An integrated map of structural variation in 2,504 human genomes

Structural variants are implicated in numerous diseases and make up the majority of varying nucleotides among human genomes. Here we describe an integrated set of eight structural variant classes comprising both balanced and unbalanced variants, which we constructed using short-read DNA sequencing data and statistically phased onto haplotype blocks in 26 human populations. Analysing this set, we identify numerous gene-intersecting structural variants exhibiting population stratification and describe naturally occurring homozygous gene knockouts that suggest the dispensability of a variety of human genes. We demonstrate that structural variants are enriched on haplotypes identified by genome-wide association studies and exhibit enrichment for expression quantitative trait loci. Additionally, we uncover appreciable levels of structural variant complexity at different scales, including genic loci subject to clusters of repeated rearrangement and complex structural variants with multiple breakpoints likely to have formed through individual mutational events. Our catalogue will enhance future studies into structural variant demography, functional impact and disease association. © 2015 Macmillan Publishers Limited. All rights reserved

Integrating sequence and array data to create an improved 1000 Genomes Project haplotype reference panel

A major use of the 1000 Genomes Project (1000GP) data is genotype imputation in genome-wide association studies (GWAS). Here we develop a method to estimate haplotypes from low-coverage sequencing data that can take advantage of single-nucleotide polymorphism (SNP) microarray genotypes on the same samples. First the SNP array data are phased to build a backbone (or 'scaffold') of haplotypes across each chromosome. We then phase the sequence data 'onto' this haplotype scaffold. This approach can take advantage of relatedness between sequenced and non-sequenced samples to improve accuracy. We use this method to create a new 1000GP haplotype reference set for use by the human genetic community. Using a set of validation genotypes at SNP and bi-allelic indels we show that these haplotypes have lower genotype discordance and improved imputation performance into downstream GWAS samples, especially at low-frequency variants. © 2014 Macmillan Publishers Limited. All rights reserved

A computational model to predict cell traction-mediated prestretch in the mitral valve

Prestretch is observed in many soft biological tissues, directly influencing the mechanical behavior of the tissue in question. The development of this prestretch occurs through complex growth and remodeling phenomena, which yet remain to be elucidated. In the present study it was investigated whether local cell-mediated traction forces can explain the development of global anisotropic tissue prestretch in the mitral valve. Towards this end, a model predicting actin stress fiber-generated traction forces was implemented in a finite element framework of the mitral valve. The overall predicted magnitude of prestretch induced valvular contraction after release of in vivo boundary constraints was in good agreement with data reported on valvular retraction after excision from the heart. Next, by using a systematic variation of model parameters and structural properties, a more anisotropic prestretch development in the valve could be obtained, which was also similar to physiological values. In conclusion, this study shows that cell-generated traction forces could explain prestretch magnitude and anisotropy in the mitral valve

Global calibration for non-targeted fraud detection in quinoa flour using portable hyperspectral imaging and chemometrics

Quinoa is one of the highest nutritious grains, and global consumption of quinoa flour has increased as people pay more attention to health. Due to its high value, quinoa flour is susceptible to adulteration. Cross-contamination between quinoa flour and other flour can be easily neglected due to their highly similar appearance. Therefore, detecting adulteration in quinoa flour is important to consumers, industries, and regulatory agencies. In this study, portable hyperspectral imaging in the visible near-infrared (VNIR) spectral range (400–1000 nm) was applied as a rapid tool to detect adulteration in quinoa flour. Quinoa flour was adulterated with wheat, rice, soybean, and corn in the range of 0–98% with 2% increments. Partial least squares regression (PLSR) models were developed, and the best model for detecting the % authentic flour (quinoa) was obtained by the raw spectral data with R2p of 0.99, RMSEP of 3.08%, RPD of 8.77, and RER of 25.32. The model was improved, by selecting only 13 wavelengths using bootstrapping soft shrinkage (BOSS), to R2p of 0.99, RMSEP of 2.93%, RPD of 9.18, and RER of 26.60. A visualization map was also generated to predict the level of quinoa in the adulterated samples. The results of this study demonstrate the ability of VNIR hyperspectral imaging for adulteration detection in quinoa flour as an alternative to the complicated traditional method