Noise-robust assessment of SNP array based CNV calls through local noise estimation of log R ratios

2018 ◽  
Vol 17 (2) ◽  
Author(s):  
Nele Cosemans ◽  
Peter Claes ◽  
Nathalie Brison ◽  
Joris Robert Vermeesch ◽  
Hilde Peeters
Keyword(s):  
Large Scale ◽  
Copy Number Variants ◽  
Snp Array ◽  
High Specificity ◽  
Noise Robustness ◽  
Nucleotide Polymorphisms ◽  
R Ratio ◽  
Specificity And Sensitivity ◽  
Multiple Threshold ◽  
Noise Robust

Abstract Arrays based on single nucleotide polymorphisms (SNPs) have been successful for the large scale discovery of copy number variants (CNVs). However, current CNV calling algorithms still have limitations in detecting CNVs with high specificity and sensitivity, especially in case of small (<100 kb) CNVs. Therefore, this study presents a simple statistical analysis to evaluate CNV calls from SNP arrays in order to improve the noise-robustness of existing CNV calling algorithms. The proposed approach estimates local noise of log R ratios and returns the probability that a certain observation is different from this log R ratio noise level. This probability can be triggered at different thresholds to tailor specificity and/or sensitivity in a flexible way. Moreover, a comparison based on qPCR experiments showed that the proposed noise-robust CNV calls outperformed original ones for multiple threshold values.

scholarly journals Competitive SNP-LAMP probes for rapid and robust single-nucleotide polymorphism detection

2021 ◽  
Author(s):  
Leland B Hyman ◽  
Clare R Christopher ◽  
Philip A Romero
Keyword(s):  
Point Of Care ◽  
High Specificity ◽  
Common Source ◽  
Lamp Method ◽  
Universal Method ◽  
Nucleotide Polymorphisms ◽  
One Pot ◽  
Single Nucleotide ◽  
Specificity And Sensitivity ◽  
And Shifts

Single-nucleotide polymorphisms (SNPs) are the most common source of genetic variation between individuals and have implications in human disease, pathogen drug resistance, and agriculture. SNPs are typically detected using DNA sequencing, which requires advanced sample preparation and instrumentation, and thus cannot be deployed for on-site testing or in low-resource settings. In this work we have developed a simple and robust assay to rapidly detect SNPs in nucleic acid samples. Our approach combines LAMP-based target amplification with fluorescent probes to detect SNPs with high specificity in a one-pot reaction format. A competitive "sink" strand preferentially binds to off-target products and shifts the free energy landscape to favor specific activation by SNP products. We demonstrated the broad utility and reliability of our SNP-LAMP method by detecting three distinct SNPs across the human genome. We also designed an assay to rapidly detect highly transmissible SARS-CoV-2 variants. This work demonstrates that competitive SNP-LAMP is a powerful and universal method that could be applied in point-of-care settings to detect any target SNP with high specificity and sensitivity.

scholarly journals Capture-based enrichment of Theileria parva DNA enables full genome assembly of first buffalo-derived strain and reveals exceptional intra-specific genetic diversity

2020 ◽  
Author(s):  
Nicholas C Palmateer ◽  
Kyle Tretina ◽  
Joshua Orvis ◽  
Olukemi O Ifeonu ◽  
Jonathan Crabtree ◽  
...  
Keyword(s):  
Vaccine Development ◽  
De Novo ◽  
High Specificity ◽  
Theileria Parva ◽  
Nucleotide Polymorphisms ◽  
Specificity And Sensitivity ◽  
Genome Wide ◽  
Dna Capture ◽  
High Level ◽  
Genome Assemblies

