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Completion of genome sequences for the diploid Setaria italica reveals features of C4 photosynthesis that could enable improvement of the polyploid biofuel crop switchgrass (Panicum virgatum). The genetic basis of biotechnologically relevant traits, including drought tolerance, photosynthetic efficiency and flowering control, is also highlighted.
Tumors vary in their ratio of normal to cancerous cells and in their genomic copy number. Carter et al. describe an analytic method for inferring the purity and ploidy of a tumor sample, enabling longitudinal studies of subclonal mutations and tumor evolution.
Functional genomics requires facile methods to recover sequences of interest. Fu et al. show that the phage proteins RecE and RecT mediate recombination between linear DNA fragments and can facilitate natural product discovery.
Small sequencing machines no bigger than a laser printer have many potential applications in diagnostics and public health. Loman et al. compare the quality, throughput and cost of instruments from Illumina, Roche and Life Technologies.
Transcription activator–like effector nucleases (TALENs) enable genetic modification at specific sites in a genome. Reyon et al. present a method for high-throughput generation of TALENs, facilitating large-scale genome engineering.
Protein nanopores are being developed as sensors that could perform rapid, electronic sequencing of long single molecules of DNA. Manrao et al. report the first demonstration of single nucleotide–resolution current traces from a nanopore, and show that these data can be mapped to known DNA sequences.
Expressing heterologous pathways in cells can create detrimental metabolic imbalances. Zhang et al. increase the yield of a biofuel by engineering regulators in Escherichia coli that sense and adjust pathway expression based on the presence of key intermediate metabolites.
The ability to identify antibodies circulating in the bloodstream would advance immunology and vaccinology research and the development of therapeutics. Cheung et al. couple proteomics with next-generation sequencing of RNA from B cells to clone antibodies directly from the sera of immunized rabbits and mice.
Methods for specific gene silencing have advanced as far as clinical trials, but a similar set of tools does not exist for increasing gene expression. Modarresi et al. demonstrate gene-specific upregulation in vivo by treating mice with oligonucleotides that inhibit the function of natural antisense transcripts.
Vaccination with a virus-expressed cDNA library derived from normal prostate cells can cure established prostate cancer in mouse models. Pulido et al. extend this approach and identify specific tumor-associated antigens from tumor-derived virus-expressed cDNA libraries that can be used in combination to cure established melanoma in mice.
Salinization of cultivated land and the need to increase agricultural productivity make the development of salt-resistant crops imperative. Field trials show that a durum wheat containing a sodium transporter derived from an ancestral wheat relative produces substantially more grain than a commercial durum wheat lacking this transporter on saline soil.
The events that lead from plated human blastocysts to embryonic stem cells are poorly understood. Close analysis reveals a transient intermediate state with a distinct molecular profile.
Cultured human pluripotent stem cells can be differentiated to immature pancreatic beta cells, but no one has yet succeeded in maturing these cells in vitro. Blum et al. define markers of beta-cell maturation that can be used to screen conditions for generating fully functional beta cells.
Two groups describe approaches for synthesizing and assaying the function of thousands of variants of mammalian DNA regulatory elements. Melnikov et al. use their results to engineer short optimized regulatory elements in human cells, whereas Patwardhan et al. study enhancers hundreds of bases long in mice.
An improved understanding of enhancers in mammalian genomes could facilitate the design of new regulatory elements. Melnikov et al. synthesize thousands of ~90 nt enhancer variants, assay their activity in human cells and use the data to rationally optimize synthetic enhancers.
PARP inhibitors have recently entered phase 3 clinical trials as cancer therapeutics, but the specificity of many of these compounds is unknown. Wahlberg et al. used biochemical approaches to show that most PARP inhibitors target multiple PARP family members.
A key obstacle to sequencing DNA as it passes through a nanopore is that the translocation rate is too fast to resolve individual bases. Cherf et al. solve this problem with an improved method for ratcheting DNA forward and backward through the nanopore using a DNA polymerase.
Sites where RNA editing occurs can be found using RNA-Seq, but false positives confound the data analysis. Peng et al. describe algorithms for accurately calling editing events, and apply them to identify ~22,600 events, mostly A→G changes, in a human transcriptome.
Baker and colleagues have already shown that protein folding can be turned into an online game played by nonscientists. Now, Foldit players tackle the problem of increasing an enzyme's catalytic activity—with promising results.
Genetic analysis of agronomic traits in crops is complicated by the long generation times and challenges of growing and phenotyping plants in large field trials. Abe et al. show how whole genome resequencing can be used to identify the genetic basis of subtle phenotypic traits in rice.