scholarly journals Integrative pipeline for profiling DNA copy number and inferring tumor phylogeny

2017 ◽  
Author(s):  
Eugene Urrutia ◽  
Hao Chen ◽  
Zilu Zhou ◽  
Nancy R Zhang ◽  
Yuchao Jiang
Keyword(s):  
Copy Number ◽  
Cancer Genomics ◽  
Supplementary Information ◽  
Single Nucleotide Variants ◽  
Genetic Studies ◽  
Number Variation ◽  
Allele Specific ◽  
Copy Number Changes ◽  
Fine Resolution ◽  
Tumor Phylogeny

AbstractSummaryCopy number variation is an important and abundant source of variation in the human genome, which has been associated with a number of diseases, especially cancer. Massively parallel next-generation sequencing allows copy number profiling with fine resolution. Such efforts, however, have met with mixed successes, with setbacks arising partly from the lack of reliable analytical methods to meet the diverse and unique challenges arising from the myriad experimental designs and study goals in genetic studies. In cancer genomics, detection of somatic copy number changes and profiling of allele-specific copy number (ASCN) are complicated by experimental biases and artifacts as well as normal cell contamination and cancer subclone admixture. Furthermore, careful statistical modeling is warranted to reconstruct tumor phylogeny by both somatic ASCN changes and single nucleotide variants. Here we describe a flexible computational pipeline, MARATHON, which integrates multiple related statistical software for copy number profiling and downstream analyses in disease genetic studies.Availability and implementationMARATHON is publicly available at https://github.com/yuchaojiang/[email protected] informationSupplementary data are available at Bioinformatics online.

scholarly journals ClinCNV: novel method for allele-specific somatic copy-number alterations detection

2019 ◽  
Author(s):  
German Demidov ◽  
Stephan Ossowski
Keyword(s):  
Copy Number ◽  
Read Depth ◽  
Copy Number Alterations ◽  
Single Nucleotide Variants ◽  
Small Indels ◽  
Whole Exome ◽  
Allele Specific ◽  
Copy Number Changes ◽  
Ngs Data ◽  
Somatic Copy Number Alterations

AbstractMotivationLarge somatic copy number alterations (CNA), short indels and single nucleotide variants (SNVs) are playing important role in cancer development and can serve as a predictor for targeted therapy selection as well as prognostic factor. Genomic microarrays, FISH, MLPA and many other technologies are widely used for detection of CNAs. Whole-genome sequencing (WGS), whole-exome sequencing (WES) and targeted panel sequencing (TPS) are well established, highly accurate tools for detection of SNVs and small indels, but detection of larger structural variants using WGS, WES and TPS data remains challenging. We developed a tool for high-resolution allele-specific detection of somatic CNAs in NGS data using statistical approach.ResultsWe have developed a new method for read-depth and B-allele frequency (BAF) based multi-sample detection of copy-number changes in paired normal-tumor NGS data and showed its performance using large cohorts of WES and TPS sequenced samples.AvailabilityClinCNV is freely available on https://github.com/imgag/ClinCNV.

Transcriptional profiling of iPSC-derived neurons with reciprocal monogenic CNV in 3p26.3 region

2020 ◽  
pp. 10-11
Author(s):  
М.Е. Лопаткина ◽  
В.С. Фишман ◽  
М.М. Гридина ◽  
Н.А. Скрябин ◽  
Т.В. Никитина ◽  
...  
Keyword(s):  
Gene Expression ◽  
Copy Number ◽  
System Development ◽  
Transcriptional Profiling ◽  
Global Gene Expression ◽  
Nervous System Development ◽  
Number Variation ◽  
The Central Nervous System ◽  
Cntn6 Gene ◽  
Copy Number Changes

Проведен анализ генной экспрессии в нейронах, дифференцированных из индуцированных плюрипотентных стволовых клеток пациентов с идиопатическими интеллектуальными нарушениями и реципрокными хромосомными мутациями в регионе 3p26.3, затрагивающими единственный ген CNTN6. Для нейронов с различным типом хромосомных аберраций была показана глобальная дисрегуляция генной экспрессии. В нейронах с вариациями числа копий гена CNTN6 была снижена экспрессия генов, продукты которых вовлечены в процессы развития центральной нервной системы. The gene expression analysis of iPSC-derived neurons, obtained from patients with idiopathic intellectual disability and reciprocal microdeletion and microduplication in 3p26.3 region affecting the single CNTN6 gene was performed. The global gene expression dysregulation was demonstrated for cells with CNTN6 copy number variation. Gene expression in neurons with CNTN6 copy number changes was downregulated for genes, whose products are involved in the central nervous system development.

