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variant analytics

Po-Jung Huang, Chi-Ching Lee, Ling-Ya Chiu, Kuo-Yang Huang, Yuan-Ming Yeh, Chia-Yu Yang, Cheng-Hsun Chiu, Petrus Tang
BACKGROUND: High throughput sequencing technologies have been an increasingly critical aspect of precision medicine owing to a better identification of disease targets, which contributes to improved health care cost and clinical outcomes. In particular, disease-oriented targeted enrichment sequencing is becoming a widely-accepted application for diagnostic purposes, which can interrogate known diagnostic variants as well as identify novel biomarkers from panels of entire human coding exome or disease-associated genes...
May 9, 2018: BMC Genomics
Gregory J Hogan, Valentina S Vysotskaia, Kyle A Beauchamp, Stefanie Seisenberger, Peter V Grauman, Kevin R Haas, Sun Hae Hong, Diana Jeon, Shera Kash, Henry H Lai, Laura M Melroy, Mark R Theilmann, Clement S Chu, Kevin Iori, Jared R Maguire, Eric A Evans, Imran S Haque, Rebecca Mar-Heyming, Hyunseok P Kang, Dale Muzzey
BACKGROUND: By identifying pathogenic variants across hundreds of genes, expanded carrier screening (ECS) enables prospective parents to assess the risk of transmitting an autosomal recessive or X-linked condition. Detection of at-risk couples depends on the number of conditions tested, the prevalence of the respective diseases, and the screen's analytical sensitivity for identifying disease-causing variants. Disease-level analytical sensitivity is often <100% in ECS tests because copy number variants (CNVs) are typically not interrogated because of their technical complexity...
May 14, 2018: Clinical Chemistry
Abhishek Kumar Dubey, Alexandros-Stavros Iliopoulos, Xiaobai Sun, Fang-Fang Yin, Lei Ren
PURPOSE: Often, the inverse deformation vector field (DVF) is needed together with the corresponding forward DVF in 4D reconstruction and dose calculation, adaptive radiation therapy, and simultaneous deformable registration. This study aims at improving both accuracy and efficiency of iterative algorithms for DVF inversion, and advancing our understanding of divergence and latency conditions. METHOD: We introduce a framework of fixed-point iteration algorithms with active feedback control for DVF inversion...
May 14, 2018: Medical Physics
Phillip N Gray, Pei Tsai, Daniel Chen, Sitao Wu, Jayne Hoo, Wenbo Mu, Bing Li, Huy Vuong, Hsiao-Mei Lu, Navanjot Batth, Sara Willett, Lisa Uyeda, Swati Shah, Chia-Ling Gau, Monalyn Umali, Carin Espenschied, Mike Janicek, Sandra Brown, David Margileth, Lavinia Dobrea, Lawrence Wagman, Huma Rana, Michael J Hall, Theodora Ross, Jonathan Terdiman, Carey Cullinane, Savita Ries, Ellen Totten, Aaron M Elliott
The current algorithm for Lynch syndrome diagnosis is highly complex with multiple steps which can result in an extended time to diagnosis while depleting precious tumor specimens. Here we describe the analytical validation of a custom probe-based NGS tumor panel, TumorNext-Lynch-MMR, which generates a comprehensive genetic profile of both germline and somatic mutations that can accelerate and streamline the time to diagnosis and preserve specimen. TumorNext-Lynch-MMR can detect single nucleotide variants, small insertions and deletions in 39 genes that are frequently mutated in Lynch syndrome and colorectal cancer...
