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Antisense oligonucleotide therapy for calmodulinopathy

GSE245945 Homo sapiens (human) RNA-seq (gene expression) 18 samples Submitted 2024/06/13 Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 18 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
18 samples
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
Antisense Oligonucleotide Therapy for CalmodulinopathyCirculation · 2024
Summary (written by the submitters)
Calmodulinopathies are rare inherited arrhythmia syndromes caused by dominant gain of function variants in one of three genes, CALM1, CALM2, and CALM3, which each encode the identical calmodulin (CaM) protein. We hypothesized that antisense oligonucleotide (ASO)-mediated depletion of an affected calmodulin gene would ameliorate disease manifestations, while the other two calmodulin genes would preserve CaM level and function.
Read the full summary ↓
Here we tested this hypothesis using human induced pluripotent stem cell-derived cardiomyocyte (iPSC-CM) and mouse models of CALM1 pathogenic variants. Human CALM1F142L/+ iPSC-CMs exhibited prolonged action potentials, modeling congenital long QT syndrome. CALM1-depleting ASOs did not alter CaM protein level and normalized repolarization of CALM1F142L/+ iPSC-CMs. Similarly, an ASO targeting murine Calm1 depleted Calm1 transcript without affecting CaM protein level. This ASO alleviated drug-induced arrhythmia in CalmN98S/+ mice without causing observable toxicity. These results provide proof-of-concept that ASOs targeting individual calmodulin genes are potentially effective and safe therapies for calmodulinopathies.
Published in
Antisense Oligonucleotide Therapy for Calmodulinopathy
Bortolin RH, Nawar F, Park C et al. · Circulation 2024 · PMID 39155863 · doi:10.1161/CIRCULATIONAHA.123.068111
This dataset
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.

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 GSE245945_RAW.tar (it can run to tens of gigabytes).

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.

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 PRJNA1030420 and SRA study SRP467595. Searching any of these in the dataset finder brings you back here.

Samples in this study

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