Biology subjects

Yau, T. O.

Publications and source records attributed to Yau, T. O..

5 recordsLinked to original sources

bioRxiv2021

Hyperactive chemotaxis contributes to anti-TNFα treatment resistance in inflammatory bowel disease

Background & AimsAnti-tumour necrosis factor-alpha (anti-TNF) agents have been used for inflammatory bowel disease (IBD), however, it has up to 30% non-response rate. Identifying molecular pathways and finding reliable diagnostic biomarkers for patient response to anti-TNF treatment are clearly needed. MethodsPublicly available transcriptomic data from IBD patients receiving anti-TNF therapy was systemically collected and integrated. In silico flow cytometry approaches and MetaScape were applied to evaluate immune cell populations and to perform gene enrichment analysis, respectively. Genes identified within enrichment pathways validated in neutrophils were tracked in an anti-TNF-treated animal model (with lipopolysaccharide (LPS)-induced inflammation). The receiver operating characteristic (ROC) curve was applied to all genes to identify the best prediction biomarkers. ResultsA total of 449 samples were retrieved from control, baseline and after primary anti-TNF therapy or placebo. No statistically significant differences were observed between anti-TNF treatment responders and non-responders at baseline in immune microenvironment scores. Neutrophils, endothelial and B cell populations were higher in baseline non-responders and chemotaxis pathways may contribute to the treatment resistance. Genes related to chemotaxis pathways were significantly up-regulated in LPS-induced neutrophils but no statistically significant changes were observed in neutrophils treated with anti-TNF. Interleukin 13 receptor subunit alpha 2 (IL13RA2) is the best predictor (ROC: 80.7%, 95% CI: 73.8% - 87.5%) with a sensitivity of 68.13% and specificity of 84.93%, and significantly higher in non-responders compared to responders (p < 0.0001). ConclusionsHyperactive chemotaxis influences responses to anti-TNF treatment and IL13RA2 is a potential biomarker to predict anti-TNF treatment response.

molecular biology↗

bioRxiv2021

Precise annotation of Drosophila mitochondrial genomes leads to insights into AT-rich regions

In the present study, we performed precise annotation of Drosophila melanogaster, D. simulans, D. grimshawi, Bactrocera oleae mitochondrial (mt) genomes by pan RNA-seq analysis. Our new annotations corrected or modified some of the previous annotations and two important findings were reported for the first time, including the discovery of the conserved polyA(+) and polyA(-) motifs in the control regions (CRs) of insect mt genomes and the adding of CCAs to the 3 ends of two antisense tRNAs in D. melanogaster mt genome. Using PacBio cDNA-seq data from D. simulans, we precisely annotated the Transcription Initiation Sites (TISs) of the mt Heavy and Light strands in Drosophila mt genomes and reported that the polyA(+) and polyA(-) motifs in the CRs are associated with TISs. The discovery of the conserved polyA(+) and polyA(-) motifs provides insights into many polyA and polyT sequences in CRs of insect mt genomes, leading to reveal the mt transcription and its regulation in invertebrates. In addition, we provided a high-quality, well-curated and precisely annotated D. simulans mt genome (GenBank: MN611461), which should be included into the NCBI RefSeq database to replace the current reference genome NC_005781.

bioinformatics↗

bioRxiv2021

Full-length Genome of the Ogataea polymorpha strain HU-11 reveals large duplicated segments in subtelomeic regions

