scholarly journals High-resolution population-specific recombination rates and their effect on phasing and genotype imputation

2020 ◽  
Author(s):  
Shabbeer Hassan ◽  
Ida Surakka ◽  
Marja-Riitta Taskinen ◽  
Veikko Salomaa ◽  
Aarno Palotie ◽  
...  
Keyword(s):  
High Resolution ◽  
Error Rates ◽  
Rapid Expansion ◽  
Genotype Imputation ◽  
Specific Reference ◽  
Founder Population ◽  
Recombination Rates ◽  
Isolated Populations ◽  
Haplotype Phasing ◽  
Population Genomic

AbstractFounder population size, demographic changes (eg. population bottlenecks or rapid expansion) can lead to variation in recombination rates across different populations. Previous research has shown that using population-specific reference panels has a significant effect on downstream population genomic analysis like haplotype phasing, genotype imputation and association, especially in the context of population isolates. Here, we developed a high-resolution recombination rate mapping at 10kb and 50kb scale using high-coverage (20-30x) whole-genome sequenced 55 family trios from Finland and compared it to recombination rates of non-Finnish Europeans (NFE). We tested the downstream effects of the population-specific recombination rates in statistical phasing and genotype imputation in Finns as compared to the same analyses performed by using the NFE-based recombination rates. We found that Finnish recombination rates have a moderately high correlation (Spearman’s ρ =0.67-0.79) with non-Finnish Europeans, although on average (across all autosomal chromosomes), Finnish rates (2.268±0.4209 cM/Mb) are 12-14% lower than NFE (2.641±0.5032 cM/Mb). Finnish recombination map was found to have no significant effect in haplotype phasing accuracy (switch error rates ~ 2%) and average imputation concordance rates (97-98% for common, 92-96% for low frequency and 78-90% for rare variants). Our results suggest that downstream population genomic analyses like haplotype phasing and genotype imputation mostly depend on population-specific contexts like appropriate reference panels and their sample size, but not on population-specific recombination maps or effective population sizes. Currently, available HapMap recombination maps seem robust for population-specific phasing and imputation pipelines, even in the context of relatively isolated populations like Finland.

scholarly journals High-resolution population-specific recombination rates and their effect on phasing and genotype imputation

2020 ◽  
Author(s):  
Shabbeer Hassan ◽  
Ida Surakka ◽  
Marja-Riitta Taskinen ◽  
Veikko Salomaa ◽  
Aarno Palotie ◽  
...  
Keyword(s):  
High Resolution ◽  
Recombination Rate ◽  
Rare Variants ◽  
Error Rates ◽  
Genotype Imputation ◽  
Specific Reference ◽  
Recombination Rates ◽  
Isolated Populations ◽  
High Coverage ◽  
Haplotype Phasing

AbstractPrevious research has shown that using population-specific reference panels has a significant effect on downstream population genomic analyses like haplotype phasing, genotype imputation, and association, especially in the context of population isolates. Here, we developed a high-resolution recombination rate mapping at 10 and 50 kb scale using high-coverage (20–30×) whole-genome sequenced data of 55 family trios from Finland and compared it to recombination rates of non-Finnish Europeans (NFE). We tested the downstream effects of the population-specific recombination rates in statistical phasing and genotype imputation in Finns as compared to the same analyses performed by using the NFE-based recombination rates. We found that Finnish recombination rates have a moderately high correlation (Spearman’s ρ = 0.67–0.79) with NFE, although on average (across all autosomal chromosomes), Finnish rates (2.268 ± 0.4209 cM/Mb) are 12–14% lower than NFE (2.641 ± 0.5032 cM/Mb). Finnish recombination map was found to have no significant effect in haplotype phasing accuracy (switch error rates ~2%) and average imputation concordance rates (97–98% for common, 92–96% for low frequency and 78–90% for rare variants). Our results suggest that haplotype phasing and genotype imputation mostly depend on population-specific contexts like appropriate reference panels and their sample size, but not on population-specific recombination maps. Even though recombination rate estimates had some differences between the Finnish and NFE populations, haplotyping and imputation had not been noticeably affected by the recombination map used. Therefore, the currently available HapMap recombination maps seem robust for population-specific phasing and imputation pipelines, even in the context of relatively isolated populations like Finland.

scholarly journals Ultrasound imaging identifies life history variation in resident Cutthroat Trout

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0246365
Author(s):  
Kellie J. Carim ◽  
Scott Relyea ◽  
Craig Barfoot ◽  
Lisa A. Eby ◽  
John A. Kronenberger ◽  
...  
Keyword(s):  
Life History ◽  
Ultrasound Imaging ◽  
Life Histories ◽  
Cutthroat Trout ◽  
Error Rates ◽  
Reproductive Status ◽  
Lifetime Reproductive Success ◽  
Life History Variation ◽  
Westslope Cutthroat Trout ◽  
Isolated Populations

