GEO series

Nonclinical cardiovascular safety evaluation of romosozumab, an inhibitor of sclerostin for the treatment of osteoporosis in postmenopausal women at high risk of fracture

GSE142634 Mus musculus (mouse) RNA-seq (gene expression) 29 samples Submitted 2020/12/31 Platform GPL13112

At a glance

RNA-seq (gene expression) · mouse · 29 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: Mus musculus (mouse)
Samples: 29 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.

Summary (written by the submitters)

Romosozumab is a humanized monoclonal antibody that inhibits sclerostin, an extracellular inhibitor of the canonical Wnt signaling pathway, expressed in osteocytes. Romosozumab results in increased bone formation and decreased bone resorption and has been approved in several countries for the treatment of osteoporosis in postmenopausal women at high risk of fracture.

Read the full summary ↓

Sclerostin is also expressed in aortic vascular smooth muscle cells, the function of which is unclear but has been proposed to be an inhibitor of vascular calcification, atheroprogression, and associated inflammation. A slight increase in serious cardiovascular adverse events (CV AEs) was observed in romosozumab-treated subjects in a clinical trial comparing alendronate with romosozumab (ARCH; NCT01631214) but was not observed in a placebo-controlled trial (FRAME; NCT01575834). To investigate biological plausibility of the role of romosozumab in cardiovascular disease, a comprehensive nonclinical package with additional cardiovascular studies was conducted including studies in two murine models of atherosclerosis. Results of these studies demonstrated that the effects of romosozumab or a surrogate sclerostin antibody were either a direct or indirect consequence of its pharmacodynamic effects on bone. There were with no functional or morphologic effects on the cardiovascular system in animal models in the presence or absence of atherosclerosis. The totality of these nonclinical data has not identified a biologically plausible mechanism to explain the increase in serious CV AEs in the ARCH trial.

This dataset

Open GSE142634 in finder → Find more mouse 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 GSE142634_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 PRJNA597784 and SRA study SRP238852. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗

Samples in this study

The sample list for this study is not cached yet. Press Load samples and it will be fetched from NCBI.

+ 29 more — browse all 29 samples with per-sample file links →

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Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.