Biology subjects

Meng, Q.

Publications and source records attributed to Meng, Q..

At least 55 records · Page 3Linked to original sources

bioRxiv2021

Fully resolved assembly of Cryptosporidium parvum

BackgroundCryptosporidium parvum is an apicomplexan parasite commonly found across many host species with a global infection prevalence in human populations of 7.6%. As such, it is important to understand the diversity and genomic makeup of this prevalent parasite to fight established infections and prohibit further transmission. The basis of every genomic study is a high quality reference genome that has continuity and completeness, thus enabling comprehensive comparative studies. FindingsHere, we provide a highly accurate and complete reference genome of Cryptosporidium parvum. The assembly is based on Oxford Nanopore reads and was improved using Illumina reads for error correction. We also outline how to evaluate and choose from different assembly methods based on two main approaches that can be applied to other Cryptosporidium species. The assembly encompasses 8 chromosomes and includes 13 telomeres that were resolved. Overall, the assembly shows a high completion rate with 98.4% single copy BUSCO genes. ConclusionsThis high quality reference genome of a zoonotic IIaA17G2R1 C. parvum subtype isolate provides the basis for subsequent comparative genomic studies across the Cryptosporidium clade. This will enable improved understanding of diversity, functional and association studies.

genomics↗

bioRxiv2021

Construction of a new chromosome-scale, long-read reference genome assembly of the Syrian hamster, Mesocricetus auratus

BackgroundThe Syrian hamster (Mesocricetus auratus) has been suggested as a useful mammalian model for a variety of diseases and infections, including infection with respiratory viruses such as SARS-CoV-2. The MesAur1.0 genome assembly was generated in 2013 using whole-genome shotgun sequencing with short-read sequence data. Current more advanced sequencing technologies and assembly methods now permit the generation of near-complete genome assemblies with higher quality and greater continuity. FindingsHere, we report an improved assembly of the M. auratus genome (BCM_Maur_2.0) using Oxford Nanopore Technologies long-read sequencing to produce a chromosome-scale assembly. The total length of the new assembly is 2.46 Gbp, similar to the 2.50 Gbp length of a previous assembly of this genome, MesAur1.0. BCM_Maur_2.0 exhibits significantly improved continuity with a scaffold N50 that is 6.7 times greater than MesAur1.0. Furthermore, 21,616 protein coding genes and 10,459 noncoding genes are annotated in BCM_Maur_2.0 compared to 20,495 protein coding genes and 4,168 noncoding genes in MesAur1.0. This new assembly also improves the unresolved regions as measured by nucleotide ambiguities, where approximately 17.11% of bases in MesAur1.0 were unresolved compared to BCM_Maur_2.0 in which the number of unresolved bases is reduced to 3.00%. ConclusionsAccess to a more complete reference genome with improved accuracy and continuity will facilitate more detailed, comprehensive, and meaningful research results for a wide variety of future studies using Syrian hamsters as models.

genomics↗

bioRxiv2021

NanoSpring: reference-free lossless compression of nanopore sequencing reads using an approximate assembly approach

The amount of data produced by genome sequencing experiments has been growing rapidly over the past several years, making compression important for efficient storage, transfer and analysis of the data. In recent years, nanopore sequencing technologies have seen increasing adoption since they are portable, real-time and provide long reads. However, there has been limited progress on compression of nanopore sequencing reads obtained in FASTQ files since most existing tools are either general-purpose or specialized for short read data. We present NanoSpring, a reference-free compressor for nanopore sequencing reads, relying on an approximate assembly approach. We evaluate NanoSpring on a variety of datasets including bacterial, metagenomic, plant, animal, and human whole genome data. For recently basecalled high quality nanopore datasets, NanoSpring, which focuses only on the base sequences in the FASTQ file, uses just 0.35-0.65 bits per base which is 3-6x lower than general purpose compressors like gzip. NanoSpring is competitive in compression ratio and compression resource usage with the state-of-the-art tool CoLoRd while being significantly faster at decompression. NanoSpring is available on GitHub at https://github.com/qm2/NanoSpring.

bioinformatics↗

bioRxiv2021

Genome of the giant panda roundworm illuminates its host shift and parasitic adaptation

