Search

Researchers say that infrequent visits are hindering studies of the nearest planet.

NASA's Mars Science Laboratory needs more money to reach the launch pad, and has less time.

Understanding the basis of phenotypic variation is one of the most challenging problems in biology. The arrival of high-throughput genomic technologies now looks set to allow an integrative systems genetic approach to dissecting the genetic component of complex traits.

Could crevasses in the ice have been caused by a recent volcanic eruption?

Dead microbes and skin flakes from Earthlings may scupper the search for organic molecules.

Adam Bass, Gad Getz and colleagues report whole-exome sequencing of 149 esophageal adenocarcinomas (EACs) and whole-genome sequencing of 15 EACs. They identify a mutational signature defined by a high prevalence of A>C transversions, as well as 26 genes mutated at high frequency in EACs.

Mission to Martian moon is the country's first interplanetary attempt since 1996.

A long intergenic noncoding RNA, Firre, is now shown to localize to a domain across its own chromosomal locus and to distinct interacting transchromosomal loci in mouse and human cells. In addition, Firre interacts with nuclear-matrix factor hnRNPU. These results lead to a model in which Firre functions as a nuclear-organization factor modulating the topological organization of multiple chromosomes.

The Human Microbiome Project Consortium reports the first results of their analysis of microbial communities from distinct, clinically relevant body habitats in a human cohort; the insights into the microbial communities of a healthy population lay foundations for future exploration of the epidemiology, ecology and translational applications of the human microbiome.

Paz Polak, Jaegil Kim, Lior Z. Braunstein and colleagues have identified patterns of genome-wide mutation in certain breast cancers that can be used to identify those with DNA-repair deficiencies that make the tumor more likely to respond to therapies based on PARP inhibitors or platinum. In contrast, oncogenic mutations in several other DNA-repair genes do not generate these patterns.

Exome sequence analysis of nearly 10,000 people was carried out to identify alleles associated with early-onset myocardial infarction; mutations in low-density lipoprotein receptor (LDLR) or apolipoprotein A-V (APOA5) were associated with disease risk, identifying the key roles of low-density lipoprotein cholesterol and metabolism of triglyceride-rich lipoproteins.

The Cancer Genome Atlas presents an integrative genome-wide analysis of genetic alterations in 279 head and neck squamous cell carcinomas (HNSCCs), which are classified by human papillomavirus (HPV) status; alterations in EGFR, FGFR, PIK3CA and cyclin-dependent kinases are shown to represent candidate targets for therapeutic intervention in most HNSCCs.

Jens Lykke-Andersen, Frank Baas, Joseph Gleeson and colleagues report that mutations in the 3′ exonuclease TOE1 cause pontocerebellar hypoplasia type 7. They further show that these mutations result in the accumulation of incompletely processed small nuclear RNAs, leading to severe, early-onset neurodegeneration.

Exome sequencing of 175 autism spectrum disorder parent–child trios reveals that few de novo point mutations have a role in autism spectrum disorder and those that do are distributed across many genes and are incompletely penetrant, further supporting extreme genetic heterogeneity of this spectrum disorder.

Almost two hundred years ago Thomas Jefferson was alleged to have fathered children by his slave Sally Hemings. The charges have remained controversial. Now, DNA analysis confirms that Jefferson was indeed the father of at least one of Hemings' children.

This study uses chromatin marks in four mouse cell types to identify ∼1,600 large multi-exonic transcriptional units that do not overlap known protein-coding loci and are highly conserved. Putative functions are assigned to each of these large intervening non-coding RNAs, which range from ES pluripotency to cell proliferation.

Arrays of element antennas in radio interferometry enable the study of celestial objects with angular resolutions comparable with, or surpassing, optical imaging at wavelengths thousands of times shorter. In this Primer, Asaki et al. describe aperture synthesis, the basic instrumental components and data calibration.

Mark Daly and colleagues present a statistical framework to evaluate the role of de novo mutations in human disease by calibrating a model of de novo mutation rates at the individual gene level. The mutation probabilities defined by their model and list of constrained genes can be used to help identify genetic variants that have a significant role in disease.

