scholarly journals Combination of Fetal Fraction Estimators Based on Fragment Lengths and Fragment Counts in Non-Invasive Prenatal Testing

2019 ◽  
Vol 20 (16) ◽  
pp. 3959 ◽  
Author(s):  
Juraj Gazdarica ◽  
Rastislav Hekel ◽  
Jaroslav Budis ◽  
Marcel Kucharik ◽  
Frantisek Duris ◽  
...  
Keyword(s):  
State Of The Art ◽  
Prenatal Testing ◽  
The State ◽  
Accurate Estimation ◽  
Special Focus ◽  
Dna Fragments ◽  
Sources Of Information ◽  
Non Invasive ◽  
Genomic Locations ◽  
Fetal Fraction

The reliability of non-invasive prenatal testing is highly dependent on accurate estimation of fetal fraction. Several methods have been proposed up to date, utilizing different attributes of analyzed genomic material, for example length and genomic location of sequenced DNA fragments. These two sources of information are relatively unrelated, but so far, there have been no published attempts to combine them to get an improved predictor. We collected 2454 single euploid male fetus samples from women undergoing NIPT testing. Fetal fractions were calculated using several proposed predictors and the state-of-the-art SeqFF method. Predictions were compared with the reference Y-based method. We demonstrate that prediction based on length of sequenced DNA fragments may achieve nearly the same precision as the state-of-the-art methods based on their genomic locations. We also show that combination of several sample attributes leads to a predictor that has superior prediction accuracy over any single approach. Finally, appropriate weighting of samples in the training process may achieve higher accuracy for samples with low fetal fraction and so allow more reliability for subsequent testing for genomic aberrations. We propose several improvements in fetal fraction estimation with a special focus on the samples most prone to wrong conclusion.

Correlation between Z score, fetal fraction, and sequencing reads in non-invasive prenatal testing

2017 ◽  
Vol 37 (9) ◽  
pp. 943-945 ◽  
Author(s):  
Marie Balslev-Harder ◽  
Stine R. Richter ◽  
Susanne Kjaergaard ◽  
Peter Johansen
Keyword(s):  
Prenatal Testing ◽  
Z Score ◽  
Non Invasive ◽  
Fetal Fraction

High- T c superconductors tailored on the nanometre-scale

1995 ◽  
Vol 353 (1703) ◽  
pp. 377-385 ◽  
Keyword(s):  
Josephson Junction ◽  
Coherence Length ◽  
State Of The Art ◽  
The State ◽  
Special Focus ◽  
Length Scale ◽  
Considerable Effort ◽  
New Concepts

High- T c superconductors are characterized by an unusually small coherence length, which amounts to a few angstroms only. As the coherence length is the length scale in which a superconductor has to be structured to achieve Josephson junction behaviour, considerable effort has been devoted by many groups to modify high- T c films in the nanometre scale. Because the high- T c cuprates do not lend themselves for nanostructuring, new concepts have to be developed to achieve this goal. These developments will be discussed and an overview of the state of the art of the field will be presented with a special focus on the ultimate limitations of nanoscale structuring of superconductors.

scholarly journals Lipid Metabolism Affects Fetal Fraction and Screen Failures in Non-invasive Prenatal Testing

2022 ◽  
Vol 8 ◽  
Author(s):  
Jun Cao ◽  
Longwei Qiao ◽  
Jieyu Jin ◽  
Sheng Zhang ◽  
Ping Chen ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Pregnant Women ◽  
Serum Lipid ◽  
Univariate Analysis ◽  
Multivariate Logistic Regression Analysis ◽  
Density Lipoprotein ◽  
Prenatal Testing ◽  
Lipoprotein Cholesterol ◽  
Non Invasive ◽  
Fetal Fraction

Objective: To assess the association between lipid metabolism and fetal fraction, which is a critical factor in ensuring a highly accurate non-invasive prenatal testing (NIPT), and on the rate of screen failures or “no calls” in NIPT.Methods: A total of 4,514 pregnant women at 12–26 weeks of gestation underwent NIPT sequencing and serum lipid measurements. Univariate analysis and multivariate regression models were used to evaluate the associations of serum lipid concentrations with the fetal fraction and the rate of screen failures.Results: The fetal fraction decreased with increased low-density lipoprotein cholesterol and triglyceride (TG) levels, which were significant factors (standardized coefficient: −0.11). Conversely, high-density lipoprotein cholesterol and the interval between the two tests were positively correlated with the fetal fraction. The median fetal fraction was 10.88% (interquartile range, 8.28–13.89%) and this decreased with TG from 11.56% at ≤1.10 mmol/L to 9.51% at >2.30 mmol/L. Meanwhile, multivariate logistic regression analysis revealed that increased TG levels were independently associated with the risk of screen failures. The rate of screen failures showed an increase with TG levels from 1.20% at ≤1.70 mmol/L to 2.41% at >2.30 mmol/L.Conclusions: The fetal fraction and the rate of screen failures in NIPT are affected by TG levels. Meanwhile, in pregnant women with high TG levels, delaying the time between NIPT blood collections can significantly increase the fetal fraction.

