Biology subjects

Ruan, Y.

Publications and source records attributed to Ruan, Y..

8 recordsLinked to original sources

bioRxiv2018

Crop Information Engine and Research Assistant (CIERA) for managing genealogy, phenotypic and genotypic data for breeding programs

BackgroundWith the advent of next-generation marker platforms and phenomics in crop breeding programs, the volume of both the genotypic and phenotypic data produced has increased exponentially. Often the data remain underutilized if not properly collated, managed and accessed. Effective management of the data is paramount to making sound and timely decision on cross planning in order to accelerate genetic gain ({Delta}G) in crops for disease resistance, agronomic and end-use quality traits.\n\nResultsTo address the challenges in managing and efficient utilization of the sheer volume of data generated in a crop breeding program, we developed an electronic information system called the Crop Information Engine and Research Assistant (CIERA). The CIERA, written in Visual Basic, runs on the Microsoft Windows operating system and requires the .Net Framework 4.7 as well as the MySQL Community Server 5.7. The highly intuitive graphical user interface of CIERA includes user-friendly query tools to facilitate the collation of data across relevant phenotypic environments from its phenotypic data management database and can combine that information with the genealogy and genetic data from its genealogy management and genetic data management databases, respectively.\n\nConclusionsUsing CIERA, breeders can build a comprehensive profile of germplasm, within a few minutes, to assist them in planning crosses for enhancing genetic gain by selecting superior lines for crosses.

bioinformatics↗

bioRxiv2018

Spatial Chromatin Architecture Alteration by Structural Variations in Human Genomes at Population Scale

This genome-wide study is focused on the impact of structural variants identified in individuals from 26 human populations onto three-dimensional structures of their genomes. We assess the tendency of structural variants to accumulate in spatially interacting genomic segments and design a high-resolution computational algorithm to model the 3D conformational changes resulted by structural variations. We show that differential gene transcription is closely linked to variation in chromatin interaction networks mediated by RNA polymerase II. We also demonstrate that CTCF-mediated interactions are well conserved across population, but enriched with disease-associated SNPs. Altogether, this study assesses the critical impact of structural variants on the higher order organization of chromatin folding and provides unique insight into the mechanisms regulating gene transcription at the population scale, among which the local arrangement of chromatin loops seems to be the leading one. It is the first insight into the variability of the human 3D genome at the population scale.

genomics↗

bioRxiv2018

EndoC-βH1 multi-genomic profiling defines gene regulatory programs governing human pancreatic β cell identity and function

EndoC-{beta}H1 is emerging as a critical human beta cell model to study the genetic and environmental etiologies of beta cell function, especially in the context of diabetes. Comprehensive knowledge of its molecular landscape is lacking yet required to fully take advantage of this model. Here, we report extensive chromosomal (spectral karyotyping), genetic (genotyping), epigenetic (ChIP-seq, ATAC-seq), chromatin interaction (Hi-C, Pol2 ChIA-PET), and transcriptomic (RNA-seq, miRNA-seq) maps of this cell model. Integrated analyses of these maps define known (e.g., PDX1, ISL1) and putative (e.g., PCSK1, mir-375) beta cell-specific chromatin interactions and transcriptional cis-regulatory networks, and identify allelic effects on cis-regulatory element use and expression.\n\nImportantly, comparative analyses with maps generated in primary human islets/beta cells indicate substantial preservation of chromatin looping, but also highlight chromosomal heterogeneity and fetal genomic signatures in EndoC-{beta}H1. Together, these maps, and an interactive web application we have created for their exploration, provide important tools for the broad community in the design and success of experiments to probe and manipulate the genetic programs governing beta cell identity and (dys)function in diabetes.

genomics↗

bioRxiv2018

Coordinative Metabolism of Glutamine Carbon and Nitrogen in proliferating Cancer Cells Under Hypoxia

Under hypoxia, most of glucose is converted to secretory lactate, which leads to the lack of carbon source from glucose and thus the overuse of glutamine-carbon. However, under such a condition how glutamine nitrogen is disposed to avoid releasing potentially toxic ammonia remains to be determined. Here we identify a metabolic flux of glutamine to secretory dihydroorotate under hypoxia. We found that glutamine nitrogen is indispensable to nucleotide biosynthesis, but enriched in dihyroorotate and orotate rather than processing to its downstream uridine monophosphate under hypoxia. Dihyroorotate, not orotate, is then secreted out of cells. The specific metabolic pathway occurs in vivo and is required for tumor growth. Such a metabolic pathway renders glutamine mainly to acetyl coenzyme A for lipogenesis, with the rest carbon and nitrogen being safely removed. Our results reveal how glutamine carbon and nitrogen are coordinatively metabolized under hypoxia, and provide a comprehensive understanding on glutamine metabolism.\n\nSignificanceTumor cells often addict to glutamine, and particularly utilize its carbon for lipogenesis under hypoxia. We reveal that tumor cells package the excessive glutamine-nitrogen into secretory dihydroorotate, instead of toxic ammonia. This specifically reprogrammed pathway supports in vivo tumor growth, and could offer diagnostic markers and therapeutic targets for cancers.