An international consortium reports the genomic sequence for ten Drosophila species, and compares them to two other previously published Drosophila species. These data are invaluable for drawing evolutionary conclusions across an entire phylogeny of species at once.

Efficient clinical trials are crucial for advancing cancer care. In this Perspective, the authors propose a platform that leverages circulating tumour DNA to identify patients with early-stage cancer at high risk of recurrence and enrol them onto therapeutic clinical trials. This approach would enable faster, smaller trials and streamline evaluation of drugs aimed at preventing disease recurrence and increasing cure.

Neoantigen-targeting vaccines are a feasible therapy for tumours with a low mutation burden and immunologically ‘cold’ tumour microenvironment, as neoantigen-specific T cells from the peripheral blood migrate into intracranial glioblastoma, thereby altering the immune milieu of the glioblastoma.

Long noncoding RNAs are investigated using a CRISPR–Cas9 activation screen and shown to confer BRAF inhibitor resistance on melanoma cells through various local mechanisms.

As the sample size in cancer genome studies increases, the list of genes identified as significantly mutated is likely to include more false positives; here, this problem is identified as stemming largely from mutation heterogeneity, and a new analytical methodology designed to overcome this problem is described.

Genome-wide polygenic risk scores derived from GWAS data for five common diseases can identify subgroups of the population with risk approaching or exceeding that of a monogenic mutation.

Genome-scale DNA methylation profiles have been generated at nucleotide resolution in mammalian cells using a combination of high-throughput bisulphite sequencing and single molecule-based sequencing. The DNA methylation maps cover the vast majority of CpG islands, as well as several other genomic regions, in murine embryonic stem cells, cells derived from ES cells and various primary cells.

Experiments in developing human erythroid cells show that LIN28B controls hemoglobin switching by directly suppressing BCL11A translation, independently of its role in regulating let-7 microRNA biogenesis.

Golub and colleagues tested thousands of drugs not originally developed for oncology across 578 human cancer cell lines, revealing growth-inhibitory effects and providing a resource to identify drugs with the potential to be repurposed for cancer.

A framework of patient-partnered research allows patients with angiosarcoma to share their samples and clinical records securely to accelerate molecular characterization of tumors and identification of therapeutic approaches.

A blueprint for the genomic era.

Levi Garraway and colleagues report exome sequencing of 112 prostate adenocarcinomas and matched normal tissues. They identify novel recurrent mutations in several genes, including MED12, FOXA1 and SPOP. They find that tumors harboring SPOP mutations lack the TMPRSS2-ERG fusion or other ETS rearrangements, supporting the hypothesis that SPOP mutation is an early driver event in prostate tumorigenesis.

The class 2 type VI RNA-guided RNA-targeting CRISPR–Cas effector Cas13 can be engineered for RNA knockdown and binding, expanding the CRISPR toolset with a flexible platform for studying RNA in mammalian cells and therapeutic development.

George Daley and John Rinn and colleagues identify large intergenic non-coding RNAs that are upregulated during reprogramming of induced pluripotent stem cells, and they show a functional role for large intergenic non-coding RNA-RoR in induced pluripotent stem cell derivation.

KRAS is a proto-oncogene that is mutated in a wide variety of human cancers. Although this makes KRAS an obvious candidate for the development of targeted therapies, it has so far remained refractory to this approach. Systematic RNA interference is now used to detect synthetic lethal partners of oncogenic KRAS, revealing that TBK1 and NF-κB signalling are essential in KRAS mutant tumours. This may provide an alternative approach for targeting KRAS therapeutically.

By sequencing the exomes of 10,503 individuals living in Pakistan, the authors identify rare predicted loss-of-function mutations that are estimated to knock out genes and correlate these mutations with a broad range of phenotypes, providing a framework for a human knockout project.

A large-scale study that analyses gene copy number changes in lung cancer identifies 31 recurrent focal events, which include amplification of the transcription factor NKX2.1 (also called TTF1), shown to act as an oncogene.

Inhibition of DOT1L, the H3K79 histone methyltransferase, increases cell reprogramming and substituted for KLF4 and c-Myc, showing that chromatin-modifying enzymes act not only as facilitators but also as barriers to reprogramming.