scholarly journals Proposal of a Methodology for the Estimation of Slope, Water Depth and Cross-sectional Area by Using the State Function, Ф (T): Testing With the Measurements Made by H. Fischer in M. Keck Channel Laboratory of Caltech University

2021 ◽  
Vol 15 ◽  
pp. 213-219
Author(s):  
Carlos Peña-Guzmán ◽  
Alfredo Constain ◽  
Gina Peña-Olarte
Keyword(s):  
Cross Sections ◽  
Thermodynamic Potential ◽  
Dispersion Coefficient ◽  
State Of The Art ◽  
The State ◽  
Accurate Estimation ◽  
State Function ◽  
Average Difference ◽  
Longitudinal Dispersion Coefficient ◽  
Cross Sectional

A basic topic in river studies, whether in hydrodynamics or water quality, is the accurate estimation of both geomorphological and geometric characteristics in cross sections in streams or channels. Many measurements or methodologies that are within the state of the art, are not direct or easy by several aspects. For this reason, this article analyses the application of a state function, Ф (t), which, acting as a thermodynamic potential, allows the magnitudes of the cross sections, depth of the water sheet, slope and longitudinal dispersion coefficient to be obtained directly, using NaCl as a tracer. In order to apply and validate this new method properly, an experiment conducted in 1966 by H.B. Fischer in the W.M. Keck Laboratory of Caltech in USA was studied on two points of the canal. It found average differences of 0.016 m2 (with reference) in the area of the canal, 0.015 m of the height of the water sheet and an average difference of -0.00015 in the slope of the canal

scholarly journals Topical problems in the theory of planet formation: formation of planetesimals

2019 ◽  
pp. 104-121
Author(s):  
A. B. Makalkin ◽  
I. N. Ziglina ◽  
M. E. Artyushkova
Keyword(s):  
Planet Formation ◽  
State Of The Art ◽  
The State ◽  
Special Focus ◽  
Formation Theory ◽  
History Of Development ◽  
The Earth ◽  
History Of ◽  
Academy Of Sciences ◽  
Schmidt Institute

The development of the Earth’s and planets formation theory over 70 years is considered with a special focus on the history of development of this theory at the Schmidt Institute of Physics of the Earth of the Russian Academy of Sciences (IPE RAS) where this direction of research was founded by Otto Schmidt. The state of the art of the theory is outlined. In particular, the planetesimals formation problem currently belonging to the key unsolved issues in the theory of planet formation is discussed. Recent results of the studies aimed at solving this problem at IPE RAS are presented.

scholarly journals Non-invasive prenatal testing by low coverage genomic sequencing: Detection limits of screened chromosomal microdeletions

2019 ◽  
Author(s):  
Marcel Kucharik ◽  
Andrej Gnip ◽  
Michaela Hyblova ◽  
Jaroslav Budis ◽  
Lucia Strieskova ◽  
...  
Keyword(s):  
In Silico ◽  
Detection Limits ◽  
Prenatal Testing ◽  
Systematic Evaluation ◽  
Whole Genome Sequencing Data ◽  
Detection Accuracy ◽  
Sequencing Data ◽  
Non Invasive ◽  
Microdeletion Syndromes ◽  
Fetal Fraction

