Circulating Cell-Free RNA Provides ‘Dynamic’ Diagnostic Picture
Measuring circulating cell-free RNA can provide a noninvasive, tissue-specific way to monitor fetal development and changes in disease status, according to a study published May 5 in the Proceedings of the National Academy of Sciences. The authors say that RNA, a measure of gene expression, provides a more dynamic picture of health and development than […]
Measuring circulating cell-free RNA can provide a noninvasive, tissue-specific way to monitor fetal development and changes in disease status, according to a study published May 5 in the Proceedings of the National Academy of Sciences. The authors say that RNA, a measure of gene expression, provides a more dynamic picture of health and development than the snapshot provided by DNA in applications like noninvasive prenatal testing, molecular tissue-typing, and tumor characterization. “We’ve moved beyond just detecting gene sequences to really analyzing and understanding patterns of gene activity,” said senior author Stephen Quake, Ph.D., Stanford University (Palo Alto, Calif.), in a statement. “Analyzing the RNA enables a much broader perspective of what’s going on in the body at any particular time. ”Using a combination of microarray and next-generation sequencing technologies, the researchers were able to characterize the sequences and relative levels of RNA in the blood of pregnant women, healthy volunteers, and Alzheimer’s patients. By focusing on RNA messages, encoding proteins produced only in certain tissues, the researchers were able to track the relative proportions of specific RNA circulating and could assess the development or health of particular organs over time. By analyzing combined cell-free RNA transcriptomes (100 genes whose RNA transcripts contained paternal single nucleotide polymorphisms that were distinct from the maternal inheritance) in 11 pregnant women across all three trimesters, the researchers were able to track longitudinal phenotypic changes and trace the development of specific tissues, including the fetal brain, liver, and placenta. The weighted average fetal fraction of cell-free RNA increased from 0.4 percent in the first trimester to 3.4 percent in the second trimester and 15.4 percent in the third trimester. The increase in the number of genes detected across the different trimesters suggests that these unique transcripts are expressed specifically during particular time intervals in the developing fetus. Additionally, by comparing neuron-specific transcripts from blood samples of both healthy adults and those with Alzheimer’s disease, disease-specific neural transcripts were identified at increased levels in affected participants. “We think of this technique as a kind of ‘molecular stethoscope,’ and it’s broadly useful for any tissue you care to analyze,” said Quake. In the paper he adds, “We anticipate these results are a stepping stone toward translating the temporal dynamics of plasma mRNA for clinical diagnosis of pregnancy-associated complications and developmental diseases, especially those that are temporal in nature and involve cellular apoptosis.” Takeaway: RNA may prove to be a broadly applicable diagnostic marker, as it provides a dynamic picture of disease state and development, yet can be tissue-specific.