TAD boundary and strength prediction by integrating sequence and epigenetic profile information.

Topologically associated domains (TADs) are one of the important higher order chromatin structures with various sizes in the eukaryotic genomes. TAD boundaries, as the flanking regions between adjacent domains, can restrict the interactions of regulatory elements, including enhancers and promoters, and are generally dynamic and variable in different cells. However, the influence of sequence and epigenetic profile-based features in the identification of TAD boundaries is largely unknown. In this work, we proposed a method called pTADS (prediction of TAD boundary and strength), to predict TAD boundaries and boundary strength across multiple cell lines with DNA sequence and epigenetic profile information. The performance was assessed in seven cell lines and three TAD calling methods. The results demonstrate that the TAD boundary can be well predicted by the selected shared features across multiple cell lines. Especially, the model can be transferable to predict the TAD boundary from one cell line to other cell lines. The boundary strength can be characterized by boundary score with good performance. The predicted TAD boundary and TAD boundary strength are further confirmed by three Hi-C contact matrix-based methods across multiple cell lines. The codes and datasets are available at https://github.com/chrom3DEpi/pTADS.

Ultrasensitive and Simultaneous Detection of Multielements in Aqueous Samples Based on Biomimetic Array Combined with Laser-Induced Breakdown Spectroscopy.

Ultrasensitive detection of metallic elements in liquids has attracted considerable attention in fields such as environmental pollution monitoring and drinking water quality control. Hence, it is of great significance to develop a sensitive and simultaneous detection strategy for multiple metal elements in liquid. Laser-induced breakdown spectroscopy (LIBS) technology shows unique advantages because of its simple, rapid, and real-time in situ detection, but the laser energy will be greatly attenuated in the liquids; thus, the sensitivity of LIBS for direct detection of metal elements in liquid samples will decrease sharply. In this study, inspired by the structure of Stenocara beetle's back, a superhydrophobic biomimetic interface with hydrophilic array was prepared for enriching low-concentration targets into detection regions, and the biomimetic array LIBS (BA-LIBS) was successfully established. The ultrasensitive and simultaneous detection of nine metal elements in drinking water was realized based on the effective enrichment method. The limits of detection of the nine metal elements in mixed solution ranged from 8.3 ppt to 13.49 ppb. With these excellent properties, this facile and ultrasensitive BA-LIBS strategy might provide a new idea for the prevention and control of metal hazards in the liquid environment.

The effects of Arabidopsis genome duplication on the chromatin organization and transcriptional regulation.

Autopolyploidy is widespread in higher plants and important for agricultural yield and quality. However, the effects of genome duplication on the chromatin organization and transcriptional regulation are largely unknown in plants. Using High-throughput Chromosome Conformation Capture (Hi-C), we showed that autotetraploid Arabidopsis presented more inter-chromosomal interactions and fewer short-range chromatin interactions compared with its diploid progenitor. In addition, genome duplication contributed to the switching of some loose and compact structure domains with altered H3K4me3 and H3K27me3 histone modification status. 539 genes were identified with altered transcriptions and chromatin interactions in autotetraploid Arabidopsis. Especially, we found that genome duplication changed chromatin looping and H3K27me3 histone modification in Flowering Locus C. We propose that genome doubling modulates the transcription genome-wide by changed chromatin interactions and at the specific locus by altered chromatin loops and histone modifications.

Direct and sensitive determination of Cu, Pb, Cr and Ag in soil by laser ablation microwave plasma torch optical emission spectrometry.

Based on microwave plasma torch optical emission spectrometry combined with laser ablation, a direct solid sample detection device was developed for sensitive determination of heavy metals in soil. In the proposed laser ablation microwave plasma torch optical emission spectrometry (LA-MPT-OES) device, a new ablation chamber was designed, which the washout time and the relative standard deviation of this chamber were almost one-third of those of the conventional one, indicating that the proposed chamber had a smaller dead volume to provide efficient and stable transport of ablated sample particles. Meanwhile, to ensure a high signal intensity during a long exposure time, the moving sampling method was used to guarantee a sufficient injection amount. With the optimal experimental parameters, the limits of detection (LODs) of Cu, Pb, Cr and Ag were 0.075, 0.093, 0.068, 0.009 mg·kg-1, respectively, which was reduced by one to two orders of magnitude compared with that of laser-induced breakdown spectroscopy and X-ray fluorescence and was similar to the LODs of the digestion-required techniques (e.g., ICP-OES and MP-AES) and other LA-related techniques (e.g., LA-ICP-MS). Furthermore, the LA-MPT-OES was applied to the quantitative analysis of standard samples and actual samples, and the obtained determination results were in agreement with the standard values and that of atomic absorption spectrometry. The practicability and accuracy (relative errors were 0.95%-25.9%) of LA-MPT-OES determination of heavy metal elements were also validated.

