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The Lancet. Digital Health Jan 2023One challenge in the field of in-vitro fertilisation is the selection of the most viable embryos for transfer. Morphological quality assessment and morphokinetic...
BACKGROUND
One challenge in the field of in-vitro fertilisation is the selection of the most viable embryos for transfer. Morphological quality assessment and morphokinetic analysis both have the disadvantage of intra-observer and inter-observer variability. A third method, preimplantation genetic testing for aneuploidy (PGT-A), has limitations too, including its invasiveness and cost. We hypothesised that differences in aneuploid and euploid embryos that allow for model-based classification are reflected in morphology, morphokinetics, and associated clinical information.
METHODS
In this retrospective study, we used machine-learning and deep-learning approaches to develop STORK-A, a non-invasive and automated method of embryo evaluation that uses artificial intelligence to predict embryo ploidy status. Our method used a dataset of 10 378 embryos that consisted of static images captured at 110 h after intracytoplasmic sperm injection, morphokinetic parameters, blastocyst morphological assessments, maternal age, and ploidy status. Independent and external datasets, Weill Cornell Medicine EmbryoScope+ (WCM-ES+; Weill Cornell Medicine Center of Reproductive Medicine, NY, USA) and IVI Valencia (IVI Valencia, Health Research Institute la Fe, Valencia, Spain) were used to test the generalisability of STORK-A and were compared measuring accuracy and area under the receiver operating characteristic curve (AUC).
FINDINGS
Analysis and model development included the use of 10 378 embryos, all with PGT-A results, from 1385 patients (maternal age range 21-48 years; mean age 36·98 years [SD 4·62]). STORK-A predicted aneuploid versus euploid embryos with an accuracy of 69·3% (95% CI 66·9-71·5; AUC 0·761; positive predictive value [PPV] 76·1%; negative predictive value [NPV] 62·1%) when using images, maternal age, morphokinetics, and blastocyst score. A second classification task trained to predict complex aneuploidy versus euploidy and single aneuploidy produced an accuracy of 74·0% (95% CI 71·7-76·1; AUC 0·760; PPV 54·9%; NPV 87·6%) using an image, maternal age, morphokinetic parameters, and blastocyst grade. A third classification task trained to predict complex aneuploidy versus euploidy had an accuracy of 77·6% (95% CI 75·0-80·0; AUC 0·847; PPV 76·7%; NPV 78·0%). STORK-A reported accuracies of 63·4% (AUC 0·702) on the WCM-ES+ dataset and 65·7% (AUC 0·715) on the IVI Valencia dataset, when using an image, maternal age, and morphokinetic parameters, similar to the STORK-A test dataset accuracy of 67·8% (AUC 0·737), showing generalisability.
INTERPRETATION
As a proof of concept, STORK-A shows an ability to predict embryo ploidy in a non-invasive manner and shows future potential as a standardised supplementation to traditional methods of embryo selection and prioritisation for implantation or recommendation for PGT-A.
FUNDING
US National Institutes of Health.
Topics: United States; Pregnancy; Female; Humans; Male; Young Adult; Adult; Middle Aged; Retrospective Studies; Artificial Intelligence; Preimplantation Diagnosis; Semen; Ploidies; Blastocyst; Aneuploidy
PubMed: 36543475
DOI: 10.1016/S2589-7500(22)00213-8 -
Cells Jun 2023The adult heart is made up of cardiomyocytes (CMs) that maintain pump function but are unable to divide and form new myocytes in response to myocardial injury. In... (Review)
Review
The adult heart is made up of cardiomyocytes (CMs) that maintain pump function but are unable to divide and form new myocytes in response to myocardial injury. In contrast, the developmental cardiac tissue is made up of proliferative CMs that regenerate injured myocardium. , CMs during development are diploid and mononucleated. In response to cardiac maturation, CMs undergo polyploidization and binucleation associated with CM functional changes. The transition from mononucleation to binucleation coincides with unique metabolic changes and shift in energy generation. Recent studies provide evidence that metabolic reprogramming promotes CM cell cycle reentry and changes in ploidy and nucleation state in the heart that together enhances cardiac structure and function after injury. This review summarizes current literature regarding changes in CM ploidy and nucleation during development, maturation and in response to cardiac injury. Importantly, how metabolism affects CM fate transition between mononucleation and binucleation and its impact on cell cycle progression, proliferation and ability to regenerate the heart will be discussed.
