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PNAS Papers Explore Transcriptomic, Epigenomic Differences in Glioblastoma Models; Small Volume ExRNA Sequencing; More

A British Columbia Cancer Agency- and University of British Columbia-led team describes transcriptomic and epigenomic sequence differences in brain tumor-initiating cells (BTIC) or orthotopic xenograft models of glioblastoma multiforme (GBM) compared with matched brain tumor samples used to produce them. When the researchers did whole-genome sequence data on 46 matched BTIC-tumor pairs and 15 tumor-BTIC-xenograft trios; RNA sequencing on 37 sample pairs and 10 trios; and array-based methylation profiling for 35 paired samples and four trios, they saw that although the BTICs and xenografts matched parent tumors when it came to genome sequences, they diverged somewhat at the messenger RNA expression and cytosine methylation levels. "These findings suggest that a comprehensive genomic understanding of in vitro and in vivo GBM model systems is crucial for interpreting data from drug screens," they write, "and can help control for biases introduced by cell culture conditions and the microenvironment in mouse models."

Researchers from the University of California, San Diego, Genemo, and elsewhere explore extracellular RNA (exRNA) profiles in small volumes of human blood serum with their small volume sequencing strategy, adapted from single-cell RNA sequencing. Using "small input liquid volume extracellular RNA sequencing," or SILVER-seq, the team attempted to tease out exRNAs and exRNA fragments in blood serum samples as small as five to seven microliters, comparing the resulting sequence profiles to those established with other RNA sequencing approaches applied to larger sample volumes. In serum droplet samples from more than 150 volunteers between the ages of 18 and 48 years old, for example, the authors reported they uncovered exRNAs corresponding with a significant subset of human genes with SILVER-seq. They also used the approach to search for informative exRNAs in miniscule blood samples from breast cancer patients.

A team from the University of Edinburgh and elsewhere report on population genetic patterns in mainland Scotland and nearby Isles such as the Hebrides, Shetland, and the Isle of Man. The researchers assessed genotype profiles for more than 2,500 individuals from Scotland and surrounding Isles, comparing them with genetic profiles from individuals in Scandinavia and beyond. Their results revealed population structure differences between northeastern and southwestern parts of mainland Scotland, for example, along with more subtle population differences across smaller geographic areas. "We demonstrate widespread structure across Scotland that echoes past kingdoms, and quantify the considerable structure that is found on its surrounding isles," the authors report. "Furthermore, we show the extent of Norse Viking ancestry across northern Britain and estimate a region of origin for ancient Gaelic Icelanders."