOSITIS, IMMUNOSUPPRESSIVE agents, DISEASE management, EXERCISE therapy, DISEASE complications, CHILDREN, ADULTS, ADOLESCENCE
Abstract

The article presents a guideline from the British Society for Rheumatology for the management of patients with idiopathic inflammatory myopathy (IIM) in the United Kingdom (UK). The guideline used the Appraisal of Guidelines for Research and Evaluation II (AGREEII) methodology. The guideline includes treatment for diseases like skeletal muscle inflammation (myositis).

Published
2022
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