Topics: Animals; Adult; Humans; Myocytes, Cardiac; Myocardium; Ploidies; Heart Injuries; Cell Cycle; Mammals
PubMed: 37371041
DOI: 10.3390/cells12121571 -
Bioinformatics (Oxford, England) Jul 2023The resemble between relatives computed from pedigree and genomic data is an important resource for geneticists and ecologists, who are interested in understanding how...
MOTIVATION
The resemble between relatives computed from pedigree and genomic data is an important resource for geneticists and ecologists, who are interested in understanding how genes influence phenotypic variation, fitness adaptation, and population dynamics.
RESULTS
The AGHmatrix software is an R package focused on the construction of pedigree (A matrix) and/or molecular markers (G matrix), with the possibility of building a combined matrix of pedigree corrected by molecular markers (H matrix). Designed to estimate the relationships for any ploidy level, the software also includes auxiliary functions related to filtering molecular markers, and checks pedigree errors in large data sets. After computing the relationship matrices, results from the AGHmatrix can be used in different contexts, including on prediction of (genomic) estimated breeding values and genome-wide association studies.
AVAILABILITY AND IMPLEMENTATION
AGHmatrix v2.1.0 is available under GPL-3 license in CRAN at https://cran.r-project.org/web/packages/AGHmatrix/index.html and also in GitHub at https://github.com/rramadeu/AGHmatrix. It has a comprehensive tutorial, and it follows with real data examples.
Topics: Genome-Wide Association Study; Software; Genomics; Ploidies; Pedigree
PubMed: 37471595
DOI: 10.1093/bioinformatics/btad445 -
Philosophical Transactions of the Royal... Dec 2016Rapid responses to acute stresses are essential for stress survival and are critical to the ability of fungal pathogens to adapt to new environments or hosts. The rapid... (Review)
Review
Rapid responses to acute stresses are essential for stress survival and are critical to the ability of fungal pathogens to adapt to new environments or hosts. The rapid emergence of drug resistance is used as a model for how fungi adapt and survive stress conditions that inhibit the growth of progenitor cells. Aneuploidy and loss of heterozygosity (LOH), which are large-scale genome shifts involving whole chromosomes or chromosome arms, occur at higher frequency than point mutations and have the potential to mediate stress survival. Furthermore, the stress of exposure to an antifungal drug can induce elevated levels of LOH and can promote the formation of aneuploids. This occurs via mitotic defects that first produce tetraploid progeny with extra spindles, followed by chromosome mis-segregation. Thus, drug exposure induces elevated levels of aneuploidy, which can alter the copy number of genes that improve survival in a given stress or drug. Selection then acts to increase the proportion of adaptive aneuploids in the population. Because aneuploidy is a common property of many pathogenic fungi, including those posing emerging threats to plants, animals and humans, we propose that aneuploid formation and LOH often accompanying it contribute to the rapid generation of diversity that can facilitate the emergence of fungal pathogens to new environmental niches and/or new hosts, as well as promote antifungal drug resistance that makes emerging fungal infections ever more difficult to contain.This article is part of the themed issue 'Tackling emerging fungal threats to animal health, food security and ecosystem resilience'.