Baylisascaris schroederi, a bamboo-feeding giant panda (Ailuropoda melanoleuca)-specific roundworm (ascaridoid) parasite, is the causative agent of baylisascariasis, which represents a leading reason for the mortality of wild giant panda populations and therefore poses a significant threat to giant panda conservation. Here we present a 293-Mb chromosome-level genome assembly of B. schroederi to inform its biology, including host adaptations. Comparative genomics revealed an evolutionary trajectory accompanied by host-shift events in ascaridoid parasite lineages after host separations, suggesting their potential transmissions and fast adaptations to hosts. Genomic and anatomical lines of evidence, including expansion and positive selection of genes related to cuticle and basal metabolisms, indicates that B. schroederi undergoes specific adaptations to survive in the sharp-edged bamboo enriched gut of giant panda by structurally increasing its cuticle thickness and efficiently utilizing host nutrients during gut parasitism. Also, we characterized the secretome and predicted potential drug and vaccine targets for new interventions. Overall, this genome resource provides new insights into the host adaptation of B. schroederi to giant panda as well as the host-shift events in ascaridoid parasite lineages. These findings also add to our knowledge on the unique biology of the giant panda roundworm and aid the development of much-needed novel strategies for the control of baylisascariasis and thus the protection of giant panda populations.

genomics↗

bioRxiv2021

The Impact of a Dynamic Working Environment on Human Gut Microbiota

Gut microbiota dysbiosis is associated with a variety of diseases, such as inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS), metabolic diseases, allergic diseases, neurodevelopmental disorders and cancer. The human gut microbiota can be influenced by a variety of factors, including geography, dietary habits, living environment, age and altered lifestyle etc. This study was conducted to explore the gut microbiota compositions in officials who are in a stable working environment and train drivers who are in a dynamic working environment. Microbiota communities in the feces of 80 officials and 88 train drivers were analyzed using Illumina MiSeq sequencing targeting the V3-V4 region of 16S ribosomal RNA (rRNA) gene and ITS1 region of fungi. There were significant differences between the two groups in diversity and richness of gut microbiota, while the microbial community compositions of the two groups were similar. The relationship between gut microbiota and clinical characteristics was investigated. We found that more bacteria and fungi were positively correlated with clinical characteristics. Functional prediction analysis of the gut microbiota between the two groups by PICRUSt2 revealed significant differences between the official group and the train driver group. Elucidating these differences of the microbiome between the two groups will provide a foundation understanding of the impact of a dynamic environment on gut microbiota.

microbiology↗

bioRxiv2021

Neptune: An environment for the delivery of genomic medicine

PurposeGenomic medicine holds great promise for improving healthcare, but integrating searchable and actionable genetic data into electronic health records remains a challenge. Here, we describe Neptune, a system for managing the interaction between a clinical laboratory and an electronic health record system. MethodsWe developed Neptune and applied it to two clinical sequencing projects that required report customization, variant reanalysis and EHR integration. ResultsNeptune enabled the analysis of data for generation of and delivery to EHR systems of over 15,000 clinical genomic reports. These projects demanded customizable clinical reports that contained a variety of genetic data types including SNVs, CNVs, pharmacogenomics and polygenic risk scores. Two variant reanalysis activities were also supported, highlighting this important workflow. ConclusionsMethods are needed for delivering structured genetic data to EHRs. This need extends beyond developing data formats to providing infrastructure that manages the reporting process itself. Neptune was successfully applied on two high-throughput clinical sequencing projects to build and deliver clinical reports to EHR systems. The software is open and available at https://gitlab.com/bcm-hgsc/neptune.

bioinformatics↗

bioRxiv2020

Functional tagging of endogenous proteins and rapid selection of cell pools (Rapid generation of endogenously tagged piwi in ovarian somatic sheath cells.)

