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Biology subjects

Xie, S.-Q.

Publications and source records attributed to Xie, S.-Q..

5 recordsLinked to original sources

IL-33 Involved in the Progression of Liver Fibrosis Through Innate Immunity Cells (MΦ) Regulated by ICOS/ICOSL Signaling in Early Stage of Mice Schistosomiasis

Schistosomiasis liver fibrosis is characterized by the foci of a classical type 2 granulomatous inflammation in response to egg soluble antigen. The inducible costimulator (ICOS)/ICOSL signaling can mediate Th2 polarization and regulate the disease process of chronic schistosomiasis by adaptive immune response. ICOS/ICOSL signaling could regulate innate immune cells, including B cells and macrophage (M{varphi}), and participate in pulmonary fibrosis. The purpose of the study was to identify whether ICOS/ICOSL signaling could regulate the polarization of M{varphi}, and to explore the potential role of IL-33 in ICOSL knockout (ICOSL-KO) mice with schistosomiasis. Firstly, the expression level of CD86, CD206 and IL-33 was checked respectively in ICOSL-KO and WT mice infected with Schistosoma japonicum (S. japonicum). Then recombinant IL-33 (rIL-33) was injected into ICOSL-KO mice infected with S. japonicum. Our experiments showed that the liver M{varphi} was successfully polarized toward to classical activated M{varphi} (M1) and the expression of IL-33 was inhibited in ICOSL-KO mice. Furthermore, the injection of rIL-33 successfully aggravated liver fibrosis in ICOSL-KO mice, increased the numbers of lymphocyte antigen 6C (Ly6C)hi, enhanced the expression of C-C chemokine ligand (CCL)2,, CCL5 and C-X-C motif chemokine 2 (CXCL2), and promoted polarization of T helper (Th) cells to Th2 cells, as well as induced the autophagy and apoptosis of hepatic stellate cells (HSCs). Overall, the liver fibrosis was alleviated in ICOSL-KO mice along with the reduced expression of IL-33, which could skew the polarization of M{varphi} toward to M1, induce Th cells activation, HSCs apoptosis and autophagy through Smad2/3 and TGF-{beta} signaling pathway, thus participated in the homeostasis of liver fibrosis of schistosomiasis.

immunology↗

HIT-scISOseq: High-throughput and High-accuracy Single-cell Full-length Isoform Sequencing for Corneal Epithelium

Single-cell isoform sequencing can reveal transcriptomic dynamics in individual cells invisible to bulk- and single-cell RNA analysis based on short-read sequencing. However, current long-read single-cell sequencing technologies have been limited by low throughput and high error rate. Here we introduce HIT-scISOseq for high-throughput single-cell isoform sequencing. This method was made possible by full-length cDNA capture using biotinylated PCR primers, and by our novel library preparation procedure that combines head-to-tail concatemeric full-length cDNAs into a long SMRTbell insert for high-accuracy PacBio sequencing. HIT-scISOseq yields > 10 million high-accuracy full-length isoforms in a single PacBio Sequel II 8M SMRT Cell, providing > 8 times more data output than the standard single-cell isoform PacBio sequencing protocol. We exemplified HIT-scISOseq by first studying transcriptome profiles of 4,000 normal and 8,000 injured corneal epitheliums from cynomolgus monkeys. We constructed dynamic transcriptome landscapes of known and rare cell types, revealed novel isoforms, and identified injury-related splicing and switching events that are previously not accessible with low throughput isoform sequencing. HIT-scISOseq represents a high-throughput, cost-effective, and technically simple method to accelerate the burgeoning field of long-read single-cell transcriptomics.

genomics↗

Fast and accurate assembly of Nanopore reads via progressive error correction and adaptive read selection

Although long Nanopore reads are advantageous in de novo genome assembly, applying Nanopore reads in genomic studies is still hindered by their complex errors. Here, we developed NECAT, an error correction and de novo assembly tool designed to overcome complex errors in Nanopore reads. We proposed an adaptive read selection and two-step progressive method to quickly correct Nanopore reads to high accuracy. We introduced a two-stage assembler to utilize the full length of Nanopore reads. NECAT achieves superior performance in both error correction and de novo assembly of Nanopore reads. NECAT requires only 7,225 CPU hours to assemble a 35X coverage human genome and achieves a 2.28-fold improvement in NG50. Furthermore, our assembly of the human WERI cell line showed an NG50 of 29 Mbp. The high-quality assembly of Nanopore reads can significantly reduce false positives in structure variation detection.

bioinformatics↗

N6-Methyladenine DNA Modification in Human Genome

DNA N6-methyladenine (6mA) modification is the most prevalent DNA modification in prokaryotes, but whether it exists in human cells and whether it plays a role in human diseases remain enigmatic. Here, we showed that 6mA is extensively present in human genome, and we cataloged 881,240 6mA sites accounting for [~]0.051% of the total adenines. [G/C]AGG[C/T] was the most significantly associated motif with 6mA modification. 6mA sites were enriched in the coding regions and mark actively transcribed genes in human cells. We further found that DNA N6-methyladenine and N6-demethyladenine modification in human genome were mediated by methyltransferase N6AMT1 and demethylase ALKBH1, respectively. The abundance of 6mA was significantly lower in cancers, accompaning with decreased N6AMT1 and increased ALKBH1 levels, and down-regulation of 6mA modification levels promoted tumorigenesis. Collectively, our results demonstrate that DNA 6mA modification is extensively present in human cells and the decrease of genomic DNA 6mA promotes human tumorigenesis.

genomics↗

MECAT: an ultra-fast mapping, error correction and de novo assembly tool for single-molecule sequencing reads

The high computational cost of current assembly methods for the long, noisy single molecular sequencing (SMS) reads has prevented them from assembling large genomes. We introduce an ultra-fast alignment method based on a novel global alignment score. For large human SMS data, our method is 7X faster than MHAP for pairwise alignment and 15X faster than BLASR for reference mapping. We develop a Mapping, Error Correction and de novo Assembly Tool (MECAT) by integrating our new alignment and error correction methods, with the Celera Assembler. MECAT is capable of producing high quality de novo assembly of large genome from SMS reads with low computational cost. MECAT produces reference-quality assemblies of Saccharomyces cerevisiae, Arabidopsis thaliana, Drosophila melanogaster and reconstructs the human CHM1 genome with 15% longer NG50 in only 7600 CPU core hours using 54X SMS reads and a Chinese Han genome in 19200 CPU core hours using 102X SMS reads.

bioinformatics↗