Jingyao Zhang

Bio: Jingyao Zhang is an academic researcher from Genome Institute of Singapore. The author has contributed to research in topics: Chromatin immunoprecipitation & ChIA-PET. The author has an hindex of 3, co-authored 3 publications receiving 1164 citations. Previous affiliations of Jingyao Zhang include Agency for Science, Technology and Research.

Chromatin Interaction Analysis with Paired-End Tag Sequencing (ChIA-PET) for mapping chromatin interactions and understanding transcription regulation.

Abstract: Genomes are organized into three-dimensional structures, adopting higher-order conformations inside the micron-sized nuclear spaces 7, 2, 12. Such architectures are not random and involve interactions between gene promoters and regulatory elements 13. The binding of transcription factors to specific regulatory sequences brings about a network of transcription regulation and coordination 1, 14. Chromatin Interaction Analysis by Paired-End Tag Sequencing (ChIA-PET) was developed to identify these higher-order chromatin structures 5,6. Cells are fixed and interacting loci are captured by covalent DNA-protein cross-links. To minimize non-specific noise and reduce complexity, as well as to increase the specificity of the chromatin interaction analysis, chromatin immunoprecipitation (ChIP) is used against specific protein factors to enrich chromatin fragments of interest before proximity ligation. Ligation involving half-linkers subsequently forms covalent links between pairs of DNA fragments tethered together within individual chromatin complexes. The flanking MmeI restriction enzyme sites in the half-linkers allow extraction of paired end tag-linker-tag constructs (PETs) upon MmeI digestion. As the half-linkers are biotinylated, these PET constructs are purified using streptavidin-magnetic beads. The purified PETs are ligated with next-generation sequencing adaptors and a catalog of interacting fragments is generated via next-generation sequencers such as the Illumina Genome Analyzer. Mapping and bioinformatics analysis is then performed to identify ChIP-enriched binding sites and ChIP-enriched chromatin interactions 8. We have produced a video to demonstrate critical aspects of the ChIA-PET protocol, especially the preparation of ChIP as the quality of ChIP plays a major role in the outcome of a ChIA-PET library. As the protocols are very long, only the critical steps are shown in the video.

Preferential Adsorption Performance of Ethane in a Robust Nickel-Based Metal–Organic Framework for Separating Ethane from Ethylene

Abstract: Development of an ethane-selective adsorbent to separate ethane from ethylene is a challenging issue with great significance for ethylene purification. The adsorptive separation technique based on physical adsorption holds a great promise to address this issue. Herein, we report a robust ethane-selective metal–organic framework, Ni(BODC)(TED), and investigate its separation performance on C2H6/C2H4. The as-synthesized Ni(BODC)(TED) exhibits excellent water vapor stability and high capacity of C2H6 molecules with an uptake of 3.36 mmol/g at 298 K and 100 kPa, higher than those of many adsorbents reported in recent years. Its C2H6/C2H4 selectivity predicted by the ideal adsorbed solution theory (IAST) model reaches 1.79. A molecular simulation is applied to unveil the preferential adsorption mechanism of ethane. Calculation shows that five strong C–H···H interactions are formed between C2H6 and the framework of Ni(BODC)(TED), and the isosteric heat of ethane on Ni(BODC)(TED) is 27.02 kJ/mol, higher than that of ethylene, resulting in preferential adsorption of ethane. Ni(BODC)(TED) would become a promising member of the family of ethane-selective materials for the industrial separation of ethane from ethylene.

Characterizing Variances of Adulterated Extra Virgin Olive Oils by UV-Vis Spectroscopy Combined with Analysis of Variance-Projected Difference Resolution (ANOVA-PDR) and Multivariate Classification

Abstract: The analysis of variance-projected difference resolution (ANOVA-PDR) was proposed and compared with multivariate classification for its potential in detecting possible food adulteration in extra virgin olive oils (EVOOs) by UV-Vis spectra. Three factors including origin, adulteration level, and adulteration type were systematically examined by the ANOVA-derived methods. The ANOVA-PDR quantitatively presented the separation of the internal classes according to the three main factors. Specifically, the average ANOVA-derived PDRs of the EVOO origination and adulteration level, respectively, is 4.01 and 1.78, while the conventional PDRs of the three factors are all less than 1.5. Furthermore, the partial least-squares-discriminant analysis (PLS-DA) and the PLS regression (PLSR) modeling with the selected sub-datasets from different origins were used to verify the results. The resulting models suggested that the three main factors and their interactions were all important sources of spectral variations.