Human activities that fragment fish habitat have isolated inland salmonid populations. This isolation is associated with loss of migratory life histories and declines in population density and abundance. Isolated populations exhibiting only resident life histories may be more likely to persist if individuals can increase lifetime reproductive success by maturing at smaller sizes or earlier ages. Therefore, accurate estimates of age and size at maturity across resident salmonid populations would improve estimates of population viability. Commonly used methods for assessing maturity such as dissection, endoscopy and hormone analysis are invasive and may disturb vulnerable populations. Ultrasound imaging is a non-invasive method that has been used to measure reproductive status across fish taxa. However, little research has assessed the accuracy of ultrasound for determining maturation status of small-bodied fish, or reproductive potential early in a species’ reproductive cycle. To address these knowledge gaps, we tested whether ultrasound imaging could be used to identify maturing female Westslope Cutthroat Trout (Oncorhynchus clarkii lewisi). Our methods were accurate at identifying maturing females reared in a hatchery setting up to eight months prior to spawning, with error rates ≤ 4.0%; accuracy was greater for larger fish. We also imaged fish in a field setting to examine variation in the size of maturing females among six wild, resident populations of Westslope Cutthroat Trout in western Montana. The median size of maturing females varied significantly across populations. We observed oocyte development in females as small as 109 mm, which is smaller than previously documented for this species. Methods tested in this study will allow researchers and managers to collect information on reproductive status of small-bodied salmonids without disrupting fish during the breeding season. This information can help elucidate life history traits that promote persistence of isolated salmonid populations.

scholarly journals COVID-19: Impact on linguistic and genetic isolates of India

2021 ◽  
Author(s):  
Prajjval Pratap Singh ◽  
Prashanth Suravajhala ◽  
Chandana Basu Mallick ◽  
Rakesh Tamang ◽  
Ashutosh Kumar Rai ◽  
...  
Keyword(s):  
South Asia ◽  
Indigenous Communities ◽  
Rapid Expansion ◽  
Indigenous Populations ◽  
Runs Of Homozygosity ◽  
Isolated Populations ◽  
Asian Populations ◽  
Genetic Isolates ◽  
General Populations ◽  
The Impact

AbstractThe rapid expansion of coronavirus SARS-CoV-2 has impacted various ethnic groups all over the world. The burden of infectious diseases including COVID-19 are generally reported to be higher for the Indigenous people. The historical knowledge have also suggested that the indigenous populations suffer more than the general populations in the pandemic. Recently, it has been reported that the indigenous groups of Brazil have been massively affected by COVID-19. Series of studies have shown that many of the indigenous communities reached at the verge of extinction due to this pandemic. Importantly, South Asia also has several indigenous and smaller communities, that are living in isolation. Till date, despite the two consecutive waves in India, there is no report on the impact of COVID-19 for indigenous tribes. Since smaller populations experiencing drift may have greater risk of such pandemic, we have analysed Runs of Homozygosity (ROH) among South Asian populations and identified several populations with longer homozygous segments. The longer runs of homozygosity at certain genomic regions may increases the susceptibility for COVID-19. Thus, we suggest extreme careful management of this pandemic among isolated populations of South Asia.

scholarly journals High resolution analysis of cervical cells--a progress report.

1977 ◽  
Vol 25 (7) ◽  
pp. 689-695 ◽  
Author(s):  
R S Poulsen ◽  
L H Oliver ◽  
R L Cahn ◽  
C Louis ◽  
G Toussaint
Keyword(s):  
High Resolution ◽  
False Positive ◽  
False Negative ◽  
Error Rates ◽  
Cell Segmentation ◽  
Negative Error ◽  
False Negative Error ◽  
High Resolution Analysis ◽  
Resolution Analysis ◽  
Cervical Cells

This paper presents preliminary results of research toward the development of a high resolution analysis stage for a dual resolution image processing-based prescreening device for cervical cytology. Experiments using both manual and automatic methods for cell segmentation are described. In both cases, 1500 cervical cells were analyzed and classified as normal or abnormal (dysplastic or malignant) using a minimum Mahalanobis distance classifier with eight subclasses of normal cells, and five subclasses of abnormal cells. With manual segmentation, false positive and false negative error rates of 2.98 and 7.73% were obtained. Similar experiments using automatic cell segmentation methods yielded false positive and false negative error rates of 3.90 and 11.56%, respectively. In both cases, independent training and testing data were used.

scholarly journals Electrical Stimulus Artifact Cancellation and Neural Spike Detection on Large Multi-Electrode Arrays