Low-cost smartphone-based LIBS combined with deep learning image processing for accurate lithology recognition.

A low-cost and multi-channel smartphone-based spectrometer was developed for LIBS. As the CMOS detector is two-dimensional, simultaneous multichannel detection was achieved by coupling a linear array of fibres for light collection. Thus, besides the atomic information, the spectral images containing the propagation and spatial distribution characters of a laser induced plasma plume could be recorded. With these additional features, accurate rock type prediction was achieved by processing the raw data directly through a deep learning model.

Single-Cell Analysis of the Pan-Cancer Immune Microenvironment and scTIME Portal.

Single-cell sequencing opens a new era for the investigation of tumor immune microenvironments (TIME). However, at single-cell resolution, a pan-cancer analysis that addresses the identity and diversity of TIMEs is lacking. Here, we first built a pan-cancer single-cell reference of TIMEs with refined subcell types and recognized new cell type-specific transcription factors. We then presented a pan-cancer view of the common features of the TIME and compared the variation of each immune cell type across patients and tumor types in the aspects of abundance, cell states, and cell communications. We found that the abundance and the cell states of dysfunctional T cells were most variable, whereas those of regulatory T cells were relatively stable. A subset of tumor-associated macrophages (TAM), PLTP + C1QC + TAMs, may regulate the abundance of dysfunctional T cells through cytokine/chemokine signaling. The ligand-receptor communication network of TIMEs was tumor-type specific and dominated by the tumor-enriched immune cells. We additionally developed the single-cell TIME (scTIME) portal (http://scTIME.sklehabc.com) with the scTIME-specific analysis modules and a unified cell annotation. In addition to the immune cell compositions and correlation analysis using refined cell type classifications, the portal also provides cell-cell interaction and cell type-specific gene signature analysis. Our single-cell pan-cancer analysis and scTIME portal will provide more insights into the features of TIMEs, as well as the molecular and cellular mechanisms underlying immunotherapies.

Asymmetric epigenome maps of subgenomes reveal imbalanced transcription and distinct evolutionary trends in Brassica napus.

The complexity of the epigenome landscape and transcriptional regulation is significantly increased during plant polyploidization, which drives genome evolution and contributes to the increased adaptability to diverse environments. However, a comprehensive epigenome map of Brassica napus is still unavailable. In this study, we performed integrative analysis of five histone modifications, RNA polymerase II occupancy, DNA methylation, and transcriptomes in two B. napus lines (2063A and B409), and established global maps of regulatory elements, chromatin states, and their dynamics for the whole genome (including the An and Cn subgenomes) in four tissue types (young leaf, flower bud, silique, and root) of these two lines. Approximately 65.8% of the genome was annotated with different epigenomic signals. Compared with the Cn subgenome, the An subgenome possesses a higher level of active epigenetic marks and lower level of repressive epigenetic marks. Genes from subgenome-unique regions contribute to the major differences between the An and Cn subgenomes. Asymmetric histone modifications between homeologous gene pairs reflect their biased expression patterns. We identified a novel bivalent chromatin state (with H3K4me1 and H3K27me3) in B. napus that is associated with tissue-specific gene expression. Furthermore, we observed that different types of duplicated genes have discrepant patterns of histone modification and DNA methylation levels. Collectively, our findings provide a valuable epigenetic resource for allopolyploid plants.

Chromatin loops associated with active genes and heterochromatin shape rice genome architecture for transcriptional regulation.

Insight into high-resolution three-dimensional genome organization and its effect on transcription remains largely elusive in plants. Here, using a long-read ChIA-PET approach, we map H3K4me3- and RNA polymerase II (RNAPII)-associated promoter-promoter interactions and H3K9me2-marked heterochromatin interactions at nucleotide/gene resolution in rice. The chromatin architecture is separated into different independent spatial interacting modules with distinct transcriptional potential and covers approximately 82% of the genome. Compared to inactive modules, active modules possess the majority of active loop genes with higher density and contribute to most of the transcriptional activity in rice. In addition, promoter-promoter interacting genes tend to be transcribed cooperatively. In contrast, the heterochromatin-mediated loops form relative stable structure domains in chromatin configuration. Furthermore, we examine the impact of genetic variation on chromatin interactions and transcription and identify a spatial correlation between the genetic regulation of eQTLs and e-traits. Thus, our results reveal hierarchical and modular 3D genome architecture for transcriptional regulation in rice.