Biology subjects

Shebl, O.

Publications and source records attributed to Shebl, O..

3 recordsLinked to original sources

bioRxiv2025

ImplantoMetrics - Multidimensional trophoblast invasion assessment by combining 3D-in-vitro modeling and deep learning analysis

Infertility affects millions of couples worldwide, and in vitro fertilization is a key therapeutic strategy for achieving parenthood. Despite advances, the first IVF attempt fails in [~]60% of patients, highlighting the need for innovative solutions to improve clinical outcomes. Challenges include the limited ability to study embryo implantation, inadequate methods to test therapeutic drugs, and lack of metrics to evaluate implantation images. To address these issues, we developed ImplantoMetrics, a Fiji plugin for quantitative assessment of trophoblast invasion in combination with a 3D-in-vitro model. ImplantoMetrics uses Convolutional Neural Network and XGBoosting to accurately measure multidimensional expansion patterns. It allows quantitative evaluation of therapeutic interventions, and enables a complex study of trophoblast invasion. Compared to manual methods, ImplantoMetrics is [~]13-times faster and reduces errors through automation. Beyond implantation research, ImplantoMetrics offers a comprehensive tool to study spheroid invasion in different biological contexts, as e.g. demonstrated here for cancer research.

developmental biology↗

bioRxiv2024

Mitochondrial DNA mutations in human oocytes undergo frequency-dependent selection but do not increase with age

Mitochondria, cellular powerhouses, harbor DNA (mtDNA) inherited from the mothers. MtDNA mutations can cause diseases, yet whether they increase with age in human germline cells--oocytes--remains understudied. Here, using highly accurate duplex sequencing of full-length mtDNA, we detected de novo mutations in single oocytes, blood, and saliva in women between 20 and 42 years of age. We found that, with age, mutations increased in blood and saliva but not in oocytes. In oocytes, mutations with high allele frequencies ([≥]1%) were less prevalent in coding than non-coding regions, whereas mutations with low allele frequencies (<1%) were more uniformly distributed along mtDNA, suggesting frequency-dependent purifying selection. In somatic tissues, mutations caused elevated amino acid changes in protein-coding regions, suggesting positive or destructive selection. Thus, mtDNA in human oocytes is protected against accumulation of mutations having functional consequences and with aging. These findings are particularly timely as humans tend to reproduce later in life. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/627454v1_ufig1.gif" ALT="Figure 1"> View larger version (40K): org.highwire.dtl.DTLVardef@18242f6org.highwire.dtl.DTLVardef@fa5a97org.highwire.dtl.DTLVardef@51a452org.highwire.dtl.DTLVardef@1fb2374_HPS_FORMAT_FIGEXP M_FIG C_FIG

genomics↗

bioRxiv2021

Discovery of an unusual high number of de novo mutations in sperm of older men using duplex sequencing

De novo mutations (DNMs) are an important player in heritable diseases and evolution. Of particular interest are highly recurrent DNMs associated with congenital disorders that have been described as selfish mutations expanding in the male germline, thus becoming more frequent with age. Here, we have adapted duplex sequencing (DS), an ultra-deep sequencing method that renders sequence information on both DNA strands; thus, one mutation can be reliably called in millions of sequenced bases. With DS, we examined [~]4.5 kb of the FGFR3 coding region in sperm DNA from older and younger donors. We identified sites with variant frequencies of 10-4 to 10-5, with an overall mutation frequency of the region of [~]6x10-7. Some of the substitutions were re-current and were found at a higher variant frequency in older donors than in younger ones, or exclusively, in older donors. Also, older donors harbored more mutations associated with congenital disorders. Other mutations were present in both age groups suggesting that these might result from a different mechanism (e.g., post-zygotic mosaicism). We also observed that independent of age, the frequency and deleteriousness of the mutational spectra was more similar to COSMIC than to gnomAD variants. Our approach is an important strategy to identify mutations that could be associated with a gain-of-function of the receptor tyrosine kinase activity, with unexplored consequences in a society with delayed fatherhood.

genetics↗