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This Week in PNAS: Mar 15, 2016

In the early, online edition of the Proceedings of the National Academy of Sciences, an international team demonstrates that methylation markers in cell-free circulating DNA may offer clues to cell death occurring within a particular tissue type. Starting from publicly available databases containing tissue-specific methylation information, the researchers came up with tissue-specific methylation markers that they subsequently applied to do sequencing-based methylation profiling on cfDNA from individuals with or without conditions affecting tissue health. In their proof-of-principle experiments, for example, the approach picked up cfDNA from pancreatic beta-cells, oligodendrocytes, or neuronal/glial tissues in individuals with type 1 diabetes, multiple sclerosis, or traumatic brain injury, respectively. GenomeWeb has more on the study, here.

Researchers from the UK describe the subtractive RNA sequencing method they used to assess the cell surface proteome of Ewing sarcoma tumor cells — molecules refereeing cancer-stroma interactions that are expected to influence cancer response to antibody-mediated therapies. By filtering deep RNA-seq data with the help of a database of known or suspected cell surface proteins, the team attempted to uncover 'surfaceome' features differing between Ewing sarcoma cells and non-cancerous progenitor mesenchymal stem cells. The search led to LINGO1, a protein enhanced on the surface of more than 90 percent of the Ewing sarcoma cells tested. "We found that the LINGO1 protein acts as a gateway protein internalizing into the tumor cells when engaged by antibody," investigators note, "and can carry antibody conjugated with drugs to kill Ewing sarcoma cells."

Finally, a team from the US and Austria present findings from a genome sequencing study of Escovopsis weberi, a fungal species that parasitizes beneficial fungi cultivated by ants. The researchers sequenced, assembled, and analyzed the genome of an E. weberi strain that had been isolated from a leaf-cutting ant's fungal garden, identifying an estimated 6,870 protein-coding genes in the compact 27-million-base genome assembly. Through comparisons with other fungal sequences, the study's authors found that the E. weberi genome has streamlined its carbohydrate metabolism and jettisoned some genes involved in sexual reproduction, while boosting its ability to produce secondary metabolites that appear to be involved in attacking host fungi.