Biology subjects

Liang, Z.

Publications and source records attributed to Liang, Z..

6 recordsLinked to original sources

bioRxiv2017

N6-Methyladenine DNA Modification in Human Genome

DNA N6-methyladenine (6mA) modification is the most prevalent DNA modification in prokaryotes, but whether it exists in human cells and whether it plays a role in human diseases remain enigmatic. Here, we showed that 6mA is extensively present in human genome, and we cataloged 881,240 6mA sites accounting for [~]0.051% of the total adenines. [G/C]AGG[C/T] was the most significantly associated motif with 6mA modification. 6mA sites were enriched in the coding regions and mark actively transcribed genes in human cells. We further found that DNA N6-methyladenine and N6-demethyladenine modification in human genome were mediated by methyltransferase N6AMT1 and demethylase ALKBH1, respectively. The abundance of 6mA was significantly lower in cancers, accompaning with decreased N6AMT1 and increased ALKBH1 levels, and down-regulation of 6mA modification levels promoted tumorigenesis. Collectively, our results demonstrate that DNA 6mA modification is extensively present in human cells and the decrease of genomic DNA 6mA promotes human tumorigenesis.

genomics↗

bioRxiv2017

Conventional and hyperspectral time-series imagingof maize lines widely used in field trials

Maize (Zea mays ssp. mays) is one of three crops, along with rice and wheat, responsible for more than 1/2 of all calories consumed around the world. Increasing the yield and stress tolerance of these crops is essential to meet the growing need for food. The cost and speed of plant phenotyping is currently the largest constraint on plant breeding efforts. Datasets linking new types of high throughput phenotyping data collected from plants to the performance of the same genotypes under agronomic conditions across a wide range of environments are essential for developing new statistical approaches and computer vision based tools. A set of maize inbreds - primarily recently off patent lines - were phenotyped using a high throughput platform at University of Nebraska-Lincoln. These lines have been previously subjected to high density genotyping, and scored for a core set of 13 phenotypes in field trials across 13 North American states in two years by the Genomes to Fields consortium. A total of 485 GB of image data including RGB, hyperspectral, fluorescence and thermal infrared photos has been released. Correlations between image-based measurements and manual measurements demonstrated the feasibility of quantifying variation in plant architecture using image data. However, naive approaches to measuring traits such as biomass can introduce nonrandom measurement errors confounded with genotype variation. Analysis of hyperspectral image data demonstrated unique signatures from stem tissue. Integrating heritable phenotypes from high-throughput phenotyping data with field data from different environments can reveal previously unknown factors influencing yield plasticity.

plant biology↗

bioRxiv2017

Simultaneous GCaMP6-based Fiber Photometry and fMRI in Rats

Understanding the relationship between neural and vascular signals is essential for interpretation of functional MRI (fMRI) results with respect to underlying neuronal activity. Simultaneously measuring neural activity using electrophysiology with fMRI has been highly valuable in elucidating the neural basis of the blood oxygenation-level dependent (BOLD) signal. However, this approach is also technically challenging due to the electromagnetic interference that is observed in electrophysiological recordings during MRI scanning. Recording optical correlates of neural activity, such as calcium signals, avoids this issue, and has opened a new avenue to simultaneously acquire neural and BOLD signals. The present study is the first to demonstrate the feasibility of simultaneously and repeatedly acquiring calcium and BOLD signals in animals using a genetically encoded calcium indicator, GCaMP6. This approach was validated with a visual stimulation experiment, during which robust increases of both calcium and BOLD signals in the superior colliculus were observed. In addition, repeated measurement in the same animal demonstrated reproducible calcium and BOLD responses to the same stimuli. Taken together, simultaneous GCaMP6-based fiber photometry and fMRI recording presents a novel, artifact-free approach to simultaneously measuring neural and fMRI signals. Furthermore, given the cell-type specificity of GCaMP6, this approach has the potential to mechanistically dissect the contributions of individual neuron populations with respect to BOLD signal, and ultimately reveal its underlying neural mechanisms.

neuroscience↗

bioRxiv2017

Differentially regulated ortholog analysis demonstrations that early transcriptional responses to cold have diverged slowly than downstream responses in panicoid grasses