2016 ◽  
Author(s):  
Gonzalo E. Mena ◽  
Lauren E. Grosberg ◽  
Sasidhar Madugula ◽  
Paweł Hottowy ◽  
Alan Litke ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
High Resolution ◽  
Action Potentials ◽  
Process Model ◽  
Error Rates ◽  
Neural Interfaces ◽  
Spike Sorting ◽  
Electrode Arrays ◽  
Retinal Prostheses ◽  
Sorting Process

AbstractSimultaneous electrical stimulation and recording using multi-electrode arrays can provide a valuable technique for studying circuit connectivity and engineering neural interfaces. However, interpreting these measurements is challenging because the spike sorting process (identifying and segregating action potentials arising from different neurons) is greatly complicated by electrical stimulation artifacts across the array, which can exhibit complex and nonlinear waveforms, and overlap temporarily with evoked spikes. Here we develop a scalable algorithm based on a structured Gaussian Process model to estimate the artifact and identify evoked spikes. The effectiveness of our methods is demonstrated in both real and simulated 512-electrode recordings in the peripheral primate retina with single-electrode and several types of multi-electrode stimulation. We establish small error rates in the identification of evoked spikes, with a computational complexity that is compatible with real-time data analysis. This technology may be helpful in the design of future high-resolution sensory prostheses based on tailored stimulation (e.g., retinal prostheses), and for closed-loop neural stimulation at a much larger scale than currently possible.Author SummarySimultaneous electrical stimulation and recording using multi-electrode arrays can provide a valuable technique for studying circuit connectivity and engineering neural interfaces. However, interpreting these recordings is challenging because the spike sorting process (identifying and segregating action potentials arising from different neurons) is largely stymied by electrical stimulation artifacts across the array, which are typically larger than the signals of interest. We develop a novel computational framework to estimate and subtract away this contaminating artifact, enabling the large-scale analysis of responses of possibly hundreds of cells to tailored stimulation. Importantly, we suggest that this technology may also be helpful for the development of future high-resolution neural prosthetic devices (e.g., retinal prostheses).

scholarly journals 807. Same-day Transmission Analysis of Nosocomial Transmission Using Nanopore Whole Genome Sequencing

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S497-S498
Author(s):  
Mohamad Sater ◽  
Remy Schwab ◽  
Ian Herriott ◽  
Tim Farrell ◽  
Miriam Huntley
Keyword(s):  
High Resolution ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Variant Calling ◽  
Cost Effective ◽  
Error Rates ◽  
Sequencing Error ◽  
Snp Analysis ◽  
Whole Genome ◽  
Snp Calling

Abstract Background Healthcare associated infections (HAIs) are a major contributor to patient morbidity and mortality worldwide. HAIs are increasingly important due to the rise of multidrug resistant pathogens which can lead to deadly nosocomial outbreaks. Current methods for investigating transmissions are slow, costly, or have poor detection resolution. A rapid, cost-effective and high-resolution method to identify transmission events is imperative to guide infection control. Whole genome sequencing of infecting pathogens paired with a single nucleotide polymorphism (SNP) analysis can provide high-resolution clonality determination, yet these methods typically have long turnaround times. Here we examined the utility of the Oxford Nanopore Technologies (ONT) platform, a rapid sequencing technology, for whole genome sequencing based transmission analysis. Methods We developed a SNP calling pipeline customized for ONT data, which exhibit higher sequencing error rates and can therefore be challenging for transmission analysis. The pipeline leverages the latest basecalling tools as well as a suite of custom variant calling and filtering algorithms to achieve highest accuracy in clonality calls compared to Illumina-based sequencing. We also capitalize on ONT long reads by assembling outbreak-specific genomes in order to overcome the need for an external reference genome. Results We examined 20 bacterial isolates from 5 HAI investigations previously performed at Day Zero Diagnostics as part of epiXact®, our commercialized Illumina-based HAI sequencing and analysis service. Using the ONT data and pipeline, we achieved greater than 90% SNP-calling sensitivity and precision, allowing 100% accuracy of clonality classification compared to Illumina-based results across common HAI species. We demonstrate the validity and increased resolution of our SNP analysis pipeline using assembled genomes from each outbreak. We also demonstrate that this ONT-based workflow can produce isolate to transmission determination (i.e. including WGS and analysis) in less than 24 hours. SNP calling performance ONT-based SNP calling sensitivity and precision compared to Illumina-based pipeline Conclusion We demonstrate the utility of ONT for HAI investigation, establishing the potential to transform healthcare epidemiology with same-day high-resolution transmission determination. Disclosures Mohamad Sater, PhD, Day Zero Diagnostics (Employee, Shareholder) Remy Schwab, MSc, Day Zero Diagnostics (Employee, Shareholder) Ian Herriott, BS, Day Zero Diagnostics (Employee, Shareholder) Tim Farrell, MS, Day Zero Diagnostics, Inc. (Employee, Shareholder) Miriam Huntley, PhD, Day Zero Diagnostics (Employee, Shareholder)

