Biology subjects

Peng, M.

Publications and source records attributed to Peng, M..

43 records · Page 3Linked to original sources

bioRxiv2019

Whole-genome and RNA sequencing reveal variation and transcriptomic coordination in the developing human prefrontal cortex

Variation in gene expression underlies neurotypical development, while genomic variants contribute to neuropsychiatric disorders. BrainVar is a unique resource of paired whole-genome sequencing and bulk-tissue RNA-sequencing from the human dorsolateral prefrontal cortex of 176 neurotypical individuals across prenatal and postnatal development, providing the opportunity to assay genomic and transcriptomic variation in tandem. Leveraging this resource, we identified rare premature stop codons with commensurate reduced and allele-specific expression of corresponding genes, and common variants that alter gene expression (expression quantitative trait loci, eQTLs). Categorizing eQTLs by prenatal and postnatal effect, genes affected by temporally-specific eQTLs, compared to constitutive eQTLs, are enriched for haploinsufficiency, protein-protein interactions, and neuropsychiatric disorder risk loci. Expression levels of over 12,000 genes rise or fall in a concerted late-fetal transition, with the transitional genes enriched for cell type specific genes and neuropsychiatric disorder loci, underscoring the importance of cataloguing developmental trajectories in understanding cortical physiology and pathology.\n\nHighlightsO_LIWhole-genome and RNA-sequencing across human prefrontal cortex development in BrainVar\nC_LIO_LIGene-specific developmental trajectories characterize the late-fetal transition\nC_LIO_LIIdentification of constitutive, prenatal-specific, postnatal-specific, and rare eQTLs\nC_LIO_LIIntegrated analysis reveals genetic and developmental influences on CNS traits and disorders\nC_LI

neuroscience↗

bioRxiv2019

Prevention of enteric bacterial infections and modulation of gut microbiota composition with conjugated linoleic acids producing Lactobacillus in mice

Probiotics are recognized to outcompete pathogenic bacteria by receptor-mediated colonizing and secreting functional metabolites which have direct antimicrobial activities towards pathogens and/or improving hosts gut health and immunity. We have constructed a Lactobacillus casei (LC) probiotic strain, LC+mcra, by inserting mcra (myosin cross-reactive antigen) gene, which stimulates the conversion of conjugated linoleic acids. In this study, we evaluated the protective roles of LC+mcra against pathogenic Salmonella enterica serovar Typhimurium (ST) and enterohaemorrhagic E. coli (EHEC) infection in BALB/cJ mice. Through a series of in vivo investigation, we observed that LC+mcra colonized efficiently in mice gut and competitively reduced the infection with ST and EHEC in various locations of small and large intestine, specifically cecum, jejunum, and ileum (p<0.05). The cecal microbiota in ST-challenged mice with LC+mcra protection were positively modulated with higher relative abundances Firmicutes but lower Proteobacteria plus increased bacterial species diversity/richness based on 16S metagenomic sequencing. Based on cytokine gene expression analysis by qRT-PCR, mice pretreated with LC+mcra were found with attenuated bacterial pathogen-induced gut inflammation. Furthermore, mice fed LC+mcra daily for one week could protect themselves from the impairments caused by enteric infections with ST or EHEC. These impairments include weight loss, negative hematological changes, intestinal histological alterations, and potential death. This in vivo study suggests that daily consumption of novel conjugated linoleic acids over-producing probiotic might be efficient in improving gut intestinal microbiome composition and preventing/combating foodborne enteric bacterial infections with pathogenic Salmonella and diarrheagenic E. coli.\n\nAuthor summaryNumerous bacteria colonize throughout the gastrointestinal tract and form a complex microbial ecosystem known as gut microbiota. A balanced microbial composition is crucial for maintaining proper gut health and host defense against pathogenic microbes. However, enteric bacterial infections could cause illness and even lead to death of host when foodborne pathogens like Salmonella and enterohaemorrhagic E. coli (EHEC) invade gut intestine and cause imbalance of gut microbiota. Beneficial microbes in gastrointestinal tract such as Lactobacillus and their secreted bio-active metabolites, are potential bio-agents to improve gut immunity and outcompete bacterial pathogens. In this study, to evaluate roles of novel Lactobacillus strain LC+mcra which produce higher amount of a group of beneficial secondary metabolites called conjugated linoleic acids, we have shown that daily oral administration of this LC+mcra for one-week in mice lead to higher proportion of beneficial bacterial colonization in different locations of intestine and a significant reduction of pathogenic Salmonella and EHEC colonization. Furthermore, mice fed with LC+mcra restore and modulate Salmonella infection-induced negative impact on gut microbiota composition and protect themselves from various levels of physiological damage.

microbiology↗

bioRxiv2019

A chromosome-level genome of black rockfish, Sebastes schlegelii, provides insights into the evolution of live birth

Black rockfish (Sebastes schlegelii) is a teleost species where eggs are fertilized internally and retained in the maternal reproductive system, where they undergo development until live birth (termed viviparity). In the present study, we report a chromosome-level black rockfish genome assembly. High-throughput transcriptome analysis (RNA-seq and ATAC-seq), coupled with in situ hybridization (ISH) and immunofluorescence, identify several candidate genes for maternal preparation, sperm storage and release, and hatching. We propose that zona pellucida (ZP) genes retain sperm at the oocyte envelope, while genes in two distinct astacin metalloproteinase subfamilies serve to release sperm from the ZP and free the embryo from chorion at pre-hatching stage. Finally, we present a model of black rockfish reproduction, and propose that the rockfish ovarian wall has a similar function to uterus of mammals. Taken together, these genomic data reveal unprecedented insights into the evolution of an unusual teleost life history strategy, and provide a sound foundation for studying viviparity in non-mammalian vertebrates and an invaluable resource for rockfish ecology and evolution research.

