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Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration Volume 24, 2023 - Issue 7-8
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Genomics

SOD1-ALS-Browser: a web-utility for investigating the clinical phenotype in SOD1 amyotrophic lateral sclerosis

Thomas P Spargo1 Maurice Wohl Clinical Neuroscience Institute, King”s College London, Department of Basic and Clinical Neuroscience, London, UK;2 NIHR Maudsley Biomedical Research Centre (BRC) at South London and Maudsley NHS Foundation Trust and King”s College London, London, UKView further author information
,
Sarah Opie-Martin1 Maurice Wohl Clinical Neuroscience Institute, King”s College London, Department of Basic and Clinical Neuroscience, London, UKORCID Iconhttps://orcid.org/0000-0003-0951-8589View further author information
ORCID Icon,
Guy P Hunt3 Department of Biostatistics and Health Informatics, King”s College London, London, UK;4 Perron Institute for Neurological and Translational Science, Nedlands, WA, 6009, Australia;5 Centre for Molecular Medicine and Innovative Therapeutics, Murdoch University, Murdoch, WA, 6150, AustraliaView further author information
,
Munishikha Kalia1 Maurice Wohl Clinical Neuroscience Institute, King”s College London, Department of Basic and Clinical Neuroscience, London, UK;2 NIHR Maudsley Biomedical Research Centre (BRC) at South London and Maudsley NHS Foundation Trust and King”s College London, London, UKView further author information
,
Ahmad Al Khleifat1 Maurice Wohl Clinical Neuroscience Institute, King”s College London, Department of Basic and Clinical Neuroscience, London, UKORCID Iconhttps://orcid.org/0000-0002-7406-9831View further author information
ORCID Icon,
Simon D Topp1 Maurice Wohl Clinical Neuroscience Institute, King”s College London, Department of Basic and Clinical Neuroscience, London, UKView further author information
,
Christopher E Shaw1 Maurice Wohl Clinical Neuroscience Institute, King”s College London, Department of Basic and Clinical Neuroscience, London, UK;6 UK Dementia Research Institute Centre at King”s College London, School of Neuroscience, King”s College London, Strand, London, WC2R 2LS, UK;7 Centre for Brain Research, University of Auckland, 85 Park Road, Grafton, Auckland, 1023, New ZealandView further author information
,
Ammar Al-Chalabi1 Maurice Wohl Clinical Neuroscience Institute, King”s College London, Department of Basic and Clinical Neuroscience, London, UK;8 King”s College Hospital, Bessemer Road, London, SE5 9RS, UKView further author information
,
Alfredo Iacoangeli1 Maurice Wohl Clinical Neuroscience Institute, King”s College London, Department of Basic and Clinical Neuroscience, London, UK;2 NIHR Maudsley Biomedical Research Centre (BRC) at South London and Maudsley NHS Foundation Trust and King”s College London, London, UK;3 Department of Biostatistics and Health Informatics, King”s College London, London, UKCorrespondence[email protected]
ORCID Iconhttps://orcid.org/0000-0002-5280-5017View further author information
ORCID Icon & The Project Mine ALS Sequencing Consortium show all
Pages 736-745 | Received 18 Apr 2023, Accepted 30 Jun 2023, Published online: 03 Aug 2023

Figures & data

Table 1. Data summary for case studies. For disease duration analysis, restricted mean and median estimates are obtained from the survival curve and the standard error (SE) and 95% confidence interval (CI) indicates certainty in this estimate; the distribution of disease duration in non-censored individuals is reported directly. In age of onset analysis no person is censored, therefore estimates correspond with the raw descriptive statistics. *Minimum and maximum shown because disease duration was only available for two people. SD = standard deviation.

Figure 1 Variant characteristics for the native dataset. Panel A: The canonical SOD1 amino acid sequence (bold) and variants recorded at each residue, denoted using IUPAC amino acid nomenclature (Citation16), where “X” indicates protein truncating variants. Alternating background shading indicates residues encoded from different exons of the SOD1 gene. Panel B: The number of variants with at least a certain number of records available across different thresholds.

Figure 1 Variant characteristics for the native dataset. Panel A: The canonical SOD1 amino acid sequence (bold) and variants recorded at each residue, denoted using IUPAC amino acid nomenclature (Citation16), where “X” indicates protein truncating variants. Alternating background shading indicates residues encoded from different exons of the SOD1 gene. Panel B: The number of variants with at least a certain number of records available across different thresholds.

Table 2 Inferential statistics for survival analyses across case studies. Bold values denote nominal p values <0.05. * controlling for sex in the age of onset analysis and for sex and age of onset in the disease duration analysis. #Hazard ratios greater than 1 indicate earlier age of onset/shorter disease duration in the non-reference group. †No p.G94S variants were available for the disease duration analysis. CPH = Cox proportional-hazards.

Figure 2 Kaplan-Meier survival curves for age of onset and disease duration analyses. Analysis shown: Panels A-B: trends associated with wild type and variant amino acid hydrophobicity; Panels C-D: Any SOD1 p.G94 variant versus non-p.G94 SOD1 variants (OtherVariant). Panels E-F: individual p.G94 variants versus non-p.G94 SOD1 variants. Panels A, C, and E are for age of onset analysis, and B, D, and F describe disease duration. Panels A and B display all hydrophobicity groups in a single figure for each analysis and confidence intervals are not displayed to maximize visual clarity; Figure S1 visualizes trends in age of onset and disease duration for these groups after stratifying across panels according to the hydrophobicity group of the wild type residue.

Figure 2 Kaplan-Meier survival curves for age of onset and disease duration analyses. Analysis shown: Panels A-B: trends associated with wild type and variant amino acid hydrophobicity; Panels C-D: Any SOD1 p.G94 variant versus non-p.G94 SOD1 variants (OtherVariant). Panels E-F: individual p.G94 variants versus non-p.G94 SOD1 variants. Panels A, C, and E are for age of onset analysis, and B, D, and F describe disease duration. Panels A and B display all hydrophobicity groups in a single figure for each analysis and confidence intervals are not displayed to maximize visual clarity; Figure S1 visualizes trends in age of onset and disease duration for these groups after stratifying across panels according to the hydrophobicity group of the wild type residue.
Supplemental material

Supplemental Table

Download MS Excel (27.6 KB)

Data availability statement

All data associated with this manuscript can be accessed from the web-utility: https://sod1-als-browser.rosalind.kcl.ac.uk/.

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