biochemistry↗

bioRxiv2018

Multiplex Chromatin Interaction Analysis with Single-Molecule Precision

We describe a microfluidics-based strategy for genome-wide analysis of multiplex chromatin interactions with single-molecule precision. In multiplex chromatin interaction analysis (multi-ChIA), individual chromatin complexes are partitioned into droplets that contain a gel bead with unique DNA barcode, in which tethered chromatin DNA fragments are barcoded and amplified for sequencing and mapping to demarcate chromatin contacts. Thus, multi-ChIA has the unprecedented ability to uncover multiplex chromatin interactions at single-molecule level, which has been impossible using previous methods that rely on analyzing pairwise contacts via proximity ligation. We demonstrate that multiplex chromatin interactions predominantly contribute to topologically associated domains, and clusters of gene promoters and enhancers provide a fundamental topological framework for co-transcriptional regulation.

genomics↗

bioRxiv2018

Observing the Cell in Its Native State: Imaging Subcellular Dynamics in Multicellular Organisms

True physiological imaging of subcellular dynamics requires studying cells within their parent organisms, where all the environmental cues that drive gene expression, and hence the phenotypes we actually observe, are present. A complete understanding also requires volumetric imaging of the cell and its surroundings at high spatiotemporal resolution without inducing undue stress on either. We combined lattice light sheet microscopy with two-channel adaptive optics to achieve, across large multicellular volumes, noninvasive aberration-free imaging of subcellular processes, including endocytosis, organelle remodeling during mitosis, and the migration of axons, immune cells, and metastatic cancer cells in vivo. The technology reveals the phenotypic diversity within cells across different organisms and developmental stages, and may offer insights into how cells harness their intrinsic variability to adapt to different physiological environments.\n\nOne Sentence SummaryCombining lattice light sheet microscopy with adaptive optics enables high speed, high resolution in vivo 3D imaging of dynamic processes inside cells under physiological conditions within their parent organisms.

cell biology↗

bioRxiv2018

Electron transfer dictates metabolic reprogramming in proliferating cells under hypoxia

Metabolic reprogramming extensively occurs in proliferating cancer cells. This phenomenon occurs highly heterogeneously, but its origin has remained unclear. Here we use a physicochemical concept of free electron potential (FEP) and its equation of state to profile metabolites. We demonstrate that FEP change between substrates and products exactly reflects electrons dissipated in a metabolic transformation. Based on the law of conservation of electron in chemical reactions, a function of FEP change for central metabolism in proliferating cells are further derived, and it can accurately predict metabolic behaviors under hypoxia by maximizing the cellular FEP change to consume electrons. Therefore, enabling electron transfer dictates metabolic reprogramming in hypoxic cells, which underlies the major findings in cancer metabolism and is supported by our experiments. Importantly, our model established on FEP helps to reveal a combination of promising targets to inhibit tumor growth under hypoxia by blocking electron consumption, and could also guide future studies on cancer metabolism under hypoxia.

biochemistry↗

bioRxiv2017

The Tandem Duplicator Phenotype is a prevalent genome-wide cancer configuration driven by distinct gene mutations

The tandem duplicator phenotype (TDP) is a genome-wide instability configuration primarily observed in breast, ovarian and endometrial carcinomas. Here, we stratify TDP tumors by classifying their tandem duplications (TDs) into three span intervals, with modal values of 11 Kb, 231 Kb, and 1.7 Mb. TDPs with prominent ~11 Kb TDs feature the conjoint loss of TP53 and BRCA1. TDPs with ~231 Kb and ~1.7 Mb TDs associate with CCNE1 pathway activation or CDK12 disruptions, in conjunction with TP53 mutations. We prove the driver role of TP53 and BRCA1 abrogation for TDP induction by generating short-span TDP mammary tumors in genetically modified mouse models harboring deleterious mutations in only these two genes. Lastly, heterogeneous combinations of mutations mediated by TDs are selected for and contribute to the oncogenic burden of TDP tumors.

genomics↗