DOI: 10.34894/j9mzro
title: Diminished plasma serotonin and taurine levels are a metabolic feature of age-related macular degeneration
title: Dataset and scripts

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&lt;p&gt;This dataset contains metabolomics data from samples collected from patients with Age-Related Macular Degeneration (AMD) and control participants. The data includes processed metabolomic measurements, clinical data, and genetic risk scores (GRS) for each sample, as well as allele scores for 52 single nucleotide polymorphisms (SNPs) associated with AMD.&lt;/p&gt;

&lt;h3&gt;Information about the data:&lt;/h3&gt;

&lt;h4&gt;The dataset contains &lt;b&gt;99 samples&lt;/b&gt;, which are organized as follows:&lt;/h4&gt;
&lt;ul&gt;
 &lt;li&gt;&lt;strong&gt;Controls&lt;/strong&gt; (noAMD): 39 samples&lt;/li&gt;
 &lt;li&gt;&lt;strong&gt;Early / Intermediate AMD&lt;/strong&gt; (eAMD): 21 samples&lt;/li&gt;
 &lt;li&gt;&lt;strong&gt;Late AMD&lt;/strong&gt; (lAMD): 39 samples&lt;/li&gt;
&lt;/ul&gt;

One AMD sample (I-AMD 041) and one control sample (I-AMD HC 021) were excluded from the analysis. These samples remain in the dataset but were not included in the analysis due to diagnoses of unrelated disease conditions after sampling that did not meet the study's inclusion criteria.

&lt;h3&gt;Information about the uploaded dataset files:&lt;/h3&gt;
&lt;p&gt;A complete overview of all data files is described in &lt;a href="https://dataverse.nl/api/access/datafile/607664"&gt;README&lt;/a&gt;.&lt;/p&gt;

&lt;p&gt;Go to the Files tab and click on "Change view to Tree" to view the folder structure. The dataset consists of the following main parts:&lt;/p&gt;
&lt;ul&gt;
&lt;li&gt;&lt;a href="https://dataverse.nl/api/access/datafile/607634"&gt;&lt;b&gt;paper_analysis.Rmd&lt;/b&gt;&lt;/a&gt;, which is used to perform statistical analysis and generate figures and tables for the paper (see also &lt;a href="https://dataverse.nl/api/access/datafile/607665"&gt;paper_analysis.html&lt;/a&gt;). This RMD file relies on the functions defined in &lt;a href="https://dataverse.nl/api/access/datafile/607630" &gt;00_functions.R&lt;/a&gt; from the &lt;b&gt;R&lt;/b&gt; folder.&lt;/li&gt;

 &lt;li&gt;The &lt;b&gt;Data&lt;/b&gt; folder, containing both the raw and processed data files, as well as metadata files.&lt;/li&gt;
 &lt;li&gt;The &lt;b&gt;Output&lt;/b&gt; folder, which stores the results of the analysis, including figures, tables, and cached data files.&lt;/li&gt;
 &lt;li&gt;The &lt;b&gt;R&lt;/b&gt; folder, containing the R scripts used for data processing and analysis.&lt;/li&gt;
 &lt;li&gt;The &lt;b&gt;External Files&lt;/b&gt; folder, containing any additional external resources such as figure made in illustrator.&lt;/li&gt;
&lt;/ul&gt;

&lt;p&gt;All folders have been organized and uploaded in a way that aligns with the structure of an R project. If you download all the files at once, you can directly load the dataset into an R environment, and the folder structure will be preserved, allowing you to use the project seamlessly without any further setup.&lt;/p&gt;

&lt;h4&gt;The &lt;b&gt;Metadata&lt;/b&gt; folder:&lt;/h4&gt;

&lt;p&gt;The metadata for the study consists of clinical and genetic information. The &lt;a href="https://dataverse.nl/api/access/datafile/607649"&gt;`clinicaldata.csv`&lt;/a&gt; file contains clinical details for all participants, such as sex, age, smoking status, AMD stage, and medication usage. The &lt;a href="https://dataverse.nl/api/access/datafile/607651"&gt;`GRS_df.csv`&lt;/a&gt; file includes genetic risk scores (GRS-52) and allele scores for 52 SNPs associated with AMD risk. These two files were merged into &lt;a href="https://dataverse.nl/api/access/datafile/607647"&gt;`participant_info.csv`&lt;/a&gt; using the &lt;a href="https://dataverse.nl/api/access/datafile/607639"&gt;`R/01_metadata_processing.R`&lt;/a&gt; script, which combined the metadata for analysis.&lt;/p&gt;