April 17, 2018: Oncotarget
Gedeon Loules, Maria Zamanakou, Faidra Parsopoulou, Sofia Vatsiou, Fotis Psarros, Dorottya Csuka, Grzegorz Porebski, Krystyna Obtulowicz, Anna Valerieva, Maria Staevska, Alberto López-Lera, Margarita López-Trascasa, Dumitru Moldovan, Markus Magerl, Marcus Maurer, Matthaios Speletas, Henriette Farkas, Anastasios E Germenis
SERPING1 genotyping of subjects suspicious for hereditary angioedema due to C1-INH deficiency (C1-INH-HAE) is important for clinical practice as well as for research reasons. Conventional approaches towards the detection of C1-INH-HAE-associated SERPING1 variants are cumbersome and time-demanding with many pitfalls. To take advantage of the benefits of next-generation sequencing (NGS) technology, we developed and validated a custom NGS platform that, by targeting the entire SERPING1 gene, facilitates genetic testing of C1-INH-HAE patients in clinical practice...
May 10, 2018: Gene
Weizhen Xie, Marcus Cappiello, Ming Meng, Robert Rosenthal, Weiwei Zhang
This meta-analytical review examines whether a deletion variant in ADRA2B, a gene that encodes α2B adrenoceptor in the regulation of norepinephrine availability, influences cognitive processing of emotional information in human observers. Using a multilevel modeling approach, this meta-analysis of 16 published studies with a total of 2,752 participants showed that ADRA2B deletion variant was significantly associated with enhanced perceptual and cognitive task performance for emotional stimuli. In contrast, this genetic effect did not manifest in overall task performance when non-emotional content was used...
May 8, 2018: Neuroscience and Biobehavioral Reviews
Marco Müller, Katharina Wasmer, Walter Vetter
Countercurrent chromatography (CCC) is an all liquid based separation technique typically used for the isolation and purification of natural compounds. The simplicity of the method makes it easy to scale up CCC separations from analytical to preparative and even industrial scale. However, scale-up of CCC separations requires two different instruments with varying coil dimensions. Here we developed two variants of the CCC multiple injection mode as an alternative to increase the throughput and enhance productivity of a CCC separation when using only one instrument...
May 1, 2018: Journal of Chromatography. A
Niladri Banerjee, Tatiana Polushina, Francesco Bettella, Sudheer Giddaluru, Vidar M Steen, Ole A Andreassen, Stephanie Le Hellard
BACKGROUND: One explanation for the persistence of schizophrenia despite the reduced fertility of patients is that it is a by-product of recent human evolution. This hypothesis is supported by evidence suggesting that recently-evolved genomic regions in humans are involved in the genetic risk for schizophrenia. Using summary statistics from genome-wide association studies (GWAS) of schizophrenia and 11 other phenotypes, we tested for enrichment of association with GWAS traits in regions that have undergone methylation changes in the human lineage compared to Neanderthals and Denisovans, i...
May 11, 2018: BMC Evolutionary Biology
William La Cava, Thomas Helmuth, Lee Spector, Jason H Moore
Lexicase selection is a parent selection method that considers training cases individually, rather than in aggregate, when performing parent selection. Whereas previous work has demonstrated the ability of lexicase selection to solve difficult problems in program synthesis and symbolic regression, the central goal of this paper is to develop the theoretical underpinnings that explain its performance. To this end, we derive an analytical formula that gives the expected probabilities of selection under lexicase selection, given a population and its behavior...
May 10, 2018: Evolutionary Computation
Adam B Burkholder, Scott A Lujan, Christopher A Lavender, Sara A Grimm, Thomas A Kunkel, David C Fargo
BACKGROUND: Identification of mutations from next-generation sequencing data typically requires a balance between sensitivity and accuracy. This is particularly true of DNA insertions and deletions (indels), that can impart significant phenotypic consequences on cells but are harder to call than substitution mutations from whole genome mutation accumulation experiments. To overcome these difficulties, we present muver, a computational framework that integrates established bioinformatics tools with novel analytical methods to generate mutation calls with the extremely low false positive rates and high sensitivity required for accurate mutation rate determination and comparison...
