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.

scholarly journals Cell-free DNA screening for aneuploidies in 7113 pregnancies: single Italian centre study

2020 ◽  
Vol 102 ◽  
Author(s):  
Alvaro Mesoraca ◽  
Katia Margiotti ◽  
Claudio Dello Russo ◽  
Anthony Cesta ◽  
Antonella Cima ◽  
...  
Keyword(s):  
Sex Chromosome ◽  
Clinical Performance ◽  
False Negative ◽  
Prenatal Testing ◽  
High Sensitivity ◽  
Trisomy 13 ◽  
Sequencing Platform ◽  
Non Invasive ◽  
Negative Results ◽  
False Negative Results

Abstract Introduction Non-invasive prenatal testing (NIPT) using cell-free foetal DNA has been widely accepted in recent years for detecting common foetal chromosome aneuploidies, such as trisomies 13, 18 and 21, and sex chromosome aneuploidies. In this study, the practical clinical performance of our foetal DNA testing was evaluated for analysing all chromosome aberrations among 7113 pregnancies in Italy. Methods This study was a retrospective analysis of collected NIPT data from the Ion S5 next-generation sequencing platform obtained from Altamedica Medical Centre in Rome, Italy. Results In this study, NIPT showed 100% sensitivity and 99.9% specificity for trisomies 13, 18 and 21. Out of the 7113 samples analysed, 74 cases (1%) were positive by NIPT testing; foetal karyotyping and follow-up results validated 2 trisomy 13 cases, 5 trisomy 18 cases, 58 trisomy 21 cases and 10 sex chromosome aneuploidy cases. There were no false-negative results. Conclusion In our hands, NIPT had high sensitivity and specificity for common chromosomal aneuploidies such as trisomies 13, 18 and 21.

scholarly journals Non-invasive prenatal testing: what an obstetrician needs to know

2020 ◽  
Vol 9 (12) ◽  
pp. 5200
Author(s):  
Mishu Mangla
Keyword(s):  
Health Care Providers ◽  
Prenatal Screening ◽  
Prenatal Testing ◽  
High Sensitivity ◽  
Target Population ◽  
Care Providers ◽  
Advantages And Disadvantages ◽  
Non Invasive ◽  
Primary Health Care Providers ◽  
First Choice

No field in obstetrics has seen such fast advancement, as the field of prenatal screening and diagnosis. A wide variety of tests are available today, and this at times becomes confusing both for the patient and the treating doctor that which screening test would be best suited in the given circumstances. Non-invasive prenatal screening, with its numerous advantages is rapidly becoming the test of first choice, especially in the affording set of population.  Although, the test has a very high sensitivity and a very good positive predictive value, this too suffers from some disadvantages which should be clear to the obstetrician ordering the test. A good knowledge about the test, the ideal target population in which this should be offered as the primary screening tool and limitations of the test should be known to all practicing obstetricians and primary health care providers. The current review aims to provide a simplified and updated knowledge regarding non-invasive prenatal testing (NIPT), its major advantages and disadvantages and summarizes the role of ultrasound in patients with negative NIPT.

scholarly journals Sequencing Shorter cfDNA Fragments Decreases the False Negative Rate of Non-invasive Prenatal Testing

2020 ◽  
Vol 11 ◽  
Author(s):  
Ying Xue ◽  
Guodong Zhao ◽  
Longwei Qiao ◽  
Jiafeng Lu ◽  
Bin Yu ◽  
...  
Keyword(s):  
False Negative ◽  
False Negative Rate ◽  
Prenatal Testing ◽  
Non Invasive ◽  
Negative Rate

scholarly journals Faucet: streaming de novo assembly graph construction

2017 ◽  
Author(s):  
Roye Rozov ◽  
Gil Goldshlager ◽  
Eran Halperin ◽  
Ron Shamir
Keyword(s):  
Resource Use ◽  
De Novo ◽  
State Of The Art ◽  
Supplementary Information ◽  
De Bruijn Graph ◽  
Assembly Quality ◽  
Metagenome Assembly ◽  
Streaming Algorithm ◽  
Supplementary Material ◽  
De Bruijn

