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1,807 results on '"Warrell"'

1. Single-cell genomics and regulatory networks for 388 human brains.

Author

Emani, Prashant, Liu, Jason, Clarke, Declan, Jensen, Matthew, Warrell, Jonathan, Gupta, Chirag, Meng, Ran, Lee, Che Yu, Xu, Siwei, Dursun, Cagatay, Lou, Shaoke, Chen, Yuhang, Chu, Zhiyuan, Galeev, Timur, Hwang, Ahyeon, Li, Yunyang, Ni, Pengyu, Zhou, Xiao, Bakken, Trygve, Bendl, Jaroslav, Bicks, Lucy, Chatterjee, Tanima, Cheng, Lijun, Cheng, Yuyan, Dai, Yi, Duan, Ziheng, Flaherty, Mary, Fullard, John, Gancz, Michael, Garrido-Martín, Diego, Gaynor-Gillett, Sophia, Grundman, Jennifer, Hawken, Natalie, Henry, Ella, Hoffman, Gabriel, Huang, Ao, Jiang, Yunzhe, Jin, Ting, Jorstad, Nikolas, Kawaguchi, Riki, Khullar, Saniya, Liu, Jianyin, Liu, Junhao, Liu, Shuang, Ma, Shaojie, Margolis, Michael, Mazariegos, Samantha, Moore, Jill, Moran, Jennifer, Nguyen, Eric, Phalke, Nishigandha, Pjanic, Milos, Pratt, Henry, Quintero, Diana, Rajagopalan, Ananya, Riesenmy, Tiernon, Shedd, Nicole, Shi, Manman, Spector, Megan, Terwilliger, Rosemarie, Travaglini, Kyle, Wamsley, Brie, Wang, Gaoyuan, Xia, Yan, Xiao, Shaohua, Yang, Andrew, Zheng, Suchen, Gandal, Michael, Lee, Donghoon, Lein, Ed, Roussos, Panos, Sestan, Nenad, Weng, Zhiping, White, Kevin, Won, Hyejung, Girgenti, Matthew, Zhang, Jing, Wang, Daifeng, Geschwind, Daniel, and Gerstein, Mark

Subjects
Humans, Aging, Brain, Cell Communication, Chromatin, Gene Regulatory Networks, Genomics, Mental Disorders, Prefrontal Cortex, Quantitative Trait Loci, Single-Cell Analysis
Abstract

Single-cell genomics is a powerful tool for studying heterogeneous tissues such as the brain. Yet little is understood about how genetic variants influence cell-level gene expression. Addressing this, we uniformly processed single-nuclei, multiomics datasets into a resource comprising >2.8 million nuclei from the prefrontal cortex across 388 individuals. For 28 cell types, we assessed population-level variation in expression and chromatin across gene families and drug targets. We identified >550,000 cell type-specific regulatory elements and >1.4 million single-cell expression quantitative trait loci, which we used to build cell-type regulatory and cell-to-cell communication networks. These networks manifest cellular changes in aging and neuropsychiatric disorders. We further constructed an integrative model accurately imputing single-cell expression and simulating perturbations; the model prioritized ~250 disease-risk genes and drug targets with associated cell types.

Published
2024

4. Study protocol: a randomised controlled trial of multiple and single dose activated charcoal for acute self-poisoning

Author

Mohammed Fahim, Senarathna Lalith, Buckley Nick A, Juszczak Edmund, Eddleston Michael, Allen Stuart, Dissanayake Wasantha, Hittarage Ariyasena, Azher Shifa, Jeganathan K, Jayamanne Shaluka, Sheriff MH Rezvi, and Warrell David A

Subjects
Special situations and conditions, RC952-1245, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Abstract Background The case fatality for intentional self-poisoning in rural Asia is 10–30 times higher than in the West, mostly due to the use of highly toxic poisons. Activated charcoal is a widely available intervention that may – if given early – bind to poisons in the stomach and prevent their absorption. Current guidelines recommend giving a single dose of charcoal (SDAC) if patients arrive within an hour of ingestion. Multiple doses (MDAC) may increase poison elimination at a later time by interrupting any enterohepatic or enterovascular circulations. The effectiveness of SDAC or MDAC is unknown. Since most patients present to hospital after one hour, we considered MDAC to have a higher likelihood of clinical benefit and set up a study to compare MDAC with no charcoal. A third arm of SDAC was added to help determine whether any benefit noted from MDAC resulted from the first dose or all doses. Methods/design We set up a randomised controlled trial assessing the effectiveness of superactivated charcoal in unselected adult self-poisoning patients admitted to the adult medical wards of three Sri Lankan secondary hospitals. Patients were randomised to standard treatment or standard treatment plus either a single 50 g dose of superactivated charcoal dissolved in 300 ml of water or six doses every four hours. All patients with a history of poison ingestion were approached concerning the study and written informed consent taken from each patient, or their relative (for unconscious patients or those 72 hrs post-ingestion, and previous recruitment. The primary outcome was in-hospital mortality; secondary outcomes included the occurrence of serious complications (need for intubation, time requiring assisted ventilation, fits, cardiac dysrhythmias). Analysis will be on an intention-to-treat basis; the effects of reported time to treatment after poisoning and status on admission will also be assessed. Discussion This trial will provide important information on the effectiveness of both single and multiple dose activated charcoal in the forms of poisoning commonly seen in rural Asia. If charcoal is found to be effective, it should be possible to make it widely available across rural Asia in an affordable formulation. Trial registration Current Controlled Trials ISRCTN02920054

Published
2007
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6. An integrative ENCODE resource for cancer genomics.

