Biology subjects

Xia, Z.

Publications and source records attributed to Xia, Z..

5 recordsLinked to original sources

bioRxiv2018

Mate-pair Library Construction with Controlled Polymerization Enables Comprehensive Structural Rearrangement Detection

The diversity of disease presentations warrants one single assay for detection and delineation of various genomic disorders. Herein, we describe a gel-free and biotin-capture-free mate-pair method through coupling Controlled Polymerizations by Adapter-Ligation (CP-AL). We first demonstrated the feasibility and ease-of-use in monitoring DNA nick-translation and primer extension by limiting the nucleotide input. By coupling these two controlled polymerizations by a reported non-conventional adapter ligation reaction 3 branch ligation, we evidenced that CP-AL significantly increased DNA-circularization efficiency (by 4-fold) and was applicable for different sequencing methods but at a faction of current cost. Its advantages were further demonstrated by fully elimination of small-insert-contaminated (by 39.3-fold) with a ~50% increment of physical coverage, and producing uniform genome/exome coverage and the lowest chimeric rate. It achieved single-nucleotide variants detection with sensitivity and specificity up to 97.3 and 99.7%, respectively, compared with data from small-insert libraries. In addition, this method can provide a comprehensive delineation of structural rearrangements, evidenced by a potential diagnosis in a patient with oligo-atheno-terato-spermia. Moreover, it enables accurate mutation identification by integration of genomic variants from different aberration types. Overall, it provides a potential single-integrated solution for detecting various genomic variants, facilitating a genetic diagnosis in human diseases.

genomics↗

bioRxiv2018

Membrane proteins with high N-glycosylation, high expression, and multiple interaction partners were preferred by mammalian viruses as receptors

Receptor mediated entry is the first step for viral infection. However, the relationship between viruses and receptors is still obscure. Here, by manually curating a high-quality database of 268 pairs of mammalian virus-host receptor interaction, which included 128 unique viral species or sub-species and 119 virus receptors, we found the viral receptors were structurally and functionally diverse, yet they had several common features when compared to other cell membrane proteins: more protein domains, higher level of N-glycosylation, higher ratio of self-interaction and more interaction partners, and higher expression in most tissues of the host. Additionally, the receptors used by the same virus tended to co-evolve. Further correlation analysis between viral receptors and the tissue and host specificity of the virus shows that the virus receptor similarity was a significant predictor for mammalian virus cross-species. This work could deepen our understanding towards the viral receptor selection and help evaluate the risk of viral zoonotic diseases.

microbiology↗

bioRxiv2017

Scalable and efficient single-cell DNA methylation sequencing by combinatorial indexing.

Here we present a novel method: single-cell combinatorial indexing for methylation analysis (sci-MET), which is the first highly scalable assay for whole genome methylation profiling of single cells. We use sci-MET to produce 2,697 total single-cell bisulfite sequencing libraries and achieve read alignment rates of 69 {+/-} 7%, comparable to those of bulk cell methods. As a proof of concept, we applied sci-MET to successfully deconvolve the cellular identity of a mixture of three human cell lines.

genomics↗

bioRxiv2017

IFNα, a potential biomarker for stress vitiligo risk

Neural hypothesis has become an important aspect of vitiligo, yet without corresponding diagnostic indicators. We preliminarily found 32 cases of vitiligo patients with certain aggregation of mental factors. In peripheral blood mononuclear cells (PBMCs) of these patients, transcriptome analyses revealed that the circulation expression of a type I interferon (IFN-I)-dependent genes was induced. Also, serum IFN was elevated in vitiligo patients with depression. Therefore, our hypothesis is whether IFN levels predict the occurrence of psychiatric vitiligo. Through the establishment of stress-induced depigmentation model, serum IFN also showed increase. Intracerebroventricular and subcutaneous IFN injection can both elicit not only depressive behavior but also vitiligo-like characteristics. Mechanistically, central IFN induces the release of dorsal root ganglion (DRG) substance P (SP) to inhibit melanogenesis. Peripheral IFN disturbs cutaneous-neuro-endocrine microenvironment. Type I IFN (IFN) pathway-related genes in stress vitiligo were significantly discriminating from non-stress vitiligo, while that of type II IFN pathway was not.

physiology↗

bioRxiv2017

Poly(A)-ClickSeq: click-chemistry for next-generation 3´-end sequencing without RNA enrichment or fragmentation

The recent emergence of alternative polyadenylation (APA) as an engine driving transcriptomic diversity has stimulated the development of sequencing methodologies designed to assess genome-wide polyadenylation events. The goal of these approaches is to enrich, partition, capture, and ultimately sequence poly(A) site junctions. However, these methods often require poly(A) enrichment, 3{acute} linker ligation steps, and RNA fragmentation, which can necessitate higher levels of starting RNA, increase experimental error, and potentially introduce bias. We recently reported a click-chemistry based method for generating RNAseq libraries called \"ClickSeq\". Here, we adapt this method to direct the cDNA synthesis specifically toward the 3{acute} UTR/poly(A) tail junction of cellular RNA. With this novel approach, we demonstrate sensitive and specific enrichment for poly(A) site junctions without the need for complex sample preparation, fragmentation or purification. Poly(A)-ClickSeq (PAC-seq) is therefore a simple procedure that generates high-quality RNA-seq poly(A) libraries. As a proof-of-principle, we utilized PAC-seq to explore the poly(A) landscape of both human and Drosophila cells in culture and observed outstanding overlap with existing poly(A) databases and also identified previously unannotated poly(A) sites. Moreover, we utilize PAC-seq to quantify and analyze APA events regulated by CFIm25 illustrating how this technology can be harnessed to identify alternatively polyadenylated RNA.

molecular biology↗