scholarly journals Quantification of read species behavior within whole genome sequencing of cancer genomes for the stratification and visualization of genomic variation

2016 ◽  
Vol 44 (9) ◽  
pp. e81-e81
Author(s):  
Dror Hibsh ◽  
Kenneth H. Buetow ◽  
Gur Yaari ◽  
Sol Efroni
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Genomic Variation ◽  
Whole Genome ◽  
Cancer Genomes

scholarly journals Assessing genomic diversity and signatures of selection in Jiaxian Red cattle using whole-genome sequencing data

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Xiaoting Xia ◽  
Shunjin Zhang ◽  
Huaju Zhang ◽  
Zijing Zhang ◽  
Ningbo Chen ◽  
...  
Keyword(s):  
Population Structure ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Genomic Variation ◽  
Genomic Diversity ◽  
System Response ◽  
Whole Genome ◽  
Population Structure Analysis ◽  
Native Cattle ◽  
Genomic Regions

Abstract Background Native cattle breeds are an important source of genetic variation because they might carry alleles that enable them to adapt to local environment and tough feeding conditions. Jiaxian Red, a Chinese native cattle breed, is reported to have originated from crossbreeding between taurine and indicine cattle; their history as a draft and meat animal dates back at least 30 years. Using whole-genome sequencing (WGS) data of 30 animals from the core breeding farm, we investigated the genetic diversity, population structure and genomic regions under selection of Jiaxian Red cattle. Furthermore, we used 131 published genomes of world-wide cattle to characterize the genomic variation of Jiaxian Red cattle. Results The population structure analysis revealed that Jiaxian Red cattle harboured the ancestry with East Asian taurine (0.493), Chinese indicine (0.379), European taurine (0.095) and Indian indicine (0.033). Three methods (nucleotide diversity, linkage disequilibrium decay and runs of homozygosity) implied the relatively high genomic diversity in Jiaxian Red cattle. We used θπ, CLR, FST and XP-EHH methods to look for the candidate signatures of positive selection in Jiaxian Red cattle. A total number of 171 (θπ and CLR) and 17 (FST and XP-EHH) shared genes were identified using different detection strategies. Functional annotation analysis revealed that these genes are potentially responsible for growth and feed efficiency (CCSER1), meat quality traits (ROCK2, PPP1R12A, CYB5R4, EYA3, PHACTR1), fertility (RFX4, SRD5A2) and immune system response (SLAMF1, CD84 and SLAMF6). Conclusion We provide a comprehensive overview of sequence variations in Jiaxian Red cattle genomes. Selection signatures were detected in genomic regions that are possibly related to economically important traits in Jiaxian Red cattle. We observed a high level of genomic diversity and low inbreeding in Jiaxian Red cattle. These results provide a basis for further resource protection and breeding improvement of this breed.

scholarly journals Clinical-grade whole-genome sequencing and 3′ transcriptome analysis of colorectal cancer patients

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Agata Stodolna ◽  
Miao He ◽  
Mahesh Vasipalli ◽  
Zoya Kingsbury ◽  
Jennifer Becq ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Transcriptome Analysis ◽  
Variant Calling ◽  
Standard Of Care ◽  
Genomic Variation ◽  
Whole Genome ◽  
Clinical Grade ◽  
Pathway Gene

Abstract Background Clinical-grade whole-genome sequencing (cWGS) has the potential to become the standard of care within the clinic because of its breadth of coverage and lack of bias towards certain regions of the genome. Colorectal cancer presents a difficult treatment paradigm, with over 40% of patients presenting at diagnosis with metastatic disease. We hypothesised that cWGS coupled with 3′ transcriptome analysis would give new insights into colorectal cancer. Methods Patients underwent PCR-free whole-genome sequencing and alignment and variant calling using a standardised pipeline to output SNVs, indels, SVs and CNAs. Additional insights into the mutational signatures and tumour biology were gained by the use of 3′ RNA-seq. Results Fifty-four patients were studied in total. Driver analysis identified the Wnt pathway gene APC as the only consistently mutated driver in colorectal cancer. Alterations in the PI3K/mTOR pathways were seen as previously observed in CRC. Multiple private CNAs, SVs and gene fusions were unique to individual tumours. Approximately 30% of patients had a tumour mutational burden of > 10 mutations/Mb of DNA, suggesting suitability for immunotherapy. Conclusions Clinical whole-genome sequencing offers a potential avenue for the identification of private genomic variation that may confer sensitivity to targeted agents and offer patients new options for targeted therapies.

scholarly journals Allele-Specific Quantification of Structural Variations in Cancer Genomes

