Biology subjects

Wei, L.

Publications and source records attributed to Wei, L..

11 recordsLinked to original sources

bioRxiv2018

Cytologic, Genetic, and Proteomic Analysis of a Yellow Leaf Mutant of Sesame (Sesamum indicum L.), Siyl-1

Leaf color mutation in sesame always affects the growth and development of plantlets, and their yield. To clarify the mechanisms underlying leaf color regulation in sesame, we analyzed a yellow-green leaf mutant. Genetic analysis of the mutant selfing revealed 3 phenotypes--YY, light-yellow (lethal); Yy, yellow-green; and yy, normal green--controlled by an incompletely dominant nuclear gene, Siyl-1. In YY and Yy, the number and morphological structure of the chloroplast changed evidently, with disordered inner matter, and significantly decreased chlorophyll content. To explore the regulation mechanism of leaf color mutation, the proteins expressed among YY, Yy, and yy were analyzed. All 98 differentially expressed proteins (DEPs) were classified into 5 functional groups, in which photosynthesis and energy metabolism (82.7%) occupied a dominant position. Our findings provide the basis for further molecular mechanism and biochemical effect analysis of yellow leaf mutants in plants.

genetics↗

bioRxiv2018

Regulatory networks of gene expression in maize (Zea mays) under drought stress and re-watering

Drought can severely limit plant growth and production. However, few studies have investigated gene expression profiles in maize during drought/re-watering. We compared drought-treated and water-sufficient maize plants by measuring their leaf relative water content, superoxide dismutase and peroxidase activities, proline content, and leaf gas exchange parameters (photosynthetic rates, stomatal conductance, and transpiration rates). We conducted RNA sequencing analyses to elucidate gene expression profiles and identify miRNAs that might be related to drought resistance. A GO enrichment analysis showed that the common DEGs (differently expressed genes) between drought-treated and control plants were involved in response to stimulus, cellular process, metabolic process, cell part, and binding and catalytic activity. Analyses of gene expression profiles revealed that 26 of the DEGs under drought encoded 10 enzymes involved in proline synthesis, suggesting that increased proline synthesis was a key part of the drought response. We also investigated cell wall-related genes and transcription factors regulating abscisic acid-dependent and -independent pathways. The expression profiles of the miRNAs miR6214-3p, miR5072-3p, zma-miR529-5p, zma-miR167e-5p, zma-miR167f-5p, and zma-miR167j-5p and their relevant targets under drought conditions were analyzed. These results provide new insights into the molecular mechanisms of drought tolerance, and may identify new targets for breeding drought-tolerant maize lines.\n\nAbbreviationsleaf relative water content: RWC, superoxide dismutase activity: SOD, peroxidase activity: POD, proline content: Pro, photosynthetic rates: Pn, stomatal conductance: Cond, transpiration rates: Tr.; quantitative real-time polymerase chain reaction: qPCR; abscisic acid; ABA; polyethylene glycol :PEG; Principal component analysis :PCA; polyacrylamide gel electrophoresis :PAGE\n\nHighlightThe study of physiology and molecular mechanism of maize laid a theoretical foundation for drought resistance breeding under drought stress and re-watering.

genomics↗

bioRxiv2018

Klebsiella huaxiensis sp. nov., recovered from human urine

A Klebsiella strain, WCHKl090001, was recovered from a human urine sample in China in 2017. Phylogenetic analysis based on gyrA and rpoB housekeeping genes revealed that the strain was distinct from any previously described species of the genus Klebsiella though it was clustered with the Klebsiella oxytoca phylogroup including Klebsiella grimontii, Klebsiella michiganensis, and Klebsiella oxytoca. The whole genome sequence of strain WCHKl090001 has an up to 87.18% average nucleotide identity with those of type strains of all known Klebsiella species. In silico DNA-DNA hybridization (isDDH) values between strain WCHKl090001 and type strains of all known Klebsiella species range from 22.3 to 35.2%. Strain WCHKl090001 could be distinguished from species of the Klebsiella oxytoca phylogroup by its negative Voges-Proskauer reaction. Genotypic and phenotypic characteristics from this study indicate that strain WCHKl090001 should be considered to represent a novel species of the genus Klebsiella, for which the name Klebsiella huaxiensis sp. nov. is proposed. The type strain is WCHKl090001T (=GDMCC1.1379T = CCTCC AB 2018106 T).

microbiology↗

bioRxiv2018

Distinctive types of postzygotic single-nucleotide mosaicisms in healthy individuals revealed by genome-wide profiling of multiple organs

