Biology subjects

Ye, Y.

Publications and source records attributed to Ye, Y..

185 records · Page 11Linked to original sources

bioRxiv2018

CRISPRs for strain tracking and its application to microbiota transplantation data analysis

CRISPR-Cas systems are adaptive immune systems naturally found in bacteria and archaea. Bacteria and archaea use these systems to defend against invaders, including phages, plasmids and other mobile genetic elements. Relying on integration of invader sequences (protospacers) into CRISPR loci (forming spacers flanked by repeats), CRISPR-Cas systems store genetic memory of past invasions. While CRISPR-Cas systems have evolved in response to invading mobile elements, invaders have also developed mechanisms to avoid detection. As a result of arms-race between CRISPR-Cas systems and their targets, the CRISPR arrays typically undergo rapid turnover of the spacers with removal of old spacers and acquisition of new ones. Additionally, different individuals rarely share spacers amongst their microbiome. In this paper, we developed a pipeline (called CRISPRtrack) for strain tracking based on CRISPR spacer content, and applied it to fecal transplantation microbiome data to study the retention of donor strains in recipients. Our results demonstrate the potential use of CRISPRs as a simple yet effective tool for donor strain tracking in fecal transplantation, and also as a general purpose tool for quantifying microbiome similarity.

bioinformatics↗

bioRxiv2018

Deconvolution of single-cell multi-omics layers reveals regulatory heterogeneity

Integrative analysis of multi-omics layers at single cell level is critical for accurate dissection of cell-to-cell variation within certain cell populations. Here we report scCAT-seq, a technique for simultaneously assaying chromatin accessibility and the transcriptome within the same single cell. We show that the combined single cell signatures enable accurate construction of regulatory relationships between cis-regulatory elements and the target genes at single-cell resolution, providing a new dimension of features that helps direct discovery of regulatory patterns specific to distinct cell identities. Moreover, we generated the first single cell integrated maps of chromatin accessibility and transcriptome in human pre-implantation embryos and demonstrated the robustness of scCAT-seq in the precise dissection of master transcription factors in cells of distinct states during embryo development. The ability to obtain these two layers of omics data will help provide more accurate definitions of \"single cell state\" and enable the deconvolution of regulatory heterogeneity from complex cell populations.

genomics↗

bioRxiv2018

Construction and analysis of mRNA, miRNA, lncRNA, and TF regulatory networks reveal the key genes in prostate cancer

Purpose: Prostate cancer (PCa) causes a common male urinary system malignant tumour, and the molecular mechanisms of PCa remain poorly understood. This study aims to investigate the underlying molecular mechanisms of PCa with bioinformatics.\n\nMethods: Original gene expression profiles were obtained from the GSE64318 and GSE46602 datasets in the Gene Expression Omnibus (GEO). We conducted differential screens of the expression of genes (DEGs) between two groups using the R software limma package. The interactions between the differentially expressed miRNAs, mRNAs and lncRNAs were predicted and merged with the target genes. Co-expression of the miRNAs, lncRNAs and mRNAs were selected to construct the mRNA-miRNA and-lncRNA interaction networks. Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed for the DEGs. The protein-protein interaction (PPI) networks were constructed, and the transcription factors were annotated. The expression of hub genes in the TCGA datasets was verified to improve the reliability of our analysis.\n\nResults: The results demonstrated that 60 miRNAs, 1578 mRNAs and 61 lncRNAs were differentially expressed in PCa. The mRNA-miRNA-lncRNA networks were composed of 5 miRNA nodes, 13 lncRNA nodes, and 45 mRNA nodes. The DEGs were mainly enriched in the nuclei and cytoplasm and were involved in the regulation of transcription, related to sequence-specific DNA binding, and participated in the regulation of the PI3K-Akt signalling pathway. These pathways are related to cancer and focal adhesion signalling pathways. Furthermore, we found that 5 miRNAs, 6 lncRNAs, 6 mRNAs and 2 TFs play important regulatory roles in the interaction network. The expression levels of EGFR, VEGFA, PIK3R1, DLG4, TGFBR1 and KIT were significantly different between PCa and normal prostate tissue.\n\nConclusion: Based on the current study, large-scale effects of interrelated mRNAs, miRNAs, lncRNAs, and TFs were revealed and a model for predicting the mechanism of PCa was provided. This study provides new insight for the exploration of the molecular mechanisms of PCa and valuable clues for further research.

