Biology subjects

Yang, Z.

Publications and source records attributed to Yang, Z..

634 records · Page 36Linked to original sources

bioRxiv2017

PANINI: Pangenome Neighbor Identification for Bacterial Populations

The standard workhorse for genomic analysis of the evolution of bacterial populations is phylogenetic modelling of mutations in the core genome. However, in the current era of population genomics, a notable amount of information about evolutionary and transmission processes in diverse populations can be lost unless the accessory genome is also taken into consideration. Here we introduce PANINI, a computationally scalable method for identifying the neighbours for each isolate in a data set using unsupervised machine learning with stochastic neighbour embedding. PANINI is browser-based and integrates with the Microreact platform for rapid online visualisation and exploration of both core and accessory genome evolutionary signals together with relevant epidemiological, geographic, temporal and other metadata. Several case studies with single-and multi-clone pneumococcal populations are presented to demonstrate ability to identify biologically important signals from gene content data. PANINI is available at http://panini.wgsa.net/ and code at http://gitlab.com/cgps/panini

microbiology↗

bioRxiv2017

P53 toxicity is a hurdle to CRISPR/CAS9 screening and engineering in human pluripotent stem cells

CRISPR/Cas9 has revolutionized our ability to engineer genomes and to conduct genome-wide screens in human cells. While some cell types are easily modified with Cas9, human pluripotent stem cells (hPSCs) poorly tolerate Cas9 and are difficult to engineer. Using a stable Cas9 cell line or transient delivery of ribonucleoproteins (RNPs) we achieved an average insertion or deletion efficiency greater than 80%. This high efficiency made it apparent that double strand breaks (DSBs) induced by Cas9 are toxic and kill most treated hPSCs. Cas9 toxicity creates an obstacle to the high-throughput use CRISPR/Cas9 for genome-engineering and screening in hPSCs. We demonstrated the toxic response is tp53-dependent and the toxic effect of tp53 severely reduces the efficiency of precise genome-engineering in hPSCs. Our results highlight that CRISPR-based therapies derived from hPSCs should proceed with caution. Following engineering, it is critical to monitor for tp53 function, especially in hPSCs which spontaneously acquire tp53 mutations.

molecular biology↗

bioRxiv2017

Neural decoding of visual stimuli varies with fluctuations in global network efficiency

Functional magnetic resonance imaging (fMRI) studies have shown that neural activity fluctuates spontaneously between different states of global synchronization over a timescale of several seconds. Such fluctuations generate transient states of high and low correlation across distributed cortical areas. It has been hypothesized that such fluctuations in global efficiency might alter patterns of activity in local neuronal populations elicited by changes in incoming sensory stimuli. To test this prediction, we used a linear decoder to discriminate patterns of neural activity elicited by face and motion stimuli presented periodically while participants underwent time-resolved fMRI. As predicted, decoding was reliably higher during states of high global efficiency than during states of low efficiency, and this difference was evident across both visual and non-visual cortical regions. The results indicate that slow fluctuations in global network efficiency are associated with variations in the pattern of activity across widespread cortical regions responsible for representing distinct categories of visual stimulus. More broadly, the findings highlight the importance of understanding the impact of global fluctuations in functional connectivity on specialised, stimulus driven neural processes.

neuroscience↗

bioRxiv2016

Segregation between the parietal memory network and the default mode network: Effects of spatial smoothing and model order in ICA

A brain network consisting of two key parietal nodes, the precuneus and the posterior cingulate cortex, has emerged from recent fMRI studies. Though it is anatomically adjacent to and spatially overlaps with the default mode network (DMN), its function has been associated with memory processing, and it has been referred to as the parietal memory network (PMN). Independent component analysis (ICA) is the most common data-driven method of extracting PMN and DMN simultaneously. However, the effects of data preprocessing and parameter determination in ICA on PMN-DMN segregation are completely unknown. Here, we employ three typical algorithms of group ICA to assess how spatial smoothing and model order influence the degree of PMN-DMN segregation. Our findings indicate that PMN and DMN can only be stably separated using a combination of low-level spatial smoothing and high-order model across the three ICA algorithms. We thus argue for more considerations on parametric settings for interpreting DMN data.

neuroscience↗