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This Week in Science: Mar 2, 2018

In this week's Science Translational Medicine, a multi-institute research team describes the use of a PCR-based method to understand how HIV is able to lie dormant in certain immune cells, offering new clues about how to better combat the virus. Latently infected CD4+ T cells — which do not actively produce HIV, allowing the virus to avoid detection — are a key barrier to complete infection clearance, but the mechanisms behind this latency remain unknown. The scientists developed a new panel of reverse transcription droplet digital polymerase chain reaction assays for different HIV transcripts that define distinct blocks to transcription, which they used to analyze CD4+ T cell from 18 HIV-infected individuals. They found that while the cells initiated HIV RNA transcription, a series of blocks to proximal elongation, distal transcription/polyadenylation, and multiple splicing interfered with the process. The findings "challenge the prevailing model that HIV latency is due to a lack of transcriptional initiation … [and] should help in the design and evaluation of new therapies that can silence or kill latently HIV-infected cells," the investigators write.


And in Science Advances, a group of US and European researchers reports a new CRISPR-Cas9 method to identify tumor suppressor genes that, when mutated, are most likely to drive liver cancer. The approach, they state, may be extended to other cancer types and ultimately help in the development of precision therapeutics. While many recurrently mutated genes have been identified across multiple cancers, there has been little investigation into how these genes influence oncogenesis. To address this, the researchers used adeno-associated viruses carrying CRISPR-Cas9 single guide RNAs (sgRNAs) to knock out well-known tumor suppressor genes in mice livers. All of the animals developed and died from liver cancer, after which the scientists used molecular inversion probe sequencing of the sgRNA target sites to chart the mutational landscape of these tumors, revealing the functional consequence of multiple variants in driving liver tumorigenesis in the mice. "This new platform provides a powerful means for mapping a provisional functional cancer genome atlas of tumor suppressors, oncogenes, and other types of genetic events of tumor evolution, in isolation or as combinations and larger pools, in virtually any cancer type," they write.

The Daily Scan's sister publication, GenomeWeb Daily News, has more on this study here.

The Scan

Genetic Ancestry of South America's Indigenous Mapuche Traced

Researchers in Current Biology analyzed genome-wide data from more than five dozen Mapuche individuals to better understand their genetic history.

Study Finds Variants Linked to Diverticular Disease, Presents Polygenic Score

A new study in Cell Genomics reports on more than 150 genetic variants associated with risk of diverticular disease.

Mild, Severe Psoriasis Marked by Different Molecular Features, Spatial Transcriptomic Analysis Finds

A spatial transcriptomics paper in Science Immunology finds differences in cell and signaling pathway activity between mild and severe psoriasis.

ChatGPT Does As Well As Humans Answering Genetics Questions, Study Finds

Researchers in the European Journal of Human Genetics had ChatGPT answer genetics-related questions, finding it was about 68 percent accurate, but sometimes gave different answers to the same question.