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      Machine learning in time-lapse imaging to differentiate embryos from young vs old mice

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          Abstract

          Time-lapse microscopy for embryos is a non-invasive technology used to characterize early embryo development. This study employs time-lapse microscopy and machine learning to elucidate changes in embryonic growth kinetics with maternal aging. We analyzed morphokinetic parameters of embryos from young and aged C57BL6/NJ mice via continuous imaging. Our findings show that aged embryos accelerated through cleavage stages (from 5-cells) to morula compared to younger counterparts, with no significant differences observed in later stages of blastulation. Unsupervised machine learning identified two distinct clusters comprising of embryos from aged or young donors. Moreover, in supervised learning, the extreme gradient boosting algorithm successfully predicted the age-related phenotype with 0.78 accuracy, 0.81 precision, and 0.83 recall following hyperparameter tuning. These results highlight two main scientific insights: maternal aging affects embryonic development pace, and artificial intelligence can differentiate between embryos from aged and young maternal mice by a non-invasive approach. Thus, machine learning can be used to identify morphokinetics phenotypes for further studies. This study has potential for future applications in selecting human embryos for embryo transfer, without or in complement with preimplantation genetic testing.

          Abstract

          Maternal aging in murine in vitro fertilization shows faster cleavage and compaction stages of embryonic development by time-lapse microscopy, and artificial intelligence predicts the aging phenotype.

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          Most cited references108

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          Scikit-Learn: Machine Learning in Python

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            A guide to machine learning for biologists

            The expanding scale and inherent complexity of biological data have encouraged a growing use of machine learning in biology to build informative and predictive models of the underlying biological processes. All machine learning techniques fit models to data; however, the specific methods are quite varied and can at first glance seem bewildering. In this Review, we aim to provide readers with a gentle introduction to a few key machine learning techniques, including the most recently developed and widely used techniques involving deep neural networks. We describe how different techniques may be suited to specific types of biological data, and also discuss some best practices and points to consider when one is embarking on experiments involving machine learning. Some emerging directions in machine learning methodology are also discussed.
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              Human gene expression first occurs between the four- and eight-cell stages of preimplantation development.

              The earliest stages of development in most animals, including the few mammalian species that have been investigated, are regulated by maternally inherited information. Dependence on expression of the embryonic genome cannot be detected until the mid two-cell stage in the mouse, the four-cell stage in the pig (J. Osborn & C. Polge, personal communication), and the eight-cell stage in the sheep. Information about the timing of activation of the embryonic genome in the human is of relevance not only to the therapeutic practice of in vitro fertilization and embryo transfer (IVF), but more importantly for the successful development of techniques for the preimplantation diagnosis of certain inherited genetic diseases. We describe here changes in the pattern of polypeptides synthesized during the pre-implantation stages of human development, and demonstrate that some of the major qualitative changes which occur between the four- and eight-cell stages are dependent on transcription. In addition, it appears that cleavage is not sensitive to transcriptional inhibition until after the four-cell stage.
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                Author and article information

                Contributors
                Journal
                Biol Reprod
                Biol Reprod
                biolreprod
                Biology of Reproduction
                Oxford University Press
                0006-3363
                1529-7268
                June 2024
                30 April 2024
                30 April 2024
                : 110
                : 6
                : 1115-1124
                Affiliations
                Division of Reproductive Endocrinology and Infertility , Department of Obstetrics and Gynecology, Baylor College of Medicine , Houston, Texas, USA
                Division of Reproductive Endocrinology and Infertility , Division of Reproductive Sciences, Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine , New Haven, Connecticut, USA
                Department of Molecular and Human Genetics, Baylor College of Medicine , Houston, Texas, USA
                Department of Molecular and Human Genetics, Baylor College of Medicine , Houston, Texas, USA
                Department of Molecular and Human Genetics, Baylor College of Medicine , Houston, Texas, USA
                Department of Molecular and Human Genetics, Baylor College of Medicine , Houston, Texas, USA
                Pain Research , Informatics, Multi-morbidities, and Education (PRIME) Center, VA Connecticut Healthcare System , West Haven, Connecticut, USA
                Section of Infectious Diseases , Department of Internal Medicine, Yale School of Medicine , New Haven, Connecticut, USA
                Department of Molecular and Human Genetics, Baylor College of Medicine , Houston, Texas, USA
                Department of Molecular and Human Genetics, Baylor College of Medicine , Houston, Texas, USA
                Author notes
                Correspondence: Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, 310 Cedar Street, LSOG 305A, New Haven, CT 06510, USA. Tel: 203-737-5674; Fax: 203-785-2514; E-mail: Liubin.Yang@ 123456yale.edu
                Article
                ioae056
                10.1093/biolre/ioae056
                11180621
                38685607
                204399bc-4996-4c55-9158-cc3363202954
                © The Author(s) 2024. Published by Oxford University Press on behalf of Society for the Study of Reproduction.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 24 November 2023
                : 15 February 2024
                : 05 April 2024
                : 03 May 2024
                Page count
                Pages: 10
                Funding
                Funded by: National Human Genome Research Institute, DOI 10.13039/100000051;
                Funded by: National Institutes of Health, DOI 10.13039/100000002;
                Award ID: UM1 HG006348
                Funded by: Eunice Kennedy Shriver National Institute of Child Health and Human Development, DOI 10.13039/100009633;
                Award ID: 5K12HD047018
                Funded by: Baylor College of Medicine Department of Obstetrics and Gynecology;
                Funded by: Career Development Award;
                Funded by: Department of Veterans Affairs, Veterans Health Administration;
                Funded by: Office of Research and Development, DOI 10.13039/100006379;
                Funded by: Clinical Science Research and Development, DOI 10.13039/100015728;
                Award ID: IK2 CX001981
                Funded by: Health Services Research and Development, DOI 10.13039/100007217;
                Award ID: #CIN 13-407
                Categories
                Imaging Special Issue
                AcademicSubjects/MED00773
                AcademicSubjects/SCI01070

                machine learning,morphokinetics,preimplantation mouse embryos,time-lapse microscopy,maternal aging,predictive modeling

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