SYN500k_genotypes
Ontology highlight
ABSTRACT:
PROVIDER: EGAD00010002453 | EGA |
REPOSITORIES: EGA
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Project description:Large-scale screening studies carried out to date to elucidate the causal mechanism of an allelic imbalance are generally limited to descriptions of allele-specific differences in expression detected in vivo and to linking them to differences in cis- and trans-regulatory changes. Although such gene surveys for regulatory variation leave the underlying mechanisms unexplored, they are a first step in identifying the specific nucleotide changes that govern gene expression differences. We describe a quantitative genetics approach to distinguish between cis- and trans-regulatory changes at a genome-wide scale and, hence, to detect cis-regulatory variation. For this purpose, we took advantage of diallel designs that are often used in plant breeding programs in which the goal is the estimation of general combining abilities (GCAs) of specific inbred lines and the identification of high yielding hybrid combinations of parents based on their specific combining abilities (SCAs). We show that in a context of gene expression, empirical estimates of GCA and SCA are valid parameters to distinguish between cis- and trans-regulatory changes and, hence, to detect cis-regulatory variation. By using this approach, we identified a considerable number of genes that showed evidence of cis-regulated allele-specific expression in a total of 10 diploid Arabidopsis hybrids. The method can also be used to explore naturally occurring cis-regulatory variation among inbred lines for laboratory animals, such as mouse and rat. This experiment covers data from 10 pairs of reciprocal hybrid samples, referred to as Hx.y where x=1...10 and y=1,2; The related data from 20 Recombinant Inline Line samples is submitted as experiment : - VIB Plant Systems Biology "RIL")
2006-12-02 | E-TABM-67 | biostudies-arrayexpress
Project description:The aim of this project is to promote the breath volatile marker concept for colorectal cancer (CRC) screening by advancing developing the application of a novel hybrid analyzer for the purpose.
The hybrid analyzer concept is expected to benefit of combining metal-oxide (MOX) and infrared spectrum (IR) sensor acquired data. The current study will be the first globally to address this concept in CRC detection. In addition, traditional methods, in particular, gas chromatography coupled to mass spectrometry (GC-MS) will be used to address the biological relevance of the VOCs emission from cancer tissue and will assist in further advances of the hybrid-sensing approach.
| 2399547 | ecrin-mdr-crc
Project description:see publication, arrays from 4 sterile genotypes containing homozygous segments with a Hybrid Male Sterility factor and 1 fertile strain in which the region is a Drosophila simulans and D. mauritiana heterozygous
2011-03-07 | GSE25339 | GEO
Project description:Engineering resource allocation in biological systems is an ongoing challenge. Organisms allocate resources for ensuring survival, reducing the productivity of synthetic biology functions. Here we present a novel approach for engineering the resource allocation of Escherichia coli by rationally modifying its transcriptional regulatory network. Our method (ReProMin) identifies the minimal set of genetic interventions that maximises the savings in cell resources. To this end, we categorized Transcription Factors according to the essentiality of its targets and we used proteomic data to rank them. We designed the combinatorial removal of TFs that maximise the release of resources. Our resulting strain containing only three mutations, theoretically releasing 0.5% of its proteome, had higher proteome budget, increased production of an engineered metabolic pathway and showed that the regulatory interventions are highly specific. This approach shows that combining proteomic and regulatory data is an effective way of optimizing strains using conventional molecular methods.
2019-11-30 | GSE134335 | GEO
Project description:Synthetic transcription factors can be applied in many areas of biotechnology, medicine, and basic research. In contrast to current methods based on engineering new DNA-binding proteins, we show that Cas9 fused to a transcriptional activation domain can be targeted by combinations of guide RNA molecules to induce the expression of endogenous human genes. This simple approach for targeted gene activation circumvents the need for engineering new proteins and will enable widespread synthetic gene regulation.
2013-07-25 | GSE47114 | GEO
Project description:see publication, arrays from 4 sterile genotypes containing homozygous segments with a Hybrid Male Sterility factor and 1 fertile strain in which the region is a Drosophila simulans and D. mauritiana heterozygous Dye swaps, loop design.