BackgroundCurrently, methylotrophic yeasts (e.g., Pichia pastoris, Ogataea polymorpha, and Candida boindii) are subjects of intense genomics studies in basic research and industrial applications. In the genus Ogataea, most research is focused on three basic O. polymorpha strains--CBS4732, NCYC495, and DL-1. However, the relationship between CBS4732, NCYC495, and DL-1 remains unclear, as the genomic differences between them have not be exactly determined without their high-quality complete genomes. As a nutritionally deficient mutant derived from CBS4732, the O. polymorpha strain CBS4732 ura3{Delta} (named HU-11) is being used for high-yield production of several important proteins or peptides. HU-11 has the same reference genome as CBS4732 (noted as HU-11/CBS4732), because the only genomic difference between them is a 5-bp insertion. ResultsIn the present study, we have assembled the full-length genome of O. polymorpha HU-11/CBS4732 using high-depth PacBio and Illumina data. Long terminal repeat (LTR) retrotransposons, rDNA, 5 and 3 telomeric, subtelomeric, low complexity and other repeat regions were curated to improve the genome quality. Particularly, we detected large duplicated segments (LDSs) in the subtelomeric regions and exactly determined all the structural variations (SVs) between CBS4732 and NCYC495. New findings mainly include(1) the genomic differences between HU-11/CBS4732 and NCYC495 include single nucleotide polymorphisms, small insertions and deletions, and only three SVs; (2) six genes were incorporated into CBS4732 from Cyberlindnera jadinii by horizontal gene transfer and may bring HU-11/CBS4732 new biological functions or physiological properties; (3) many recombination events may have occurred on chromosome 4 and 5 of CBS4732 and NCYC495 ancestors and two large segments were acquired by CBS4732 and NCYC495 from chromosome 6 and C. jadinii during recombination, respectively; and (4) the genome expansion in methylotrophic yeasts is mainly driven by large segment duplication in subtelomeric regions. ConclusionsThe present study preliminarily revealed the complex relationship between CBS4732, NCYC495, and DL-1. The new findings provide new opportunities for in-depth understanding of genome evolution in methylotrophic yeasts and lay the foundations for the industrial applications of O. polymorpha CBS4732, NCYC495, DL-1, and their derivative strains. The full-length genome of the O. polymorpha strain HU-11/CBS4732 should be included into the NCBI RefSeq database for future studies of Ogataea spp..

bioinformatics↗

bioRxiv2021

How the replication and transcription complex of SARS-CoV-2 functions in leader-to-body fusion

BackgroundCoronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although unprecedented efforts are underway to develop therapeutic strategies against this disease, scientists have acquired only a little knowledge regarding the structures and functions of the CoV replication and transcription complex (RTC) and 16 non-structural proteins, named NSP1-16. ResultsIn the present study, we proposed a two-route model to answer how the RTC functions in the jumping transcription of CoVs. The key step leading to this model was that the motif AAACH for METTL3 recognition flanking the transcription regulatory sequence (TRS) motif was discovered to determine the m6A methylation of SARS-CoV-2 RNAs, by reanalyzing public Nanopore RNA-seq data. As the most important finding, TRS hairpins were reported for the first time to interpret NSP15 cleavage, RNA methylation of CoVs and their association at the molecular level. In addition, we reported canonical TRS motifs of all CoVs to prove the importance of our findings. ConclusionsThe main conclusions are: (1) TRS hairpins can be used to identify recombination regions in CoV genomes; (2) RNA methylation of CoVs participates in the determination of the RNA secondary structures by affecting the formation of base pairing; and (3) The eventual determination of the CoV RTC global structure needs to consider METTL3 in the experimental design. Our findings enrich fundamental knowledge in the field of gene expression and its regulation, providing a crucial basis for future studies.

bioinformatics↗

bioRxiv2020

The discovery of a recombinant SARS2-like CoV strain provides insights into SARS and COVID-2019 pandemics

In December 2019, the world awoke to a new zoonotic strain of coronavirus named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). In the present study, we identified key recombination regions and mutation sites cross the SARS-CoV-2, SARS-CoV and SARS-like CoV clusters of betacoronavirus subgroup B. Based on the analysis of these recombination events, we proposed that the Spike protein of SARS-CoV-2 may have more than one specific receptor for its function. In addition, we reported--for the first time--a recombination event of ORF8 at the whole-gene level in a bat and ultimately determined that ORF8 enhances the viral replication. In conjunction with our previous discoveries, we found that receptor binding abilities, junction furin cleavage sites (FCSs), strong first ribosome binding sites (RBSs) and enhanced ORF8s are main factors contributing to transmission, virulence and host adaptability of CoVs. Junction FCSs and enhanced ORF8s increase the efficiencies in viral entry into cells and replication, respectively while strong first RBSs enhance the translational initiation. The strong recombination ability of CoVs integrated these factors to generate multiple recombinant strains, two of which evolved into SARS-CoV and SARS-CoV-2 by nature selection, resulting in the SARS and COVID-19 pandemics.

bioinformatics↗