AbstractTheileria parva is an economically important, intracellular, tick-transmitted parasite of cattle. A live vaccine against the parasite is effective against challenge from cattle-transmissible T. parva but not against genotypes originating from the African Cape buffalo, a major wildlife reservoir, prompting the need to characterize genome-wide variation within and between cattle- and buffalo-associated T. parva populations. Here, we describe a capture-based target enrichment approach that enables, for the first time, de novo assembly of nearly complete T. parva genomes derived from infected host cell lines. This approach has exceptionally high specificity and sensitivity and is successful for both cattle- and buffalo-derived T. parva parasites. De novo genome assemblies generated for cattle genotypes differ from the reference by ∼54K single nucleotide polymorphisms (SNPs) throughout the 8.31 Mb genome, an average of 6.5 SNPs/kb. We report the first buffalo-derived T. parva genome, which is larger than the genome from the reference, cattle-derived, Muguga strain. The average non-synonymous nucleotide diversity (πN) per gene, between buffalo-derived T. parva and the Muguga strain, was 1.3%. This remarkably high level of genetic divergence is supported by an average FST, genome-wide, of 0.44, reflecting a degree of genetic differentiation between cattle- and buffalo-derived T. parva parasites more commonly seen between, rather than within, species, with clear implications for vaccine development. The DNA capture approach used provides clear advantages over alternative T. parva DNA enrichment methods used previously and enables in-depth comparative genomics in this apicomplexan parasite.

scholarly journals SARS-CoV-2 S1 and N-based serological assays reveal rapid seroconversion and induction of specific antibody response in COVID-19 patients

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Abdullah Algaissi ◽  
Mohamed A. Alfaleh ◽  
Sharif Hala ◽  
Turki S. Abujamel ◽  
Sawsan S. Alamri ◽  
...  
Keyword(s):  
Antibody Response ◽  
Specific Antibody ◽  
Large Scale ◽  
Disease Onset ◽  
High Specificity ◽  
Epidemiological Studies ◽  
Cross Reactivity ◽  
Enzyme Linked Immunosorbent Assay ◽  
Specificity And Sensitivity ◽  
Human Coronaviruses

Abstract As the Coronavirus Disease 2019 (COVID-19), which is caused by the novel SARS-CoV-2, continues to spread rapidly around the world, there is a need for well validated serological assays that allow the detection of viral specific antibody responses in COVID-19 patients or recovered individuals. In this study, we established and used multiple indirect Enzyme Linked Immunosorbent Assay (ELISA)-based serological assays to study the antibody response in COVID-19 patients. In order to validate the assays we determined the cut off values, sensitivity and specificity of the assays using sera collected from pre-pandemic healthy controls, COVID-19 patients at different time points after disease-onset, and seropositive sera to other human coronaviruses (CoVs). The developed SARS-CoV-2 S1 subunit of the spike glycoprotein and nucleocapsid (N)-based ELISAs not only showed high specificity and sensitivity but also did not show any cross-reactivity with other CoVs. We also show that all RT-PCR confirmed COVID-19 patients tested in our study developed both virus specific IgM and IgG antibodies as early as week one after disease onset. Our data also suggest that the inclusion of both S1 and N in serological testing would capture as many potential SARS-CoV-2 positive cases as possible than using any of them alone. This is specifically important for tracing contacts and cases and conducting large-scale epidemiological studies to understand the true extent of virus spread in populations.

scholarly journals SARS-CoV-2 S1 and N-Based Serological Assays Reveal Rapid Seroconversion and Induction of Specific Antibody Response in COVID-19 Patients

2020 ◽  
Author(s):  
Abdullah Algaissi ◽  
Mohamed A. Alfaleh ◽  
Sherif Hala ◽  
Turki S. Abujamel ◽  
Sawsan S. Alamri ◽  
...  
Keyword(s):  
Antibody Response ◽  
Specific Antibody ◽  
Large Scale ◽  
Disease Onset ◽  
High Specificity ◽  
Epidemiological Studies ◽  
Cross Reactivity ◽  
Enzyme Linked Immunosorbent Assay ◽  
Specificity And Sensitivity ◽  
Human Coronaviruses

As the coronavirus disease 2019 (COVID-19), which is caused by the novel SARS-CoV-2, continues to spread rapidly around the world, there is a need for well validated serological assays that allow the detection of viral specific antibody responses in COVID-19 patients or recovered individuals. In this study, we established and used multiple indirect Enzyme Linked Immunosorbent Assay (ELISA)-based serological assays to study the antibody response in COVID-19 patients. In order to validate the assays we determined the cut off values, sensitivity and specificity of the assays using sera collected from pre-pandemic healthy controls, COVID-19 patients at different time points after disease-onset, and seropositive sera to other human coronaviruses. The developed SARS-CoV-2 S1 subunit of the spike glycoprotein and nucleocapsid (N)-based ELISAs not only showed high specificity and sensitivity but also did not show any cross-reactivity with other CoVs. We also show that all RT-PCR confirmed COVID-19 patients tested in our study developed both virus specific IgM and IgG antibodies as early as week one after disease onset. Our data also suggest that the inclusion of both S1 and N in serological testing would capture as many potential SARS-CoV-2 positive cases as possible than using any of them alone. This is specifically important for tracing contacts and cases and conducting large-scale epidemiological studies to understand the true extent of virus spread in populations.

