Specific Tissues and Organs May Be Monitored by Whole Blood Transcriptome Analysis

A team of bioengineers has used high-throughput methods of RNA analysis such as microarrays and next-generation sequencing to characterize the global landscape of circulating RNA (the transcriptome) in human subjects.

By focusing on tissue-specific genes, investigators at Stanford University (Palo Alto, CA, USA) were able to identify the relative contributions of these tissues to circulating RNA and monitor changes during tissue development and neurodegenerative disease states. In a recently published study, they applied these techniques to analyze blood samples taken from two quite different patient pools: pregnant women, who were followed through all three trimesters and after delivery, and Alzheimer's disease patients and similarly aged controls.

In addition to the analysis of mRNA, they observed and characterized noncoding species such as long noncoding RNA and circular RNA transcripts whose presence had not been previously observed in human plasma.

Results obtained during this study demonstrated that it was possible to track specific longitudinal phenotypic changes in both the mother and the fetus and that it was possible to directly measure transcripts from a variety of fetal tissues in the maternal blood sample.

The investigators also evaluated the role of neuron-specific transcripts in the blood of healthy adults and those suffering from Alzheimer’s disease and showed that disease specific neural transcripts were present at increased levels in the blood of affected individuals.

"We think of this technique as a kind of molecular stethoscope," said senior author Dr. Stephen Quake, professor of bioengineering and applied physics at Stanford University, "and it is broadly useful for any tissue you care to analyze. There are many potential practical applications for this work. We could potentially use it to look for things going wrong in pregnancy, like preeclampsia or signs of preterm birth. And we hope to use it to track general health issues in various organs."

"We have moved beyond just detecting gene sequences to really analyzing and understanding patterns of gene activity," said Dr. Quake. "Knowing the DNA sequence of a gene in the blood has been shown to be useful in a few specific cases, like cancer, pregnancy, and organ transplantation. Analyzing the RNA enables a much broader perspective of what is going on in the body at any particular time."

The blood transcriptome study was published in the May 5, 2014, online edition of the journal Proceedings of the National Academy of Sciences of the United States of America (PNAS).

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