2016 ◽  
Author(s):  
Yang Li ◽  
Shiguo Zhou ◽  
David C. Schwartz ◽  
Jian Ma
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Copy Number ◽  
Graphical Model ◽  
Genome Structure ◽  
Cancer Genome ◽  
Whole Genome ◽  
Structural Variations ◽  
Cancer Genomes ◽  
Allele Specific

AbstractOne of the hallmarks of cancer genome is aneuploidy, resulting in abnormal copy numbers of alleles. Structural variations (SVs) can further modify the aneuploid cancer genomes into a mixture of rearranged genomic segments with extensive range of somatic copy number alterations (CNAs). Indeed, aneuploid cancer genomes have significantly higher rate of CNAs and SVs. However, although methods have been developed to identify SVs and allele-specific copy number of genome (ASCNG) separately, no existing algorithm can simultaneously analyze SVs and ASCNG. Such integrated approach is particularly important to fully understand the complexity of cancer genomes. Here we introduce a new algorithm called Weaver to provide allele-specific quantification of SVs and CNAs in aneuploid cancer genomes. Weaver uses a probabilistic graphical model by utilizing cancer whole genome sequencing data to simultaneously estimate the digital copy number and inter-connectivity of SVs. Our simulation evaluation, comparison with single-molecule Optical Mapping analysis, and real data applications (including MCF-7, HeLa, and TCGA whole genome sequencing samples) demonstrated that Weaver is highly accurate and can greatly refine the analysis of complex cancer genome structure.

scholarly journals Clinical-grade whole genome sequencing of colorectal cancer and 3’ transcriptome analysis demonstrate targetable alterations in the majority of patients

2020 ◽  
Author(s):  
Agata Stodolna ◽  
Miao He ◽  
Mahesh Vasipalli ◽  
Zoya Kingsbury ◽  
Jennifer Becq ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Transcriptome Analysis ◽  
Variant Calling ◽  
Standard Of Care ◽  
Genomic Variation ◽  
Whole Genome ◽  
Clinical Grade ◽  
Pathway Gene

AbstractIntroductionClinical grade whole genome sequencing (cWGS) has the potential to become standard of care within the clinic because of its breadth of coverage and lack of bias towards certain regions of the genome. Colorectal cancer presents a difficult treatment paradigm, with over 40% of patients presenting at diagnosis with metastatic disease. We hypothesised that cWGS coupled with 3’ transcriptome analysis would give new insights into colorectal cancer.MethodsPatients underwent PCR-free whole genome sequencing and alignment and variant calling using a standardised pipeline to output SNVs, indels, SVs and CNAs. Additional insights into mutational signatures and tumour biology were gained by the use of 3’ RNAseq.ResultsFifty-four patients were studied in total. Driver analysis identified the Wnt pathway gene APC as the only consistently mutated driver in colorectal cancer. Alterations in the PI3K/mTOR pathways were seen as previously observed in CRC. Multiple private CNAs, SVs and gene fusions were unique to individual tumours. Approximately 20% of patients had a tumour mutational burden of >10 mutations/Mb of DNA, suggesting suitability for immunotherapy.ConclusionsClinical whole genome sequencing offers a potential avenue for identification of private genomic variation that may confer sensitivity to targeted agents and offer patients new options for targeted therapies.

scholarly journals Quality of Whole Genome Sequencing from Blood versus Saliva Derived DNA in Cardiac Patients

2019 ◽  
Author(s):  
Roderick A. Yao ◽  
Oyediran Akinrinade ◽  
Marie Chaix ◽  
Seema Mital
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Copy Number Variant ◽  
Genomic Variation ◽  
Oral Microbiome ◽  
Whole Genome ◽  
Current Standard ◽  
Single Nucleotide ◽  
Sequencing Coverage

AbstractWhole-genome sequencing (WGS) is becoming an increasingly important tool for detecting genomic variation. Blood derived DNA is the current standard for WGS for research or clinical purposes. We compared the level of microbial contamination, sequencing coverage, as well as yield and concordance of single-nucleotide polymorphism (SNP) and copy number variant (CNV) calls in WGS from paired blood and saliva samples from 5 pediatric heart disease patients. We found that although saliva samples contained a higher proportion of sequence reads that map to the human oral microbiome, these reads were readily excluded by mapping the reads to the human reference genome. Sequencing coverage was low only in 1 of 5 saliva samples. Over 95% SNPs (including rare SNPs) but <80% CNVs called in blood genomes were detected in paired saliva genomes. These findings suggest that most good quality saliva samples can serve as an alternative to blood samples for detection of sequence variants from WGS in cardiovascular disease patients.