scholarly journals CNV-BAC: Copy number Variation Detection in Bacterial Circular Genome

2020 ◽  
Vol 36 (12) ◽  
pp. 3890-3891
Author(s):  
Linjie Wu ◽  
Han Wang ◽  
Yuchao Xia ◽  
Ruibin Xi
Keyword(s):  
Copy Number Variation ◽  
Copy Number ◽  
Genome Structure ◽  
Real Data ◽  
Read Depth ◽  
Supplementary Information ◽  
Circular Genome ◽  
Number Variation ◽  
Copy Number Variation Detection ◽  
Cnv Detection

Abstract Motivation Whole-genome sequencing (WGS) is widely used for copy number variation (CNV) detection. However, for most bacteria, their circular genome structure and high replication rate make reads more enriched near the replication origin. CNV detection based on read depth could be seriously influenced by such replication bias. Results We show that the replication bias is widespread using ∼200 bacterial WGS data. We develop CNV-BAC (CNV-Bacteria) that can properly normalize the replication bias and other known biases in bacterial WGS data and can accurately detect CNVs. Simulation and real data analysis show that CNV-BAC achieves the best performance in CNV detection compared with available algorithms. Availability and implementation CNV-BAC is available at https://github.com/XiDsLab/CNV-BAC. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals Genome-Wide Detection of Allele Specific Copy Number Variation Associated with Insulin Resistance in African Americans from the HyperGEN Study

PLoS ONE ◽  
2011 ◽  
Vol 6 (8) ◽  
pp. e24052 ◽  
Author(s):  
Marguerite R. Irvin ◽  
Nathan E. Wineinger ◽  
Treva K. Rice ◽  
Nicholas M. Pajewski ◽  
Edmond K. Kabagambe ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
African Americans ◽  
Copy Number Variation ◽  
Copy Number ◽  
Genome Wide ◽  
Number Variation ◽  
Allele Specific

scholarly journals tHapMix: simulating tumour samples through haplotype mixtures

2016 ◽  
Author(s):  
Sergii Ivakhno ◽  
Camilla Colombo ◽  
Stephen Tanner ◽  
Philip Tedder ◽  
Stefano Berri ◽  
...  
Keyword(s):  
Copy Number ◽  
Large Scale ◽  
Variant Calling ◽  
Copy Number Variant ◽  
Supplementary Information ◽  
Genome Diversity ◽  
Simulation Framework ◽  
Somatic Genome ◽  
Copy Number Changes ◽  
Sequencing Platforms

AbstractMotivationLarge-scale rearrangements and copy number changes combined with different modes of cloevolution create extensive somatic genome diversity, making it difficult to develop versatile and scalable oriant calling tools and create well-calibrated benchmarks.ResultsWe developed a new simulation framework tHapMix that enables the creation of tumour samples with different ploidy, purity and polyclonality features. It easily scales to simulation of hundreds of somatic genomes, while re-use of real read data preserves noise and biases present in sequencing platforms. We further demonstrate tHapMix utility by creating a simulated set of 140 somatic genomes and showing how it can be used in training and testing of somatic copy number variant calling tools.Availability and implementationtHapMix is distributed under an open source license and can be downloaded from https://github.com/Illumina/[email protected] informationSupplementary data are available at Bioinformatics online.

scholarly journals Integrative DNA copy number detection and genotyping from sequencing and array-based platforms

2017 ◽  
Author(s):  
Zilu Zhou ◽  
Weixin Wang ◽  
Li-San Wang ◽  
Nancy Ruonan Zhang
Keyword(s):  
Copy Number ◽  
Association Studies ◽  
Snp Array ◽  
Supplementary Information ◽  
Detection Accuracy ◽  
Sequencing Data ◽  
Array Data ◽  
Combining Data ◽  
Allele Specific ◽  
Cnv Detection

AbstractMotivationCopy number variations (CNVs) are gains and losses of DNA segments and have been associated with disease. Many large-scale genetic association studies are performing CNV analysis using whole exome sequencing (WES) and whole genome sequencing (WGS). In many of these studies, previous SNP-array data are available. An integrated cross-platform analysis is expected to improve resolution and accuracy, yet there is no tool for effectively combining data from sequencing and array platforms. The detection of CNVs using sequencing data alone can also be further improved by the utilization of allele-specific reads.ResultsWe propose a statistical framework, integrated Copy Number Variation detection algorithm (iCNV), which can be applied to multiple study designs: WES only, WGS only, SNP array only, or any combination of SNP and sequencing data. iCNV applies platform specific normalization, utilizes allele specific reads from sequencing and integrates matched NGS and SNP-array data by a Hidden Markov Model (HMM). We compare integrated two-platform CNV detection using iCNV to naive intersection or union of platforms and show that iCNV increases sensitivity and robustness. We also assess the accuracy of iCNV on WGS data only, and show that the utilization of allele-specific reads improve CNV detection accuracy compared to existing methods.Availabilityhttps://github.com/zhouzilu/[email protected], [email protected] informationSupplementary data are available at Bioinformatics online.