Author

Zhang, Jing, Lee, Donghoon, Dhiman, Vineet, Jiang, Peng, Xu, Jie, McGillivray, Patrick, Yang, Hongbo, Liu, Jason, Meyerson, William, Clarke, Declan, Gu, Mengting, Li, Shantao, Lou, Shaoke, Xu, Jinrui, Lochovsky, Lucas, Ung, Matthew, Ma, Lijia, Yu, Shan, Cao, Qin, Harmanci, Arif, Yan, Koon-Kiu, Sethi, Anurag, Gürsoy, Gamze, Schoenberg, Michael, Rozowsky, Joel, Warrell, Jonathan, Emani, Prashant, Yang, Yucheng, Galeev, Timur, Kong, Xiangmeng, Liu, Shuang, Li, Xiaotong, Krishnan, Jayanth, Feng, Yanlin, Rivera-Mulia, Juan, Adrian, Jessica, Broach, James, Bolt, Michael, Moran, Jennifer, Fitzgerald, Dominic, Dileep, Vishnu, Liu, Tingting, Mei, Shenglin, Sasaki, Takayo, Trevilla-Garcia, Claudia, Wang, Su, Wang, Yanli, Zang, Chongzhi, Wang, Daifeng, Klein, Robert, Snyder, Michael, Gilbert, David, Yip, Kevin, Cheng, Chao, Yue, Feng, Liu, X, White, Kevin, and Gerstein, Mark

Subjects
Cell Line, Tumor, Cell Transformation, Neoplastic, Databases, Genetic, Gene Regulatory Networks, Genomics, Humans, Mutation, Neoplasms, Reproducibility of Results, Transcription Factors
Abstract

ENCODE comprises thousands of functional genomics datasets, and the encyclopedia covers hundreds of cell types, providing a universal annotation for genome interpretation. However, for particular applications, it may be advantageous to use a customized annotation. Here, we develop such a custom annotation by leveraging advanced assays, such as eCLIP, Hi-C, and whole-genome STARR-seq on a number of data-rich ENCODE cell types. A key aspect of this annotation is comprehensive and experimentally derived networks of both transcription factors and RNA-binding proteins (TFs and RBPs). Cancer, a disease of system-wide dysregulation, is an ideal application for such a network-based annotation. Specifically, for cancer-associated cell types, we put regulators into hierarchies and measure their network change (rewiring) during oncogenesis. We also extensively survey TF-RBP crosstalk, highlighting how SUB1, a previously uncharacterized RBP, drives aberrant tumor expression and amplifies the effect of MYC, a well-known oncogenic TF. Furthermore, we show how our annotation allows us to place oncogenic transformations in the context of a broad cell space; here, many normal-to-tumor transitions move towards a stem-like state, while oncogene knockdowns show an opposing trend. Finally, we organize the resource into a coherent workflow to prioritize key elements and variants, in addition to regulators. We showcase the application of this prioritization to somatic burdening, cancer differential expression and GWAS. Targeted validations of the prioritized regulators, elements and variants using siRNA knockdowns, CRISPR-based editing, and luciferase assays demonstrate the value of the ENCODE resource.

Published
2020

9. Use of cidofovir in a patient with severe mpox and uncontrolled HIV infection

Author

Stafford, Adam, Rimmer, Stephanie, Gilchrist, Mark, Sun, Kristi, Davies, Ella P, Waddington, Claire S, Chiu, Christopher, Armstrong-James, Darius, Swaine, Thomas, Davies, Frances, Gómez, Carlos H M, Kumar, Vagish, ElHaddad, Ahmad, Awad, Zaid, Smart, Christopher, Mora-Peris, Borja, Muir, David, Randell, Paul, Peters, Joanna, Chand, Meera, Warrell, Clare E, Rampling, Tommy, Cooke, Graham, Dhanji, Sara, Campbell, Vivienne, Davies, Carys, Osman, Sana, and Abbara, Aula

Published
2023
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12. exRNA Atlas Analysis Reveals Distinct Extracellular RNA Cargo Types and Their Carriers Present across Human Biofluids

Author

Murillo, Oscar D, Thistlethwaite, William, Rozowsky, Joel, Subramanian, Sai Lakshmi, Lucero, Rocco, Shah, Neethu, Jackson, Andrew R, Srinivasan, Srimeenakshi, Chung, Allen, Laurent, Clara D, Kitchen, Robert R, Galeev, Timur, Warrell, Jonathan, Diao, James A, Welsh, Joshua A, Hanspers, Kristina, Riutta, Anders, Burgstaller-Muehlbacher, Sebastian, Shah, Ravi V, Yeri, Ashish, Jenkins, Lisa M, Ahsen, Mehmet E, Cordon-Cardo, Carlos, Dogra, Navneet, Gifford, Stacey M, Smith, Joshua T, Stolovitzky, Gustavo, Tewari, Ashutosh K, Wunsch, Benjamin H, Yadav, Kamlesh K, Danielson, Kirsty M, Filant, Justyna, Moeller, Courtney, Nejad, Parham, Paul, Anu, Simonson, Bridget, Wong, David K, Zhang, Xuan, Balaj, Leonora, Gandhi, Roopali, Sood, Anil K, Alexander, Roger P, Wang, Liang, Wu, Chunlei, Wong, David TW, Galas, David J, Van Keuren-Jensen, Kendall, Patel, Tushar, Jones, Jennifer C, Das, Saumya, Cheung, Kei-Hoi, Pico, Alexander R, Su, Andrew I, Raffai, Robert L, Laurent, Louise C, Roth, Matthew E, Gerstein, Mark B, and Milosavljevic, Aleksandar