genomics↗

bioRxiv2018

Novel genes for autism implicate both excitatory and inhibitory cell lineages in risk

We present the largest exome sequencing study to date focused on rare variation in autism spectrum disorder (ASD) (n=35,584). Integrating de novo and case-control variation with an enhanced Bayesian framework incorporating evolutionary constraint against mutation, we implicate 99 genes in ASD risk at a false discovery rate (FDR) [≤] 0.1. Of these 99 risk genes, 46 show higher frequencies of disruptive de novo variants in individuals ascertained for severe neurodevelopmental delay, while 50 show higher frequencies in individuals ascertained for ASD, and comparing ASD cases with disruptive mutations in the two groups shows differences in phenotypic presentation. Expressed early in brain development, most of the risk genes have roles in neuronal communication or regulation of gene expression, and 12 fall within recurrent copy number variant loci. In human cortex single-cell gene expression data, expression of the 99 risk genes is also enriched in both excitatory and inhibitory neuronal lineages, implying that disruption of these genes alters the development of both neuron types. Together, these insights broaden our understanding of the neurobiology of ASD.

genetics↗

bioRxiv2018

Multi-Center Study of Resectable Lung Lesions by Ultra-Deep Sequencing of Targeted Genes in Plasma Cell-Free DNA to Assess Nodule Malignancy and Detect Lung Cancers

BACKGROUNDEarly detection of lung cancer to allow curative treatment remains challenging. Cell-free circulating tumor DNA (ctDNA) analysis may aid in malignancy assessment and early cancer diagnosis of lung nodules found in screening imagery.\n\nMETHODSThe multi-center clinical study enrolled 192 patients with operable occupying lung diseases. Plasma ctDNA, white blood cell genomic DNA (gDNA) and tumor tissue gDNA of each patient were analyzed by ultra-deep sequencing to an average of 35,000X of the coding regions of 65 lung cancer-related genes.\n\nRESULTSThe cohort consists of a quarter of benign lung diseases and three quarters of cancer patients with all histopathology subtypes. 64% of the cancer patients is at Stage I. Gene mutations detection in tissue gDNA and plasma ctDNA results in a sensitivity of 91% and specificity of 88%. When ctDNA assay was used as the test, the sensitivity was 69% and specificity 96%. As for the lung cancer patients, the assay detected 63%, 83%, 94% and 100%, for Stage I, II, III and IV, respectively. In a linear discriminant analysis, combination of ctDNA, patient age and a panel of serum biomarkers boosted the overall sensitivity to 80% at a specificity of 99%. 29 out of the 65 genes harbored mutations in the lung cancer patients with the largest number found in TP53 (30% plasma and 62% tumor tissue samples) and EGFR (20% and 40%, respectively).\n\nCONCLUSIONPlasma ctDNA was analyzed in lung nodule assessment and early cancer detection while an algorithm combining clinical information enhanced the test performance.

clinical trials↗

bioRxiv2017

Identity-By-Descent Refines Mapping Of Candidate Regions For Preaxial Polydactyly In A Large Chinese Pedigree

Preaxial polydactyly (PPD) is congenital hand malformation characterized by the duplication of digit. Herein, we scan the genome-wide SNPs for a large Chinese family with PPD-II/III. We employ the refined IBD algorithm to identify the identity-by-decent (IBD) segments and compare the frequency among the patients and normal relatives. A total of 72 markers of 0.01 percentile of the permutation are identified as the peak signals. Among of them, 57markers locate on chromosome 7q36 which is associated with PPD. Further analyses refine the mapping of candidate region in chromosome 7q36 into two 380 Kb fragments within LMBR1 and SHH respectively. IBD approach is a suitable method for mapping cause gene of human disease. Target-enrichment sequencing as well as functional experiments are required to illustrate the pathogenic mechanisms for PPD in the future.

genetics↗

bioRxiv2017

A Cassava Drought Inducible CC-Type Glutaredoxin, MeGRX232, Negatively Regulates Drought Tolerance In Arabidopsis By Inhibition Of ABA-Dependent Stoma

CC-type glutaredoxins (GRXs) are a land plant-specific GRX subgroup that evolved from CGFS GRXs, and participate in organ development and stress responses through the regulation of transcription factors. Here, genome-wide analysis identified 18 CC-type GRXs in the cassava genome, of which six (MeGRX058, 232, 360, 496, 785, and 892) were induced by drought and ABA stress in cassava leaves. Furthermore, we found that overexpression of MeGRX232 results in drought hypersensitivity in soil-grown plants, with a higher water loss rate, but with increased tolerance of mannitol and ABA in Arabidopsis on the sealed agar plates. The ABA induced stomatal closure is impaired in MeGRX232-OE Arabidopsis. Further analysis reveals that the overexpression of MeGRX232 leads to more ROS accumulation in guard cells. MeGRX232 can interact with TGA5 from Arabidopsis and MeTGA074 from cassava in vitro and in vivo. The results of microarray assays show that MeGRX232-OE affected the expression of a set of drought and oxidative stress related genes. Taken together, we demonstrated that CC-type GRXs involved in ABA signal transduction and play roles in response to drought through regulating stomatal closure.\n\nNovelty statementWe found that drought and ABA stress induced the transcription of CC-type glutaredoxins (GRXs) in cassava leaves. Ectopic expression of one of them, MeGRX232 in Arabidopsis affected the sensitivity to abscisic acid (ABA) and mannitol, and caused drought hypersensitivity by impairment of ABA-dependent stomatal closure.

molecular biology↗