Cross-species comparisons of transcriptional regulation have the potential to identify functionally constrained transcriptional regulation and genes for which a change in transcriptional regulation correlates with a change in phenotype. Conventional differential gene expression analysis and a different approach based on identifying differentially regulated orthologs (DROs) are compared using paired time course gene expression data from two species which respond similarly to cold - maize (Zea mays) and sorghum (Sorghum bicolor). Both approaches suggest that, for genes conserved at syntenic positions for millions of years, the majority of cold responsive transcriptional regulation is species specific, although initial transcriptional responses to cold appear to be more conserved between the two species than later responses. In maize, the promoters of genes with both species specific and conserved transcriptional responses to cold tend to contain more micrococcal nuclease hypersensitive sites in their promoters, a proxy for open chromatin. However, genes with conserved patterns of transcriptional regulation between the two species show lower ratios of nonsynonymous to synonymous substitutions consistent with this population of genes experiencing stronger purifying selection. We hypothesize that cold responsive transcriptional regulation is a fast evolving and largely neutral molecular phenotype for the majority of genes in Andropogoneae, while a smaller core set of genes involved in perceiving and responding to cold stress are subject to functionally constrained cold responsive regulation.

genetics↗

bioRxiv2017

STAG-CNS: An Order-Aware Conserved Non-coding Sequences Discovery Tool For Arbitrary Numbers of Species

One method for identifying noncoding regulatory regions of a genome is to quantify rates of divergence between related species, as functional sequence will generally diverge more slowly. Most approaches to identifying these conserved noncoding sequences (CNS) based on alignment have had relatively large minimum sequence lengths ([>=]15 base pair) compared to the average length of known transcription factor binding sites. To circumvent this constraint, STAG-CNS integrates data from the promoters of conserved orthologous genes in three or more species simultaneously. Using data from up to six grass species made it possible to identify conserved sequences as short at 9 base pairs with FDP [<=] 0.05. These CNS exhibit greater overlap with open chromatin regions identified using DNase I hypersensitivity, and are enriched in the promoters of genes involved in transcriptional regulation. STAG-CNS was further employed to characterize loss of conserved noncoding sequences associated with retained duplicate genes from the ancient maize polyploidy. Genes with fewer retained CNS show lower overall expression, although this bias is more apparent in samples of complex organ systems containing many cell types, suggesting CNS loss may correspond to a reduced number of expression contexts rather than lower expression levels across the entire ancestral expression domain.

bioinformatics↗

bioRxiv2017

mRNA And Long Non-Coding RNA Expression Profiles In Rats Reveal Inflammatory Features In Sepsis-Associated Encephalopathy

BackgroundSepsis-associated encephalopathy (SAE) is related to cognitive sequelae in patients in the intensive care unit (ICU) and can have serious impacts on quality of life after recovery. Although various pathogenic pathways are involved in SAE development, little is known concerning the global role of long non-coding RNAs (lncRNAs) in SAE.\n\nMethodsHerein, we employed transcriptome sequencing approaches to characterize the effects of lipopolysaccharide (LPS) on lncRNA expression patterns in brain tissue isolated from Sprague-Dawley (SD) rats with and without SAE. We performed high-throughput transcriptome sequencing after LPS was intraperitoneally injected and predicted targets and functions using bioinformatics tools. Subsequently, we explored the results in detail according to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses.\n\nResultsLncRNAs were differentially expressed in brain tissue after LPS treatment. After 6 h of LPS exposure, expression of 400 lncRNAs were significantly changed, including an increase in 316 lncRNAs and a decrease in 84 lncRNAs. In addition, 155 mRNAs were differentially expressed, with 84 up-regulated and 71 down-regulated. At 24 h post-treatment, expression of 117 lncRNAs and 57 mRNAs was consistently elevated, while expression of 79 lncRNAs and 21 mRNAs was decreased (change > 1.5-fold; p < 0.05). We demonstrated for the first time that differentially expressed lncRNAs were predicted to be enriched in a post-chaperonin tubulin folding pathway (GO : 007023), which is closely related to the key step in the tubulin folding process.\n\nInterestingly, the predicted pathway (KEGG 04360: axon guidance) was significantly changed under the same conditions. These results reveal that LPS might influence the construction and polarization of microtubules, which exert predominant roles in synaptogenesis and related biofunctions in the rodent central nervous system (CNS).\n\nConclusionsAn inventory of LPS-modulated expression profiles from the rodent CNS is an important step toward understanding the function of mRNAs, including lncRNAs, and suggests that microtubule malformation and dysfunction may be involved in SAE pathogenesis.

genomics↗