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Manuscript Miscellany


Stem Cell Regulation
Gabut M, Samavarchi-Tehrani P, Wang X, et al. (2011). An alternative splicing switch regulates embryonic stem cell pluripotency and reprogramming. Cell. Epub: doi 0.1016/j.cell.2011.08.023.

Mathieu Gabut and his colleagues describe a crucial role for an alternative splicing event in the regulation of pluripotency through the control of embryonic stem cell-specific transcriptional programs. The researchers report on "an evolutionarily conserved ESC-specific alternative splicing event that alters the DNA-binding preference of the forkhead family transcription factor FOXP1." Gabut et al. show that the ESC-specific isoform of FOXP1, which promotes maintenance of ESC pluripotency and reprograms somatic cells into pluripotent stem cells, stimulates the expression of transcription factor genes required for pluripotency while simultaneously repressing ESC differentiation genes.

Mutation Spectrum
Kumar A, White TA, MacKenzie AP, et al. (2011). Exome sequencing identifies a spectrum of mutation frequencies in advanced and lethal prostate cancers. PNAS. Epub: doi 10.1073/pnas.1108745108.

The authors present their whole-exome sequencing analysis of 23 prostate cancers in an effort to catalog protein-altering mutations thought to drive the development and progression of the disease. Akash Kumar et al. say their "results indicate that point mutations arising in coding regions of advanced prostate cancers are common but, with notable exceptions, very few genes are mutated in a substantial fraction of tumors." They also identify a previously undescribed subtype of prostate cancers that exhibits hyper-mutated genomes, and suggest that increasingly robust catalogs of human germline variation could make sequencing matched tumor-normal pairs unnecessary.

Library Creation
Svensen N, Díaz-Mochón JJ, Bradley M. (2011). Micro-array generation of thousand-member oligonucleotide libraries. PLoS One. Epub: doi 10.1371/journal.pone.0024906.

Nina Svensen and her colleagues present a method to produce libraries of defined DNA for use in several applications, including directed sequencing and synthetic biology. They used DNA microarrays to linearly amplify DNA sequences, followed by PCR amplification. "Here we demonstrate an approach to the generation of DNA libraries from DNA micro-arrays allowing the efficient and inexpensive production of custom made thousand-member DNA libraries," the authors write. "The DNA libraries were generated while keeping the array intact and useable for sub-sequent applications, such as additional rounds of DNA production," they add.

Diversity in Dirt
Andersen K, Bird KL, Rasmussen M, et al. (2011). Meta-barcoding of 'dirt' DNA from soil reflects vertebrate biodiversity. Molecular Ecology. Epub: doi 10.1111/j.1365-294X.2011.05261.x.

To explore the accuracy of DNA derived from soil samples as an indicator of vertebrate diversity, Kenneth Andersen and his team combined second--generation, high-throughput sequencing with 16S mitochondrial DNA meta-barcoding. Andersen and his colleagues show that "DNA from the soil surface reflects overall taxonomic richness and relative biomass of individual species," and say that "the approach potentially provides a quick methodological alternative to classical ecological surveys of biodiversity, and most reliable results are obtained with spatial sample replicates, while relative amounts of soil processed per site is of less importance."

The Scan

Researchers Compare WGS, Exome Sequencing-Based Mendelian Disease Diagnosis

Investigators find a diagnostic edge for whole-genome sequencing, while highlighting the cost advantages and improving diagnostic rate of exome sequencing in EJHG.

Researchers Retrace Key Mutations in Reassorted H1N1 Swine Flu Virus With Avian-Like Features

Mutations in the acidic polymerase-coding gene boost the pathogenicity and transmissibility of Eurasian avian-like H1N1 swine influenza viruses, a PNAS paper finds.

Genome Sequences Reveal Evolutionary History of South America's Canids

An analysis in PNAS of South American canid species' genomes offers a look at their evolutionary history, as well as their relationships and adaptations.

Lung Cancer Response to Checkpoint Inhibitors Reflected in Circulating Tumor DNA

In non-small cell lung cancer patients, researchers find in JCO Precision Oncology that survival benefits after immune checkpoint blockade coincide with a dip in ctDNA levels.