The effect of differential reproductive rates on the survival of a gene represented in a founder population

1982 ◽  
Vol 19 (A) ◽  
pp. 19-25
Author(s):  
C. C. Heyde
Keyword(s):  
Genetic Variability ◽  
Density Dependence ◽  
Founder Population ◽  
Isolated Populations ◽  
Moran Model ◽  
Mild Conditions ◽  
Reproductive Rates

Gene survival in a population which increases without density dependence is considered using a generalization of the Moran model for haploid individuals in which we have differential reproductive rates. It is shown under very mild conditions that ultimate fixation is certain. This provides some mathematical support for the phenomenon of reduced genetic variability in isolated populations established from founder groups.

Molecular mechanisms for environmentally induced and evolutionarily rapid redistribution (plasticity) of meiotic recombination

Genetics ◽  
2021 ◽  
Author(s):  
Reine U Protacio ◽  
Tresor O Mukiza ◽  
Mari K Davidson ◽  
Wayne P Wahls
Keyword(s):  
Fission Yeast ◽  
Frequency Distribution ◽  
Meiotic Recombination ◽  
Environmental Conditions ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Dynamic Range ◽  
Recombination Rates ◽  
Isolated Populations ◽  
Broad Dynamic Range

Abstract It has long been known (circa 1917) that environmental conditions, as well as speciation, can affect dramatically the frequency distribution of Spo11/Rec12-dependent meiotic recombination. Here, by analyzing DNA sequence-dependent meiotic recombination hotspots in the fission yeast Schizosaccharomyces pombe, we reveal a molecular basis for these phenomena. The impacts of changing environmental conditions (temperature, nutrients, osmolarity) on local rates of recombination are mediated directly by DNA site-dependent hotspots (M26, CCAAT, Oligo-C). This control is exerted through environmental condition-responsive signal transduction networks (involving Atf1, Pcr1, Php2, Php3, Php5, Rst2). Strikingly, individual hotspots modulate rates of recombination over a very broad dynamic range in response to changing conditions. They can range from being quiescent to being highly proficient at promoting activity of the basal recombination machinery (Spo11/Rec12 complex). Moreover, each different class of hotspot functions as an independently controlled rheostat; a condition that increases the activity of one class can decrease the activity of another class. Together, the independent modulation of recombination rates by each different class of DNA site-dependent hotspots (of which there are many) provides a molecular mechanism for highly dynamic, large-scale changes in the global frequency distribution of meiotic recombination. Because hotspot-activating DNA sites discovered in fission yeast are conserved functionally in other species, this process can also explain the previously enigmatic, Prdm9-independent, evolutionarily rapid changes in hotspot usage between closely related species, subspecies, and isolated populations of the same species.

scholarly journals Kinpute: using identity by descent to improve genotype imputation

2019 ◽  
Vol 35 (21) ◽  
pp. 4321-4326
Author(s):  
Mark Abney ◽  
Aisha ElSherbiny
Keyword(s):  
Sequence Data ◽  
Imputation Accuracy ◽  
Genotype Imputation ◽  
Supplementary Information ◽  
Specific Reference ◽  
Imputation Methods ◽  
Identical By Descent ◽  
Novel Method ◽  
Optimal Set ◽  
Genotype Probabilities

Abstract Motivation Genotype imputation, though generally accurate, often results in many genotypes being poorly imputed, particularly in studies where the individuals are not well represented by standard reference panels. When individuals in the study share regions of the genome identical by descent (IBD), it is possible to use this information in combination with a study-specific reference panel (SSRP) to improve the imputation results. Kinpute uses IBD information—due to recent, familial relatedness or distant, unknown ancestors—in conjunction with the output from linkage disequilibrium (LD) based imputation methods to compute more accurate genotype probabilities. Kinpute uses a novel method for IBD imputation, which works even in the absence of a pedigree, and results in substantially improved imputation quality. Results Given initial estimates of average IBD between subjects in the study sample, Kinpute uses a novel algorithm to select an optimal set of individuals to sequence and use as an SSRP. Kinpute is designed to use as input both this SSRP and the genotype probabilities output from other LD-based imputation software, and uses a new method to combine the LD imputed genotype probabilities with IBD configurations to substantially improve imputation. We tested Kinpute on a human population isolate where 98 individuals have been sequenced. In half of this sample, whose sequence data was masked, we used Impute2 to perform LD-based imputation and Kinpute was used to obtain higher accuracy genotype probabilities. Measures of imputation accuracy improved significantly, particularly for those genotypes that Impute2 imputed with low certainty. Availability and implementation Kinpute is an open-source and freely available C++ software package that can be downloaded from. Supplementary information Supplementary data are available at Bioinformatics online.

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