scholarly journals Complex Structural Variants Resolved by Short-Read and Long-Read Whole Genome Sequencing in Mendelian Disorders

2018 ◽  
Author(s):  
Alba Sanchis-Juan ◽  
Jonathan Stephens ◽  
Courtney E French ◽  
Nicholas Gleadall ◽  
Karyn Mégy ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
De Novo ◽  
Genomic Variation ◽  
Mendelian Disease ◽  
Whole Genome ◽  
Structural Variants ◽  
Short Read ◽  
Long Read ◽  
Complex Structural

AbstractComplex structural variants (cxSVs) are genomic rearrangements comprising multiple structural variants, typically involving three or more breakpoint junctions. They contribute to human genomic variation and can cause Mendelian disease, however they are not typically considered during genetic testing. Here, we investigate the role of cxSVs in Mendelian disease using short-read whole genome sequencing (WGS) data from 1,324 individuals with neurodevelopmental or retinal disorders from the NIHR BioResource project. We present four cases of individuals with a cxSV affecting Mendelian disease-associated genes. Three of the cxSVs are pathogenic: a de novo duplication-inversion-inversion-deletion affecting ARID1B in an individual with Coffin-Siris syndrome, a deletion-inversion-duplication affecting HNRNPU in an individual with intellectual disability and seizures, and a homozygous deletion-inversion-deletion affecting CEP78 in an individual with cone-rod dystrophy. Additionally, we identified a de novo duplication-inversion-duplication overlapping CDKL5 in an individual with neonatal hypoxic-ischaemic encephalopathy. Long-read sequencing technology used to resolve the breakpoints demonstrated the presence of both a disrupted and an intact copy of CDKL5 on the same allele; therefore, it was classified as a variant of uncertain significance. Analysis of sequence flanking all breakpoint junctions in all the cxSVs revealed both microhomology and longer repetitive sequences, suggesting both replication and homology based processes. Accurate resolution of cxSVs is essential for clinical interpretation, and here we demonstrate that long-read WGS is a powerful technology by which to achieve this. Our results show cxSVs are an important although rare cause of Mendelian disease, and we therefore recommend their consideration during research and clinical investigations.

scholarly journals Comparative Genomics Study of Staphylococcus epidermidis Isolates from Orthopedic-Device-Related Infections Correlated with Patient Outcome

2017 ◽  
Vol 55 (10) ◽  
pp. 3089-3103 ◽  
Author(s):  
Virginia Post ◽  
Llinos G. Harris ◽  
Mario Morgenstern ◽  
Leonardos Mageiros ◽  
Matthew D. Hitchings ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Staphylococcus Epidermidis ◽  
Biofilm Formation ◽  
Genomic Variation ◽  
Whole Genome ◽  
Aminoglycoside Resistance ◽  
Transposase Gene ◽  
Content Type ◽  
Orthopedic Device

ABSTRACTStaphylococcus epidermidishas emerged as an important opportunistic pathogen causing orthopedic-device-related infections (ODRI). This study investigated the association of genome variation and phenotypic features of the infectingS. epidermidisisolate with the clinical outcome for the infected patient.S. epidermidisisolates were collected from 104 patients with ODRI. Their clinical outcomes were evaluated, after an average of 26 months, as either “cured” or “not cured.” The isolates were tested for antibiotic susceptibility and biofilm formation. Whole-genome sequencing was performed on all isolates, and genomic variation was related to features associated with “cured” and “not cured.” Strong biofilm formation and aminoglycoside resistance were associated with a “not-cured” outcome (P= 0.031 andP< 0.001, respectively). Based on gene-by-gene analysis, some accessory genes were more prevalent in isolates from the “not-cured” group. These included the biofilm-associatedbhpgene, the antiseptic resistanceqacAgene, the cassette chromosome recombinase-encoding genesccrAandccrB, and the IS256-like transposase gene. This study identifies biofilm formation and antibiotic resistance as associated with poor outcome inS. epidermidisODRI. Whole-genome sequencing identified specific genes associated with a “not-cured” outcome that should be validated in future studies. (The study has been registered at ClinicalTrials.gov with identifier NCT02640937.)

scholarly journals Genomics of AML: Clinical Applications of Next-Generation Sequencing

Hematology ◽  
2011 ◽  
Vol 2011 (1) ◽  
pp. 30-35 ◽  
Author(s):  
John S. Welch ◽  
Daniel C. Link
Keyword(s):  
Next Generation Sequencing ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Clinical Applications ◽  
Myelogenous Leukemia ◽  
Whole Genome ◽  
Next Generation ◽  
Technological Advances ◽  
Cancer Genomes ◽  
Generation Sequencing