The combination of genome-editing and epitope tagging provides a powerful strategy to study proteins with high affinity and specificity while preserving their physiological expression patterns. However, stably modifying endogenous genes in cells that do not allow for clonal selection has been challenging. Here, we present a simple and fast strategy to generate stable, endogenously tagged alleles in a non-transformed cell culture model. At the example of piwi in Drosophila ovarian somatic sheath cells, we show that this strategy enables the generation of an N-terminally tagged protein that emulates the expression level and subcellular localization of the wild type protein and forms functional Piwi-piRNA complexes. We present a concise workflow to establish modified cells, characterize the edited allele and probe the function of the tagged protein.

cell biology↗

bioRxiv2020

Oligonucleotide Capture Sequencing of the SARS-CoV-2 Genome and Subgenomic Fragments from COVID-19 Individuals

The newly emerged and rapidly spreading SARS-CoV-2 causes coronavirus disease 2019 (COVID-19). To facilitate a deeper understanding of the viral biology we developed a capture sequencing methodology to generate SARS-CoV-2 genomic and transcriptome sequences from infected patients. We utilized an oligonucleotide probe-set representing the full-length genome to obtain both genomic and transcriptome (subgenomic open reading frames [ORFs]) sequences from 45 SARS-CoV-2 clinical samples with varying viral titers. For samples with higher viral loads (cycle threshold value under 33, based on the CDC qPCR assay) complete genomes were generated. Analysis of junction reads revealed regions of differential transcriptional activity and provided evidence of expression of ORF10. Heterogeneous allelic frequencies along the 20kb ORF1ab gene suggested the presence of a defective interfering viral RNA species subpopulation in one sample. The associated workflow is straightforward, and hybridization-based capture offers an effective and scalable approach for sequencing SARS-CoV-2 from patient samples.

genomics↗

bioRxiv2020

Clonal expansion of personalized anti-tumor T cells from circulation using tumor organoid-immune co-cultures

Tumor-specific cytotoxic T cells are effective tools for cancer immunotherapy, but the ability to generate them continues to be a challenge. Furthermore, there are no compelling approaches to empirically identify tumor-targeting T cells and T cell receptors by exploiting the multitude of antigens on tumor cell surfaces. Here, we use patients peripheral blood and autologous tumor organoids to enrich tumor-specific cytotoxic T cells with patient-specific killing mechanisms and a tissue-resident memory phenotype. We further demonstrate that these organoid-primed T (opT) cells undergo several orders of magnitude of clonal expansion and express T cells receptors and check-point proteins unique to each patient. Importantly, transferring the TCRs to heterologous T cells was sufficient to confer tumor recognition in a patient-specific manner. Thus, we report a patient-specific and antigen-agnostic platform for expansion of tumor-targeting T cells and identification of cancer-targeting TCRs from the peripheral blood of pancreatic cancer patients that can be exploited for immunotherapy applications.

cancer biology↗

bioRxiv2020

Multi-tissue Multi-omics Nutrigenomics Indicates Context-specific Effects of DHA on Rat Brain

ScopeWe explored the influence of DHA on cardiometabolic and cognitive phenotypes, and multiomic alterations in the brain under two metabolic conditions to understand context-specific nutritional effects. Methods and ResultsRats were randomly assigned to a DHA-rich or a control chow diet while drinking water or high fructose solution, followed by profiling of metabolic and cognitive phenotypes and the transcriptome and DNA methylome of the hypothalamus and hippocampus. DHA reduced serum triglyceride and improved insulin resistance and memory exclusively in the fructose-consuming rats. In hippocampus, DHA affected genes related to synapse functions in the chow group but immune functions in the fructose group; in hypothalamus, DHA altered immune pathways in the chow group but metabolic pathways in the fructose group. Network modeling revealed context-specific regulators of DHA effects, including Klf4 and Dusp1 for chow condition and Lum, Fn1, and Col1a1 for fructose condition in hippocampus, as well as Cyr61, JunB, Ier2, and Pitx2 under chow condition and Hcar1, Cdh1, and Osr1 under fructose condition in hypothalamus. ConclusionDHA exhibits differential influence on epigenetic loci, genes, pathways, and metabolic and cognitive phenotypes under different dietary contexts, supporting population stratification in DHA studies to achieve precision nutrition.

systems biology↗

bioRxiv2020

Oligonucleotide capture sequencing of the SARS-CoV-2 genome and subgenomic fragments from COVID-19 individuals

microbiology↗

bioRxiv2020

SARS-CoV-2 envelope protein causes acute respiratory distress syndrome (ARDS)-like pathological damage and constitutes an antiviral target

