Technology behind Molecular Stethoscope

Enabling Analysis of Disease-related, Tissue-specific RNA in Blood

RNA as it relates to DNA

RNA is a tissue-specific copy of DNA which can be amplified by orders of magnitude to facilitate quantitative comparisons and interpretation.

Three key developments in bioinformatics and molecular biology have positioned Molecular Stethoscope to use RNA to create rapid, accurate and non-invasive organ health diagnostic tests:

  1. Modern molecular biology techniques, in combination with highly annotated and representative databases, have led to a much more comprehensive knowledge of RNA expression patterns in tissues.
  2. Progress in sequencing technology and extensive development of bioinformatics has allowed scientists to characterize short nucleic acid fragments in RNA.
  3. High-powered bioinformatics analysis methods for patient data and bioinformatics mining of relevant databases.

Molecular Stethoscope’s Blood-Based Cell-Free RNA Technology can Enable Earlier Detection of Disease

RNA represents the actual and immediate phenotype of an individual, reports the cellular function, can be organ specific, and allows a more dynamic assessment of healthy versus diseased state.

Deconvolution of cell-free RNA transcriptome
Deconvolution of cell-free RNA transcriptome

High-throughput methods of RNA analysis can be used to characterize the global landscape of circulating RNA. By focusing on genes whose expression are highly specific to certain tissues, we are able to infer the relative contributions of these tissues to circulating RNA. By characterizing large numbers of diseased and normal individuals we can determine normal values. Alternatively we can focus on the contribution of a specific organ or cell type to the blood pool.

Tissue-Specific RNA in the Blood of Healthy Individuals is Reproducible. Deviations can Indicate a problem.

RNA of healthy people
Results of circulating RNA in unique tissues is consistent from normal individual to normal individual

Through measurements of RNA from many healthy individuals, Molecular Stethoscope has established baseline levels of tissue-specific RNA which are remarkably reproducible and consistent. Deviations in these levels can be significant and can indicate organ-specific disease.

References:

Koh W, et al. (2014) Noninvasive in vivo monitoring of tissue-specific globalgene expression in humans. PNAS 111(20):7361–7366.

Damani S, et al. (2012) Characterization of circulating endothelial cells in acutemyocardial infarction. Sci Transl Med. 4(126):126ra33.

Topol E, Quake SR (2015) A stethoscope for the next 200 years. The Wall Street Journal http://www.wsj.com/articles/eric-topol-and-stephen-r-quake-a-stethoscope-for-the-next-200-years-1420242913