scholarly journals GeneHummus: A pipeline to define gene families and their expression in legumes and beyond

2018 ◽  
Author(s):  
Jose V. Die ◽  
Moamen Mahmoud Elmassry ◽  
Kimberly Hathaway LeBlanc ◽  
Olaitan I. Awe ◽  
Allissa Dillman ◽  
...  
Keyword(s):  
Large Scale ◽  
Rapid Development ◽  
High Specificity ◽  
Gene Families ◽  
Model Systems ◽  
Auxin Receptor ◽  
Plant Gene ◽  
Sequencing Technologies ◽  
Specificity And Sensitivity ◽  
The Impact

AbstractDuring the last decade, plant biotechnological laboratories have sparked a monumental revolution with the rapid development of next sequencing technologies at affordable prices. Soon, these sequencing technologies and assembling of whole genomes will extend beyond the plant computational biologists and become commonplace within the plant biology disciplines. The current availability of large-scale genomic resources for non-traditional plant model systems (the so-called ‘orphan crops’) is enabling the construction of high-density integrated physical and genetic linkage maps with potential applications in plant breeding. The newly available fully sequenced plant genomes represent an incredible opportunity for comparative analyses that may reveal new aspects of genome biology and evolution. Analysis of the expansion and evolution of gene families across species is a common approach to infer biological functions. To date, the extent and role of gene families in plants has only been partially addressed and many gene families remain to be investigated. Manual identification of gene families is highly time-consuming and laborious, requiring an iterative process of manual and computational analysis to identify members of a given family, typically combining numerous BLAST searches and manually cleaning data. Due to the increasing abundance of genome sequences and the agronomical interest in plant gene families, the field needs a clear, automated annotation tool. Here, we present the GeneHummus pipeline, a step-by-step R-based pipeline for the identification, characterization and expression analysis of plant gene families. The impact of this pipeline comes from a reduction in hands-on annotation time combined with high specificity and sensitivity in extracting only proteins from the RefSeq database and providing the conserved domain architectures based on SPARCLE. As a case study we focused on the auxin receptor factors gene (ARF) family in Cicer arietinum (chickpea) and other legumes. We anticipate that our pipeline should be suitable for any plant gene family, and likely other gene families, vastly improving the speed and ease of genomic data processing.

scholarly journals A comprehensive review and model of putative prodromal features of bipolar affective disorder

2010 ◽  
Vol 41 (8) ◽  
pp. 1567-1577 ◽  
Author(s):  
O. D. Howes ◽  
S. Lim ◽  
G. Theologos ◽  
A. R. Yung ◽  
G. M. Goodwin ◽  
...  
Keyword(s):  
Large Scale ◽  
Bipolar Affective Disorder ◽  
High Specificity ◽  
Current Evidence ◽  
Inclusion Criteria ◽  
Comprehensive Review ◽  
Specificity And Sensitivity ◽  
Comprehensive Search ◽  
Characteristic Features ◽  
Key Questions

BackgroundIdentifying prodromal features that predate the onset of bipolar disorder (BD) may enable the prevention of BD and aid early intervention. This review addresses two key questions: Is there a bipolar prodrome? And, if there is, what are its characteristic features?MethodA comprehensive search of databases (PubMed, Medline, EMBASE and PsycINFO) supplemented by hand searches was used to identify studies of symptoms preceding the onset of BD.ResultsFifty-nine studies were identified, of which 14 met inclusion criteria. Symptoms can predate the onset of BD by months to years and can be categorized as attenuated forms of BD symptoms, general symptoms common to a range of mental disorders, and personality traits, particularly cyclothymia. Two studies provided sufficient data to enable sensitivity and specificity to be calculated. Specificity of several of the features was high (>90%) but sensitivity was generally low (all <60%). We propose a model based on the findings in the studies reviewed to illustrate the potential trajectory to BD and the points at which it may be possible to intervene.ConclusionsClinical features preceding the onset of BD can be identified. However, conclusions about whether there is a distinct prodrome to BD are restricted by the limitations of current evidence. The high specificity of some features suggests they may be useful in clinical practice. Large-scale longitudinal studies are needed to validate these features and characterize their specificity and sensitivity in independent samples.