Cytokine storm and multi-organ failure are the main causes of SARS-CoV-2-related death. However, the origin of the virus excessively damaging abilities remains unknown. Here we show that the SARS-CoV-2 envelope (2-E) protein alone is sufficient to cause acute respiratory distress syndrome (ARDS)-like damage in vitro and in vivo. Overexpression of 2-E protein induced rapid pyroptosis-like cell death in various susceptible cells and robust secretion of cytokines and chemokines in macrophages. Intravenous administration of purified 2-E protein into mice caused ARDS-like pathological damage in lung and spleen. Overexpressed 2-E protein formed cation channels in host cell membranes, eventually leading to membrane rupture. Newly identified channel inhibitors exhibited potent anti-SARS-CoV-2 activity and excellent protective effects against the 2-E-induced damage both in vitro and in vivo. Importantly, their channel inhibition, cell protection and antiviral activities were positively correlated with each other, supporting 2-E is a promising drug target against SARS-CoV-2.

microbiology↗

bioRxiv2020

Identification of PDE6D as a potential target of sorafenib via PROTAC technology

The identification of unknown target of a multi-kinase inhibitor sorafenib is important to better understand the mechanism of action of this drug in anti-cancer and anti-fibrotic treatments. Here, we report the combination of PROTAC technique with quantitative proteomic analysis to identify the unknown cellular targets of sorafenib. Sorafenib-based PROTAC can strongly degrade a non-kinase target PDE{delta} in different types of cells. We also confirmed the direct binding interaction of PDE{delta} with sorafenib by CETSA and SPR assays. Together, our research suggests that PDE{delta} is a new potential target of sorafenib, and PROTAC technology may be a promising approach for cellular target identification of bioactive compounds of interest.

biochemistry↗

bioRxiv2020

A quasi-paired cohort strategy reveals the impaired detoxifying function of microbes in the gut of autistic children

Growing evidence suggests that autism spectrum disorder (ASD) is highly associated with dysbiosis in the gut microbiome. However, results of metagenome-based microbiome studies are not always consistent due to great individual diversity that overwhelms disease-associated alterations. Here, we proposed a novel analysis strategy--quasi-paired cohort and applied it to a metagenomic study of ASD microbiomes. By comparing the paired samples of ASD and neurotypical subjects, we identified significant deficiencies in ASD children in detoxifying enzymes and pathways, which showed strong correlations to mitochondrial damage. Diagnostic models with these detoxifying enzymes accurately discriminated ASD individuals from controls, and the dysfunction score inferred from the model increased with the clinical rating scores of ASD. Conclusively, our findings suggest a previously undiscovered mechanism in which impaired microbial detoxification leads to toxicant accumulation and mitochondrion damage contributes to the pathogenesis of ASD. This novel mechanism points to future therapeutic strategies of rebuilding microbial detoxification for ASD.

microbiology↗

bioRxiv2020

Concurrent MEG-articulography for investigating neuromotor control of speech articulation

Articulography and functional neuroimaging are two major tools for studying the neurobiology of speech production. Until now, however, it has generally not been possible to use both in the same experimental setup because of technical incompatibilities between the two methodologies. Here we describe results from a novel articulography system dubbed Magneto-articulography for the Assessment of Speech Kinematics (MASK), used for the first time to obtain kinematic profiles of oro-facial movements during speech together with concurrent magnetoencephalographic (MEG) measurements of neuromotor brain activity. MASK was used to characterise speech kinematics in a healthy adult, and the results were compared to measurements from the same participant with a conventional electromagnetic articulography (EMA) setup. We also characterised speech movement kinematics with MASK in a group of ten typically developing children, aged 8-12 years. Analyses targeted the gestural landmarks of the utterances /ida/, /ila/ and reiterated productions of /pataka/. These results demonstrate that the MASK technique can be used to reliably characterise movement profiles and kinematic parameters that reflect development of speech motor control, together with MEG measurements of brain responses from speech sensorimotor cortex. This new capability sets the stage for cross-disciplinary efforts to understand the developmental neurobiology of human speech production.

