DIRECT LS-TA is a novel ratio-based biomarker (RBB) method that allows for the direct quantification of single cell-type specific gene expression from peripheral blood samples, without requiring laborious and tedious prior cell sorting.
Unlike conventional bulk RNA quantification, which provides summative results confounded by changes in both gene expression within cell types and their proportional cell counts, DIRECT LS-TA delivers unconfounded results that represent the average gene expression of a single cell type.
This clarity in interpretation is a significant advantage over traditional protein markers like CRP and PCT, which only convey an overall systemic host response and lack cell-type specific information.
We identify genes whose transcripts in peripheral blood are predominantly produced by monocytes, contributing more than 50% of the mRNA transcripts of that gene in the cell-mixture sample. We've identified over 50 monocyte-informative genes, including key immune response genes.
From these informative genes, we've identified two novel and ideal monocyte informative reference genes: PSAP and CTSS. These genes exhibit low biological variation and high specificity, making them effective denominators in our ratio-based biomarker.
The DIRECT LS-TA RBB is calculated as the ratio of the transcript abundance of a monocyte informative target gene to a monocyte informative reference gene directly from the cell-mixture sample.
Results are standardised using Multiples of Median (MoM) to enable easy comparison of fold changes across different datasets and reflect gene activation relative to controls.
DIRECT LS-TA results have shown excellent correlation with gene expression obtained from gold-standard isolated monocytes, with R² values ranging from 0.55 to 0.97 for shortlisted genes. This demonstrates its reliability and accuracy in reflecting cell-type specific gene expression directly from peripheral blood.
The VNN1 ratio-based biomarker showed consistent upregulation across five datasets (median 2.7-fold, p<10⁻⁸) in bacterial infection patients compared to controls.
It exhibited good diagnostic performance, with Area Under the Curve (AUC) values ranging from 0.84 to 0.99 in Receiver Operating Characteristic (ROC) analysis for differentiating bacterial infection from controls.
Discover how DIRECT LS-TA can transform your understanding of host responses and enhance diagnostic capabilities in your clinical setting. Our innovative technology offers unparalleled insights into cell-specific gene expression without the complexity of traditional methods.
Whether you're looking to improve bacterial infection diagnosis, enhance antibiotic stewardship, or advance your research capabilities, DIRECT LS-TA provides the precision and reliability you need.
Our company stands at the forefront of innovation in gene expression diagnostics, transforming how we understand host responses and disease. Our debut product, DIRECT LS-TA (Direct Leukocyte Single cell-type Transcript Abundance), embodies our innovative approach to analysing complex cell-mixture biological samples without laborious cell sorting.