Untargeted Metabolomics Data Analysis. Data were processed with Compound Discoverer (Thermo Fischer Scientific) in an untargeted workflow that included spectral selection, retention time alignment, compound detection and grouping, gap filling, background filtering, and constant median normalization. MS2-based identities were assigned by scoring fragmentation patterns against the mzCloud and mzVault databases. A filtering process then generated a manually annotated compound table, with features assigned the highest level of confidence based on the following criteria: signal-to-noise ratio > 3, mzCloud or mzVault match score > 50, mass error within ±5 ppm, match to an in-house MS1_RT library within ±10 sec, and acceptable chromatographic peak and MS2 spectral quality.
"],"repository":["MetaboLights"],"study_status":["Public"],"ptm_modification":[""],"instrument_platform":["Liquid Chromatography MS - negative - hilic-(hydrophilic-interaction-liquid-chromatography)-/-beh-amide"],"chromatography_protocol":["Metabolites were separated on a Thermo Vanquish Horizon LC system using a Waters Premier BEH Amide column (150 mm × 2.1 mm). Mobile phase A was 10 mM ammonium bicarbonate in 5% acetonitrile (pH 9.0) and mobile phase B was 10 mM ammonium bicarbonate in 95% acetonitrile. Gradient separation transitioned from 99% B to 30% B over 12 min. Injection volume was 3.5 μL at a flow rate of 0.4 μL/min. The column temperature was maintained at 40°C and the autosampler at 5°C.
"],"publication":["Autophagy regulator ATG7 links lipid metabolism to proximal tubule cell-fate decisions in health and disease."],"submitter_affiliation":["FGCZ","Insilico Medicine"],"submitter_name":["Mikhail Korzinkin","Martina Zanella"],"organism_part":["urine"],"technology_type":["mass spectrometry assay"],"disease":[""],"extraction_protocol":["Extraction. Twenty microliters of creatinine-normalized urine were mixed with 80 μL of pre-cooled methanol. The mixture was incubated at –20°C for 1 h, then centrifuged at 10,000 rpm for 10 min at 4°C. The supernatant was transferred to a clean test tube, dried under a nitrogen stream, and reconstituted in an injection buffer (90% acetonitrile). Following a second vortex and centrifugation (10,000 rpm, 4°C, 10 min), the clear supernatant was transferred to Total Recovery Vials (Waters) for LC-MS injection. Method blanks, standard mixes, and pooled samples were prepared identically to serve as quality controls.
"],"organism":["Homo sapiens"],"full_dataset_link":["https://www.ebi.ac.uk/metabolights/MTBLS15856"],"author":["Alessandro Luciani. Institute of Physiology, University of Zurich. University of Zurich, 8057 Zurich, Switzerland. alessandro.luciani@physiol.uzh.ch.","Mikhail Korzinkin. Insilico Medicine. mike@insilicomedicine.com.","Martina Zanella. martina.zanella@fgcz.ethz.ch."],"data_transformation_protocol":["Raw files were processed using Compound Discoverer (Thermo Fisher Scientific) following an untargeted workflow: spectral selection, retention time alignment, compound detection, grouping, gap filling, background filtering, and constant median normalization. Spectral identification was performed by scoring MS2 fragmentation against mzCloud and mzVault databases. Features were filtered using signal-to-noise ratio > 3, match score > 50, mass error within ±5 ppm, and RT match within ±10 s against an in-house library.
"],"study_factor":["Patient atg7"],"submitter_email":["martina.zanella@fgcz.ethz.ch","mike@insilicomedicine.com"],"sample_collection_protocol":["Patients with an established diagnosis of ATG7-related spinocerebellar ataxia (MIM 619422), i.e. with biallelic pathogenic ATG7 variants were recruited (Family 1; ref.22). Written informed consent was obtained from the parents of the siblings in the study and controls following the Declaration of Helsinki protocols, and the experimental protocol was approved by the local institutional review board. Urine samples were collected in the morning and kept at 4°C before it was frozen at -80 °C. For immunoblot analysis, the loading volume was indexed to creatinine to correct for variations in urine concentration. Urinary creatinine levels were measured using UniCel DxC 800 proSynchron (Beckman Coulter, Fullerton, CA, USA), according to manufacturer instructions. Urinary Lipocalin 2 (LCN2) levels were measured using human LCN2/NGAL Quantikine ELISA Kit (DLCN20, Biotechne, Switzerland).
"],"omics_type":["Metabolomics"],"study_design":["ultra-performance liquid chromatography-mass spectrometry","Human","Metabolomics","Patient Atg7","Control","urine","untargeted analysis","Vanquish Horizon","Homo sapiens","Compound Discoverer","Orbitrap","Thermo Scientific Q Exactive Plus"],"curator_keywords":["ultra-performance liquid chromatography-mass spectrometry","Human","Metabolomics","Control","Patient Atg7","untargeted analysis","urine","Vanquish Horizon","Homo sapiens","Compound Discoverer","Orbitrap","Thermo Scientific Q Exactive Plus"],"mass_spectrometry_protocol":["Mass spectrometry was performed on a Thermo Q Exactive mass spectrometer coupled via a HESI source. Data were acquired in negative ion mode using a Full MS/dd-MS² (Top5) scan function across an m/z range of 70–1050. Resolving power was set to 70,000 for MS1 and >17,500 for MS2.
"],"additional_accession":[]},"is_claimable":false,"name":"Urine metabolomic profiling in two siblings with biallelic pathogenic ATG7 variants with healthy control","description":"Ultra-rare biallelic ATG7 variants were recently reported in five families presenting with neurodevelopmental disorders. Two adult female siblings (P1 and P2) from one family carried compound heterozygous loss-of-function variants (c.1975C>T [p.Arg659]; c.2080-2A>G, 39,40NM_006395.2), resulting in undetectable ATG7 protein in multiple tissues. This prompted us to test whether a congenital lack of ATG7 in humans might also cause tubular proteinuria and tubulopathy. While classical markers of PT injury (LCN2/NGAL) and tubular proteinuria (e.g., RBP, aminoaciduria) were absent in both siblings, P2 showed elevated urinary CC16 — a sensitive LMW PT dysfunction marker — compared to P1 and healthy controls. Urine metabolomic profiling revealed distinct metabolic signatures in both siblings relative to controls. Notably, P2 exhibited enrichment in pathways related to glucose, amino acid, and nucleotide metabolism, fatty acid degradation, the TCA cycle, and cancer metabolism, paralleling the metabolic abnormalities observed in ATG7-deficient preclinical models.","dates":{"publication":"2026-09-30","submission":"2026-09-29"},"accession":"MTBLS15856","cross_references":{}}