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Over 90% of human whole-genome sequencing has been performed using instruments from two companies, Illumina and Complete Genomics. Lam et al. sequence the same DNA samples with both instruments and compare their performance for calling insertions, deletions and single-nucleotide variants.
Data filters separate true genetic variants in sequencing data from sequencing errors, but their effectiveness is difficult to assess. Reumers et al. use the genome sequences of monozygotic twins to evaluate the performance of filters individually and in combination, leading to a 290-fold reduction in error rate in calling single-nucleotide variants.
Copy-number changes in cancer genomes may be caused by errors during the replication of colocalized DNA regions. De and Michor provide genome-wide evidence for this model by integrating data on DNA replication timing, the three-dimensional organization of the genome and copy-number alterations in cancer.
Copy-number changes, point mutations and rearrangements are all usually found in cancer genomes, but their relative frequencies are highly variable. Using statistical approaches to model different processes, Fudenberg et al. find that copy number gain and loss is influenced by the three-dimensional organization of the genome in the nucleus.
New instruments can measure the presence of >30 molecular markers for massive numbers of single cells, but data analysis algorithms have lagged behind. Qiu et al. describe an approach called SPADE for recovering cellular hierarchies from mass or flow cytometry data.
Capturing and sequencing only the coding regions of the human genome leverages resources in the pursuit of rare disease-causing mutations. Clark et al. compare the performance of three leading exome-capture methods and their advantages over whole-genome sequencing.
Identification of genomic structural variation from short-read sequencing data is typically accomplished by mapping reads to a reference genome. Li et al. show that de novo assembly of the reads followed by whole-genome alignment to the reference is a more comprehensive method that can also resolve complex rearrangements.
Widely applicable methods for mapping protein-RNA interactions by crosslinking achieve a resolution of ∼30–60 nucleotides. Zhang and Darnell analyze sites of mutation induced by the crosslinking to map binding at single-nucleotide resolution.
Magtanong et al. describe the first study to systematically analyze dosage suppression, a type of genetic interaction in which increased dosage of one gene compensates for mutation in another. The authors also develop reagents for future large-scale studies of dosage suppression.
When embarking on a microarray-based study of genomic copy number variation, what's helpful for navigating the myriad of available array platforms and data analysis approaches? Pinto et al. evaluate six samples from healthy controls in triplicate on commonly used combinations of commercial arrays and analytic tools, providing realistic comparisons of performance.
The experiences of patients who try drugs that aren't approved for their disease have the potential to be mined for insights into drug efficacy. Wicks et al. rapidly monitored the efficacy of lithium treatment for 149 patients with amyotrophic lateral sclerosis using an online data collection tool and a patient-matching algorithm.