bioinformatics↗

bioRxiv2018

Distinctive types of postzygotic single-nucleotide mosaicisms in healthy individuals revealed by genome-wide profiling of multiple organs

Postzygotic single-nucleotide mosaicisms (pSNMs) have been extensively studied in tumors and are known to play critical roles in tumorigenesis. However, the patterns and origin of pSNMs in normal organs of healthy humans remain largely unknown. Using whole-genome sequencing and ultra-deep amplicon re-sequencing, we identified and validated 164 pSNMs from 27 postmortem organ samples obtained from five healthy donors. The mutant allele fractions ranged from 1.0% to 29.7%. Inter- and intra-organ comparison revealed two distinctive types of pSNMs, with about half originating during early embryogenesis (embryonic pSNMs) and the remaining more likely to result from clonal expansion events that had occurred more recently (clonal expansion pSNMs). Compared to clonal expansion pSNMs, embryonic pSNMs had higher proportion of C>T mutations with elevated mutation rate at CpG sites. We observed differences in replication timing between these two types of pSNMs, with embryonic and clonal expansion pSNMs enriched in early- and late-replicating regions, respectively. An increased number of embryonic pSNMs were located in open chromatin states and topologically associating domains that transcribed embryonically. Our findings provide new insights into the origin and spatial distribution of postzygotic mosaicism during normal human development.\n\nAuthor SummaryGenomic mosaicism led by postzygotic mutation is the major cause of cancers and many non-cancer developmental disorders. Theoretically, postzygotic mutations should be accumulated during the developmental process of healthy individuals, but the genome-wide characterization of postzygotic mosaicisms across many organ types of the same individual remained limited. In this study, we identified and validated two types of postzygotic mosaicism from the whole-genomes of 27 organs obtained from five healthy donors. We further found that the postzygotic mosaicisms arising during early embryogenesis and later clonal expansion events show distinct genomic patterns in mutation spectrum, replication timing, and chromatin status.

genomics↗

bioRxiv2017

The structural basis for regulation of the nucleo-cytoplasmic distribution of Bag6 by TRC35

The metazoan protein BCL2-associated athanogene cochaperone 6 (Bag6) forms a hetero-trimeric complex with ubiquitin-like 4A (Ubl4A) and transmembrane domain recognition complex 35 (TRC35). This Bag6 complex is involved in tail-anchored protein targeting and various protein quality control pathways in the cytosol as well as regulating transcription and histone methylation in the nucleus. Here we present a crystal structure of Bag6 and its cytoplasmic retention factor TRC35, revealing that TRC35 is remarkably conserved throughout opisthokont lineage except at the C-terminal Bag6-binding groove, which evolved to accommodate a novel metazoan factor Bag6. Remarkably, while TRC35 and its fungal homolog guided entry of tail-anchored protein 4 (Get4) utilize a conserved hydrophobic patch to bind their respective C-terminal binding partners Bag6 and Get5, Bag6 wraps around TRC35 on the opposite face relative to the Get4-5 interface. We further demonstrate that the residues involved in TRC35 binding are not only critical for occluding the Bag6 nuclear localization sequence from karyopherin binding to retain Bag6 in the cytosol, but also for preventing TRC35 from succumbing to RNF126-mediated ubiquitylation and degradation. The results provide a mechanism for regulation of Bag6 nuclear localization and the functional integrity of the Bag6 complex in the cytosol.

biochemistry↗