Excel · study · 2026
A Liquid biopsy-RNAseq Method for Monitoring the Expression of Genes Involved in Drug Disposition: Proof-of-Concept Application to Cholestatic Disease
Listed in NCBI GEO
Between-patient variability in metabolism and disposition of therapeutic drugs is associated with variable expression and activity of enzymes and drug transporters.
Description
Direct measurement of the expression of such proteins in relevant organs is limited by access to tissue biopsies. Characterization of such pathways in plasma-derived extracellular vesicles (EVs) as liquid biopsy is proposed herein as a minimally invasive and widely accessible alternative to tissue biopsy.
This report provides a technical account for the extraction, characterization and RNAseq of EVs from two sets of healthy and cholestatic plasma samples (n = 3). Quality controls (QCs) implemented at different stages of the protocol ensured quality of the EVs and extracted RNA for downstream analysis. These QCs included visualization, size distribution, protein content and RNA quality and yield.
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Extracted EVs were a mixture of small and large vesicles (35-350 nm). Replicate RNAseq data reflected strong correlation (Pearson r = 1, p < 0.001), low bias (average fold error = 1), and limited scatter (absolute average fold error = 1.34) across replicates. The method was able to monitor cfRNA expression of 656 pharmacologically relevant genes, including 199 xenobiotic-metabolizing enzymes, 444 transporters, and 11 transcription factors.
Disease perturbation in expression from healthy baseline was estimated for 93% of monitored pharmacokinetic pathways. The data, along with demographic and plasma albumin changes, were used to generate a Cholestasis Population pharmacokinetic model. The model reflected exposure to budesonide and cyclosporine consistent with early-stage cholestasis.
The model also reflected increased serum bilirubin, likely due to hepatobiliary transport dysregulation.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE302nnn/GSE302189 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE302189 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1289171 ncbi.nlm.nih.gov/bioproject/PRJNA1289171 ↗
project · from NCBI GEO
- PubMed 41240411 pubmed.ncbi.nlm.nih.gov/41240411 ↗
publication · from NCBI GEO
- PubMed 42645170 pubmed.ncbi.nlm.nih.gov/42645170 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
- Inferred from text
- Disease 75% · Genetics 71% · RNA sequencing 65%
Provenance · 1 source records, 10 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE302189 | 13 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[disease].local:disease:disease | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[field].anzsrc:group:3105 | enrichment · NCBI GEO | taxonomy-embedding@1.1.0 | title+keywords+description (71%) |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[modality].local:modality:rna-seq | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (65%) |
| concepts[organism].NCBITaxon:9606 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |