@article{669ac6f5af4e47e399e5d64cc850b536,
title = "SOD1-ALS-Browser: a web-utility for investigating the clinical phenotype in SOD1 amyotrophic lateral sclerosis",
abstract = "Objective: Variants in the superoxide dismutase (SOD1) gene are among the most common genetic causes of amyotrophic lateral sclerosis. Reflecting the wide spectrum of putatively deleterious variants that have been reported to date, it has become clear that SOD1-linked ALS presents a highly variable age at symptom onset and disease duration.Methods: Here we describe an open access web tool for comparative phenotype analysis in ALS: https://sod1-als-browser.rosalind.kcl.ac.uk/. The tool contains a built-in dataset of clinical information from 1383 people with ALS harboring a SOD1 variant resulting in one of 162 unique amino acid sequence alterations and from a non-SOD1 comparator ALS cohort of 13,469 individuals. We present two examples of analyses possible with this tool, testing how the ALS phenotype relates to SOD1 variants that alter amino acid residue hydrophobicity and to distinct variants at the 94th residue of SOD1, where six are sampled.Results and conclusions: The tool provides immediate access to the datasets and enables bespoke analysis of phenotypic trends associated with different protein variants, including the option for users to upload their own datasets for integration with the server data. The tool can be used to study SOD1-ALS and provides an analytical framework to study the differences between other user-uploaded ALS groups and our large reference database of SOD1 and non-SOD1 ALS. The tool is designed to be useful for clinicians and researchers, including those without programming expertise, and is highly flexible in the analyses that can be conducted.",
author = "Thomas Spargo and Sarah Martin and Guy Hunt and Munishikha Kalia and {Al Khleifat}, Ahmad and Simon Topp and Christopher Shaw and Ammar Al-Chalabi and Alfredo Iacoangeli",
note = "Funding Information: Samples used in this research were in part obtained from the UK National DNA Bank for MND Research, funded by the MND Association and the Wellcome Trust. Part of the samples were obtained from The Project MinE and STRENGTH consortia, and MND centers internationally. We would like to thank the members of these consortia and our clinical collaborators for their contribution: Philip van Damme, Philippe Corcia, Philippe Couratier, Patrick Vourc”h, Orla Hardiman, Russell McLaughin, Marc Gotkine, Vivian Drory, Nicola Ticozzi, Vincenzo Silani, Jan H Veldink, Leonard H van den Berg, Mamede de Carvalho, Jesus S Mora Pardina, Monica Povedano, Peter Andersen, Markus Weber, Nazli A Ba{\c s}ak, Ammar Al-Chalabi, Christopher E Shaw, Pamela J Shaw, Karen E Morrison, John E Landers, Jonathan D Glass, Clifton L Dalgard, Nailah Siddique, Teepu Siddique, Kelly L Williams, Ian P Blair, Jennifer Jockel-Balsarotti, Lyndal Henden, Garth A Nicholson, Timothy Miller, Diane McKenna-Yasek, Robert H Brown, William Camu, Zorica Stevic, Lu Tang, Dong-sheng Fan. We thank people with MND and their families for their participation in this project. We acknowledge sample management undertaken by Biobanking Solutions funded by the Medical Research Council at the Center for Integrated Genomic Medical Research, University of Manchester. The authors acknowledge use of the research computing facility at King”s College London, Rosalind ( https://rosalind.kcl.ac.uk ), which is delivered in partnership with the National Institute for Health and Care Research (NIHR) Biomedical Research Centers at South London and Maudsley and Guy”s and St. Thomas” NHS Foundation Trusts, and part-funded by capital equipment grants from the Maudsley Charity (award 980) and Guy”s and St. Thomas” Charity (TR130505). The authors also acknowledge the use of the CREATE research computing facility at King”s College London (). We also acknowledge Health Data Research UK, which is funded by the UK Medical Research Council, Engineering and Physical Sciences Research Council, Economic and Social Research Council, Department of Health and Social Care (United Kingdom), Chief Scientist Office of the Scottish Government Health and Social Care Directorates, Health and Social Care Research and Development Division (Welsh Government), Public Health Agency (Northern Ireland), British Heart Foundation and Wellcome Trust. Publisher Copyright: {\textcopyright} 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.",
year = "2023",
month = aug,
day = "3",
doi = "10.1080/21678421.2023.2236650",
language = "English",
journal = "Amyotrophic lateral sclerosis & frontotemporal degeneration",
issn = "2167-8421",
publisher = "Taylor & Francis",
}