May 9, 2018: BMC Genomics
Michael R Jablonski, Nina King, Yongbao Wang, Joel G Winner, Lucas R Watterson, Sandra Gunselman, Bryan M Dechairo
AIM: The aim of this study was to validate the analytical performance of a combinatorial pharmacogenomics test designed to aid in the appropriate medication selection for neuropsychiatric conditions. MATERIALS & METHODS: Genomic DNA was isolated from buccal swabs. Twelve genes (65 variants/alleles) associated with psychotropic medication metabolism, side effects, and mechanisms of actions were evaluated by bead array, MALDI-TOF mass spectrometry, and/or capillary electrophoresis methods (GeneSight Psychotropic, Assurex Health, Inc...
February 7, 2018: Personalized Medicine
Geoffrey S Ginsburg, Kathryn A Phillips
Precision medicine is making an impact on patients, health care delivery systems, and research participants in ways that were only imagined fifteen years ago when the human genome was first sequenced. Discovery of disease-causing and drug-response genetic variants has accelerated, while adoption into clinical medicine has lagged. We define precision medicine and the stakeholder community required to enable its integration into research and health care. We explore the intersection of data science, analytics, and precision medicine in the formation of health systems that carry out research in the context of clinical care and that optimize the tools and information used to deliver improved patient outcomes...
May 2018: Health Affairs
Ettore Capoluongo, Giovanni Scambia, Jean-Marc Nabholtz
Background: Since the approval of the first poly (adenosine diphosphate [ADP]) ribose polymerase inhibitor (PARPi; olaparib [Lynparza™]) for platinum-sensitive relapsed high grade ovarian cancer, with either germline or somatic BRCA1/2 deleterious variants, the strategies for BRCA1/2 are dynamically changing. Along with germline testing within the context of familial or sporadic ovarian cancer, patients are now being referred for BRCA1/2 genetic assay above all for treatment decisions: in this setting tumour BRCA assay can allow to identify an estimated 3-9% of patients with peculiar somatic BRCA1/2 mutations...
April 13, 2018: Oncotarget
R Becker, I Lô, F Sporkert, M Baumgartner
The increasing request for hair ethyl glucuronide (HEtG) in alcohol consumption monitoring according to cut-off levels set by the Society of Hair Testing (SoHT) has triggered a proficiency testing program based on interlaboratory comparisons (ILC). Here, the outcome of nine consecutive ILC rounds organised by the SoHT on the determination of HEtG between 2011 and 2017 is summarised regarding interlaboratory reproducibility and the influence of procedural variants. Test samples prepared from cut hair (1mm) with authentic (in-vivo incorporated) and soaked (in-vitro incorporated) HEtG concentrations up to 80pg/mg were provided for 27-35 participating laboratories...
April 26, 2018: Forensic Science International
James B Smadbeck, Sarah H Johnson, Stephanie A Smoley, Athanasios Gaitatzes, Travis M Drucker, Roman M Zenka, Farhad Kosari, Stephen J Murphy, Nicole Hoppman, Umut Aypar, William R Sukov, Robert B Jenkins, Hutton M Kearney, Andrew L Feldman, George Vasmatzis
Copy number variation (CNV) is a common form of structural variation detected in human genomes, occurring as both constitutional and somatic events. Cytogenetic techniques like chromosomal microarray (CMA) are widely used in analyzing CNVs. However, CMA techniques cannot resolve the full nature of these structural variations (i.e. the orientation and location of associated breakpoint junctions) and must be combined with other cytogenetic techniques, such as karyotyping or FISH, to do so. This makes the development of a next-generation sequencing (NGS) approach capable of resolving both CNVs and breakpoint junctions desirable...
May 4, 2018: Genes, Chromosomes & Cancer
Zhongsheng Man, Zhidong Bai, Jinjian Li, Shuoshuo Zhang, Xiaoyu Li, Yuquan Zhang, Xiaolu Ge, Shenggui Fu
We propose a method to generate an optical cage using azimuthal- and radial-variant vector beams in a high numerical aperture optical system. A new kind of vector beam that has azimuthal- and radial-variant polarization states is proposed and demonstrated theoretically. Then, an integrated analytical model to calculate the electromagnetic field and Poynting vector distributions of the input azimuthal- and radial-variant vector beams is derived and built based on the vector diffraction theory of Richards and Wolf...