2011-03-07 | E-GEOD-25339 | biostudies-arrayexpress
Project description:Combinatorial genetic perturbations have been utilized to identify synthetic sick/lethal genetic interactions for cancer drug target discovery. Current methods for high-throughput combinatorial genetic screening are inefficient and cumbersome. Here we developed a simple, robust, and high-performance CRISPR-Cas12a-based approach for unbiased, combinatorial genetic screening in cancer cells.
2020-06-08 | GSE141130 | GEO
Project description:Many bacteria, often associated with eukaryotic hosts and of relevance for biotechnological applications, harbor a multipartite genome composed of more than one replicon. Biotechnologically relevant phenotypes are often encoded by genes residing on the secondary replicons. A synthetic biology approach to developing enhanced strains for biotechnological purposes could therefore involve merging pieces or entire replicons from multiple strains into a single genome. Here we report the creation of a genomic hybrid strain in a model multipartite genome species, the plant-symbiotic bacterium Sinorhizobium meliloti. We term this strain as cis-hybrid, since it is produced by genomic material coming from the same species' pangenome. In particular, we moved the secondary replicon pSymA (accounting for nearly 20% of total genome content) from a donor S. meliloti strain to an acceptor strain. The cis-hybrid strain was screened for a panel of complex phenotypes (carbon/nitrogen utilization phenotypes, intra- and extracellular metabolomes, symbiosis, and various microbiological tests). Additionally, metabolic network reconstruction and constraint-based modeling were employed for in silico prediction of metabolic flux reorganization. Phenotypes of the cis-hybrid strain were in good agreement with those of both parental strains. Interestingly, the symbiotic phenotype showed a marked cultivar-specific improvement with the cis-hybrid strains compared to both parental strains. These results provide a proof-of-principle for the feasibility of genome-wide replicon-based remodelling of bacterial strains for improved biotechnological applications in precision agriculture.
2021-03-17 | MTBLS576 | MetaboLights
Project description:R-Loops are unique RNA-containing chromatin structures, which participate in various key biological processes and associate with multiple human diseases. Accurately and comprehensively profiling R-Loops in the genome is crucial to study their functions under the physiological and pathological conditions. However, the existing methodologies have produced broad discrepancies in R-Loop profiling and an independent strategy is urgently needed. Here, we constructed an artificial DNA-RNA hybrid recognition sensor protein GST-His6-2XHBD with the hybrid-binding domain of RNase H1, and found GST-His6-2XHBD could specifically interact with DNA-RNA hybrids and behaves similarly to the anti-DNA-RNA hybrid S9.6 antibody in DRIPc-seq. Furthermore, we established a convenient method, R-loop CUT&Tag, by combination of GST-His6-2XHBD with a Tn5-based cleavage under targets and tagmentation approach. R-Loop CUT&Tag generates highly specific signals for native R-Loops, and can sensitively detect the R-Loop signals at the promoter, genebody and enhancer. R-Loop CUT&Tag also provides possibilities to genome-widely map the native R-Loops with limited materials, and may benefit the resolving of the broad discrepancies between multiple R-Loop mapping methods.
2021-02-22 | GSE156400 | GEO
Project description:Recent advances in single cell RNA sequencing allow users to pool multiple samples into one run and demultiplex in downstream analysis, greatly increasing the experimental efficiency and cost-effectiveness. However, the expensive reagents for cell labeling, limited pooling capacity, non-ideal cell recovery rate and calling accuracy remain great challenges for this approach. To date, there are two major demultiplexing methods, antibody-based cell hashing and Single Nucleotide Polymorphism (SNP)-based genomic signature profiling, and each method has advantages and limitations. Here, we propose a hybrid demultiplexing strategy that increases calling accuracy and cell recovery at the same time. We first develop a computational algorithm that significantly increases calling accuracy of cell hashing. Next, we cluster all single cells based on their SNP profiles. Finally, we integrate results from both methods to make corrections and retrieve cells that are only identifiable in one method but not the other. By testing on several real-world datasets, we demonstrate that this hybrid strategy combines advantages of both methods, resulting in increased cell recovery and calling accuracy at lower cost.
2024-05-29 | GSE230810 | GEO