Postzygotic single-nucleotide mosaicisms (pSNMs) have been extensively studied in tumors and are known to play critical roles in tumorigenesis. However, the patterns and origin of pSNMs in normal organs of healthy humans remain largely unknown. Using whole-genome sequencing and ultra-deep amplicon re-sequencing, we identified and validated 164 pSNMs from 27 postmortem organ samples obtained from five healthy donors. The mutant allele fractions ranged from 1.0% to 29.7%. Inter- and intra-organ comparison revealed two distinctive types of pSNMs, with about half originating during early embryogenesis (embryonic pSNMs) and the remaining more likely to result from clonal expansion events that had occurred more recently (clonal expansion pSNMs). Compared to clonal expansion pSNMs, embryonic pSNMs had higher proportion of C>T mutations with elevated mutation rate at CpG sites. We observed differences in replication timing between these two types of pSNMs, with embryonic and clonal expansion pSNMs enriched in early- and late-replicating regions, respectively. An increased number of embryonic pSNMs were located in open chromatin states and topologically associating domains that transcribed embryonically. Our findings provide new insights into the origin and spatial distribution of postzygotic mosaicism during normal human development.\n\nAuthor SummaryGenomic mosaicism led by postzygotic mutation is the major cause of cancers and many non-cancer developmental disorders. Theoretically, postzygotic mutations should be accumulated during the developmental process of healthy individuals, but the genome-wide characterization of postzygotic mosaicisms across many organ types of the same individual remained limited. In this study, we identified and validated two types of postzygotic mosaicism from the whole-genomes of 27 organs obtained from five healthy donors. We further found that the postzygotic mosaicisms arising during early embryogenesis and later clonal expansion events show distinct genomic patterns in mutation spectrum, replication timing, and chromatin status.

genomics↗

bioRxiv2018

Multidirectional digital scanned light-sheet microscopy enables uniform fluorescence excitation and contrast-enhanced imaging

Light-sheet fluorescence microscopy (LSFM) has emerged as a powerful method for rapid and optically efficient 3D microscopy. Initial LSFM designs utilized a static sheet of light, termed selective plane illumination microscopy (SPIM), which exhibited shadowing artifacts and deteriorated contrast due to light scattering. These issues have been addressed, in part, by multidirectional selective plane illumination microscopy (mSPIM), in which rotation of the light sheet is used to mitigate shadowing artifacts, and digital scanned light-sheet microscopy (DSLM), in which confocal line detection is used to reject scattered light. Here we present a simple passive multidirectional digital scanned light-sheet microscopy (mDSLM) architecture that combines the benefits of mSPIM and DSLM. By utilizing an elliptical Gaussian beam with increased angular diversity in the imaging plane, mDSLM provides shadow-free contrast-enhanced imaging of fluorescently labeled samples.\n\nOne Sentence SummaryGlaser et al. describe a light-sheet microscopy architecture that enables passive multidirectional illumination with confocal line detection to enable both uniform fluorescence excitation and contrast-enhanced imaging of fluorescently labeled samples.

bioengineering↗

bioRxiv2018

Regulation by competition: a hidden layer of gene regulatory network

Molecular competition is ubiquitous, essential and multifunctional throughout diverse biological processes. Competition brings about trade-offs of shared limited resources among the cellular components, and it thus introduce a hidden layer of regulatory mechanism by connecting components even without direct physical interactions. By abstracting the analogous competition mechanism behind diverse molecular systems, we built a unified coarse-grained competition motif model to systematically compare experimental evidences in these processes and analyzed general properties shared behind them. We could predict in what molecular environments competition would reveal threshold behavior or display a negative linear dependence. We quantified how competition can shape regulator-target dose-response curve, modulate dynamic response speed, control target expression noise, and introduce correlated fluctuations between targets. This work uncovered the complexity and generality of molecular competition effect, which might act as a hidden regulatory mechanism with multiple functions throughout biological networks in both natural and synthetic systems.

systems biology↗

bioRxiv2017

Neural network control of focal position during time-lapse microscopy of cells

Live-cell microscopy is quickly becoming an indispensable technique for studying the dynamics of cellular processes. Maintaining the specimen in focus during image acquisition is crucial for high-throughput applications, especially for long experiments or when a large sample is being continuously scanned. Automated focus control methods are often expensive, imperfect, or ill-adapted to a specific application and are a bottleneck for widespread adoption of high-throughput, live-cell imaging. Here, we demonstrate a neural network approach for automatically maintaining focus during bright-field microscopy. Z-stacks of yeast cells growing in a microfluidic device were collected and used to train a convolutional neural network to classify images according to their z-position. We studied the effect on prediction accuracy of the various hyperparameters of the neural network, including downsampling, batch size, and z-bin resolution. The network was able to predict the z-position of an image with {+/-}1 m accuracy, outperforming human annotators. Finally, we used our neural network to control microscope focus in real-time during a 24 hour growth experiment. The method robustly maintained the correct focal position compensating for 40 m of focal drift and was insensitive to changes in the field of view. Only ~100 annotated z-stacks were required to train the network making our method quite practical for custom autofocus applications.

cell biology↗

bioRxiv2017

Imaging-Genomics Study Of Head-Neck Squamous Cell Carcinoma: Associations Between Radiomic Phenotypes And Genomic Mechanisms Via Integration Of TCGA And TCIA

