Welcome to the SOD1-ALS-Browser website. This tool allows analysis of trends in the clinical presentation of amyotrophic lateral sclerosis (ALS) across user-defined disease subgroups.
It provides access to a large built-in dataset of people with and without mutations in SOD1.
Users are invited to apply these data, alone or with their own supplemental dataset, within the customisable analysis protocol available here.
Several pre-defined analyses can be performed using the buttons below and user-defined analysis groups can be specified using individual SOD1 variants or by aggregating across multiple variants with the 'manually select or aggregate across groups' option. A non-SOD1 comparator group can be included in these analyses, along with any additional groups from the supplemental data.
We emphasise that since the quantity of data varies greatly by variant, robust analysis may require aggregation across select subgroups.
While we hope that this tool is useful research purposes, the results of analyses performed should not be interpreted as a reliable prognostic indicator for individuals living with or at risk of developing ALS.
Define analysis strata:
Set optional parameters (click to show options):
Include samples collected from selected regions
Select options for dataset filtering; values selected will be included as strata within subsequent survival analyses. Note:
When using manual variant selection, filtering should be performed before selecting variants or variant groups of interest
Variables used in filtering cannot be selected as covariates in Cox regression; filtering options will be deactivated according to the covariates selected
The country list will only include those with data available according to the other indicated filtering options, including the region filtering above
Options for filtering will reset whenever a supplementary dataset is uploaded
Cox analysis configuration
Select strata (groups) for survival analysis
Define all variants and then press 'run analysis' to perform survival analysis.
Define all variants within a group and press 'define group'.
Press 'run analysis' once all groups are defined to perform survival analysis.
The reference SOD1 amino acid sequence of the dataset integrated within this app is aligned with methionine as the first amino acid by default.
Examples of SOD1 variants often linked to ALS include: A5V, D91A, and I114T.
The dataset can be realigned to exclude the first methionine by checking the 'Realign amino acid sequence...' field to the right.
The prior variant examples would then be coded: A4V, D90A, I113T.
Site_of_onset: Site of ALS onset (numeric: 0=bulbar, 1=mixed, 2=respiratory, 3=spinal)
Iso2c_country_code: Country of origin (character string: Denote using iso Alpha-2 code; see the iso website for details)
Missing values should be denoted using either '.' or 'N/A'.
Any empty columns in data uploaded should also be denoted in this way.
SOD1 sequence alignment
The dataset native to this tool is coded by default to include methionine at the start of the SOD1 amino acid sequence.
Correspondence in sequence allignment is expected between the native dataset and any supplementary data provided.
If the supplementary data does not include methionine at the start of the SOD1 amino acid sequence then please check the box above to
realign the native dataset accordingly, subtracting 1 from the amino acid position of each variant.
A warning may be shown if the reference sequence of protein changes included in supplementary data deviate from the expected alignment.
Data storage notice
Data uploaded to this tool are available as part of the user's session only and are removed when they disconnect or overwritten if a second supplementary dataset is uploaded.
We provide an example of a csv file which could be uploaded as supplementary data to this tool.
This provides examples of several allowed configurations for input data.
This example data includes real SOD1 variants but the data points were otherwise generated randomly.
Overview of analysis strata. Descriptive statistics are provided based on all raw data in age of onset analysis and people who are not censored in disease duration analysis. 'Estimated' values for median and mean are also shown based on the survival curve calculated by survfit, which takes into account any censoring in data. SE (standard error) and 95% CI (confidence intervals) pertain to estimated median/restricted means from the survival analysis. SD (standard deviation) and quartiles are associated with the raw data.
The following boxplots show the distribution of estimated median (blue) and restricted mean (green) age of onset (left panel) and disease duration (right panel) in analysis of the subgroups which have been aggregated into the strata of the main analyses. If the subgroup-level estimates (shown also as points) differ substantially, then the main analysis may have obscured heterogeneity in the data. Please note that estimates made for subgroups with very few records in the dataset could more easily appear as outliers as data would be insufficient for a reliable estimate.
Descriptive overview (select covariate)
Age of onset analysis
Kaplan-Meier survival curve
Differences between strata
Cox proportional-hazards model
Time-dependent effects can be examined by testing associations within a given time-interval or by specifying multiple intervals and a time-dependent variable.
Please note that sample sizes will inherently decrease at later time-points and estimate precision will decrease.
Simulated survival after controlling for covariates
Cox PH coefficients
SOD1 amino acid sequence variants represented in dataset. The canonical SOD1 amino acid sequence is shown along the bottom of the figure and all variants are displayed with respect to these positions using IUPAC amino acid nomenclature, using 'X' to denote protein truncating variants. Alternating background shading indicates residues encoded from different gene exons.
Descriptive statistics of raw data for variants occuring at least 5 times in the native dataset.
Number of records
N including age of onset
N including disease duration [N censored]
N Male: N Female [% male]
Site of onset, N bulbar: spinal: respiratory: mixed
Mean age of onset [SD] (years)
Median diagnostic delay [range] (months)
Median disease duration in people non-censored [range] (months)
Please cite all of the associated publications for any work which makes use of this resource.
A manuscript describing this app is available at:
Spargo, T. P., Opie-Martin, S., Hunt, G. P., Kalia, M., Al Khleifat, A., Topp, S. D., ..., & Iacoangeli, A. (2023). SOD1-ALS-Browser: a web-utility for investigating the clinical phenotype in SOD1 amyotrophic lateral sclerosis. Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, 1-10. doi: 10.1080/21678421.2023.2236650.
The built-in dataset was initially collected for the following study:
Opie-Martin, S., Iacoangeli, A., Topp, S. D., Abel, O., Mayl, K., Mehta, P. R., ..., & Shaw, C. E. (2022). The SOD1-mediated ALS phenotype shows a decoupling between age of symptom onset and disease duration. Nature Communications, 13(6901), 1-9. doi: 10.1038/s41467-022-34620-y.
Survival analysis is performed using the R survival package: