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Saary, P.

Publications and source records attributed to Saary, P..

2 recordsLinked to original sources

Estimating the quality of eukaryotic genomes recovered from metagenomic analysis

Eukaryotes make up a large fraction of microbial biodiversity. However, the field of metagenomics has been heavily biased towards the study of just the prokaryotic fraction. This focus has driven the necessary methodological developments to enable the recovery of prokaryotic genomes from metagenomes, which has reliably yielded genomes from thousands of novel species. More recently, microbial eukaryotes have gained more attention, but there is yet to be a parallel explosion in the number of eukaryotic genomes recovered from metagenomic samples. One of the current deficiencies is the lack of a universally applicable and reliable tool for the estimation of eukaryote genome quality. To address this need, we have developed EukCC, a tool for estimating the quality of eukaryotic genomes based on the dynamic selection of single copy marker gene sets, with the aim of applying it to metagenomics datasets. We demonstrate that our method outperforms current genome quality estimators and have applied EukCC to datasets from two different biomes to enable the identification of novel genomes, including a eukaryote found on the human skin and a Bathycoccus species obtained from a marine sample.

bioinformatics

Induced aneuploidy disrupts MCF10A acini formation and CCND1 expression

Abnormal karyotypes, namely aneuploidy, can be detected in nearly all cancer entities at different grades. The impact of these altering mutations on epigenetic regulation, especially on promoter-enhancer interactions are not well understood. Here, we applied a 3D model of MCF10A cells in a high-content screen to measure induced aneuploidy by RNA interference of 82 mitotic genes associated with aneuploidy and breast cancer. Perturbation of ESPL1 and TOP2A expression led to increased mitotic instability and subsequent aneuploidy and polylobed nuclei. During acinus formation these polylobed cells disrupted proper acinus rotation inhibiting the development of a hollow lumen and a polarized outer cell layer. Further, gene expression profiling identified upregulated CCND1 among other breast cancer related genes. We show that acquisition of aneuploidy affects the morphogenesis of MCF10A acini and expression of cancer relevant genes. By conducting 4C chromosome capturing experiments we linked the alteration of interactions of the promoter region to CCND1 upregulation.

cancer biology