Articles in 2017

In the motivation, conduct and reporting of science, there is no substitute for reason, and it must prevail whenever scientific methods are used. Similarly, scientific recommendations can only be useful if they meet with rational decision-making. Because people come to decisions from diverse viewpoints and values, listening to the values and views of scientists and non-scientists—while explicitly refraining from debate and persuasion—may point the way to determining when and where scientific ideas are of interest and likely to be adopted.

A new study reports genome-wide variation in 163 vervet monkeys from across their taxonomic and geographic ranges. The analysis suggests a complex history of admixture and identifies signals of repeated evolutionary selection, some of which may be linked to response to simian immunodeficiency virus.

The CRISPR–Cas9 system enables global screens of gene function with high sensitivity and specificity, but off-target effects have been reported for CRISPR guide RNAs targeting genes that are amplified at high copy number. A new study describes a computational approach to correct for this copy number effect, increasing the specificity of CRIPSR screens to identify essential genes.

A new analysis of cancer genomes identifies a decrease in the mutation burden of exons, but not introns, as compared to expectation. This difference can be explained by preferential recruitment of the DNA mismatch repair machinery to a protein modification that marks exons.

This study uses human astrocytes and glioma tumorspheres to generate an atlas of mutant-IDH1-induced epigenomic reprogramming. The findings have implications for understanding mutant IDH function and for optimizing approaches to target IDH-mutant tumors.

This study presents a probabilistic framework for inferring negative and positive selection in human cancers that addresses the problem of mutation rate variation. Applying the model to sequencing data from 17 cancer types identifies new significantly mutated genes and detects significant signals of negative selection in many cancer types.

Analysis of a large cohort of EGFR-mutant lung cancer cell-free DNA samples along with longitudinal samples from a patient with EGFR-mutant lung cancer identifies pathways that inhibit EGFR-inhibitor response. Co-occurring genetic alterations influence clinical outcomes and underscore the need for combination therapies.

RNA Capture Long Seq (CLS) is a new method for transcript annotation that combines targeted RNA capture with long-read sequencing. CLS reannotates GENCODE lncRNAs and increases the number of validated splice junctions and transcript models for targeted loci.

This analysis of cancer sequencing data identifies a reduced somatic mutation rate in exons and shows that this phenomenon is due to higher mismatch-repair activity in exons as compared to introns. These findings have implications for the understanding of mutational and DNA repair processes and for studying the evolution of both tumors and species.

Nelson Freimer and colleagues analyze gene expression data from multiple tissue samples combined with genotype data from vervet monkeys to catalog expression quantitative trait loci (eQTLs). They generate a transcriptome resource analogous to the GTEx project and perform comparative and eQTL enrichment analyses for various traits.

Exome-wide genetic analysis on >300,000 individuals identifies associations with plasma lipid traits. Loci significantly associated with cholesterol and triglycerides are examined together to determine the effects of alleles on type 2 diabetes and coronary artery disease risk.

This large-scale genome-wide association analysis of subjects with asthma, hay fever or eczema provides insights into the shared genetic basis of these allergic diseases. The findings suggest that these diseases partly co-occur because they share many genetic risk variants that dysregulate the expression of immune-related genes.

Analysis of whole-genome sequencing data from 163 vervet monkeys from Africa and the Caribbean shows high diversity among taxa and identifies signatures of selection. Selection signals affect viral processes, and genes that show response to SIV in vervets but not macaques have elevated selection scores.

A meta-analysis of exome-wide association studies for blood lipid levels in East Asian populations identifies a novel coding variant. Exome array data from the Global Lipids Genetics Consortium were integrated and led to the discovery of novel and population-specific variants associated with cholesterol and triglycerides.

CERES is a new computational method to estimate gene-dependency levels from CRISPR–Cas9 essentiality screens while accounting for copy number effects and variable sgRNA activity. Applying CERES to new genome-scale CRISPR–Cas9 essentiality screen data from 342 cancer cell lines and other published data sets shows that CERES decreases false-positive results and provides consistent estimates of sgRNA activity.

Citation of prior publications is essential both to claim that knowledge is needed in your area of research and to establish that you have indeed advanced understanding substantially in that area. The journal deplores and will decline to consider manuscripts that fail to identify the key findings of published articles and that—deliberately or inadvertently—omit the reason the prior work is cited.

Human-derived tumor models are becoming popular in the context of personalized medicine, but a new study shows that these models could be less representative of primary tumors than previously thought, particularly when using late passages.