Subjects
Biological Sciences, Genetics, Human Genome, Biotechnology, Adult, Body Fluids, Cell Communication, Cell-Free Nucleic Acids, Circulating MicroRNA, Extracellular Vesicles, Female, Humans, Male, RNA, Reproducibility of Results, Sequence Analysis, RNA, Software, ERCC, deconvolution, exRNA, exosomes, extracellular RNA, extracellular vesicles, lipoproteins, ribonucleoproteins, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

To develop a map of cell-cell communication mediated by extracellular RNA (exRNA), the NIH Extracellular RNA Communication Consortium created the exRNA Atlas resource (https://exrna-atlas.org). The Atlas version 4P1 hosts 5,309 exRNA-seq and exRNA qPCR profiles from 19 studies and a suite of analysis and visualization tools. To analyze variation between profiles, we apply computational deconvolution. The analysis leads to a model with six exRNA cargo types (CT1, CT2, CT3A, CT3B, CT3C, CT4), each detectable in multiple biofluids (serum, plasma, CSF, saliva, urine). Five of the cargo types associate with known vesicular and non-vesicular (lipoprotein and ribonucleoprotein) exRNA carriers. To validate utility of this model, we re-analyze an exercise response study by deconvolution to identify physiologically relevant response pathways that were not detected previously. To enable wide application of this model, as part of the exRNA Atlas resource, we provide tools for deconvolution and analysis of user-provided case-control studies.

Published
2019

13. Clinical features and management of human monkeypox: a retrospective observational study in the UK

Author

Abouyannis, Mike, Al-Balushi, Asma, Aston, Stephen, Ball, Robert, Beeching, Nicholas J, Blanchard, Thomas J, Carlin, Ffion, Davies, Geraint, Gillespie, Angela, Hicks, Scott R, Hoyle, Marie-Claire, Ilozue, Chinenye, Mair, Luke, Marshall, Suzanne, Neary, Anne, Nsutebu, Emmanuel, Parker, Samantha, Ryan, Hannah, Turtle, Lance, Smith, Chris, van Aartsen, Jon, Walker, Naomi F, Woolley, Stephen, Chawla, Anu, Hart, Ian, Smielewska, Anna, Joekes, Elizabeth, Benson, Cathryn, Brindley, Cheryl, Das, Urmi, Eyton-Chong, Chin K, Gnanalingham, Claire, Halfhide, Clare, Larru, Beatriz, Mayell, Sarah, McBride, Joanna, Oliver, Claire, Paul, Princy, Riordan, Andrew, Sridhar, Lekha, Storey, Megan, Abdul, Audrey, Abrahamsen, Jennifer, Athan, Breda, Bhagani, Sanjay, Brown, Colin S, Carpenter, Oliver, Cropley, Ian, Frost, Kerrie, Hopkins, Susan, Joyce, Jessica, Lamb, Lucy, Lyons, Adrian, Mahungu, Tabitha, Mepham, Stephen, Mukwaira, Edina, Rodger, Alison, Taylor, Caroline, Warren, Simon, Williams, Alan, Levitt, Debbie, Allen, Denise, Dixon, Jill, Evans, Adam, McNicholas, Pauline, Payne, Brendan, Price, D Ashley, Schwab, Uli, Sykes, Allison, Taha, Yusri, Ward, Margaret, Emonts, Marieke, Owens, Stephen, Botgros, Alina, Douthwaite, Sam T, Goodman, Anna, Luintel, Akish, MacMahon, Eithne, Nebbia, Gaia, O'Hara, Geraldine, Parsons, Joseph, Sen, Ashwin, Stevenson, Daniel, Sullivan, Tadgh, Taj, Usman, van Nipsen tot Pannerden, Claire, Winslow, Helen, Zatyka, Ewa, Alozie-Otuka, Ekene, Beviz, Csaba, Ceesay, Yusupha, Gargee, Latchmin, Kabia, Morloh, Mitchell, Hannah, Perkins, Shona, Sasson, Mingaile, Sehmbey, Kamal, Tabios, Federico, Wigglesworth, Neil, Aarons, Emma J, Brooks, Tim, Dryden, Matthew, Furneaux, Jenna, Gibney, Barry, Small, Jennifer, Truelove, Elizabeth, Warrell, Clare E, Firth, Richard, Hobson, Gemma, Johnson, Christopher, Dewynter, Alison, Nixon, Sebastian, Spence, Oliver, Bugert, Joachim J, Hruby, Dennis E, Adler, Hugh, Gould, Susan, Hine, Paul, Snell, Luke B, Wong, Waison, Houlihan, Catherine F, Osborne, Jane C, Rampling, Tommy, Beadsworth, Mike BJ, Duncan, Christopher JA, Dunning, Jake, Fletcher, Tom E, Hunter, Ewan R, Jacobs, Michael, Khoo, Saye H, Newsholme, William, Porter, David, Porter, Robert J, Ratcliffe, Libuše, Schmid, Matthias L, Semple, Malcolm G, Tunbridge, Anne J, Wingfield, Tom, and Price, Nicholas M