AbstractMotivationWe present Faucet, a 2-pass streaming algorithm for assembly graph construction. Faucet builds an assembly graph incrementally as each read is processed. Thus, reads need not be stored locally, as they can be processed while downloading data and then discarded. We demonstrate this functionality by performing streaming graph assembly of publicly available data, and observe that the ratio of disk use to raw data size decreases as coverage is increased.ResultsFaucet pairs the de Bruijn graph obtained from the reads with additional meta-data derived from them. We show these metadata - coverage counts collected at junction k-mers and connections bridging between junction pairs - contain most salient information needed for assembly, and demonstrate they enable cleaning of metagenome assembly graphs, greatly improving contiguity while maintaining accuracy. We compared Faucet’s resource use and assembly quality to state of the art metagenome assemblers, as well as leading resource-efficient genome assemblers. Faucet used orders of magnitude less time and disk space than the specialized metagenome assemblers MetaSPAdes and Megahit, while also improving on their memory use; this broadly matched performance of other assemblers optimizing resource efficiency - namely, Minia and LightAssembler. However, on metagenomes tested, Faucet’s outputs had 14-110% higher mean NGA50 lengths compared to Minia, and 2-11-fold higher mean NGA50 lengths compared to LightAssembler, the only other streaming assembler available.AvailabilityFaucet is available at https://github.com/Shamir-Lab/[email protected],[email protected] information:Supplementary data are available at Bioinformatics online.

scholarly journals Joint epitope selection and spacer design for string-of-beads vaccines

2020 ◽  
Vol 36 (Supplement_2) ◽  
pp. i643-i650
Author(s):  
Emilio Dorigatti ◽  
Benjamin Schubert
Keyword(s):  
Antigen Processing ◽  
State Of The Art ◽  
Supplementary Information ◽  
Current State ◽  
Fixed Set ◽  
Epitope Selection ◽  
High Chance ◽  
Selection Of ◽  
Design Steps

Abstract Motivation Conceptually, epitope-based vaccine design poses two distinct problems: (i) selecting the best epitopes to elicit the strongest possible immune response and (ii) arranging and linking them through short spacer sequences to string-of-beads vaccines, so that their recovery likelihood during antigen processing is maximized. Current state-of-the-art approaches solve this design problem sequentially. Consequently, such approaches are unable to capture the inter-dependencies between the two design steps, usually emphasizing theoretical immunogenicity over correct vaccine processing, thus resulting in vaccines with less effective immunogenicity in vivo. Results In this work, we present a computational approach based on linear programming, called JessEV, that solves both design steps simultaneously, allowing to weigh the selection of a set of epitopes that have great immunogenic potential against their assembly into a string-of-beads construct that provides a high chance of recovery. We conducted Monte Carlo cleavage simulations to show that a fixed set of epitopes often cannot be assembled adequately, whereas selecting epitopes to accommodate proper cleavage requirements substantially improves their recovery probability and thus the effective immunogenicity, pathogen and population coverage of the resulting vaccines by at least 2-fold. Availability and implementation The software and the data analyzed are available at https://github.com/SchubertLab/JessEV. Supplementary information Supplementary data are available at Bioinformatics online.

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.

scholarly journals A Review of the State of the Art in Non-Contact Sensing for COVID-19

Sensors ◽  
2020 ◽  
Vol 20 (19) ◽  
pp. 5665
Author(s):  
William Taylor ◽  
Qammer H. Abbasi ◽  
Kia Dashtipour ◽  
Shuja Ansari ◽  
Syed Aziz Shah ◽  
...  
Keyword(s):  
Healthcare Workers ◽  
State Of The Art ◽  
Future Research ◽  
Research Directions ◽  
Advantages And Disadvantages ◽  
Non Invasive ◽  
Current State ◽  
Global Pandemic ◽  
Future Research Directions ◽  
Contact Sensing

COVID-19, caused by SARS-CoV-2, has resulted in a global pandemic recently. With no approved vaccination or treatment, governments around the world have issued guidance to their citizens to remain at home in efforts to control the spread of the disease. The goal of controlling the spread of the virus is to prevent strain on hospitals. In this paper, we focus on how non-invasive methods are being used to detect COVID-19 and assist healthcare workers in caring for COVID-19 patients. Early detection of COVID-19 can allow for early isolation to prevent further spread. This study outlines the advantages and disadvantages and a breakdown of the methods applied in the current state-of-the-art approaches. In addition, the paper highlights some future research directions, which need to be explored further to produce innovative technologies to control this pandemic.

scholarly journals Fetal aneuploidy screening by non-invasive prenatal testing of maternal plasma DNA sequencing with “false negative” result due to confined placental mosaicism