Topics: Aneuploidy; Antifungal Agents; Biological Evolution; Drug Resistance, Fungal; Evolution, Molecular; Fungi; Phenotype; Ploidies
PubMed: 28080987
DOI: 10.1098/rstb.2015.0461 -
Developmental Cell Jun 2017Although haploidy has not been observed in vertebrates, its natural occurrence in various eukaryotic species that had diverged from diploid ancestors suggests that there... (Review)
Review
Although haploidy has not been observed in vertebrates, its natural occurrence in various eukaryotic species that had diverged from diploid ancestors suggests that there is an innate capacity for an organism to regain haploidy and that haploidy may confer evolutionary benefits. Haploid embryonic stem cells have been experimentally generated from mouse, rat, monkey, and humans. Haploidy results in major differences in cell size and gene expression levels while also affecting parental imprinting, X chromosome inactivation, and mitochondrial metabolism genes. We discuss here haploidy in evolution and the barriers to haploidy, in particular in the human context.
Topics: Animals; Diploidy; Embryonic Stem Cells; Genomic Imprinting; Haploidy; Humans; Pluripotent Stem Cells; X Chromosome Inactivation
PubMed: 28633015
DOI: 10.1016/j.devcel.2017.04.019 -
Current Issues in Molecular Biology 2016This article proposes the concept of genome network, describes different variations of the somatic genome network, and reviews the agricultural implications of such... (Review)
Review
This article proposes the concept of genome network, describes different variations of the somatic genome network, and reviews the agricultural implications of such variations. All genetic materials in a cell constitute the genome network of the cell and can jointly influence the cell's function and fate. The somatic genome of a plant is the genome network of cells in somatic tissues and of nonreproductive cells in pollen and ovules. Somatic genome variation (SGV, approximately equivalent to somagenetic variation) occurs at multiple levels, including stoichiometric, ploidy, and sequence variations. For a multicellular organism, the term "somatic genome variation" covers both the variation in part of the organism and the generation of new genotype individuals through somatic means from a sexually produced original genotype. For unicellular organisms, genome variation in somatic nuclei occurs at the whole organism level because there is only a single cell per individual. Growth, development and evolution of living organisms require both stability and instability of their genomes. Somatic genome variation displays many more attributes than genetic mutation and has strong implications for agriculture.
Topics: Agriculture; Animals; Evolution, Molecular; Genetic Variation; Genome; Humans; Livestock; Models, Genetic; Mutation; Ploidies
PubMed: 26636317
DOI: No ID Found -
Nucleus (Austin, Tex.) Dec 2023In adult mammals, many heart muscle cells (cardiomyocytes) are polyploid, do not proliferate (post-mitotic), and, consequently, cannot contribute to heart regeneration.... (Review)
Review
In adult mammals, many heart muscle cells (cardiomyocytes) are polyploid, do not proliferate (post-mitotic), and, consequently, cannot contribute to heart regeneration. In contrast, fetal and neonatal heart muscle cells are diploid, proliferate, and contribute to heart regeneration. We have identified interdependent changes of the nuclear lamina, nuclear pore complexes, and DNA-content (ploidy) in heart muscle cell maturation. These results offer new perspectives on how cells alter their nuclear transport and, with that, their gene regulation in response to extracellular signals. We present how changes of the nuclear lamina alter nuclear pore complexes in heart muscle cells. The consequences of these changes for cellular regeneration and stress response in the heart are discussed.
Topics: Animals; Nuclear Pore; Nuclear Lamina; Ploidies; Cell Differentiation; Lamins; Mammals
PubMed: 37606283
DOI: 10.1080/19491034.2023.2246310 -
Current Opinion in Microbiology Aug 2015Variation is the spice of life or, in the case of evolution, variation is the necessary material on which selection can act to enable adaptation. Karyotypic variation in... (Review)
Review
Variation is the spice of life or, in the case of evolution, variation is the necessary material on which selection can act to enable adaptation. Karyotypic variation in ploidy (the number of homologous chromosome sets) and aneuploidy (imbalance in the number of chromosomes) are fundamentally different than other types of genomic variants. Karyotypic variation emerges through different molecular mechanisms than other mutational events, and unlike mutations that alter the genome at the base pair level, rapid reversion to the wild type chromosome number is often possible. Although karyotypic variation has long been noted and discussed by biologists, interest in the importance of karyotypic variants in evolutionary processes has spiked in recent years, and much remains to be discovered about how karyotypic variants are produced and subsequently selected.