Published
2022
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15. Comprehensive functional genomic resource and integrative model for the human brain

Author

Wang, Daifeng, Liu, Shuang, Warrell, Jonathan, Won, Hyejung, Shi, Xu, Navarro, Fabio CP, Clarke, Declan, Gu, Mengting, Emani, Prashant, Yang, Yucheng T, Xu, Min, Gandal, Michael J, Lou, Shaoke, Zhang, Jing, Park, Jonathan J, Yan, Chengfei, Rhie, Suhn Kyong, Manakongtreecheep, Kasidet, Zhou, Holly, Nathan, Aparna, Peters, Mette, Mattei, Eugenio, Fitzgerald, Dominic, Brunetti, Tonya, Moore, Jill, Jiang, Yan, Girdhar, Kiran, Hoffman, Gabriel E, Kalayci, Selim, Gümüş, Zeynep H, Crawford, Gregory E, Roussos, Panos, Akbarian, Schahram, Jaffe, Andrew E, White, Kevin P, Weng, Zhiping, Sestan, Nenad, Geschwind, Daniel H, Knowles, James A, Gerstein, Mark B, Ashley-Koch, Allison E, Garrett, Melanie E, Song, Lingyun, Safi, Alexias, Johnson, Graham D, Wray, Gregory A, Reddy, Timothy E, Goes, Fernando S, Zandi, Peter, Bryois, Julien, Price, Amanda J, Ivanov, Nikolay A, Collado-Torres, Leonardo, Hyde, Thomas M, Burke, Emily E, Kleiman, Joel E, Tao, Ran, Shin, Joo Heon, Kundakovic, Marija, Brown, Leanne, Kassim, Bibi S, Park, Royce B, Wiseman, Jennifer R, Zharovsky, Elizabeth, Jacobov, Rivka, Devillers, Olivia, Flatow, Elie, Lipska, Barbara K, Lewis, David A, Haroutunian, Vahram, Hahn, Chang-Gyu, Charney, Alexander W, Dracheva, Stella, Kozlenkov, Alexey, Belmont, Judson, DelValle, Diane, Francoeur, Nancy, Hadjimichael, Evi, Pinto, Dalila, van Bakel, Harm, Fullard, John F, Bendl, Jaroslav, Hauberg, Mads E, Mangravite, Lara M, Peters, Mette A, Chae, Yooree, Peng, Junmin, Niu, Mingming, Wang, Xusheng, Webster, Maree J, Beach, Thomas G, Chen, Chao, and Jiang, Yi

Subjects
Human Genome, Biotechnology, Schizophrenia, Mental Health, Brain Disorders, Genetics, Neurosciences, 1.1 Normal biological development and functioning, 2.1 Biological and endogenous factors, Underpinning research, Aetiology, Mental health, Brain, Datasets as Topic, Deep Learning, Enhancer Elements, Genetic, Epigenesis, Genetic, Epigenomics, Gene Expression Regulation, Gene Regulatory Networks, Genome-Wide Association Study, Humans, Mental Disorders, Quantitative Trait Loci, Single-Cell Analysis, Transcriptome, PsychENCODE Consortium, General Science & Technology
Abstract

Despite progress in defining genetic risk for psychiatric disorders, their molecular mechanisms remain elusive. Addressing this, the PsychENCODE Consortium has generated a comprehensive online resource for the adult brain across 1866 individuals. The PsychENCODE resource contains ~79,000 brain-active enhancers, sets of Hi-C linkages, and topologically associating domains; single-cell expression profiles for many cell types; expression quantitative-trait loci (QTLs); and further QTLs associated with chromatin, splicing, and cell-type proportions. Integration shows that varying cell-type proportions largely account for the cross-population variation in expression (with >88% reconstruction accuracy). It also allows building of a gene regulatory network, linking genome-wide association study variants to genes (e.g., 321 for schizophrenia). We embed this network into an interpretable deep-learning model, which improves disease prediction by ~6-fold versus polygenic risk scores and identifies key genes and pathways in psychiatric disorders.

Published
2018

16. Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder

Author

Gandal, Michael J, Zhang, Pan, Hadjimichael, Evi, Walker, Rebecca L, Chen, Chao, Liu, Shuang, Won, Hyejung, van Bakel, Harm, Varghese, Merina, Wang, Yongjun, Shieh, Annie W, Haney, Jillian, Parhami, Sepideh, Belmont, Judson, Kim, Minsoo, Moran Losada, Patricia, Khan, Zenab, Mleczko, Justyna, Xia, Yan, Dai, Rujia, Wang, Daifeng, Yang, Yucheng T, Xu, Min, Fish, Kenneth, Hof, Patrick R, Warrell, Jonathan, Fitzgerald, Dominic, White, Kevin, Jaffe, Andrew E, Peters, Mette A, Gerstein, Mark, Liu, Chunyu, Iakoucheva, Lilia M, Pinto, Dalila, Geschwind, Daniel H, Ashley-Koch, Allison E, Crawford, Gregory E, Garrett, Melanie E, Song, Lingyun, Safi, Alexias, Johnson, Graham D, Wray, Gregory A, Reddy, Timothy E, Goes, Fernando S, Zandi, Peter, Bryois, Julien, Price, Amanda J, Ivanov, Nikolay A, Collado-Torres, Leonardo, Hyde, Thomas M, Burke, Emily E, Kleiman, Joel E, Tao, Ran, Shin, Joo Heon, Akbarian, Schahram, Girdhar, Kiran, Jiang, Yan, Kundakovic, Marija, Brown, Leanne, Kassim, Bibi S, Park, Royce B, Wiseman, Jennifer R, Zharovsky, Elizabeth, Jacobov, Rivka, Devillers, Olivia, Flatow, Elie, Hoffman, Gabriel E, Lipska, Barbara K, Lewis, David A, Haroutunian, Vahram, Hahn, Chang-Gyu, Charney, Alexander W, Dracheva, Stella, Kozlenkov, Alexey, DelValle, Diane, Francoeur, Nancy, Roussos, Panos, Fullard, John F, Bendl, Jaroslav, Hauberg, Mads E, Mangravite, Lara M, Chae, Yooree, Peng, Junmin, Niu, Mingming, Wang, Xusheng, Webster, Maree J, Beach, Thomas G, Jiang, Yi, and Grennan, Kay S

