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Genome Research Papers on Early SARS-CoV-2 Circulation in NYC, Drug Response Assay, More

SARS-CoV-2 circulated under the radar in the New York City area for a "prolonged period," according to a viral genome sequencing analysis led by investigators at the New York University Grossman School of Medicine. The researchers considered SARS-CoV-2 sequence data, infected individuals' travel or exposure histories, and other factors, focusing on 864 cases diagnosed in the NYC metro area this spring. When they placed the viral genomes in a broader collection of SARS-CoV-2 sequences from other parts of the world, the authors saw signs that "early transmission was most linked to cases in Europe," though local spread appeared to reflect more than 100 independent introductions. "Although our estimate of 109 introductions is … likely to underestimate the total number of introductions, the genomic data are sufficiently informative to outline an unrecognized early spread in February that enabled rapid development of the outbreak in March." As GenomeWeb has reported, a recent serology-based study in Nature also put SARS-CoV-2 introductions in NYC sometime in February. 

Austrian researchers report on an approach that relies on in situ sequencing, CRISPR-based pooled fluorescent protein tagging, and time-lapse imaging to interrogate cell line responses to a range of drug treatments. Starting from a set of nearly 2,900 metabolic enzyme-coding genes, the team designed more than 14,000 single guide RNAs (sgRNAs) corresponding to more than 11,600 intronic sequences in 2,387 genes, ultimately characterizing drug responses involving 953 genes with introns that had been successfully tagged with green fluorescent protein. "[W]e show the scalability of [the] strategy to enable pooled protein tagging of more than 900 metabolic enzymes and epigenetic modifiers," the authors report. "Exposing the GFP-tagged cells to compounds allows us to monitor drug effects on the localization and levels of hundreds of proteins in real time in a pooled format, followed by identification of responding clones by in situ sequencing of the expressed intron-targeting sgRNA that corresponds to the tagged protein."

Finally, a team from the US and the UK characterizes structural variant mosaicism in samples from three fetal brains. Using sequence data for neural progenitor cell clones in several brain regions, the researchers searched for mosaic structural variants, which were investigated in more detail with assembly and genotyping data. Their pipeline made it possible to focus in on structural variant breakpoints, while estimating the frequency of specific alleles, leading to four validated mosaic structural variant clones in the fetal brains considered. "Our study reveals the existence of mosaic [structural variants] in the developing human brain," the authors write, "likely arising from cell proliferation during mid-neurogenesis."

The Scan

Cancer Survival Linked to Mutational Burden in Pan-Cancer Analysis

A pan-cancer paper appearing in JCO Precision Oncology suggests tumor mutation patterns provide clues for predicting cancer survival that are independent of other prognostic factors.

Australian Survey Points to Public Support for Genetic Risk Disclosure in Relatives of At-Risk Individuals

A survey in the European Journal of Human Genetics suggests most adult Australians are in favor of finding out if a relative tests positive for a medically actionable genetic variant.

Study Links Evolution of Stony Coral Skeleton to Bicarbonate Transporter Gene

A PNAS paper focuses on a skeleton-related bicarbonate transporter gene introduced to stony coral ancestors by tandem duplication.

Hormone-Based Gene Therapy to Sterilize Domestic Cat

A new paper in Nature Communication suggests that gene therapy could be a safer alternative to spaying domestic cats.