Biology subjects

Pei, X.

Publications and source records attributed to Pei, X..

23 records · Page 2Linked to original sources

bioRxiv2021

A subset of Memory B-derived antibody repertoire from 3-dose vaccinees is ultrapotent against diverse and highly transmissible SARS-CoV-2 variants, including Omicron

Omicron, the most heavily mutated SARS-CoV-2 variant so far, is highly resistant to neutralizing antibodies, raising unprecedented concerns about the effectiveness of antibody therapies and vaccines. We examined whether sera from individuals who received two or three doses of inactivated vaccine, could neutralize authentic Omicron. The seroconversion rates of neutralizing antibodies were 3.3% (2/60) and 95% (57/60) for 2- and 3-dose vaccinees, respectively. For three-dose recipients, the geometric mean neutralization antibody titer (GMT) of Omicron was 15, 16.5-fold lower than that of the ancestral virus (254). We isolated 323 human monoclonal antibodies derived from memory B cells in 3-dose vaccinees, half of which recognize the receptor binding domain (RBD) and show that a subset of them (24/163) neutralize all SARS-CoV-2 variants of concern (VOCs), including Omicron, potently. Therapeutic treatments with representative broadly neutralizing mAbs individually or antibody cocktails were highly protective against SARS-CoV-2 Beta infection in mice. Atomic structures of the Omicron S in complex with three types of all five VOC-reactive antibodies defined the binding and neutralizing determinants and revealed a key antibody escape site, G446S, that confers greater resistance to one major class of antibodies bound at the right shoulder of RBD through altering local conformation at the binding interface. Our results rationalize the use of 3-dose immunization regimens and suggest that the fundamental epitopes revealed by these broadly ultrapotent antibodies are a rational target for a universal sarbecovirus vaccine. One sentence summaryA sub-set of antibodies derived from memory B cells of volunteers vaccinated with 3 doses of an inactivated SARS-CoV-2 vaccine work individually as well as synergistically to keep variants, including Omicron, at bay.

microbiology↗

bioRxiv2021

Identifying The "Core" Transcriptome of SARS-CoV-2 Infected Cells

In 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first emerged, causing the COVID-19 pandemic. Consequently, ongoing research has focused on better understanding the mechanisms underlying the symptoms of this disease. Although COVID-19 symptoms span a range of organ systems, the specific changes in gene regulation that lead to the variety of symptoms are still unclear. In our study, we used publicly available transcriptome data from previous studies on SARS-CoV-2 to identify commonly regulated genes across cardiomyocytes, human bronchial epithelial cells, alveolar type II cells, lung adenocarcinoma, human embryonic kidney cells, and patient samples. Additionally, using this common "core" transcriptome, we could identify the genes that were specifically and uniquely regulated in bronchial epithelial cells, embryonic kidney cells, or cardiomyocytes. For example, we found that genes related to cell metabolism were uniquely upregulated in kidney cells, providing us with the first mechanistic clue about specifically how kidney cells may be affected by SARS-CoV-2. Overall, our results uncover connections between the differential gene regulation in various cell types in response to the SARS-CoV-2 infection and help identify targets of potential therapeutics.

bioinformatics↗

bioRxiv2021

Accurate and fast cell marker gene identification with COSG

Accurate cell classification is the groundwork for downstream analysis of single-cell sequencing data, yet how to identify marker genes to distinguish different cell types still remains as a big challenge. We developed COSG as a cosine similarity-based method for more accurate and scalable marker gene identification. COSG is applicable to single-cell RNA sequencing data, single-cell ATAC sequencing data and spatially resolved transcriptome data. COSG is fast and scalable for ultra-large datasets of million-scale cells. Application on both simulated and real experimental datasets demonstrates the superior performance of COSG in terms of both accuracy and efficiency as compared with other available methods. Marker genes or genomic regions identified by COSG are more indicative and with greater cell-type specificity.

bioinformatics↗

bioRxiv2019

Long noncoding RNAs sustain high expression of exogenous Oct4 by sponging miRNA during reprogramming

Long noncoding RNAs (lncRNAs) modulate gene expression as competing endogenous RNAs (ceRNAs) via sponging microRNAs (miRNAs). However, the extent and functional consequences of ceRNAs in diverse cellular context still need to be proven. Using a doxycycline inducible expression of Yamanaka four factors to generate induced pluripotent stem cells (iPSCs) from mouse embryonic fibroblasts (MEFs), we found the miRNAs from MEFs remained highly expressed from day 0 to day 6 after doxycycline induction; unexpectedly, many genes targeted by these miRNAs were actually up-regulated; meanwhile, long intergenic noncoding RNAs (lincRNAs) and circular RNAs (circRNAs) which have complementary binding sites with the miRNAs were highly expressed, indicating lincRNAs and circRNAs (linc/circRNAs) may serve as sponges for miRNAs to block their activities during reprogramming. Intriguingly, the knockdown of the linc/circRNAs sponging the miRNAs targeting Oct4 mRNA resulted in down-regulation of exogenous Oct4 expression, decrease of reprogramming efficiency, and low-grade chimera forming iPSCs. Our results suggest that the ceRNA network plays an important role in reprogramming somatic cells to pluripotent stem cells.

cell biology↗

bioRxiv2018

Recent mixing of Vibrio parahaemolyticus populations

BackgroundHumans have profoundly affected the ocean environment but little is known about anthropogenic effects on the distribution of microbes. Vibrio parahaemolyticus is found in warm coastal waters and causes gastroenteritis in humans and economically significant disease in shrimps.\n\nResultsBased on data from 1,103 genomes, we show that V. parahaemolyticus is divided into four diverse populations, VppUS1, VppUS2, VppX and VppAsia. The first two are largely restricted to the US and Northern Europe, while the others are found worldwide, with VppAsia making up the great majority of isolates in the seas around Asia. Patterns of diversity within and between the populations are consistent with them having arisen by progressive divergence via genetic drift during geographical isolation. However, we find that there is substantial overlap in their current distribution. These observations can be reconciled without requiring genetic barriers to exchange between populations if dispersal between oceans has increased dramatically in the recent past. We found that VppAsia isolates from the US have an average of 1.01% more shared ancestry with VppUS1 and VppUS2 isolates than VppAsia isolates from Asia itself. Based on time calibrated trees of divergence within epidemic lineages, we estimate that recombination affects about 0.017% of the genome per year, implying that the genetic mixture has taken place within the last few decades.\n\nConclusionsThese results suggest that human activity, such as shipping and aquatic products trade, are responsible for the change of distribution pattern of this marine species.

microbiology↗