Biette, K. M. | Search bioRxiv

bioRxiv2023

Colocalization of Cancer Associated Biomarkers on Single Extracellular Vesicles for Early Cancer Detection

Detection of cancer early, when it is most treatable, remains a significant challenge due to the lack of diagnostic methods sufficiently sensitive to detect nascent tumors. Early-stage tumors are small relative to their tissue of origin, heterogeneous, and infrequently manifest in clinical symptoms. Detection of their presence is made more difficult by a lack of abundant tumor-specific indicators (i.e., protein biomarkers, circulating tumor DNA, etc.) that would enable detection using a non-invasive diagnostic assay. In addition, many benign conditions manifest in a similar manner, thus discriminating an early-stage cancerous lesion from a benign tumor can present additional challenges and result in unnecessary medical procedures. To overcome these obstacles, we have developed a liquid biopsy assay that interrogates circulating extracellular vesicles (EVs) to detect tumor-specific biomarkers colocalized on the surface of individual EVs. Extracellular vesicles from all cell types, including early-stage tumors, are known to be abundant in blood, are remarkably stable, and serve as a biopsy of their cell of origin. The detection of a colocalized combination of cancer associated biomarkers that provide tumor specificity on the surface of extracellular vesicles enables the discrimination of early- and late-stage cancer from non-malignant conditions.

cancer biology↗

bioRxiv2018

Computations performed by shadow enhancers and enhancer duplications vary across the Drosophila embryo

Transcription of developmental genes is controlled by multiple enhancers. Frequently, more than one enhancer can activate transcription from the same promoter in the same cells. In these cases, how is regulatory information from multiple enhancers combined to determine the overall expression output of their shared promoter? To investigate this question, we quantified nascent transcription driven by a pair shadow enhancers, each individual of the pair, and their duplications in Drosophila embryos using live imaging. This set of constructs allows us to quantify the \"computation\" made by the pairs of enhancers: their combined output expression as a function of the expression that they drive separately. We show that the computation performed by these shadow enhancers and duplications varies across the expression pattern, implying that how their activities are combined depends on the transcriptional regulators bound to the enhancers in different parts of the embryo. Characterizing the computation made by multiple enhancers is a critical first step in developing conceptual and computational models of gene expression at the locus level, where multiple enhancers collaborate.

systems biology↗