An integrated encyclopedia of DNA elements in the human genome

Abstract: The human genome encodes the blueprint of life, but the function of the vast majority of its nearly three billion bases is unknown. The Encyclopedia of DNA Elements (ENCODE) project has systematically mapped regions of transcription, transcription factor association, chromatin structure and histone modification. These data enabled us to assign biochemical functions for 80% of the genome, in particular outside of the well-studied protein-coding regions. Many discovered candidate regulatory elements are physically associated with one another and with expressed genes, providing new insights into the mechanisms of gene regulation. The newly identified elements also show a statistical correspondence to sequence variants linked to human disease, and can thereby guide interpretation of this variation. Overall, the project provides new insights into the organization and regulation of our genes and genome, and is an expansive resource of functional annotations for biomedical research.

An integrated encyclopedia of DNA elements in the human genome.

Abstract: The human genome encodes the blueprint of life, but the function of the vast majority of its nearly three billion bases is unknown. The Encyclopedia of DNA Elements (ENCODE) project has systematically mapped regions of transcription, transcription factor association, chromatin structure and histone modification. These data enabled us to assign biochemical functions for 80% of the genome, in particular outside of the well-studied protein-coding regions. Many discovered candidate regulatory elements are physically associated with one another and with expressed genes, providing new insights into the mechanisms of gene regulation. The newly identified elements also show a statistical correspondence to sequence variants linked to human disease, and can thereby guide interpretation of this variation. Overall, the project provides new insights into the organization and regulation of our genes and genome, and is an expansive resource of functional annotations for biomedical research.

Systematic localization of common disease-associated variation in regulatory DNA.

Abstract: Genome-wide association studies have identified many noncoding variants associated with common diseases and traits. We show that these variants are concentrated in regulatory DNA marked by deoxyribonuclease I (DNase I) hypersensitive sites (DHSs). Eighty-eight percent of such DHSs are active during fetal development and are enriched in variants associated with gestational exposure–related phenotypes. We identified distant gene targets for hundreds of variant-containing DHSs that may explain phenotype associations. Disease-associated variants systematically perturb transcription factor recognition sequences, frequently alter allelic chromatin states, and form regulatory networks. We also demonstrated tissue-selective enrichment of more weakly disease-associated variants within DHSs and the de novo identification of pathogenic cell types for Crohn’s disease, multiple sclerosis, and an electrocardiogram trait, without prior knowledge of physiological mechanisms. Our results suggest pervasive involvement of regulatory DNA variation in common human disease and provide pathogenic insights into diverse disorders.

The accessible chromatin landscape of the human genome

Abstract: DNase I hypersensitive sites (DHSs) are markers of regulatory DNA and have underpinned the discovery of all classes of cis-regulatory elements including enhancers, promoters, insulators, silencers and locus control regions. Here we present the first extensive map of human DHSs identified through genome-wide profiling in 125 diverse cell and tissue types. We identify ∼2.9 million DHSs that encompass virtually all known experimentally validated cis-regulatory sequences and expose a vast trove of novel elements, most with highly cell-selective regulation. Annotating these elements using ENCODE data reveals novel relationships between chromatin accessibility, transcription, DNA methylation and regulatory factor occupancy patterns. We connect ∼580,000 distal DHSs with their target promoters, revealing systematic pairing of different classes of distal DHSs and specific promoter types. Patterning of chromatin accessibility at many regulatory regions is organized with dozens to hundreds of co-activated elements, and the transcellular DNase I sensitivity pattern at a given region can predict cell-type-specific functional behaviours. The DHS landscape shows signatures of recent functional evolutionary constraint. However, the DHS compartment in pluripotent and immortalized cells exhibits higher mutation rates than that in highly differentiated cells, exposing an unexpected link between chromatin accessibility, proliferative potential and patterns of human variation. An extensive map of human DNase I hypersensitive sites, markers of regulatory DNA, in 125 diverse cell and tissue types is described; integration of this information with other ENCODE-generated data sets identifies new relationships between chromatin accessibility, transcription, DNA methylation and regulatory factor occupancy patterns. This paper describes the first extensive map of human DNaseI hypersensitive sites — markers of regulatory DNA — in 125 diverse cell and tissue types. Integration of this information with other data sets generated by ENCODE (Encyclopedia of DNA Elements) identified new relationships between chromatin accessibility, transcription, DNA methylation and regulatory-factor occupancy patterns. Evolutionary-conservation analysis revealed signatures of recent functional constraint within DNaseI hypersensitive sites.