neuroscience↗

bioRxiv2020

Lateralised cerebral processing of abstract linguistic structure in clear and degraded speech

Providing a plausible neural substrate of speech processing and language comprehension, cortical activity has been shown to track different levels of linguistic structure in connected speech (syllables, phrases and sentences), independent of the physical regularities of the acoustic stimulus. In the current study, we investigated the effect of speech intelligibility on this brain activity as well as the underlying neural sources. Using magnetoencephalography (MEG), brain responses to natural speech and noise-vocoded (spectrally-degraded) speech in nineteen normal hearing participants were measured. Results showed that cortical MEG coherence to linguistic structure changed parametrically with the intelligibility of the speech signal. Cortical responses coherent with phrase and sentence structures were lefthemisphere lateralized, whereas responses coherent to syllable/word structure were bilateral. The enhancement of coherence to intelligible compared to unintelligible speech was also left lateralized and localized to the parasylvian cortex. These results demonstrate that cortical responses to higher level linguistics structures (phrase and sentence level) are sensitive to speech intelligibility. Since the noise-vocoded sentences simulate the auditory input provided by a cochlear implant, such objective neurophysiological measures have potential clinical utility for assessment of cochlear implant performance.

neuroscience↗

bioRxiv2019

\"GPress: a framework for querying General Feature Format (GFF) files and feature expression files in a compressed form\"

11.1 MotivationSequencing data are often summarized at different annotation levels for further analysis. The general feature format (GFF) and its descendants, the gene transfer format (GTF) and GFF3, are the most commonly used data formats for genomic annotations. These files are extensively updated, queried and shared, and hence as the number of generated GFF files increases, efficient data storage and retrieval are becoming increasingly important. Existing GFF utilities for accessing these files, like gffutils and gffread, do not focus on reducing the storage space, significantly increasing it in some cases. Hence, we propose GPress, a framework for querying GFF files in a compressed form. In addition, GPress can also incorporate and compress feature expression files, supporting simultaneous queries on both files.\n\n1.2 ResultsWe tested GPress on several GFF files of different organisms, and showed that it achieves on average a 98% reduction in size, while being able to retrieve all annotations for a given identifier or a range of coordinates in a few seconds. For example, on a Human GFF file, GPress can find all items with a unique identifier in 2.47 seconds and all items with coordinates within the range of 1,000 to 100,000 in 4.61 seconds. In contrast, gffutils provides faster retrieval but doubles the size of the GFF files. When additionally linking an expression file, we show that GPress can reduce the size of the expression file by more than 92%, while still retrieving the information within seconds. GPress is freely available at https://github.com/qm2/gpress.

bioinformatics↗

bioRxiv2019

Angle-tuned Coil: A Focal Spot-size Adjustable Transcranial Magnetic Stimulator

BackgroundConventional transcranial magnetic stimulation (TMS) coils are limited by the depth-focality tradeoff rule and the emission field intensity from coils with either small or large apertures will diverge quickly at less than one aperture diameter distance away from the coil. To utilize a better depth-focality tradeoff rule and accomplish deep and focused stimulation, a new approach needs to be employed.\n\nObjectivesWe report a new TMS coil design that can deliver deep and spot size adjustable stimulation to deep brain regions.\n\nMethodsIn our design, we introduce a magnetic core at the center of a coil to help confine the magnetic field and prevent leakage. We further tilted the wire wrapping angle of the coil to break its ring symmetry and accomplish tunable focusing by adjusting the tilting angle.\n\nResultsBy comparing the electric field decay curves of five types of coils, our results concluded the proposed novel method to improve the coils depth-focality profile. Both theoretical calculations and experimental data collectively demonstrated that by using a larger tilting angle, we were able to accomplish a more tightly focused stimulation at any distance away from the coil.\n\nConclusionEnlarging the tilting angle of the coil wire wrapping and applying magnetic core significantly improved the spatial resolution of the field without inducing considerable effect on field decay speed. Our novel TMS coil design plots a new curve in the depth-focality profile with better performance than the existing conventional coil designs in the tradeoff rule.

bioengineering↗