Since its inception 40 years ago, in vitro fertilization (IVF) has resulted in the birth of more than 1 million babies in the United States, and has revolutionized the field of reproductive medicine. Unfortunately, the success rate of IVF is still exceedingly low, especially for women >40 years old, with only 15.5% of implanted embryos resulting in pregnancy. This is partly due to the cytological method used for pre-implantation screening, which cannot detect the most common genetic defect during IVF, aneuploidy (i.e. chromosomal copy-number variation). Aneuploidy is linked to higher rates of miscarriage, and occurs more often in women >40 years of age; thus, aneuploidy has been a frequent target for genetic screening to improve IVF outcomes. Pre-implantation genetic testing for aneuploidy (PGT-A) refers to a variety of techniques aimed at detecting changes in chromosomal copy number, with the goal of identifying high-quality euploid embryos for implantation. Recent advances in next-generation sequencing (NGS) technologies have made it possible to screen embryos at higher levels of precision, and across a wider range of genetic defects, including mosaicism, triploidy and single nucleotide polymorphisms (SNPs). Despite these remarkable advances, there are still significant challenges with PGT-A sequencing. Indeed, the most commonly implemented software for PGT-A (i.e. BlueFuse® ) are bundled with specific sequencing platforms (i.e. VeriSeq®), and are only designed to test for aneuploidy. Furthermore, existing pipelines are not user-friendly or customizable, which is a serious obstacle prohibiting the use of NGS by clinicians / embryologists. A more accessible bioinformatics platform is desperately needed that will bridge the gap between PGT-A sequencing and IVF outcomes. Basepair⢠is an innovator in efficient, user-friendly, web-based NGS analysis systems, with fully automated ChIP-, RNA-, ATAC-, and DNA-Seq bioinformatics pipelines available online. Here, Basepair will deliver PiNDAâ¢, the first fully integrated software solution for comprehensive PGT-A analysis. In Aim 1, we will develop modules to test for specific chromosomal abnormalities, including mosaicism and triploidy, and validate each model with training data derived from somatic cell lines with known chromosomal aberrations. In Aim 2, we will integrate our modules into the PiNDA software system, creating a user-friendly, web-based interface that will perform full data analysis (raw data to full summary report) in <15 minutes, with no manual input required. Final data will be accessible via Basepairâs online portal, facilitating rapid data transfer from embryologists to physicians, and supporting the integration of NGS tests in IVF. Our innovative bioinformatics platform will accelerate NGS analysis for IVF, improving rates of pregnancy and advancing research in the success of IVF procedures.
Public Health Relevance Statement: PROJECT NARRATIVE In vitro fertilization (IVF) methods have begun to leverage next-generation sequencing technologies for pre-implantation genetic testing of aneuploidy (PGT-A), expanding the array of chromosomal abnormalities that can be accurately detected. However, the vast majority of software can only distinguish one type of genetic defect (i.e. aneuploidy), are difficult to use, and are tied to distinct sequencing platforms, limiting the clinical utility of resulting analyses. Basepair⢠Inc. is a pioneer in user-friendly, web-based bioinformatics pipelines, providing comprehensive services for a wide range of sequencing projects. Here, Basepair will develop an inclusive suite of software for PGT-A, compatible with sequencing data from multiple platforms. This product will be of high value to the field and will help bridge the gap between advances in DNA sequencing and IVF technology.
Project Terms: Age-Years; Algorithms; analysis pipeline; Aneuploid Cells; Aneuploidy; aneuploidy analysis; ATAC-seq; Bioinformatics; Biopsy; Birth; Cell division; cell free DNA; Cell Line; Centers for Disease Control and Prevention (U.S.); ChIP-seq; Chromosome abnormality; Clinical; Complex; Computer software; Copy Number Polymorphism; Culture Media; Cytology; Data; Data Analyses; design; DNA sequencing; early embryonic stage; egg; Embryo; Feedback; Fertility Agents; Fertilization in Vitro; Genetic Screening; Goals; Harvest; Implant; implantation; improved; innovation; Letters; Link; Machine Learning; Manuals; Methods; Modeling; Morphology; Mosaicism; Mutation; natural Blastocyst Implantation; next generation sequencing; Online Systems; Outcome; Phase; phase 1 study; Physicians; Polymorphism Analysis; Pregnancy; Pregnancy Rate; preimplantation; Preimplantation Diagnosis; Procedures; Reporting; Reproductive Medicine; Research; Role; Sampling; screening; sequencing platform; Services; Single Nucleotide Polymorphism; software development; software systems; Somatic Cell; Specificity; sperm cell; Spontaneous abortion; success; Summary Reports; System; Systems Analysis; Techniques; Technology; Testing; Training; transcriptome sequencing; Triploidy; United States; user-friendly; Uterus; web based interfa