&lt;h4&gt;The &lt;b&gt;Data&lt;/b&gt; folder:&lt;/h4&gt;

&lt;p&gt;The raw data for the metabolomics analysis is provided in the &lt;a href="https://dataverse.nl/api/access/datafile/607645"&gt;`Results_P-21050.zip`&lt;/a&gt; archive, which contains the experimental results. Additionally, the &lt;a href="https://dataverse.nl/api/access/datafile/607626"&gt;`Quant_500_Metabolic_Indicators.csv`&lt;/a&gt; file provides metabolic indicators used in the analysis, including formulas and identifiers. These raw data files are processed using the &lt;a href="https://dataverse.nl/api/access/datafile/607642"&gt;`R/02_data_processing.R`&lt;/a&gt; script, which performs preprocessing of the data for further analysis.&lt;/p&gt;
&lt;p&gt;The processed data includes multiple versions of the metabolomics data after various processing steps, including normalization, filtering, Box-Cox transformation, and standardization relative to controls. The following files are included:&lt;/p&gt;
&lt;ul&gt;
 &lt;li&gt;&lt;a href="https://dataverse.nl/api/access/datafile/607627"&gt;`mdat_wmi_nf.csv`&lt;/a&gt;: CSV file with metabolomics data that has been normalized and filtered.&lt;/li&gt;
 &lt;li&gt;&lt;a href="https://dataverse.nl/api/access/datafile/607656"&gt;`mdat_wmi_nfb.csv`&lt;/a&gt;: CSV file containing metabolomics data with normalization, filtering, and Box-Cox transformation applied.&lt;/li&gt;
 &lt;li&gt;&lt;a href="https://dataverse.nl/api/access/datafile/607657"&gt;`mdat_wmi_nfbs.csv`&lt;/a&gt;: CSV file with metabolomics data that has undergone normalization, filtering, Box-Cox transformation, and standardization relative to controls.&lt;/li&gt;
&lt;/ul&gt;

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description: R, 4·4.2 (2024-10-31)
description: Age-related macular degeneration (AMD) is a leading cause of vision loss in older adults, but its precise pathogenic mechanisms remain incompletely understood. The emerging evidence suggests that metabolic alterations contribute to AMD, but this has not been exhaustively investigated and may provide new insights into the disease's pathophysiology. This study compares the metabolic profiles of peripheral blood plasma of early and late AMD patients with controls without AMD. Peripheral blood plasma was profiled with a 622-plex targeted metabolomic array using liquid chromatography–mass spectrometry in patients with early AMD (n = 21), late AMD (n = 39), and control participants without AMD (n = 39). The study participants underwent ophthalmological examinations and imaging and were classified as AMD according to the criteria of the Age-Related Eye Disease Study (AREDS). The AMD Genetic Risk Score (GRS-52) was calculated using genotype data obtained from the custom SNP assay. No metabolites were significantly associated with the GRS-52 (or individual risk variants). Using a regression model correcting for age, sex, and smoking status, we identified significant changes in 3 small molecules, 5 lipids, and 5 metabolic indicators between late AMD patients (n = 39) and controls (n = 39). The plasma levels of these metabolites increased or decreased incrementally from control, to early, to late AMD, following the disease's clinical course. A strong decrease in plasma serotonin (P = 1.03 × 10-13) and taurine (P = 2.36 × 10-9) were the most significant metabolic changes detected. The decrease of serotonin in AMD patients could not be attributed to serotonin reuptake inhibitors (SRIs) use. Analysis of predefined sums and ratios of metabolites (metaboINDICATOR™ analysis) confirmed a strong reduction in serotonin and taurine synthesis in late AMD (P = 4.41 × 10-14; P = 2.3 × 10-29). These findings suggest that AMD is characterized by metabolic changes in peripheral blood plasma, including a strong and clinically progressive depletion of plasma serotonin and taurine levels.
description: Error corrected in data request information.