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Science Papers Present Way to Molecularly Classify Prostate Cancer, Saliva-Based SARS-CoV-2 Test, More

Using a combination of sequencing technologies, a team led by Weill Cornell Medicine investigators has developed an approach for molecularly classifying prostate tumors that could help guide treatment decisions. Prostate cancers frequently progress to be the more deadly castration-resistant prostate cancer (CRPC), which lose the dependence on androgen receptor (AR) signaling found in earlier-stage tumors. In light of the dearth of therapeutic options for CRPC, the researchers used an assay for transposase-accessible chromatin sequencing, RNA sequencing, and DNA sequencing to study 22 metastatic human prostate cancer organoids, 6 patient-derived xenografts, and 12 cell lines. In addition to two well-characterized cancer subtypes, they identify two AR-negative/-low molecular subtypes, one of which proved highly common in a group of 366 patient samples, as reported in this week's Science. Further investigation revealed the master transcription factors driving these two subtypes. "Overall, our results show how stratification of CRPC patients into four subtypes using their transcriptomes can potentially inform appropriate clinical decisions," the researchers write.

A saliva-based SARS-CoV-2 detection technology is reported in this week's Science Advances, offering a rapid point-of-care testing approach that performs as well as RT-PCR methods. The in situ immunoassay technology uses a portable nanoporous membrane resonator that generates a rapid oscillating flow to purify and concentrate fully intact SARS-CoV-2 virus in raw saliva for viral antigen detection via chemiluminescence. According to its developers at WellSIM Biomedical Technologies, the method achieves a detection sensitivity below 100 copies/ml of virus, comparable to the bench-top PCR equipment, and can improve detection specificity by the direct monitoring of viral loads.

By building and analyzing a transcriptomic atlas of the entire cell population of the developing female and male gonads during the process of mouse sex determination, a team led by University of Geneva researchers has identified a previously uncharacterized population of cells involved in gonad development. The process of gonadal sex determination has been studied for decades, yet a complete understanding of the different cell lineages forming the developing testis and ovary remains elusive. To investigate, the scientists densely sampled gene expression at the single-cell level in developing mouse gonads during the critical period of sex determination, identifying a rare, previously overlooked gonadal cell lineage — dubbed supporting-like cells (SLCs) — that is closely related to the coelomic epithelium and specified as early as embryonic day 10.5, making it the first somatic lineage to be specified in the bipotential gonad. Other findings include a crucial regulator of the SLC lineage that is required for the normal development of the rete testis.

The Scan

Positive Framing of Genetic Studies Can Spark Mistrust Among Underrepresented Groups

Researchers in Human Genetics and Genomics Advances report that how researchers describe genomic studies may alienate potential participants.

Small Study of Gene Editing to Treat Sickle Cell Disease

In a Novartis-sponsored study in the New England Journal of Medicine, researchers found that a CRISPR-Cas9-based treatment targeting promoters of genes encoding fetal hemoglobin could reduce disease symptoms.

Gut Microbiome Changes Appear in Infants Before They Develop Eczema, Study Finds

Researchers report in mSystems that infants experienced an enrichment in Clostridium sensu stricto 1 and Finegoldia and a depletion of Bacteroides before developing eczema.

Acute Myeloid Leukemia Treatment Specificity Enhanced With Stem Cell Editing

A study in Nature suggests epitope editing in donor stem cells prior to bone marrow transplants can stave off toxicity when targeting acute myeloid leukemia with immunotherapy.