Synthetic chromosome fusion: Effects on mitotic and meiotic genome structure and function

We designed and synthesized synI, which is ~21.6% shorter than native chrI, the smallest chromosome in Saccharomyces cerevisiae. SynI was designed for attachment to another synthetic chromosome due to concerns surrounding potential instability and karyotype imbalance and is now attached to synIII, yielding the first synthetic yeast fusion chromosome. Additional fusion chromosomes were constructed to study nuclear function. ChrIII-I and chrIX-III-I fusion chromosomes have twisted structures, which depend on silencing protein Sir3. As a smaller chromosome, chrI also faces special challenges in assuring meiotic crossovers required for efficient homolog disjunction. Centromere deletions into fusion chromosomes revealed opposing effects of core centromeres and pericentromeres in modulating deposition of the crossover-promoting protein Red1. These effects extend over 100 kb and promote disproportionate Red1 enrichment, and thus crossover potential, on small chromosomes like chrI. These findings reveal the power of synthetic genomics to uncover new biology and deconvolute complex biological systems  </p

Octree Representation Improves Data Fidelity of Cardiac CT Images and Convolutional Neural Network Semantic Segmentation of Left Atrial and Ventricular Chambers

PurposeTo assess whether octree representation and octree-based convolutional neural networks (CNNs) improve segmentation accuracy of three-dimensional images.Materials and methodsCardiac CT angiographic examinations from 100 patients (mean age, 67 years ± 17 [standard deviation]; 60 men) performed between June 2012 and June 2018 with semantic segmentations of the left ventricular (LV) and left atrial (LA) blood pools at the end-diastolic and end-systolic cardiac phases were retrospectively evaluated. Image quality (root mean square error [RMSE]) and segmentation fidelity (global Dice and border Dice coefficients) metrics of the octree representation were compared with spatial downsampling for a range of memory footprints. Fivefold cross-validation was used to train an octree-based CNN and CNNs with spatial downsampling at four levels of image compression or spatial downsampling. The semantic segmentation performance of octree-based CNN (OctNet) was compared with the performance of U-Nets with spatial downsampling.ResultsOctrees provided high image and segmentation fidelity (median RMSE, 1.34 HU; LV Dice coefficient, 0.970; LV border Dice coefficient, 0.843) with a reduced memory footprint (87.5% reduction). Spatial downsampling to the same memory footprint had lower data fidelity (median RMSE, 12.96 HU; LV Dice coefficient, 0.852; LV border Dice coefficient, 0.310). OctNet segmentation improved the border segmentation Dice coefficient (LV, 0.612; LA, 0.636) compared with the highest performance among U-Nets with spatial downsampling (Dice coefficients: LV, 0.579; LA, 0.592).ConclusionOctree-based representations can reduce the memory footprint and improve segmentation border accuracy.Keywords CT, Cardiac, Segmentation, Supervised Learning, Convolutional Neural Network (CNN), Deep Learning Algorithms, Machine Learning Algorithms© RSNA, 2021

Synthetic chromosome fusion: Effects on mitotic and meiotic genome structure and function

International audienceWe designed and synthesized synI, which is ∼21.6% shorter than native chrI, the smallest chromosome in Saccharomyces cerevisiae. SynI was designed for attachment to another synthetic chromosome due to concerns surrounding potential instability and karyotype imbalance and is now attached to synIII, yielding the first synthetic yeast fusion chromosome. Additional fusion chromosomes were constructed to study nuclear function. ChrIII-I and chrIX-III-I fusion chromosomes have twisted structures, which depend on silencing protein Sir3. As a smaller chromosome, chrI also faces special challenges in assuring meiotic crossovers required for efficient homolog disjunction. Centromere deletions into fusion chromosomes revealed opposing effects of core centromeres and pericentromeres in modulating deposition of the crossover-promoting protein Red1. These effects extend over 100 kb and promote disproportionate Red1 enrichment, and thus crossover potential, on small chromosomes like chrI. These findings reveal the power of synthetic genomics to uncover new biology and deconvolute complex biological systems