Subjects
Pharmacology and Pharmaceutical Sciences, Biological Sciences, Biomedical and Clinical Sciences, Genetics, Mental Health, Intellectual and Developmental Disabilities (IDD), Neurosciences, Mental Illness, Human Genome, Schizophrenia, Biotechnology, Serious Mental Illness, Autism, Brain Disorders, Bipolar Disorder, 2.1 Biological and endogenous factors, 1.1 Normal biological development and functioning, Neurological, Mental health, Good Health and Well Being, Autism Spectrum Disorder, Brain, Genetic Predisposition to Disease, Humans, Protein Isoforms, RNA Splicing, Sequence Analysis, RNA, Transcriptome, PsychENCODE Consortium, General Science & Technology
Abstract

Most genetic risk for psychiatric disease lies in regulatory regions, implicating pathogenic dysregulation of gene expression and splicing. However, comprehensive assessments of transcriptomic organization in diseased brains are limited. In this work, we integrated genotypes and RNA sequencing in brain samples from 1695 individuals with autism spectrum disorder (ASD), schizophrenia, and bipolar disorder, as well as controls. More than 25% of the transcriptome exhibits differential splicing or expression, with isoform-level changes capturing the largest disease effects and genetic enrichments. Coexpression networks isolate disease-specific neuronal alterations, as well as microglial, astrocyte, and interferon-response modules defining previously unidentified neural-immune mechanisms. We integrated genetic and genomic data to perform a transcriptome-wide association study, prioritizing disease loci likely mediated by cis effects on brain expression. This transcriptome-wide characterization of the molecular pathology across three major psychiatric disorders provides a comprehensive resource for mechanistic insight and therapeutic development.

Published
2018

20. Interrogating RNA and protein spatial subcellular distribution in smFISH data with DypFISH

Author

Savulescu, Anca F., Brackin, Robyn, Bouilhol, Emmanuel, Dartigues, Benjamin, Warrell, Jonathan H., Pimentel, Mafalda R., Beaume, Nicolas, Fortunato, Isabela C., Dallongeville, Stephane, Boulle, Mikaël, Soueidan, Hayssam, Agou, Fabrice, Schmoranzer, Jan, Olivo-Marin, Jean-Christophe, Franco, Claudio A., Gomes, Edgar R., Nikolski, Macha, and Mhlanga, Musa M.

Published
2021
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23. Quantum computing at the frontiers of biological sciences

Author

Emani, Prashant S., Warrell, Jonathan, Anticevic, Alan, Bekiranov, Stefan, Gandal, Michael, McConnell, Michael J., Sapiro, Guillermo, Aspuru-Guzik, Alán, Baker, Justin T., Bastiani, Matteo, Murray, John D., Sotiropoulos, Stamatios N., Taylor, Jacob, Senthil, Geetha, Lehner, Thomas, Gerstein, Mark B., and Harrow, Aram W.

Published
2021
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24. Predicting spatially resolved gene expression via tissue morphology using adaptive spatial GNNs.

Author

Song, Tianci, Cosatto, Eric, Wang, Gaoyuan, Kuang, Rui, Gerstein, Mark, Min, Martin Renqiang, and Warrell, Jonathan

Subjects
GRAPH neural networks, GENE expression, TRANSCRIPTOMES, GENE mapping, BREAST cancer
Abstract

Motivation Spatial transcriptomics technologies, which generate a spatial map of gene activity, can deepen the understanding of tissue architecture and its molecular underpinnings in health and disease. However, the high cost makes these technologies difficult to use in practice. Histological images co-registered with targeted tissues are more affordable and routinely generated in many research and clinical studies. Hence, predicting spatial gene expression from the morphological clues embedded in tissue histological images provides a scalable alternative approach to decoding tissue complexity. Results Here, we present a graph neural network based framework to predict the spatial expression of highly expressed genes from tissue histological images. Extensive experiments on two separate breast cancer data cohorts demonstrate that our method improves the prediction performance compared to the state-of-the-art, and that our model can be used to better delineate spatial domains of biological interest. Availability and implementation https://github.com/song0309/asGNN/ [ABSTRACT FROM AUTHOR]

Published
2024
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25. Ambulatory induction phase treatment of cryptococcal meningitis in HIV integrated primary care clinics, Yangon, Myanmar

Author

Clare E. Warrell, Catriona Macrae, Alistair R. D. McLean, Edmund Wilkins, Elizabeth A. Ashley, Frank Smithuis, and Ni Ni Tun

