GenomeMixer and TRUST: Novel bioinformatics tools to improve reliability of Non-Invasive Prenatal Testing (NIPT) for fetal aneuploidies.

Non-invasive prenatal testing (NIPT) screens for common fetal chromosomal abnormalities through analysis of circulating cell-free DNA in maternal blood by massive parallel sequencing. NIPT reliability relies on both the estimation of the fetal fraction (ff) and on the sequencing depth (sd) but how these parameters are linked is unknown. Several bioinformatics tools have been developed to determine the ff but there is no universal ff threshold applicable across diagnostics laboratories. Thus, we developed two tools allowing the implementation of a strategy for NIPT results validation in clinical practice: GenomeMixer, a semi-supervised approach to create synthetic sequences and to estimate confidence intervals for NIPT validation and TRUST to estimate the reliability of NIPT results based on confidence intervals found in this study. We retrospectively validated these new tools on 2 cohorts for a total of 1439 samples with 31 confirmed aneuploidies. Through the analysis of the interrelationship between ff, sd and chromosomal aberration detection, we demonstrate that these parameters are profoundly connected and cannot be considered independently. Our tools take in account this critical relationship to improve NIPT reliability and facilitate cross laboratory standardization of this screening test.

Cardiac dyspnea risk zones in the South of France identified by geo-pollution trends study.

The incidence of cardiac dyspnea (CD) and the distribution of pollution in the south of France suggests that environmental pollution may have a role in disease triggering. CD is a hallmark symptom of heart failure leading to reduced ability to function and engage in activities of daily living. To show the impact of short-term pollution exposure on the increment of CD emergency room visits, we collected pollutants and climate measurements on a daily basis and 43,400 events of CD in the Région Sud from 2013 to 2018. We used a distributed lag non-linear model (DLNM) to assess the association between air pollution and CD events. We divided the region in 357 zones to reconciliate environmental and emergency room visits data. We applied the DLNM on the entire region, on zones grouped by pollution trends and on singular zones. Each pollutant has a significant effect on triggering CD. Depending on the pollutant, we identified four shapes of exposure curves to describe the impact of pollution on CD events: early and late effect for NO2; U-shape and rainbow-shape (or inverted U) for O3; all the four shapes for PM10. In the biggest cities, O3 has the most significant association along with the PM10. In the west side, a delayed effect triggered by PM10 was found. Zones along the main highway are mostly affected by NO2 pollution with an increase of the association for a period up to 9 days after the pollution peak. Our results can be used by local authorities to set up specific prevention policies, public alerts that adapt to the different zones and support public health prediction-making. We developed a user-friendly web application called Health, Environment in PACA Region Tool (HEART) to collect our results. HEART will allow citizens, researchers and local authorities to monitor the impact of pollution trends on local public health.

NiPTUNE: an automated pipeline for noninvasive prenatal testing in an accurate, integrative and flexible framework.

Noninvasive prenatal testing (NIPT) consists of determining fetal aneuploidies by quantifying copy number alteration from the sequencing of cell-free DNA (cfDNA) from maternal blood. Due to the presence of cfDNA of fetal origin in maternal blood, in silico approaches have been developed to accurately predict fetal aneuploidies. Although NIPT is becoming a new standard in prenatal screening of chromosomal abnormalities, there are no integrated pipelines available to allow rapid, accurate and standardized data analysis in any clinical setting. Several tools have been developed, however often optimized only for research purposes or requiring enormous amount of retrospective data, making hard their implementation in a clinical context. Furthermore, no guidelines have been provided on how to accomplish each step of the data analysis to achieve reliable results. Finally, there is no integrated pipeline to perform all steps of NIPT analysis. To address these needs, we tested several tools for performing NIPT data analysis. We provide extensive benchmark of tools performances but also guidelines for running them. We selected the best performing tools that we benchmarked and gathered them in a computational pipeline. NiPTUNE is an open source python package that includes methods for fetal fraction estimation, a novel method for accurate gender prediction, a principal component analysis based strategy for quality control and fetal aneuploidies prediction. NiPTUNE is constituted by seven modules allowing the user to run the entire pipeline or each module independently. Using two cohorts composed by 1439 samples with 31 confirmed aneuploidies, we demonstrated that NiPTUNE is a valuable resource for NIPT analysis.

Numerical simulation of a stroke: computational problems and methodology.

We discuss the difficulties of the numerical simulation of a stroke, and we describe the numerical methods which we have developed and used to obtain some realistic results. Nowadays, the computations are performed in two-dimensional slices of a brain, but the strategies to obtain full three-dimensional simulations are explored. This paper is written so as to be understandable by non-mathematicians.