Medicine ◽  
2020 ◽  
Vol 99 (29) ◽  
pp. e20848
Author(s):  
Xiaozhou Li ◽  
Duan Ju ◽  
Yunfang Shi ◽  
Yan Li ◽  
Haiwei Dong ◽  
...  
Keyword(s):  
Dna Sequencing ◽  
False Negative ◽  
Prenatal Testing ◽  
Maternal Plasma ◽  
False Negative Result ◽  
Plasma Dna ◽  
Aneuploidy Screening ◽  
Non Invasive ◽  
Fetal Aneuploidy ◽  
Placental Mosaicism

scholarly journals Unexplained False Negative Results in Noninvasive Prenatal Testing: Two Cases Involving Trisomies 13 and 18

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
R. Hochstenbach ◽  
G. C. M. L. Page-Christiaens ◽  
A. C. C. van Oppen ◽  
K. D. Lichtenbelt ◽  
J. J. T. van Harssel ◽  
...  
Keyword(s):  
False Negative ◽  
Prenatal Testing ◽  
High Sensitivity ◽  
Trisomy 13 ◽  
Maternal Weight ◽  
Noninvasive Prenatal Testing ◽  
Root Cause ◽  
Negative Results ◽  
False Negative Results ◽  
Negative Case

Noninvasive prenatal testing (NIPT) validation studies show high sensitivity and specificity for detection of trisomies 13, 18, and 21. False negative cases have rarely been reported. We describe a false negative case of trisomy 13 and another of trisomy 18 in which NIPT was commercially marketed directly to the clinician. Both cases came to our attention because a fetal anatomy scan at 20 weeks of gestation revealed multiple anomalies. Karyotyping of cultured amniocytes showed nonmosaic trisomies 13 and 18, respectively. Cytogenetic investigation of cytotrophoblast cells from multiple placental biopsies showed a low proportion of nontrisomic cells in each case, but this was considered too small for explaining the false negative NIPT result. The discordant results also could not be explained by early gestational age, elevated maternal weight, a vanishing twin, or suboptimal storage or transport of samples. The root cause of the discrepancies could, therefore, not be identified. The couples involved experienced difficulties in accepting the unexpected and late-adverse outcome of their pregnancy. We recommend that all parties involved in caring for couples who choose NIPT should collaborate to clarify false negative results in order to unravel possible biological causes and to improve the process of patient care from initial counseling to communication of the result.

scholarly journals A comparative study between placental alpha microglobulin-1 rapid immunoassay and standard diagnostic methods for detection of rupture of membranes

2018 ◽  
Vol 7 (5) ◽  
pp. 1813
Author(s):  
Hemant Deshpande ◽  
Umesh Sabale ◽  
C. S. Madkar ◽  
Anuja Bobe
Keyword(s):  
False Negative ◽  
High Sensitivity ◽  
Diagnostic Methods ◽  
Step Test ◽  
Non Invasive ◽  
Emergency Cesarean ◽  
One Step ◽  
Conventional Methods ◽  
Sensitivity Specificity ◽  
Very High

Background: To determine the efficacy of an immunoassay to measure levels of placental alpha-microglobulin-1 in cervico-vaginal secretions.Methods: 100 ANC cases admitted in Dr D. Y. Patil Hospital with symptoms of rupture of membranes during study period. Inclusion criteria-Pregnant women who presented with symptoms of ROM either in labour or not in labour, gestational age from 28 weeks onwards and who have given consent.Results: In 9 cases, the immunoassay test was negative, in 91 cases, it was positive and in one case, the liquor had a lot of meconium, the woman had to undergo an emergency cesarean section. This patient was deemed to have a false negative result by the test. Pooling was positive in 87 cases, nitrazine test in 86 cases and ferning in 88 cases. Hence, in comparison to immunoassay test which had 100% specificity and 98.91% sensitivity due to incomplete evaluation, nitrazine test had 95.58% sensitivity and 100% specificity, Pooling has 97.79% sensitivity and 100% specificity, whereas ferning has 98.34% sensitivity and 100% specificity.Conclusions: The PAMG1 is a non-invasive, rapid, one step test with very high sensitivity, specificity and accuracy as compared to the conventional methods together and also individually. Preforming this test instead of conventional methods can aid the early detection of rupture of membranes and largely affect the outcome of maternal and fetal health as timely decision can be taken once diagnosis is confirmed.

Sign in / Sign up

Export Citation Format

Share Document