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Description
Competence Centre on Health Technologies, is an Estonian company and research institute that joints basic research and genetic testing. NIPT (Non-Invasive Prenatal Screening) is widely accepted as an advanced method in prenatal screening with high validity for assessing the risks for foetal severe chromosomal diseases, like trisomy 18 (Edwards syndrome), trisomy 13 (Patau syndrome) and trisomy 21 (Down syndrome). The global uptake of NIPT method has been rapid and many professional organisations in more than 60 countries have already recommended to include NIPT as part of routine pregnancy monitoring, including Estonian Gynaecologists’ Society. However, due to the higher cost of the NIPT test as compared to traditional screening, it is not reimbursed nationally in all countries and is not available to everyone, thus creating inequalities in access to healthcare services. Thus, with the exception of Belgium, Netherlands and Estonia, NIPT is generally not included to the national health insurance plans.
The main goal of the project is to develop the internationally scalable certified product NIPTIFY+ test, which will be able to discover not only foetal chromosomal disorders, but also maternal genetic-based health conditions, like preeclampsia, gestational diabetes, and premature birth. All these maternal diseases can be prognosed based on maternal genetic predisposition towards these diseases and can be prevented with the right medical care and life-style recommendations. Thus, NIPTIFY+ helps to avoid several procedures and prevents the appearance of the diseases by early risk estimation. The main objective will be achieved by development of internationally scalable product with the full product and service chain containing building blocks to be provided fully or partly by CCHT together with local health care providers.
Summary of project results
Project aimed to develop the processes and services to promote the possibilities of prenatal personalised medicine, in order to improve the individual health indicators and quality of life of expectant mothers and new-born children through innovative prenatal screening solutions and services. The aim was to develop such products and services related to the above objectives, focusing on the development of standardised sample handling, laboratory and computational analysis procedures methodologies using new solutions of health data analysis for more efficient solutions in prenatal personal medicine.
The primary goal of the project was to develop laboratory and bioinformatic/computational analysis processes and methods for a more comprehensive analysis of possible fetal chromosomal diseases. The main goal of the project''s bioinformatic developments was to develop computational workflows for further and more accurate analysis of the raw data obtained from the sequencing of low-coverage sequenced NIPT samples. As a result of the project, a computational methodology and software BinDel (https://github.com/seqinfo /BinDel) were developed to assess the risk of clinically significant microdeletions in the fetus from NIPT data.
In addition, technical and clinical validation of the developed product and the creation of a road map for its certification and the creation of the technical documentation necessary to obtain the CE-IVD mark were to be performed. Also, the creation of cooperation networks with local stakeholders, especially clinics, specialists and midwives, by including samples collected in Estonia in the development of a new and more accurate NIPTIFY3 screening test, to map the needs and possibilities and know-how of clinical practice. By involving top specialists in clinical genetics from Estonia, Norway and the Belgian university KU Leuven, the most frequent clinically relevant fetal microdeletions and the corresponding genomic regions were defined. Using NIPT samples with confirmed pathogenic microdeletions collected both in Estonia and Belgium, we validated the developed methodology and software for clinical use in assessing the risk of microdeletions from NIPT samples. This work has been documented as a pre-print article and is currently being published in an international scientific journal. The BinDel software developed and validated during the project was integrated into the NIPTIFY3 computational workflow for fetal chromosomal disease risk assessment. As part of this pilot, the BinDel microdeletion risk estimates for each sample analyzed in the service will be analyzed and evaluated, and if necessary, the sensitivity of the software will be calibrated and additional analyzes will be performed on the sample under study. The BinDel NIPTIFY3 assay is then integrated and formalized into a result-determining tool for microdeletion analysis.
In parallel, a computational methodology was developed for the assessment of genetic transgenomic polygenic risks of maternal diseases during pregnancy. A computational workflow to calculate polygenic risk scores (PRS) was developed and the developed workflow was tested on 100 low-coverage WGS NIPT samples to calculate PRS for gestational diabetes.
The developed solution is a service intended for clinics and specialists as well as private clients, which significantly improves the quality of life of patients.