Subjects
Cryptococcal meningitis, HIV, Opportunistic infections, Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background Cryptococcal meningitis (CM) is a common HIV-associated opportunistic-infection worldwide. Existing literature focusses on hospital-based outcomes of induction treatment. This paper reviews outpatient management in integrated primary care clinics in Yangon. Method This retrospective case note review analyses a Myanmar HIV-positive patient cohort managed using ambulatory induction-phase treatment with intravenous amphotericin-B-deoxycholate (0.7–1.0 mg/kg) and oral fluconazole (800 mg orally/day). Results Seventy-six patients were diagnosed between 2010 and 2017. The median age of patients diagnosed was 35 years, 63% were male and 33 (45%) were on concurrent treatment for tuberculosis. The median CD4 count was 60 at the time of diagnosis. Amphotericin-B-deoxycholate infusions precipitated 56 episodes of toxicity, namely hypokalaemia, nephrotoxicity, anaemia, febrile reactions, phlebitis, observed in 44 patients (58%). One-year survival (86%) was higher than existing hospital-based treatment studies. Conclusion Ambulation of patients in this cohort saved 1029 hospital bed days and had better survival outcomes when compared to hospital-based studies in other resource constrained settings.

Published
2021
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28. Passenger Mutations in More Than 2,500 Cancer Genomes: Overall Molecular Functional Impact and Consequences

Author

Kumar, Sushant, Warrell, Jonathan, Li, Shantao, McGillivray, Patrick D., Meyerson, William, Salichos, Leonidas, Harmanci, Arif, Martinez-Fundichely, Alexander, Chan, Calvin W.Y., Nielsen, Morten Muhlig, Lochovsky, Lucas, Zhang, Yan, Li, Xiaotong, Lou, Shaoke, Pedersen, Jakob Skou, Herrmann, Carl, Getz, Gad, Khurana, Ekta, and Gerstein, Mark B.

Published
2020
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29. Internet Research Ethics and the Policy Gap for Ethical Practice in Online Research Settings

Author

Warrell, Jacqueline G. and Jacobsen, Michele

Abstract

A growing number of education and social science researchers design and conduct online research. In this review, the Internet Research Ethics (IRE) policy gap in Canada is identified along with the range of stakeholders and groups that either have a role or have attempted to play a role in forming better ethics policy. Ethical issues that current policy and guidelines fail to address are interrogated and discussed. Complexities around applying the human subject model to internet research are explored, such as issues of privacy, anonymity, and informed consent. The authors call for immediate action on the Canadian ethics policy gap and urge the research community to consider the situational, contextual, and temporal aspects of IRE in the development of flexible and responsive policies that address the complexity and diversity of internet research spaces.

Published
2014

30. An integrative ENCODE resource for cancer genomics

Author

Jing Zhang, Donghoon Lee, Vineet Dhiman, Peng Jiang, Jie Xu, Patrick McGillivray, Hongbo Yang, Jason Liu, William Meyerson, Declan Clarke, Mengting Gu, Shantao Li, Shaoke Lou, Jinrui Xu, Lucas Lochovsky, Matthew Ung, Lijia Ma, Shan Yu, Qin Cao, Arif Harmanci, Koon-Kiu Yan, Anurag Sethi, Gamze Gürsoy, Michael Rutenberg Schoenberg, Joel Rozowsky, Jonathan Warrell, Prashant Emani, Yucheng T. Yang, Timur Galeev, Xiangmeng Kong, Shuang Liu, Xiaotong Li, Jayanth Krishnan, Yanlin Feng, Juan Carlos Rivera-Mulia, Jessica Adrian, James R Broach, Michael Bolt, Jennifer Moran, Dominic Fitzgerald, Vishnu Dileep, Tingting Liu, Shenglin Mei, Takayo Sasaki, Claudia Trevilla-Garcia, Su Wang, Yanli Wang, Chongzhi Zang, Daifeng Wang, Robert J. Klein, Michael Snyder, David M. Gilbert, Kevin Yip, Chao Cheng, Feng Yue, X. Shirley Liu, Kevin P. White, and Mark Gerstein

Subjects
Science
Abstract

ENCODE is a resource comprising thousands of functional genomic datasets. Here, the authors present custom annotation within ENCODE for cancer, highlighting a workflow that can help prioritise key elements in oncogenesis.

Published
2020
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33. Analyses of non-coding somatic drivers in 2,658 cancer whole genomes.

