GEO series

NGLY1 mutations cause protein aggregation in human neurons

GSE197454 Homo sapiens (human) RNA-seq (gene expression) 16 samples Submitted 2025/02/13 Platform GPL16791

At a glance

RNA-seq (gene expression) · human · 16 samples

What it is: RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism: Homo sapiens (human)
Samples: 16 samples: 8 conditions, mostly in duplicateGroups are read from the sample names, not from the paper. Check the list below.
Data you can get: A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper: NGLY1 mutations cause protein aggregation in human neuronsCell reports · 2023

Summary (written by the submitters)

Biallelic mutations in the gene that encodes the enzyme N-glycanase 1 (NGLY1) cause a rare disease with multi-symptomatic features including developmental delay, intellectual disability, neuropathy and seizures. NGLY1’s activity in human neural cells is currently not well understood. To understand how NGLY1 gene loss leads to the specific phenotypes of NGLY1 deficiency, we employed direct conversion of NGLY1 patient-derived induced pluripotent stem cells (iPSCs) to functional cortical neurons.

Read the full summary ↓

Transcriptomic, proteomic, and functional studies of iPSC-derived neurons lacking NGLY1 function revealed several major cellular processes that were altered, including protein aggregate-clearing functionality, mitochondrial homeostasis, and synaptic dysfunctions. These phenotypes were rescued by introduction of a functional NGLY1 gene and were observed in iPSC-derived mature neurons, but not astrocytes. Finally, laser capture microscopy followed by mass spectrometry provided detailed characterization of the composition of protein aggregates specific to NGLY1-deficient neurons. Future studies will harness this knowledge for therapeutic development.

Published in

NGLY1 mutations cause protein aggregation in human neurons

Manole A, Wong T, Rhee A et al. · Cell reports 2023 · PMID 38039131 · doi:10.1016/j.celrep.2023.113466

This dataset

Open GSE197454 in finder → Find more human RNA-seq datasets →

Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓

2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE197454_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓

3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA810420 and SRA study SRP361462. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 38039131) ↗

Study design

8 conditions, mostly in duplicate

Mut1_cl1_patient_wk ×2 Mut2_cl2_patient_wk ×2 Mut1_cl2_patient_wk ×2 Mut2_cl1_patient_wk ×2 Mut3_cl1_patient_wk ×2 WT1_cl1_control_wk ×2 WT2_cl1_control_wk ×2 WT3_cl1_control_wk ×2

Supports a case/control comparison: 10 samples read as cases, 6 as controls.

How we read this: 8 replicated groups read from 16 sample titles; they account for 16 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study

GSM5917813 Mut1_cl1_patient_wk4 Mut1_cl1_patient_wk
GSM5917814 Mut2_cl2_patient_wk4 Mut2_cl2_patient_wk
GSM5917815 Mut1_cl2_patient_wk4 Mut1_cl2_patient_wk
GSM5917816 Mut2_cl1_patient_wk4 Mut2_cl1_patient_wk
GSM5917817 Mut3_cl1_patient_wk4 Mut3_cl1_patient_wk
GSM5917818 WT1_cl1_control_wk4 WT1_cl1_control_wk
GSM5917819 WT2_cl1_control_wk4 WT2_cl1_control_wk
GSM5917820 WT3_cl1_control_wk4 WT3_cl1_control_wk
GSM5917821 Mut1_cl1_patient_wk2 Mut1_cl1_patient_wk
GSM5917822 Mut2_cl2_patient_wk2 Mut2_cl2_patient_wk
GSM5917823 WT1_cl1_control_wk2 WT1_cl1_control_wk
GSM5917824 WT3_cl1_control_wk2 WT3_cl1_control_wk
GSM5917825 WT2_cl1_control_wk2 WT2_cl1_control_wk
GSM5917826 Mut3_cl1_patient_wk2 Mut3_cl1_patient_wk
GSM5917827 Mut2_cl1_patient_wk2 Mut2_cl1_patient_wk
GSM5917828 Mut1_cl2_patient_wk2 Mut1_cl2_patient_wk

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