A resource of lipidomics and metabolomics data from individuals with undiagnosed diseases

Abstract

Every year individuals experience symptoms that remain undiagnosed by healthcare providers. In the United States, these rare diseases are defined as a condition that affects fewer than 200,000 individuals. However, there are an estimated 7000 rare diseases, and there are an estimated 25-30 million Americans in total (7.6-9.2% of the population as of 2018) affected by such disorders. The NIH Common Fund Undiagnosed Diseases Network (UDN) seeks to provide diagnoses for individuals with undiagnosed disease. Mass spectrometry-based metabolomics and lipidomics analyses could advance the collective understanding of individual symptoms and advance diagnoses for individuals with heretofore undiagnosed disease. Here, we report the mass spectrometry-based metabolomics and lipidomics analyses of blood plasma, urine, and cerebrospinal fluid from 148 patients within the UDN and their families, as well as from a reference population of over 100 individuals with no known metabolic diseases. The raw and processed data are available to the research community so that they might be useful in the diagnoses of current or future patients suffering from undiagnosed disorders.

Fig. 1

Overview of the study design. Biofluid samples were collected from probands at the UDN clinical sites and then extracted for metabolomics (urine, plasma, CSF) and lipidomics (plasma and CSF) analyses using chromatography coupled to mass spectrometry (GC-MS for metabolomics and LC-MS/MS for lipidomics). Data were pre-processed, including data quality checks, normalized, and compared against data from the reference population of healthy individuals. Metabolomics and lipidomics results in the form of Z-score, log2 fold change and p-value per metabolite and lipid of the proband (and associated family members, if applicable) were reported back to the respective UDN Clinical Site for diagnostic assistance.

Fig. 2

Z-score map of plasma lipidomics data for all UDN individuals (n = 294). One proband (P) and her mother (M) had samples analysed in multiple batches over the course of one year. The proband’s samples were collected at different times for each batch and analysed on the MS in October 2016 (2 batches, 2 samples per batch) and October 2017 (1 batch, 5 samples). The proband’s lipid profile remained very similar between each analysis batch. Top coloured bar indicates the different batches over time.