scholarly journals Rapid surveillance platforms for key SARS-CoV-2 mutations in Denmark

2021 ◽  
Author(s):  
Katja Spiess ◽  
Vithiagaran Gunalan ◽  
Ellinor Marving ◽  
Sofie Holdflod Nielsen ◽  
Michelle G. P. Joergensen ◽  
...  
Keyword(s):  
Immune Evasion ◽  
Large Scale ◽  
Public Health System ◽  
High Specificity ◽  
Specificity And Sensitivity ◽  
Rapid Control ◽  
Qpcr Platform ◽  
Detection Of Mutations ◽  
Local Transmission ◽  
Large Scale Screening

Multiple mutations in SARS-CoV-2 variants of concern (VOCs) may increase, transmission, disease severity, immune evasion and facilitate zoonotic or anthoprozoonotic infections. Four such mutations, ΔH69/V70, L452R, E484K and N501Y, occur in the SARS-CoV-2 spike glycoprotein in combinations that allow detection of the most important VOCs. Here we present two flexible RT-qPCR platforms for small- and large-scale screening to detect these mutations, and schemes for adapting the platforms for future mutations. The large-scale RT-qPCR platform, was validated by pair-wise matching of RT-qPCR results with WGS consensus genomes, showing high specificity and sensitivity. Detection of mutations using this platform served as an important interventive measure for the Danish public health system to delay the emergence of VOCs and to gain time for vaccine administration. Both platforms are valuable tools for WGS-lean laboratories, as well for complementing WGS to support rapid control of local transmission chains worldwide.

scholarly journals Multiple Indirect ELISAs for Serological Detection of SARS-CoV-2 Antibodies

2020 ◽  
Author(s):  
Abdullah Algaissi ◽  
Mohamed A. Alfaleh ◽  
Sherif Hala ◽  
Turki S. Abujamel ◽  
Sawsan S. Alamari ◽  
...  
Keyword(s):  
Antibody Response ◽  
Large Scale ◽  
Disease Onset ◽  
High Specificity ◽  
Epidemiological Studies ◽  
Cross Reactivity ◽  
Enzyme Linked Immunosorbent Assay ◽  
Serological Tests ◽  
Specificity And Sensitivity ◽  
Novel Coronavirus

As the coronavirus disease 2019 (COVID-19), which is caused by the novel coronavirus SARS-CoV-2, continues to spread rapidly around the world, there is an urgent need for validated serological assays to evaluate viral specific antibody responses in COVID-19 patients or recovered individuals. In this study, we established and used indirect Enzyme Linked Immunosorbent Assay (ELISA)-based serological tests to study the antibody response in COVID-19 patients. In order to validate the assays, we determined the cut-off values, sensitivity and specificity of the developed assays using sera collected from COVID-19 patients in Saudi Arabia at different time points after disease onset, as well as sera that are seropositive to other human CoVs; namely MERS-CoV, hCoV-OC43, hCoV-NL63, hCoV-229E, and hCoV-HKU1. The SARS-CoV-2 S1 subunit of the spike glycoprotein and nucleocapsid (N) ELISAs that we developed here not only showed high specificity and sensitivity, but also did not show any cross-reactivity with other CoVs. We also showed that all RT-PCR confirmed COVID-19 patients included in our study developed both virus specific IgM and IgG as early as one week after the onset of disease. The availability of these validated assays will enable us to determine the nature and duration of the antibody response mounted in response to SARS-CoV-2 infection. It will also allow conducting large-scale epidemiological studies to determine evidence of previous exposure to the virus and assess the true extent of virus spread within communities.

scholarly journals A Genome-Wide Detection of Copy Number Variations Using SNP Genotyping Arrays in Braque Français Type Pyrénées Dogs