Topics: Cell Physiological Phenomena; Genetic Variation; Karyotype; Ploidies; Selection, Genetic
PubMed: 26321163
DOI: 10.1016/j.mib.2015.06.010 -
The Plant Journal : For Cell and... Apr 2012The study of plant biology in the 21st century is, and will continue to be, vastly different from that in the 20th century. One driver for this has been the use of... (Review)
Review
The study of plant biology in the 21st century is, and will continue to be, vastly different from that in the 20th century. One driver for this has been the use of genomics methods to reveal the genetic blueprints for not one but dozens of plant species, as well as resolving genome differences in thousands of individuals at the population level. Genomics technology has advanced substantially since publication of the first plant genome sequence, that of Arabidopsis thaliana, in 2000. Plant genomics researchers have readily embraced new algorithms, technologies and approaches to generate genome, transcriptome and epigenome datasets for model and crop species that have permitted deep inferences into plant biology. Challenges in sequencing any genome include ploidy, heterozygosity and paralogy, all which are amplified in plant genomes compared to animal genomes due to the large genome sizes, high repetitive sequence content, and rampant whole- or segmental genome duplication. The ability to generate de novo transcriptome assemblies provides an alternative approach to bypass these complex genomes and access the gene space of these recalcitrant species. The field of genomics is driven by technological improvements in sequencing platforms; however, software and algorithm development has lagged behind reductions in sequencing costs, improved throughput, and quality improvements. It is anticipated that sequencing platforms will continue to improve the length and quality of output, and that the complementary algorithms and bioinformatic software needed to handle large, repetitive genomes will improve. The future is bright for an exponential improvement in our understanding of plant biology.
Topics: Algorithms; Computational Biology; Epigenomics; Genome Size; Genome, Plant; Genomics; Plants; Ploidies; Sequence Analysis, DNA; Software; Transcriptome
PubMed: 22449051
DOI: 10.1111/j.1365-313X.2012.04894.x -
International Journal of Molecular... Mar 2022DNA replication during cell proliferation is 'vertical' copying, which reproduces an initial amount of genetic information. Polyploidy, which results from whole-genome... (Review)
Review
DNA replication during cell proliferation is 'vertical' copying, which reproduces an initial amount of genetic information. Polyploidy, which results from whole-genome duplication, is a fundamental complement to vertical copying. Both organismal and cell polyploidy can emerge via premature cell cycle exit or via cell-cell fusion, the latter giving rise to polyploid hybrid organisms and epigenetic hybrids of somatic cells. Polyploidy-related increase in biological plasticity, adaptation, and stress resistance manifests in evolution, development, regeneration, aging, oncogenesis, and cardiovascular diseases. Despite the prevalence in nature and importance for medicine, agri- and aquaculture, biological processes and epigenetic mechanisms underlying these fundamental features largely remain unknown. The evolutionarily conserved features of polyploidy include activation of transcription, response to stress, DNA damage and hypoxia, and induction of programs of morphogenesis, unicellularity, and longevity, suggesting that these common features confer adaptive plasticity, viability, and stress resistance to polyploid cells and organisms. By increasing cell viability, polyploidization can provide survival under stressful conditions where diploid cells cannot survive. However, in somatic cells it occurs at the expense of specific function, thus promoting developmental programming of adult cardiovascular diseases and increasing the risk of cancer. Notably, genes arising via evolutionary polyploidization are heavily involved in cancer and other diseases. Ploidy-related changes of gene expression presumably originate from chromatin modifications and the derepression of bivalent genes. The provided evidence elucidates the role of polyploidy in evolution, development, aging, and carcinogenesis, and may contribute to the development of new strategies for promoting regeneration and preventing cardiovascular diseases and cancer.
Topics: Adaptation, Physiological; Carcinogenesis; Cardiovascular Diseases; Diploidy; Humans; Neoplasms; Polyploidy
PubMed: 35408902
DOI: 10.3390/ijms23073542