May 1, 2018: Applied Optics
Blair Lawley, Manuela Centanni, Jun Watanabe, Ian Sims, Susan Carnachan, Roland Broadbent, Pheng Soon Lee, Khai Hong Wong, Gerald W Tannock
Members of the bacterial genus Bifidobacterium generally dominate the faecal microbiota of infants. The species B. longum is prevalent, but the subspecies longum and infantis that are known to colonize the infant bowel are not usually differentiated in microbiota investigations. These subspecies differ in their capacity to metabolize Human Milk Oligosaccharides (HMO) and may have differing ecological and symbiotic roles in humans. Quantitative PCR provides a quick analytical method by which to accurately ascertain the abundances of target species in microbiotas and microcosms...
April 27, 2018: Applied and Environmental Microbiology
Thomas R Caulfield, John E Richter, Emily E Brown, Ahmed N Mohammad, Daniel P Judge, Paldeep S Atwal
BACKGROUND: Haploinsufficiency of TAB2 is known to cause congenital heart defects and cardiomyopathy due to its important roles in cardiovascular tissue, both during development and through adult life. We report a sibling pair displaying adult-onset cardiomyopathy, hypermobility, and mild myopia. Our proband, a 39-year-old male, presents only with the above symptoms, while his 36-year-old sister was also notable for a ventricular septal defect in her infancy. METHODS: Whole-exome sequencing was utilized to identify the molecular basis of the phenotype found in two siblings...
April 26, 2018: Molecular Genetics & Genomic Medicine
Donna M Werling, Harrison Brand, Joon-Yong An, Matthew R Stone, Lingxue Zhu, Joseph T Glessner, Ryan L Collins, Shan Dong, Ryan M Layer, Eirene Markenscoff-Papadimitriou, Andrew Farrell, Grace B Schwartz, Harold Z Wang, Benjamin B Currall, Xuefang Zhao, Jeanselle Dea, Clif Duhn, Carolyn A Erdman, Michael C Gilson, Rachita Yadav, Robert E Handsaker, Seva Kashin, Lambertus Klei, Jeffrey D Mandell, Tomasz J Nowakowski, Yuwen Liu, Sirisha Pochareddy, Louw Smith, Michael F Walker, Matthew J Waterman, Xin He, Arnold R Kriegstein, John L Rubenstein, Nenad Sestan, Steven A McCarroll, Benjamin M Neale, Hilary Coon, A Jeremy Willsey, Joseph D Buxbaum, Mark J Daly, Matthew W State, Aaron R Quinlan, Gabor T Marth, Kathryn Roeder, Bernie Devlin, Michael E Talkowski, Stephan J Sanders
Genomic association studies of common or rare protein-coding variation have established robust statistical approaches to account for multiple testing. Here we present a comparable framework to evaluate rare and de novo noncoding single-nucleotide variants, insertion/deletions, and all classes of structural variation from whole-genome sequencing (WGS). Integrating genomic annotations at the level of nucleotides, genes, and regulatory regions, we define 51,801 annotation categories. Analyses of 519 autism spectrum disorder families did not identify association with any categories after correction for 4,123 effective tests...
April 26, 2018: Nature Genetics
John J Scarcelli, Megan Hone, Kathryn Beal, Alejaida Ortega, Bruno Figueroa, Jason A Starkey, Karin Anderson
During development of a cell line intended to support production of an IgG2 monoclonal antibody, a sequence variant caused by a genetic mutation was identified in the bulk drug substance. Gene copy number analysis together with the level of the observed variant in genomic DNA indicated that the master cell bank was a mixed population of cells; some harboring the variant copy and some mutation free. Since the cell bank had been single-cell cloned, this variant could be used as a biomarker to demonstrate either that the bank was not derived from a single cell, or that the variant was a result of a post-cloning genetic event, leading to a mixed population of cells...
April 25, 2018: Biotechnology Progress
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