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Biology subjects

Zhan, Q.

Publications and source records attributed to Zhan, Q..

3 recordsLinked to original sources

Robust Automated Assessment of Human Blastocyst Quality using Deep Learning

Morphology assessment has become the standard method for evaluation of embryo quality and selecting human blastocysts for transfer in in vitro fertilization (IVF). This process is highly subjective for some embryos and thus prone to human bias. As a result, morphological assessment results may vary extensively between embryologists and in some cases may fail to accurately predict embryo implantation and live birth potential. Here we postulated that an artificial intelligence (AI) approach trained on thousands of embryos can reliably predict embryo quality without human intervention.\n\nTo test this hypothesis, we implemented an AI approach based on deep neural networks (DNNs). Our approach called STORK accurately predicts the morphological quality of blastocysts based on raw digital images of embryos with 98% accuracy. These results indicate that a DNN can automatically and accurately grade embryos based on raw images. Using clinical data for 2,182 embryos, we then created a decision tree that integrates clinical parameters such as embryo quality and patient age to identify scenarios associated with increased or decreased pregnancy chance. This IVF data-driven analysis shows that the chance of pregnancy varies from 13.8% to 66.3%.\n\nIn conclusion, our AI-driven approach provides a novel way to assess embryo quality and uncovers new, potentially personalized strategies to select embryos with an improved likelihood of pregnancy outcome.

bioinformatics

Tripolar mitosis drives the association between maternal genotypes of PLK4 and aneuploidy in human preimplantation embryos

Aneuploidy is prevalent in human preimplantation embryos and is the leading cause of pregnancy loss. Many aneuploidies arise during oogenesis, increasing in frequency with maternal age. Superimposed on these meiotic aneuploidies are a range of errors occurring during early mitotic divisions of the embryo, contributing to widespread chromosomal mosaicism. Here we reanalyzed a published dataset comprising preimplantation genetic testing for aneuploidy in 24,653 blastomere biopsies from day-3 cleavage-stage embryos, as well as 17,051 trophectoderm biopsies from day-5 blastocysts. We focused on complex abnormalities that affected multiple chromosomes simultaneously, seeking to quantify their incidences and gain insight into their mechanisms of formation. In addition to well-described patterns such as triploidy and haploidy, we identified 4.7% of day-3 blastomeres possessing karyotypes suggestive of tripolar mitosis in normally-fertilized diploid zygotes or descendant diploid cells. We further supported this hypothesis using time-lapse data from an intersecting set of 77 cleavage-stage embryos. The diploid tripolar signature was rare among day-5 blastocyst biopsies (0.5%), suggesting that complex aneuploidy generated by tripolar mitosis impairs cellular and/or early embryonic survival. Strikingly, we found that the tripolar mitosis mechanism is responsible for the previously described association with common maternal genetic variants spanning PLK4. Our findings are consistent with the role of PLK4 as the master regulator of centriole duplication with a known capacity to induce tripolar mitosis when mutated or mis-expressed. Taken together, we propose that tripolar mitosis is a key mechanism generating karyotype-wide aneuploidy in cleavage-stage embryos and implicate PLK4-mediated centrosome abnormality as a factor influencing its occurrence.

genetics

A novel method for large-scale identification of polymorphic microsatellites through comparative transcriptome analysis

Microsatellite (SSR) is one of the most popular markers for applied genetic research, but generally the current methods to develop SSRs are relatively time-consuming and expensive. Although high-throughput sequencing (HTS) approach has become a practical and relatively inexpensive option so far, only a small percentage of SSR markers turn out to be polymorphic. Here, we designed a new method to enrich polymorphic SSRs through the comparative transcriptome analysis. This program contains five main steps: 1) transcriptome data downloading or RNA-seq; 2) sequence assembly; 3) SSR mining and enrichment of sequences containing SSRs; 4) sequence alignment; 5) enrichment of sequences containing polymorphic SSRs. A validation experiment was performed and the results showed almost all markers (> 90%) that were indicated as putatively polymorphic by this method were indeed polymorphic. The frequency of polymorphic SSRs was significantly higher (P < 0.05) but the cost and running time were much lower than those of traditional and HTS approaches. The method has a practical value for polymorphic SSRs development and might be widely used for genetic analyses in any species.

bioinformatics