Genetics of Schizophrenia and Bipolar Disorder

2017 ◽  
Author(s):  
Alexander Charney ◽  
Pamela Sklar
Keyword(s):  
Bipolar Disorder ◽  
Copy Number ◽  
Psychotic Disorders ◽  
Copy Number Variants ◽  
Nucleotide Polymorphisms ◽  
Common Variants ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
Number Variation

Schizophrenia and bipolar disorder are the classic psychotic disorders. Both diseases are strongly familial, but have proven recalcitrant to genetic methodologies for identifying the etiology until recently. There is now convincing genetic evidence that indicates a contribution of many DNA changes to the risk of becoming ill. For schizophrenia, there are large contributions of rare copy number variants and common single nucleotide variants, with an overall highly polygenic genetic architecture. For bipolar disorder, the role of copy number variation appears to be much less pronounced. Specific common single nucleotide polymorphisms are associated, and there is evidence for polygenicity. Several surprises have emerged from the genetic data that indicate there is significantly more molecular overlap in copy number variants between autism and schizophrenia, and in common variants between schizophrenia and bipolar disorder.

scholarly journals Quantification of aneuploidy in targeted sequencing data using ASCETS

2020 ◽  
Author(s):  
Liam F Spurr ◽  
Mehdi Touat ◽  
Alison M Taylor ◽  
Adrian M Dubuc ◽  
Juliann Shih ◽  
...  
Keyword(s):  
Copy Number ◽  
Large Scale ◽  
Genomic Analysis ◽  
Targeted Sequencing ◽  
Supplementary Information ◽  
Supplementary Data ◽  
Sequencing Data ◽  
Copy Number Changes ◽  
Panel Sequencing ◽  
Chromosome Level

Abstract Summary The expansion of targeted panel sequencing efforts has created opportunities for large-scale genomic analysis, but tools for copy-number quantification on panel data are lacking. We introduce ASCETS, a method for the efficient quantitation of arm and chromosome-level copy-number changes from targeted sequencing data. Availability and implementation ASCETS is implemented in R and is freely available to non-commercial users on GitHub: https://github.com/beroukhim-lab/ascets, along with detailed documentation. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals Long read sequencing reveals Poxvirus evolution through rapid homogenization of gene arrays

2018 ◽  
Author(s):  
Thomas A. Sasani ◽  
Kelsey R. Cone ◽  
Aaron R. Quinlan ◽  
Nels C. Elde
Keyword(s):  
Copy Number ◽  
Gene Copy Number ◽  
Gene Copy ◽  
Single Nucleotide Variants ◽  
Sequencing Platform ◽  
Sequencing Technologies ◽  
Gene Copy Number Variation ◽  
Large Gene ◽  
Long Read ◽  
Number Variation

AbstractLarge DNA viruses rapidly evolve to defeat host defenses. Poxvirus adaptation can involve combinations of recombination-driven gene copy number variation and beneficial single nucleotide variants (SNVs) at the same locus, yet how these distinct mechanisms of genetic diversification might simultaneously facilitate adaptation to immune blocks is unknown. We performed experimental evolution with a vaccinia virus population harboring a SNV in a gene actively undergoing copy number amplification. Comparisons of virus genomes using the Oxford Nanopore Technologies sequencing platform allowed us to phase SNVs within large gene copy arrays for the first time, and uncovered a mechanism of adaptive SNV homogenization reminiscent of gene conversion, which is actively driven by selection. Our work reveals a new mechanism for the fluid gain of beneficial mutations in genetic regions undergoing active recombination in viruses, and illustrates the value of long read sequencing technologies for investigating complex genome dynamics in diverse biological systems.

Allelic Copy Number Variation inFSCN2Detected Using Allele-Specific Genotyping and Multiplex Real-Time PCRs

2008 ◽  
Vol 49 (9) ◽  
pp. 3799 ◽  
Author(s):  
Zi-Bing Jin ◽  
Michiko Mandai ◽  
Kohei Homma ◽  
Chie Ishigami ◽  
Yasuhiko Hirami ◽  
...  
Keyword(s):  
Copy Number Variation ◽  
Real Time ◽  
Copy Number ◽  
Number Variation ◽  
Allele Specific ◽  
Allelic Copy Number
Sign in / Sign up

Export Citation Format

Share Document