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This Week in PNAS: Mar 28, 2017

Stanford University researchers introduce a transcribed genome array (TGA) approach to tease out biophysical interactions between RNA binding proteins and the broader transcriptome with a hardware and software system that builds from the Illumina MiSeq flow cell as a biochemical platform. The team's proof-of-principle analyses applied TGA to track transcriptome-wide binding affinities for the Saccharomyces cerevisiae RNA-binding protein Vts1, which is conserved in animals and appears to regulate some developmental features. "Our work couples transcriptome-wide measurements of binding affinity, sequence, and structural determinants of binding, and phenotypic outcomes to provide a comprehensive portrait of Vts function," the authors write, noting that the approach "is easily extensible to other RNA-binding proteins involved in disease and development, and facilitates diverse applications in systems biochemistry."

A team from Houston Methodist Research Institute, Arizona State University, and elsewhere describe a strategy for quantifying levels of antigen peptides associated with active Mycobacterium tuberculosis infections in blood samples from infected individuals. The so-called NanoDisk-MS approach relies on nanodisk-bound antibodies that enrich for peptides specific to active M. tuberculosis cases, the researchers explain, followed by high-throughput mass spectrometry. They demonstrated the specificity and sensitivity of the method in samples from participants with or without HIV infections who were participating in a tuberculosis surveillance study in Texas.

Investigators from Finland and Canada find evidence of balancing selection for variants in two brain-expressed genes implicated in mammalian behavior: Avpr1a and Oxtr, which fall in vasopressin and oxytocin pathways, respectively. The team used the bank vole (Myodes glareolus) as a model, tracking reproductive success in field studies of voles with variable-length microsatellite polymorphisms in regulatory regions of Avpr1a and Oxtr. Though population density was also a factor, the experiments suggested long Avpr1a regulatory region-associated microsatellites (RRAM) and short Oxtr RRAMs boosted reproductive success in male bank voles, while females with short Avpr1a RRAMs and longer Oxtr RRAMs were more successful. "[B]alancing selection through sexually antagonistic fitness effects and density-related social influences is capable of maintaining microsatellite length polymorphisms at both genes," the authors suggest.