AbstractObjectiveTo study the detection limits of chromosomal microaberrations in non-invasive prenatal testing with aim for five target microdeletion syndromes, including DiGeorge, Prader-Willi/Angelman, 1p36, Cri-Du-Chat, and Wolf-Hirschhorn syndromes.MethodWe used known cases of pathogenic deletions from ISCA database to specifically define regions critical for the target syndromes. Our approach to detect microdeletions, from whole genome sequencing data, is based on sample normalization and read counting for individual bins. We performed both an in-silico study using artificially created data sets and a laboratory test on mixed DNA samples, with known microdeletions, to assess the sensitivity of prediction for varying fetal fractions, deletion lengths, and sequencing read counts.ResultsThe in-silico study showed sensitivity of 79.3% for 10% fetal fraction with 20M read count, which further increased to 98.4% if we searched only for deletions longer than 3Mb. The test on laboratory-prepared mixed samples was in agreement with in-silico results, while we were able to correctly detect 24 out of 29 control samples.ConclusionOur results suggest that it is possible to incorporate microaberration detection into basic NIPT as part of the offered screening/diagnostics procedure, however, accuracy and reliability depends on several specific factors.What’s already known about this topic?Microdeletion detection accuracy, similarly to most common trisomies detection, was found to be dependent mostly on technical and biological parameters of the test and tested samples, such as coverage of target region, fetal fraction, size and positions of the deletions.What does this study add?Estimation of relevant regions for five chosen microdeletion syndromes. Confirmation and improvement upon previous methods. Systematic evaluation of sensitivity of microdeletion detection with read counts from 10M to 20M.

scholarly journals Innovative method for reducing uninformative calls in non-invasive prenatal testing

2018 ◽  
Author(s):  
Jaroslav Budis ◽  
Juraj Gazdarica ◽  
Jan Radvanszky ◽  
Gabor Szucs ◽  
Marcel Kucharik ◽  
...  
Keyword(s):  
State Of The Art ◽  
False Negative ◽  
Prenatal Testing ◽  
Obstetric Care ◽  
High Sensitivity ◽  
Supplementary Information ◽  
Non Invasive ◽  
Current State ◽  
Z Scores ◽  
Supplementary Material

AbstractMotivationNon-invasive prenatal testing or NIPT is currently among the top researched topic in obstetric care. While the performance of the current state-of-the-art NIPT solutions achieve high sensitivity and specificity, they still struggle with a considerable number of samples that cannot be concluded with certainty. Such uninformative results are often subject to repeated blood sampling and re-analysis, usually after two weeks, and this period may cause a stress to the future mothers as well as increase the overall cost of the test.ResultsWe propose a supplementary method to traditional z-scores to reduce the number of such uninformative calls. The method is based on a novel analysis of the length profile of circulating cell free DNA which compares the change in such profiles when random-based and length-based elimination of some fragments is performed. The proposed method is not as accurate as the standard z-score; however, our results suggest that combination of these two independent methods correctly resolves a substantial portion of healthy samples with an uninformative result. Additionally, we discuss how the proposed method can be used to identify maternal aberrations, thus reducing the risk of false positive and false negative calls.Availability and ImplementationA particular implementation of the proposed methods is not provided with the manuscript.ContactCorrespondence regarding the manuscript should be directed at Frantisek Duris ([email protected]).Supplementary InformationNo additional supplementary information is available.

Not Ready for Prime Time

2011 ◽  
Vol 2 (4) ◽  
pp. 49-61 ◽  
Author(s):  
Jostein Jensen ◽  
Martin Gilje Jaatun
Keyword(s):  
Software Development ◽  
Empirical Research ◽  
State Of The Art ◽  
Empirical Studies ◽  
Empirical Work ◽  
The State ◽  
Prime Time ◽  
Special Focus ◽  
Model Driven Development ◽  
Model Driven

Model Driven Development (MDD) is by many considered a promising approach for software development. This article reports the results of a systematic survey to identify the state-of-the-art within the topic of security in model driven development, with a special focus on finding empirical studies. The authors provide an introduction to the major secure MDD initiatives, but the survey shows that there is a lack of empirical work on the topic. The authors conclude that better standardization initiatives and more empirical research in the field is necessary before it can be considered mature.

Not Ready for Prime Time

2012 ◽  
pp. 77-90
Author(s):  
Jostein Jensen ◽  
Martin Gilje Jaatun
Keyword(s):  
Software Development ◽  
Empirical Research ◽  
State Of The Art ◽  
Empirical Studies ◽  
Empirical Work ◽  
The State ◽  
Prime Time ◽  
Special Focus ◽  
Model Driven Development ◽  
Model Driven

Model Driven Development (MDD) is by many considered a promising approach for software development. This article reports the results of a systematic survey to identify the state-of-the-art within the topic of security in model driven development, with a special focus on finding empirical studies. The authors provide an introduction to the major secure MDD initiatives, but the survey shows that there is a lack of empirical work on the topic. The authors conclude that better standardization initiatives and more empirical research in the field is necessary before it can be considered mature.

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