scholarly journals Detection of Autosomal Hemizygous Regions in the Fleckvieh Population Based on SNP-chip Data and Parent Offspring Pairs

2019 ◽  
Vol 67 (6) ◽  
pp. 1447-1452
Author(s):  
Judith Himmelbauer ◽  
Gábor Mészáros ◽  
Johann Sölkner
Keyword(s):  
Dna Sequence ◽  
Genome Sequencing ◽  
Copy Number ◽  
Population Based ◽  
Whole Genome Sequencing Data ◽  
Whole Genome ◽  
Sequencing Data ◽  
Chip Data ◽  
Snp Chip ◽  
Number Variation

A Copy Number Variation (CNV) is a loss or a gain in the DNA sequence, ranging from 50 basepairs to a few megabasepairs. Most studies use whole genome sequencing data to detect deletions. Due to the fact that SNP-chip data is more commonly used in livestock, especially in cattle, the detection of deletions based on SNP-chip data is of interest. In the present study an approach based on SNP chip data and the analysis of Mendelian mismatches in parent-offspring-pairs was developed. Use was made of the fact that deletions appear as homozygous after SNP Chip genotyping. For some SNPs with high number of mismatches, the inheritance of the mismatches could be traced back to one or a few bulls and thereby regions of possible deletions were defined. The study has shown that an approach based on Mendelian mismatches and SNP-chip data is a promising way of detecting deletions.

The average copy number variation (CNVA) of chromosome fragments is a potential surrogate marker for TMB in predicting responses to immunotherapy in Non-small cell lung cancer

2020 ◽  
Author(s):  
Yuan yuan Lei ◽  
Guo chao Zhang ◽  
Chao qi Zhang ◽  
li yan xue ◽  
Zhen lin Yang ◽  
...  
Keyword(s):  
T Cells ◽  
Copy Number Variation ◽  
Genomic Instability ◽  
Genome Sequencing ◽  
Copy Number ◽  
Whole Genome Sequencing Data ◽  
Whole Genome ◽  
Sequencing Data ◽  
Number Variation ◽  
Average Copy

Abstract Background: Genomic instability plays a large role in the process of cancer. Tumor mutational burden (TMB) is closely related to immunotherapy outcome and is an important manifestation of genomic instability. However, the cost of TMB detection is extremely high, which limits the use of TMB in clinical practice. Another new indicator of genome instability, CNVA (the average copy number variation) which calculates the changes of 0.5 Mb chromosomal fragments, requires extremely low sequencing depth, and is expected to replace TMB as a new marker of immune efficacy.Methods: A total of 50 samples (23 of which came from patients who received immunotherapy) were subjected to low-depth (10X) chromosome sequencing on the MGI platform. CNVA was calculated by the formula avg (abs (copy number-2)). Then, we analyzed the relationship between CNVA and immune infiltration or immunotherapy efficacy. In addition, through the analysis of whole genome sequencing data of 509 lung adenocarcinoma in the TCGA database, we compared CNVA with classic marker TMB to evaluate the value of CNVA as an immune evaluation index.Results: Compared with the low CNVA group, the high CNVA group had higher expression of PD-L1, CD39 and CD19, and more infiltration of CD8 + T cells and CD3 + T cells. Among the 23 patients treated with immunotherapy, the average CNVA value of the SD (stable disease)/PR (partial response) group was higher than that of the PD (progressive disease) group (P <0.05). The data of whole genome sequencing data of 509 lung adenocarcinomas from TCGA and real-time quantitative PCR results of 22 frozen specimens found that CNVA was more correlated with CD8 and PD-L1 than TMB. In addition, CNVA showed a specific positive correlation with TMB (r = 0.2728, p < 0.0001).Conclusion: CNVA can be a good indicator of immune infiltration and predicting immunotherapy efficacy. With its low cost and potential clinical application for testing, it is expected to become a substitute for TMB.

scholarly journals Identification of Medium-Sized Copy Number Alterations in Whole-Genome Sequencing

2014 ◽  
Vol 13s3 ◽  
pp. CIN.S14023
Author(s):  
Hatice Gulcin Ozer ◽  
Aisulu Usubalieva ◽  
Adrienne Dorrance ◽  
Ayse Selen Yilmaz ◽  
Michael Caligiuri ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Copy Number ◽  
Whole Genome Sequencing Data ◽  
Whole Genome ◽  
Copy Number Alterations ◽  
Sequencing Data ◽  
Entire Genome ◽  
Multiple Challenges ◽  
Cost Efficient

The genome-wide discoveries such as detection of copy number alterations (CNA) from high-throughput whole-genome sequencing data enabled new developments in personalized medicine. The CNAs have been reported to be associated with various diseases and cancers including acute myeloid leukemia. However, there are multiple challenges to the use of current CNA detection tools that lead to high false-positive rates and thus impede widespread use of such tools in cancer research. In this paper, we discuss these issues and propose possible solutions. First, since the entire genome cannot be mapped due to some regions lacking sequence uniqueness, current methods cannot be appropriately adjusted to handle these regions in the analyses. Thus, detection of medium-sized CNAs is also being directly affected by these mappability problems. The requirement for matching control samples is also an important limitation because acquiring matching controls might not be possible or might not be cost efficient. Here we present an approach that addresses these issues and detects medium-sized CNAs in cancer genomes by (1) masking unmappable regions during the initial CNA detection phase, (2) using pool of a few normal samples as control, and (3) employing median filtering to adjust CNA ratios to its surrounding coverage and eliminate false positives.

scholarly journals A Bioinformatics Pipeline for Estimating Mitochondria DNA Copy Number and Heteroplasmy Levels from Whole Genome Sequencing Data

