The Sequence Alignment/Map format and SAMtools

Summary: The Sequence Alignment/Map (SAM) format is a generic alignment format for storing read alignments against reference sequences, supporting short and long reads (up to 128 Mbp) produced by different sequencing platforms. It is flexible in style, compact in size, efficient in random access and is the format in which alignments from the 1000 Genomes Project are released. SAMtools implements various utilities for post-processing alignments in the SAM format, such as indexing, variant caller and alignment viewer, and thus provides universal tools for processing read alignments

Improving the altimetric rain record from Jason-1 & Jason-2

Dual-frequency rain-flagging has long been a standard part of altimetric data analysis, both for quality control of the data and for the study of rain itself, because altimeters can provide a finer spatial sampling of rain than can passive microwave instruments. However, there have been many varied implementations, using different records of the surface backscatter and different thresholds. This paper compares four different measures available for the recently-launched Jason-2. The evaluation compares these measures against clearly desired properties, finding that in most cases the adjusted backscatter and that from the ice retracker perform much better than that recommended in the users' handbook. The adjusted backscatter measure also provides a much better link to observations from Jason-1, opening up a much longer period for consistent rain investigations, and enabling greatly improved analysis of the short-scale variability of precipitation. Initial analysis shows that although the spatial and temporal gradients of backscatter increase at very low winds, the spatial gradients in rain attenuation are concentrated where rainfall is greatest, whilst the temporal changes have a simple broad latitudinal pattern

The game-changing impact of POLE mutations in oncology—a review from a gynecologic oncology perspective

Somatic mutations within the exonuclease proofreading domain (EDM) of the DNA polymerase Pol ϵ (POLE) gene are increasingly being discovered in ovarian, colorectal, urological, and, especially, endometrial carcinoma (EC), where these are found in up to 10% of the cases. In EC, there are five confirmed pathogenic somatic POLE-EDM mutations that are located at codons 286, 411, 297, 456, and 459, and these are called “hotspot” mutations. POLE mutant tumors are ultramutated entities with a frequency of base substitution mutations that is among the highest in human tumors. Interestingly, these mutations are associated with excellent clinical outcome in EC. An additional six “non-hotspot” POLE-EDM EC mutations are also considered pathogenic, and they also confer a favorable prognosis. Currently, de-escalation of adjuvant treatment is recommended for patients with EC with stage I–II tumors involving any of these 11 EDM mutations, even in patients with other clinicopathological risk factors. The high tumor mutational burden and the consequent increased infiltration of immune cells due to the overexpression of different neoantigens are probably responsible for the improved prognosis. Ongoing studies are examining POLE hotspot mutations among many non-gynecologic tumors, although the impact of such mutations on clinical outcomes is still a topic of debate. Therapeutic modalities for these hypermutated tumors are also an important consideration, including the need for or de-escalation of adjuvant treatments and the response to immune therapy. This review addresses the critical role of POLE mutations in gynecologic oncology and oncology in general, focusing on definitions, variants, underlying pathogenic mechanisms, upcoming developments in the field, and the clinic behavior associated with such mutations

The variant call format and VCFtools

Summary: The variant call format (VCF) is a generic format for storing DNA polymorphism data such as SNPs, insertions, deletions and structural variants, together with rich annotations. VCF is usually stored in a compressed manner and can be indexed for fast data retrieval of variants from a range of positions on the reference genome. The format was developed for the 1000 Genomes Project, and has also been adopted by other projects such as UK10K, dbSNP and the NHLBI Exome Project. VCFtools is a software suite that implements various utilities for processing VCF files, including validation, merging, comparing and also provides a general Perl API

Longitudinal Assessment of Older Drivers in a DMV Setting

A brief battery of functional assessments designed to detect crash riskamong older drivers was developed and evaluated initially in 1999 in Marylandmotor vehicle licensing sites following the routine vision screening exam. Thisbattery contained a number of cognitive tests (e.g., UFOV® subtest 2, the closuresubtest of the Motor Free Visual Perception Test (MVPT), Trails A and B, cuedrecall, delayed recall), and several physical measures (e.g., Rapid Pace Walk,Head and Neck Rotation, Foot Tap, Arm Reach). Older adults (N=4,173; meanage = 69 years) were approached by the staff after license renewal and asked tohelp evaluate the brief battery. Of the 4,173 older adults approached at the fieldsites, 2,114 individuals 55-96 years of age participated. Subsequently, the originalsample of 2,114 participants was invited to come in once again, during their fiveyearlicense renewal cycle, and the functional tests were administered once again.To date, 939 individuals have completed the second screening evaluation. Anexamination of the crash data from the interval between assessments for theseindividuals indicates that the same cognitive measures are predictive of at-faultcrashes. Furthermore, approximately 10% of those passing the assessment in 1999are now failing the assessment in 2004. Performance-based cognitive measuresare predictive of future at-fault motor vehicle collisions among older adults.Cognitive performance, in particular, is a salient predictor of subsequent crashinvolvement among older adults. High-risk older drivers can be identified throughbrief, performance-based measures administered in a DMV setting

A standard variation file format for human genome sequences

Here we describe the Genome Variation Format (GVF) and the 10Gen dataset. GVF, an extension of Generic Feature Format version 3 (GFF3), is a simple tab-delimited format for DNA variant files, which uses Sequence Ontology to describe genome variation data. The 10Gen dataset, ten human genomes in GVF format, is freely available for community analysis from the Sequence Ontology website and from an Amazon elastic block storage (EBS) snapshot for use in Amazon's EC2 cloud computing environment

Interferon-gamma in the first-line therapy of ovarian cancer: a randomized phase III trial

Intraperitoneal treatment with interferon-γ (IFN-γ) has been shown to achieve surgically documented responses in the second-line therapy of ovarian cancer. To assess its efficacy in the first-line therapy, we conducted a randomized controlled trial with 148 patients who had undergone primary surgery for FIGO stage Ic–IIIc ovarian cancer. In the control arm women received 100 mg m−2cisplatin and 600 mg m−2cyclophosphamide, the experimental arm included the above regimen with IFN-γ 0.1 mg subcutaneously on days 1, 3, 5, 15, 17 and 19 of each 28-day cycle. Progression-free survival at 3 years was improved from 38% in controls to 51% in the treatment group corresponding to median times to progression of 17 and 48 months (P = 0.031, relative risk of progression 0.48, confidence interval 0.28–0.82). Three-year overall survival was 58% and 74% accordingly (n.s., median not yet reached). Complete clinical responses were observed in 68% with IFN-γ versus 56% in controls (n.s.). Toxicity was comparable in both groups except for a mild flu-like syndrome, experienced by most patients after administration of IFN-γ. Thus, with acceptable toxicity, the inclusion of IFN-γ in the first-line chemotherapy of ovarian cancer yielded a benefit in prolonging progression-free survival. © 2000 Cancer Research Campaig