Animals ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. 77 ◽  
Author(s):  
Rosalia Di Gerlando ◽  
Salvatore Mastrangelo ◽  
Maria Teresa Sardina ◽  
Marco Ragatzu ◽  
Andrea Spaterna ◽  
...  
Keyword(s):  
Copy Number ◽  
Copy Number Variants ◽  
Snp Array ◽  
Quality Criteria ◽  
Enrichment Analysis ◽  
Copy Number Variations ◽  
High Density ◽  
Nucleotide Polymorphisms ◽  
Hunting Behavior ◽  
A Genome

Copy number variants (CNVs) are an important source of genetic variation complementary to single nucleotide polymorphisms (SNPs). Only few studies have been conducted in dogs on CNVs derived from high-density SNP array data, and many canine breeds still remain uncharacterized, e.g., the Braque Français, type Pyrénées breed (BRA). Therefore, in an effort to more comprehensively investigate the canine genome for CNVs, we used a high-density SNP array (170 K) to discover CNVs in BRA. The CNV regions (CNVRs) were identified through the merging of two different CNVRs datasets, obtained separately from SNP data using the PennCNV and SVS software. A total of 45 stringent CNVRs, ranging from 3.5 kb to 458,716 kb in length were detected in 26 dog samples. Results overlapped moderately in comparison with previous studies on CNVs in dogs, leading to the identification of 16 novel CNVRs. A total of 159 genes were annotated in the CNVRs detected with stringent quality criteria in particular high classification stringency and false discovery rate correction. The gene ontology enrichment analysis provided information on biological processes and cellular components related to muscle structure development and muscle cell differentiation. Considering that BRA is a breed used for speed in hunting and retrieval, for the ability to find feathered game, and for pointing, we can hypothesize that selection for such hunting behavior could have driven, at least in part, the presence of these genes into the CNVRs.

scholarly journals Capture-based enrichment of Theileria parva DNA enables full genome assembly of first buffalo-derived strain and reveals exceptional intra-specific genetic diversity

2020 ◽  
Vol 14 (10) ◽  
pp. e0008781
Author(s):  
Nicholas C. Palmateer ◽  
Kyle Tretina ◽  
Joshua Orvis ◽  
Olukemi O. Ifeonu ◽  
Jonathan Crabtree ◽  
...  
Keyword(s):  
Vaccine Development ◽  
De Novo ◽  
High Specificity ◽  
Fixation Index ◽  
Theileria Parva ◽  
Nucleotide Polymorphisms ◽  
Specificity And Sensitivity ◽  
Genome Wide ◽  
High Level ◽  
Genome Assemblies

Theileria parva is an economically important, intracellular, tick-transmitted parasite of cattle. A live vaccine against the parasite is effective against challenge from cattle-transmissible T. parva but not against genotypes originating from the African Cape buffalo, a major wildlife reservoir, prompting the need to characterize genome-wide variation within and between cattle- and buffalo-associated T. parva populations. Here, we describe a capture-based target enrichment approach that enables, for the first time, de novo assembly of nearly complete T. parva genomes derived from infected host cell lines. This approach has exceptionally high specificity and sensitivity and is successful for both cattle- and buffalo-derived T. parva parasites. De novo genome assemblies generated for cattle genotypes differ from the reference by ~54K single nucleotide polymorphisms (SNPs) throughout the 8.31 Mb genome, an average of 6.5 SNPs/kb. We report the first buffalo-derived T. parva genome, which is ~20 kb larger than the genome from the reference, cattle-derived, Muguga strain, and contains 25 new potential genes. The average non-synonymous nucleotide diversity (πN) per gene, between buffalo-derived T. parva and the Muguga strain, was 1.3%. This remarkably high level of genetic divergence is supported by an average Wright’s fixation index (FST), genome-wide, of 0.44, reflecting a degree of genetic differentiation between cattle- and buffalo-derived T. parva parasites more commonly seen between, rather than within, species. These findings present clear implications for vaccine development, further demonstrated by the ability to assemble nearly all known antigens in the buffalo-derived strain, which will be critical in design of next generation vaccines. The DNA capture approach used provides a clear advantage in specificity over alternative T. parva DNA enrichment methods used previously, such as those that utilize schizont purification, is less labor intensive, and enables in-depth comparative genomics in this apicomplexan parasite.

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