Biology subjects

Xia, Y.

Publications and source records attributed to Xia, Y..

221 records · Page 13Linked to original sources

bioRxiv2017

Tracking the dynamic functional connectivity structure of the human brain across the adult lifespan

The transition from early adulthood to older is marked by pronounced functional and structural brain transformations that impact cognition and behaviour. Here, we use dynamic functional network connectivity method to examine resting state functional network changes over aging process. In general, the features of dynamic functional states are generally varying across ages, such as the frequency of expression and the amount of time spent in the certain state. Increasing age is associated with less variability of functional state across time at rest period. From age point of view, examining the age-related difference of topology index revealed 19-30 age range has the significant largest global efficiency, largest local efficiency of default-mode network (DMN), cognitive control network (CCN) and salience network (SN). As for functional states, one state displayed the whole positive connectivity, in the meantime, it has the largest global efficiency and local efficiency of three subnetworks. Besides, the frequency of another state was negatively correlated to the box block (The Wechsler Adult Intelligence Scale subset, which is thought to evaluate fine motor skills, processing speed, and visuospatial ability), while positively correlated with age, and the box block was inversely correlated to age. The results suggested that cognitive aging may be characterized by the dynamic functional network connectivity. Taken together, these findings suggested the importance of a dynamic approach to understanding cognitive aging in lifespan.

neuroscience↗

bioRxiv2017

The pomegranate (Punica granatum L.) genome provides insights into fruit quality and ovule developmental biology

Pomegranate (Punica granatum L.) with an uncertain taxonomic status has an ancient cultivation history, and has become an emerging fruit due to its attractive features such as the bright red appearance and the high abundance of medicinally valuable ellagitannin-based compounds in its peel and aril. However, the absence of genomic resources has restricted further elucidating genetics and evolution of these interesting traits. Here we report a 274-Mb high-quality draft pomegranate genome sequence, which covers approximately 81.5% of the estimated 336 Mb genome, consists of 2,177 scaffolds with an N50 size of 1.7 Mb, and contains 30,903 genes. Phylogenomic analysis supported that pomegranate belongs to the Lythraceae family rather than the monogeneric Punicaceae family, and comparative analyses showed that pomegranate and Eucalyptus grandis shares the paleotetraploidy event. Integrated genomic and transcriptomic analyses provided insights into the molecular mechanisms underlying the biosynthesis of ellagitannin-based compounds, the color formation in both peels and arils during pomegranate fruit development, and the unique ovule development processes that are characteristic of pomegranate. This genome sequence represents the first reference in Lythraceae, providing an important resource to expand our understanding of some unique biological processes and to facilitate both comparative biology studies and crop breeding.

genomics↗

bioRxiv2017

Positional effects revealed in Illumina Methylation Array and the impact on analysis

With the evolution of rapid epigenetic research, Illumina Infinium HumanMethylation BeadChips have been widely used to study DNA methylation. However, in evaluating the accuracy of this method, we found that the commonly used Illumina HumanMethylation BeadChips are substantially affected by positional effects; the DNA samples location in a chip affects the measured methylation levels. We analyzed three HumanMethylation450 and three HumanMethylation27 datasets by using four methods to prove the existence of positional effects. Three datasets were analyzed further for technical replicate analysis or differential methylation CpG sites analysis. The pre- and post-correction comparisons indicate that the positional effects could alter the measured methylation values and downstream analysis results. Nevertheless, ComBat, linear regression and functional normalization could all be used to minimize such artifact. We recommend performing ComBat to correct positional effects followed by the correction of batch effects in data preprocessing as this procedure slightly outperforms the others. In addition, randomizing the sample placement should be a critical laboratory practice for using such experimental platforms. Code for our method is freely available at: https://github.com/ChuanJ/posibatch.

bioinformatics↗

bioRxiv2017

Contextual diversity of the human cell-essential proteome

Essential genes define central biological functions required for cell growth, proliferation and survival, but the nature of gene essentiality across human cell types is not well understood. We assessed essential gene function in a Cas9-inducible human B-cell lymphoma cell line using an extended knockout (EKO) library of 278,754 sgRNAs that targeted 19,084 RefSeq genes, 20,852 alternatively-spliced exons and 3,872 hypothetical genes. A new statistical analysis tool called RANKS identified 2,280 essential genes, 234 of which had not been reported previously. Essential genes exhibited a bimodal distribution across 10 cell lines screened in different studies, consistent with a continuous variation in essentiality as a function of cell type. Genes essential in more lines were associated with more severe fitness defects and encoded the evolutionarily conserved structural cores of protein complexes. Genes essential in fewer lines tended to form context-specific modules and encode subunits at the periphery of essential complexes. The essentiality of individual protein residues across the proteome correlated with evolutionary conservation, structural burial, modular domains, and protein interaction interfaces. Many alternatively-spliced exons in essential genes were dispensable and tended to encode disordered regions. We also detected a significant fitness defect for 44 newly evolved hypothetical reading frames. These results illuminate the nature and evolution of essential gene functions in human cells.

genomics↗

bioRxiv2016

DNA damage in 3D constricted migration or after lamin-A depletion in 2D: shared mechanisms of repair factor mis-localization under nuclear stress

Cells that migrate through small, rigid pores and that have normal levels of the nuclear structure protein lamin-A exhibit an increase in DNA damage, which is also observed with lamin-A depletion in diseases such as cancer and with many lamin-A mutations. Here we show nuclear envelope rupture is a shared feature that increases in standard culture after lamin-A knockdown, which causes nuclear loss of multiple DNA repair factors and increased DNA damage. Some repair factors are merely mis-localized to cytoplasm whereas others are partially depleted unless rescued by lamin-A expression. Compared to standard cultures on rigid glass coverslips, the growth of lamin-A low cells on soft matrix relaxes cytoskeletal stress on the nucleus, suppresses the mis-localization of DNA repair factors, and minimizes DNA damage nearly to wildtype levels. Conversely, constricted migration of the lamin-A low cells causes abnormally high levels of DNA damage, consistent with sustained loss of repair factors. The findings add insight into why monogenic progeroid syndromes that often associate with increased DNA damage and predominantly impact cells in stiff tissues result from mutations only in lamin-A or DNA repair factors.

cell biology↗