Author

Esther Rheinbay, Morten Muhlig Nielsen, Federico Abascal, Jeremiah Wala, Ofer Shapira, Grace Tiao, Henrik Hornshøj, Julian M. Hess, Randi Istrup Juul, Ziao Lin, Lars Feuerbach, Radhakrishnan Sabarinathan, Tobias Madsen, Jaegil Kim, Loris Mularoni, Shimin Shuai, Andrés Lanzós, Carl Herrmann, Yosef E. Maruvka, Ciyue Shen, Samirkumar B. Amin, Pratiti Bandopadhayay, Johanna Bertl, Keith A. Boroevich, John Busanovich, Joana Carlevaro-Fita, Dimple Chakravarty, Calvin Wing Yiu Chan, David Craft, Priyanka Dhingra, Klev Diamanti, Nuno A. Fonseca, Abel Gonzalez-Perez, Qianyun Guo, Mark P. Hamilton, Nicholas J. Haradhvala, Chen Hong, Keren Isaev, Todd A. Johnson, Malene Juul, André Kahles, Abdullah Kahraman, Youngwook Kim, Jan Komorowski, Kiran Kumar, Sushant Kumar, Donghoon Lee 0006, Kjong-Van Lehmann, Yilong Li, Eric Minwei Liu, Lucas Lochovsky, Keunchil Park, Oriol Pich, Nicola D. Roberts, Gordon Saksena, Steven E. Schumacher, Nikos Sidiropoulos, Lina Sieverling, Nasa Sinnott-Armstrong, Chip Stewart, David Tamborero, Jose M. C. Tubio, Husen M. Umer, Liis Uusküla-Reimand, Claes Wadelius, Lina Wadi, Xiaotong Yao, Cheng-Zhong Zhang, Jing Zhang 0062, James E. Haber, Asger Hobolth, Marcin Imielinski, Manolis Kellis, Michael S. Lawrence, Christian von Mering, Hidewaki Nakagawa, Benjamin J. Raphael, Mark A. Rubin, Chris Sander, Lincoln D. Stein, Joshua M. Stuart, Tatsuhiko Tsunoda, David A. Wheeler, Rory Johnson, Jüri Reimand, Mark Gerstein, Ekta Khurana, Peter J. Campbell, Núria López-Bigas, Gary D. Bader, Jonathan Barenboim, Rameen Beroukhim, Søren Brunak, Ken Chen, Jung Kyoon Choi, Jordi Deu-Pons, J. Lynn Fink, Joan Frigola, Carlo Gambacorti Passerini, Dale W. Garsed, Gad Getz, Ivo Glynne Gut, David Haan, Arif Ozgun Harmanci, Mohamed Helmy, Ermin Hodzic, José M. G. Izarzugaza, Jong K. Kim, Jan O. Korbel, Erik Larsson, Shantao Li, Xiaotong Li, Shaoke Lou, Kathleen Marchal, Iñigo Martincorena, Alexander Martínez-Fundichely, Patrick D. McGillivray, William Meyerson, Ferran Muiños, Marta Paczkowska, Kiejung Park, Jakob Skou Pedersen, Tirso Pons, Sergio Pulido-Tamayo, Iker Reyes-Salazar, Matthew A. Reyna, Carlota Rubio-Perez, Süleyman Cenk Sahinalp, Leonidas Salichos, Mark Shackleton, Raunak Shrestha, Alfonso Valencia, Miguel Vazquez, Lieven P. C. Verbeke, Jiayin Wang, Jonathan Warrell, Sebastian M. Waszak, Joachim Weischenfeldt, Guanming Wu, Jun Yu, Xuanping Zhang, Yan Zhang 0032, Zhongming Zhao, Lihua Zou, Kadir C. Akdemir, Eva G. Alvarez, Adrian Baez-Ortega, Paul C. Boutros, David D. L. Bowtell, Benedikt Brors, Kathleen H. Burns, Kin Chan, Isidro Cortés-Ciriano, Ana Dueso-Barroso, Andrew J. Dunford, Paul A. Edwards, Xavier Estivill, Dariush Etemadmoghadam, Milana Frenkel-Morgenstern, Dmitry A. Gordenin, Barbara Hutter, David T. W. Jones, Young Seok Ju, Marat D. Kazanov, Leszek J. Klimczak, Youngil Koh, Eunjung Alice Lee, Jake June-Koo Lee, Andy G. Lynch, Geoff MacIntyre, Florian Markowetz, Matthew Meyerson, Satoru Miyano, Fabio C. P. Navarro, Stephan Ossowski, Peter J. Park, John V. Pearson, Montserrat Puiggròs, Karsten Rippe, Steven A. Roberts, Bernardo Rodriguez-Martin, Ralph Scully, David Torrents, Izar Villasante, Nicola Waddell, Jeremiah A. Wala, Lixing Yang, Sung-Soo Yoon, and Jorge Zamora

Published
2020
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36. Estimating growth patterns and driver effects in tumor evolution from individual samples

Author

Leonidas Salichos, William Meyerson, Jonathan Warrell, and Mark Gerstein

Subjects
Science
Abstract

There are many methods to detect cancer-driving mutations. Here, the authors harness the variant allele frequency of mutations in tumor cells of a single individual to present a method that can estimate growth patterns and identify driver gene evolution at a patient specific level.

Published
2020
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38. A Cross-Sectional Evaluation of the Virtual Outpatient Management of People With Mpox.

Author

Warrell, Clare E, Chaudhry, Zain, Shawe-Taylor, Marianne, Mastoraki, Evanthia, Sen, Ashwin Delmonte, Rafferty, Hannah, Wilton, Angus De, Mescall, Naomi, Houlihan, Catherine, Gothard, Philip, Jungmann, Eva, Logan, Sarah, Rampling, Tommy, Waters, Laura, Browne, Rita, Marks, Michael, and Shaw, Emily

Subjects
*SEXUALLY transmitted diseases, *MONKEYPOX, *HIV, *PUBLIC hospitals, *COMMUNICABLE diseases
Abstract