2021 ◽  
Author(s):  
Stephanie L Battle ◽  
Daniela Puiu ◽  
Eric Boerwinkle ◽  
Kent Taylor ◽  
Jerome Rotter ◽  
...  
Keyword(s):  
Mitochondrial Genome ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Copy Number ◽  
Whole Genome Sequencing Data ◽  
Whole Genome ◽  
Dna Molecules ◽  
Sequencing Data ◽  
Bioinformatics Pipeline ◽  
Accurate Identification

Mitochondrial diseases are a heterogeneous group of disorders that can be caused by mutations in the nuclear or mitochondrial genome. Mitochondrial DNA variants may exist in a state of heteroplasmy, where a percentage of DNA molecules harbor a variant, or homoplasmy, where all DNA molecules have a variant. The relative quantity of mtDNA in a cell, or copy number (mtDNA-CN), is associated with mitochondrial function, human disease, and mortality. To facilitate accurate identification of heteroplasmy and quantify mtDNA-CN, we built a bioinformatics pipeline that takes whole genome sequencing data and outputs mitochondrial variants, and mtDNA-CN. We incorporate variant annotations to facilitate determination of variant significance. Our pipeline yields uniform coverage by remapping to a circularized chrM and recovering reads falsely mapped to nuclear-encoded mitochondrial sequences. Notably, we construct a consensus chrM sequence for each sample and recall heteroplasmy against the sample's unique mitochondrial genome. We observe an approximately 3-fold increased association with age for heteroplasmic variants in non-homopolymer regions and, are better able to capture genetic variation in the D-loop of chrM compared to existing software. Our bioinformatics pipeline more accurately captures features of mitochondrial genetics than existing pipelines that are important in understanding how mitochondrial dysfunction contributes to disease.

scholarly journals SARS-CoV-2 Whole Genome Amplification and Sequencing for Effective Population-Based Surveillance and Control of Viral Transmission

2020 ◽  
Vol 66 (11) ◽  
pp. 1450-1458 ◽  
Author(s):  
Divinlal Harilal ◽  
Sathishkumar Ramaswamy ◽  
Tom Loney ◽  
Hanan Al Suwaidi ◽  
Hamda Khansaheb ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Social Life ◽  
Population Based ◽  
Viral Transmission ◽  
Whole Genome Sequencing Data ◽  
Whole Genome ◽  
Sequencing Data ◽  
Genome Amplification ◽  
And Control

Abstract Background With the gradual reopening of economies and resumption of social life, robust surveillance mechanisms should be implemented to control the ongoing COVID-19 pandemic. Unlike RT-qPCR, SARS-CoV-2 whole genome sequencing (cWGS) has the added advantage of identifying cryptic origins of the virus, and the extent of community-based transmissions versus new viral introductions, which can in turn influence public health policy decisions. However, the practical and cost considerations of cWGS should be addressed before it is widely implemented. Methods We performed shotgun transcriptome sequencing using RNA extracted from nasopharyngeal swabs of patients with COVID-19, and compared it to targeted SARS-CoV-2 genome amplification and sequencing with respect to virus detection, scalability, and cost-effectiveness. To track virus origin, we used open-source multiple sequence alignment and phylogenetic tools to compare the assembled SARS-CoV-2 genomes to publicly available sequences. Results We found considerable improvement in whole genome sequencing data quality and viral detection using amplicon-based target enrichment of SARS-CoV-2. With enrichment, more than 99% of the sequencing reads mapped to the viral genome, compared to an average of 0.63% without enrichment. Consequently, an increase in genome coverage was obtained using substantially less sequencing data, enabling higher scalability and sizable cost reductions. We also demonstrated how SARS-CoV-2 genome sequences can be used to determine their possible origin through phylogenetic analysis including other viral strains. Conclusions SARS-CoV-2 whole genome sequencing is a practical, cost-effective, and powerful approach for population-based surveillance and control of viral transmission in the next phase of the COVID-19 pandemic.

scholarly journals Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing

2018 ◽  
Author(s):  
Isidro Cortés-Ciriano ◽  
June-Koo Lee ◽  
Ruibin Xi ◽  
Dhawal Jain ◽  
Youngsook L. Jung ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Copy Number ◽  
Human Cancer ◽  
Whole Genome Sequencing Data ◽  
Whole Genome ◽  
Sequencing Data ◽  
End Joining ◽  
Cancer Types ◽  
Non Homologous End Joining

SummaryChromothripsis is a newly discovered mutational phenomenon involving massive, clustered genomic rearrangements that occurs in cancer and other diseases. Recent studies in cancer suggest that chromothripsis may be far more common than initially inferred from low resolution DNA copy number data. Here, we analyze the patterns of chromothripsis across 2,658 tumors spanning 39 cancer types using whole-genome sequencing data. We find that chromothripsis events are pervasive across cancers, with a frequency of >50% in several cancer types. Whereas canonical chromothripsis profiles display oscillations between two copy number states, a considerable fraction of the events involves multiple chromosomes as well as additional structural alterations. In addition to non-homologous end-joining, we detect signatures of replicative processes and templated insertions. Chromothripsis contributes to oncogene amplification as well as to inactivation of genes such as mismatch-repair related genes. These findings show that chromothripsis is a major process driving genome evolution in human cancer.

scholarly journals ascatNgs: Identifying Somatically Acquired Copy-Number Alterations from Whole-Genome Sequencing Data

2016 ◽  
Vol 56 (1) ◽  
pp. 15.9.1-15.9.17 ◽  
Author(s):  
Keiran M. Raine ◽  
Peter Van Loo ◽  
David C. Wedge ◽  
David Jones ◽  
Andrew Menzies ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Copy Number ◽  
Whole Genome Sequencing Data ◽  
Whole Genome ◽  
Copy Number Alterations ◽  
Sequencing Data
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