Abstract In the past decade, a series of technological advances have revolutionized our ability to interrogate cancer genomes, culminating in whole-genome sequencing, which provides genome-wide coverage at a single base-pair resolution. As sequencing technologies improve and costs decrease, it is likely that whole-genome sequencing of cancer cells will become commonplace in the diagnostic workup of patients with acute myelogenous leukemia (AML) and other cancers. The unprecedented molecular characterization provided by whole-genome sequencing offers the potential for an individualized approach to treatment in AML, bringing us one step closer to personalized medicine. In this chapter, we discuss how next-generation sequencing is being used to study cancer genomes. Recent publications of whole-genome sequencing in AML are reviewed and current limitations of whole-genome sequencing are examined, as well as current and potential future clinical applications of whole-genome sequencing.

scholarly journals Whole genome sequencing provides insights into the genetic determinants of invasiveness inSalmonellaDublin

2016 ◽  
Vol 144 (11) ◽  
pp. 2430-2439 ◽  
Author(s):  
M. MOHAMMED ◽  
M. CORMICAN
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Virulence Factors ◽  
Invasive Disease ◽  
Genomic Variation ◽  
Whole Genome ◽  
Secretion Systems ◽  
Genetic Determinants ◽  
Non Invasive ◽  
Lambdoid Prophage

SUMMARYSalmonella entericasubsp.entericaserovar Dublin (S.Dublin) is one of the non-typhoidalSalmonella(NTS); however, a relatively high proportion of human infections are associated with invasive disease. We applied whole genome sequencing to representative invasive and non-invasive clinical isolates ofS.Dublin to determine the genomic variations among them and to investigate the underlying genetic determinants associated with invasiveness inS.Dublin. Although no particular genomic variation was found to differentiate in invasive and non-invasive isolates four virulence factors were detected within the genome of all isolates including two different type VI secretion systems (T6SS) encoded on twoSalmonellapathogenicity islands (SPI), including SPI-6 (T6SSSPI-6) and SPI-19 (T6SSSPI-19), an intact lambdoid prophage (Gifsy-2-like prophage) that contributes significantly to the virulence and pathogenesis ofSalmonellaserotypes in addition to a virulence plasmid. These four virulence factors may all contribute to the potential ofS.Dublin to cause invasive disease in humans.

scholarly journals Whole Genome Sequencing for Revealing the Point Mutations of SARS-CoV-2 Genome in Bangladeshi Isolates and their Structural Effects on Viral Proteins

2020 ◽  
Author(s):  
Mohammad Uzzal Hossain ◽  
Ishtiaque Ahammad ◽  
Md. Tabassum Hossain Emon ◽  
Arittra Bhattacharjee ◽  
Zeshan Mahmud Chowdhury ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Scientific Evidence ◽  
Protein Structures ◽  
Point Mutations ◽  
Viral Proteins ◽  
Drug Binding ◽  
Genomic Variation ◽  
N Gene ◽  
Whole Genome

AbstractCoronavirus disease-19 (COVID-19) is the recent global pandemic caused by the virus Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). The virus has already killed more than one million people worldwide and billions are at risk of getting infected. As of now, there is neither any drug nor any vaccine in sight with conclusive scientific evidence that it can cure or provide protection against the illness. Since novel coronavirus is a new virus, mining its genome sequence is of crucial importance for drug/vaccine(s) development. Whole genome sequencing is a helpful tool in identifying genetic changes that occur in a virus when it spreads through the population. In this study, we performed complete genome sequencing of SARS-CoV-2 to unveil the genomic variation and indel, if present. We discovered thirteen (13) mutations in Orf1ab, S and N gene where seven (7) of them turned out to be novel mutations from our sequenced isolate. Besides, we found one (1) insertion and seven (7) deletions from the indel analysis among the 323 Bangladeshi isolates. However, the indel did not show any effect on proteins. Our energy minimization analysis showed both stabilizing and destabilizing impact on viral proteins depending on the mutation. Interestingly, all the variants were located in the binding site of the proteins. Furthermore, drug binding analysis revealed marked difference in interacting residues in mutants when compared to the wild type. Our analysis also suggested that eleven (11) mutations could exert damaging effects on their corresponding protein structures. The analysis of SARS-CoV-2 genetic variation and their impacts presented in this study might be helpful in gaining a better understanding of the pathogenesis of this deadly virus.

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