Background To report on the implementation and outcomes of a virtual ward established for the management of mpox during the 2022 outbreak, we conducted a 2-center, observational, cross-sectional study over a 3-month period. Methods All patients aged ≥17 years with laboratory polymerase chain reaction–confirmed monkeypox virus managed between 14 May and 15 August 2022, at the Hospital for Tropical Diseases at University College London Hospitals National Health Service (NHS) Foundation Trust and sexual health services at Central North and West London NHS Foundation Trust, were included. Main outcomes included the proportion of patients managed exclusively on the virtual ward, proportion of patients requiring inpatient admission, proportion of patients with human immunodeficiency virus, and duration of lesion reepithelialization. Results Among confirmed cases (N = 221), 86% (191/221) were managed exclusively on the virtual ward, while 14% (30/221) required admission. Treatment for concomitant sexually transmitted infections was provided to 25% (55/221) of patients, antibiotics for other infective complications to 16% (35/221), and symptomatic relief to 27% (60/221). The median time from onset to complete lesion reepithelialization and de-isolation was 18 days (range, 8–56 days). Eleven percent (24/221) of individuals disengaged from services within 4 days of testing. Conclusions The virtual ward model facilitated safe and holistic outpatient management of mpox, while minimizing admissions. This approach could serve as a model for future outbreak responses. [ABSTRACT FROM AUTHOR]

Published
2024
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41. Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder

Author

PsychENCODE Consortium, Gandal, Michael J., Zhang, Pan, Hadjimichael, Evi, Walker, Rebecca L., Chen, Chao, Liu, Shuang, Won, Hyejung, van Bakel, Harm, Varghese, Merina, Wang, Yongjun, Shieh, Annie W., Haney, Jillian, Parhami, Sepideh, Belmont, Judson, Kim, Minsoo, Losada, Patricia Moran, Khan, Zenab, Mleczko, Justyna, Xia, Yan, Dai, Rujia, Wang, Daifeng, Yang, Yucheng T., Xu, Min, Fish, Kenneth, Hof, Patrick R., Warrell, Jonathan, Fitzgerald, Dominic, White, Kevin, Jaffe, Andrew E., Peters, Mette A., Gerstein, Mark, Liu, Chunyu, Iakoucheva, Lilia M., Pinto, Dalila, and Geschwind, Daniel H.

Published
2018

42. Comprehensive functional genomic resource and integrative model for the human brain

Author

PsychENCODE Consortium, Wang, Daifeng, Liu, Shuang, Warrell, Jonathan, Won, Hyejung, Shi, Xu, Navarro, Fabio C. P., Clarke, Declan, Gu, Mengting, Emani, Prashant, Yang, Yucheng T., Xu, Min, Gandal, Michael J., Lou, Shaoke, Zhang, Jing, Park, Jonathan J., Yan, Chengfei, Rhie, Suhn Kyong, Manakongtreecheep, Kasidet, Zhou, Holly, Nathan, Aparna, Peters, Mette, Mattei, Eugenio, Fitzgerald, Dominic, Brunetti, Tonya, Moore, Jill, Jiang, Yan, Girdhar, Kiran, Hoffman, Gabriel E., Kalayci, Selim, Gümüş, Zeynep H., Crawford, Gregory E., Roussos, Panos, Akbarian, Schahram, Jaffe, Andrew E., P.White, Kevin, Weng, Zhiping, Sestan, Nenad, Geschwind, Daniel H., Knowles, James A., and Gerstein, Mark B.

Published
2018

48. A Bayesian phase 2 model based adaptive design to optimise antivenom dosing: Application to a dose-finding trial for a novel Russell's viper antivenom in Myanmar.

Author

James A Watson, Thomas Lamb, Jane Holmes, David A Warrell, Khin Thida Thwin, Zaw Lynn Aung, Min Zaw Oo, Myat Thet Nwe, Frank Smithuis, and Elizabeth A Ashley

Subjects
Arctic medicine. Tropical medicine, RC955-962, Public aspects of medicine, RA1-1270
Abstract

For most antivenoms there is little information from clinical studies to infer the relationship between dose and efficacy or dose and toxicity. Antivenom dose-finding studies usually recruit too few patients (e.g. fewer than 20) relative to clinically significant event rates (e.g. 5%). Model based adaptive dose-finding studies make efficient use of accrued patient data by using information across dosing levels, and converge rapidly to the contextually defined 'optimal dose'. Adequate sample sizes for adaptive dose-finding trials can be determined by simulation. We propose a model based, Bayesian phase 2 type, adaptive clinical trial design for the characterisation of optimal initial antivenom doses in contexts where both efficacy and toxicity are measured as binary endpoints. This design is illustrated in the context of dose-finding for Daboia siamensis (Eastern Russell's viper) envenoming in Myanmar. The design formalises the optimal initial dose of antivenom as the dose closest to that giving a pre-specified desired efficacy, but resulting in less than a pre-specified maximum toxicity. For Daboia siamensis envenoming, efficacy is defined as the restoration of blood coagulability within six hours, and toxicity is defined as anaphylaxis. Comprehensive simulation studies compared the expected behaviour of the model based design to a simpler rule based design (a modified '3+3' design). The model based design can identify an optimal dose after fewer patients relative to the rule based design. Open source code for the simulations is made available in order to determine adequate sample sizes for future adaptive snakebite trials. Antivenom dose-finding trials would benefit from using standard model based adaptive designs. Dose-finding trials where rare events (e.g. 5% occurrence) are of clinical importance necessitate larger sample sizes than current practice. We will apply the model based design to determine a safe and efficacious dose for a novel lyophilised antivenom to treat Daboia siamensis envenoming in Myanmar.

Published
2020
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