BioProject

Circulating cell-free RNA in the blood provides a potential window into the health, phenotype, and developmental programs of a variety of human organs. More...

Circulating cell-free RNA in the blood provides a potential window into the health, phenotype, and developmental programs of a variety of human organs. We employed high throughput methods of RNA analysis such as microarrays and next-generation sequencing to characterize the global landscape circulating RNA in a cohort of human subjects. By focusing on genes whose expression is highly specific to certain tissues, we were able to identify the relative contributions of these tissues to circulating RNA, and to monitor changes in tissue development and health. As one such application of this approach, we performed a longitudinal study on pregnant women and analyzed their combined cell-free RNA transcriptomes across all three trimesters of pregnancy and after delivery. In addition to the presence of messenger RNA, we observed and characterized non-coding species such as long non-coding RNA and circular RNA transcripts whose presence had not been previously observed in human plasma. We demonstrate that it is possible to track specific longitudinal phenotypic changes in both the mother and the fetus, and that it is possible to directly measure transcripts from a variety of fetal tissues in the maternal blood sample. We also studied the role of neuron specific transcripts in the blood of healthy adults and those suffering from the neurodegenerative disorder Alzheimer’s disease, and showed that disease specific neural transcripts are present at increased levels in the blood of affected patients. Characterization of the cell-free transcriptome in its entirety may thus provide broad insights into human health and development without the need for invasive tissue sampling. Overall design: Cell-free RNA are extracted from pregnant women on the first, second and third trimester and immediately post-partum. Temporal trends are extracted from individual patients. Less...