PurposeRecent data suggest that imaging radiomics features for a tumor could predict important genomic biomarkers. Understanding the relationship between radiomic and genomic features is important for basic cancer research and future patient care. For Head and Neck Squamous Cell Carcinoma (HNSCC), we perform a comprehensive study to discover the imaging-genomics associations and explore the potential of predicting tumor genomic alternations using radiomic features.\n\nMethodsOur retrospective study integrates whole-genome multi-omics data from The Cancer Genome Atlas (TCGA) with matched computed tomography imaging data from The Cancer Imaging Archive (TCIA) for the same set of 126 HNSCC patients. Linear regression analysis and gene set enrichment analysis are used to identify statistically significant associations between radiomic imaging features and genomic features. Random forest classifier is used to predict two key HNSCC molecular biomarkers, the status of human papilloma virus (HPV) and disruptive TP53 mutation, based on radiomic features.\n\nResultsWide-spread and statistically significant associations are discovered between genomic features (including miRNA expressions, protein expressions, somatic mutations, and transcriptional activities, copy number variations, and promoter region DNA methylation changes of pathways) and radiomic features characterizing the size, shape, and texture of tumor. Prediction of HPV and TP53 mutation status using radiomic features achieves an area under the receiver operating characteristics curve (AUC) of 0.71 and 0.641, respectively.\n\nConclusionOur analysis suggests that radiomic features are associated with genomic characteristics in HNSCC and provides justification for continued development of radiomics as biomarkers for relevant genomic alterations in HNSCC.

cancer biology↗

bioRxiv2017

TCGA-Assembler 2: Software Pipeline for Retrieval and Processing of TCGA/CPTAC Data

MotivationThe Cancer Genome Atlas (TCGA) program has produced huge amounts of cancer genomics data providing unprecedented opportunities for research. In 2014, we developed TCGA-Assembler (Zhu et al, 2014), a software pipeline for retrieval and processing of public TCGA data. In 2016, TCGA data were transferred from the TCGA data portal to the Genomic Data Commons (GDC), which is supported by a different set of data storage and retrieval mechanisms. In addition, new proteomics data of TCGA samples have been generated by the Clinical Proteomic Tumor Analysis Consortium (CPTAC) program, which were not available for downloading through TCGA-Assembler. It is desirable to acquire and integrate data from both GDC and CPTAC.\n\nResultsWe develop TCGA-Assembler 2 (TA2) to automatically download and integrate data from GDC and CPTAC. We make substantial improvement on the functionality of TA2 to enhance user experience and software performance. TA2 together with its previous version have helped more than 2,000 researchers from 64 countries to access and utilize TCGA and CPTAC data in their research. Availability of TA2 will continue to allow existing and new users to conduct reproducible research based on TCGA and CPTAC data.\n\nAvailabilityhttp://www.compgenome.org/TCGA-Assembler/\n\nContactkoaeraser@gmail.com or zhuyitan@gmail.com

bioinformatics↗

bioRxiv2017

DNA 5-Hydroxymethylcytosines from Cell-free Circulating DNA as Diagnostic Biomarkers for Human Cancers

DNA modifications such as 5-methylcytosines (5mC) and 5-hydroxymethylcytosines (5hmC) are epigenetic marks known to affect global gene expression in mammals(1, 2). Given their prevalence in the human genome, close correlation with gene expression, and high chemical stability, these DNA epigenetic marks could serve as ideal biomarkers for cancer diagnosis. Taking advantage of a highly sensitive and selective chemical labeling technology(3), we report here genome-wide 5hmC profiling in circulating cell-free DNA (cfDNA) and in genomic DNA of paired tumor/adjacent tissues collected from a cohort of 90 healthy individuals and 260 patients recently diagnosed with colorectal, gastric, pancreatic, liver, or thyroid cancer. 5hmC was mainly distributed in transcriptionally active regions coincident with open chromatin and permissive histone modifications. Robust cancer-associated 5hmC signatures in cfDNA were identified with specificity for different cancers. 5hmC-based biomarkers of circulating cfDNA demonstrated highly accurate predictive value for patients with colorectal and gastric cancers versus healthy controls, superior to conventional biomarkers, and comparable to 5hmC biomarkers from tissue biopsies. This new strategy could lead to the development of effective blood-based, minimally-invasive cancer diagnosis and prognosis approaches.

cancer biology↗

bioRxiv2016

A compound that directly and selectively stalls PCSK9 translation

Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) plays a key role in regulating the levels of plasma low density lipoprotein cholesterol (LDL-C). Here we demonstrate that the compound PF-06446846 inhibits translation of PCSK9 by inducing the ribosome to stall around codon 34, mediated by the sequence of the nascent chain within the exit tunnel. We further show that PF-06446846 reduces plasma PCSK9 and total cholesterol levels in rats following oral dosing. Using ribosome profiling, we demonstrate that PF-06446846 is highly selective for the inhibition of PCSK9 translation. The mechanism of action employed by PF-06446846 reveals a previously unexpected tunability of the human ribosome, which allows small molecules to specifically block translation of individual transcripts.\n\nOne Sentence SummaryA small-molecule PCSK9 inhibitor targets the human ribosome and selectively prevents PCSK9 synthesis.

systems biology↗