Biology subjects

Huang, Q.

Publications and source records attributed to Huang, Q..

11 recordsLinked to original sources

bioRxiv2018

DNA copy number imbalances in primary cutaneous lymphomas (PCL)

Cutaneous lymphomas (CL) represent a clinically defined group of extranodal non-Hodgkin lymphomas harboring heterogeneous and incompletely delineated molecular aberrations. Over the past decades, molecular studies have identified several chromosomal aberrations, but the interpretation of individual genomic studies can be challenging.\n\nWe conducted a meta-analysis to delineate genomic alterations for different types of PCL. Searches of PubMed and ISI Web of Knowledge for the years 1996 to 2016 identified 32 publications reporting the investigation of PCL for genome-wide copy number alterations, by means of comparative genomic hybridization techniques and whole genome and exome sequencing. For 449 samples from 22 publications, copy number variation data was accessible for sample based meta-analysis. Summary profiles for genomic imbalances, generated from case-specific data, identified complex genomic imbalances, which could discriminate between different subtypes of CL and promise a more accurate classification. The collected data presented in this study are publicly available through the \"Progenetix\" online repository.

cancer biology↗

bioRxiv2018

Divergence in the face of gene flow in two Charadrius plovers along the Chinese coast

Speciation with gene flow is an alternative to the nascence of new taxa in strict allopatric separation. Indeed, many taxa have parapatric distributions at present. It is often unclear if these are secondary contacts, e.g. caused by past glaciation cycles or the manifestation of speciation with gene flow, which hampers our understanding of how different forces drive diversification. Here we studied genetic, phenotypic and ecological aspects of divergence in a pair of incipient species, the Kentish (Charadrius alexandrinus) and the white-faced Plovers (C. dealbatus), shorebirds with parapatric breeding ranges along the Chinese coast. We assessed divergence based on molecular markers with different modes of inheritance and quantified phenotypic and ecological divergence in aspects of morphometric, dietary and climatic niches. These analyses revealed small to moderate levels of genetic and phenotypic distinctiveness with symmetric gene flow across the contact area at the Chinese coast. The two species diverged approximately half a million years ago in dynamical isolation and secondary contact due to cycling sea level changes between the Eastern and Southern China Sea in the mid-late Pleistocene. We found evidence of character displacement and ecological niche differentiation between the two species, invoking the role of selection in facilitating divergence despite gene flow. These findings imply that the ecology can indeed counter gene flow through divergent selection and thus contribute to incipient speciation in these plovers. Furthermore, our study highlights the importance of using integrative datasets to reveal the evolutionary history and underlying mechanisms of speciation.

evolutionary biology↗

bioRxiv2018

BAMM-SC: A Bayesian mixture model for clustering droplet-based single cell transcriptomic data from population studies

The recently developed droplet-based single cell transcriptome sequencing (scRNA-seq) technology makes it feasible to perform a population-scale scRNA-seq study, in which the transcriptome is measured for tens of thousands of single cells from multiple individuals. Despite the advances of many clustering methods, there are few tailored methods for population-scale scRNA-seq studies. Here, we have developed a BAyesiany Mixture Model for Single Cell sequencing (BAMM-SC) method to cluster scRNA-seq data from multiple individuals simultaneously. Specifically, BAMM-SC takes raw data as input and can account for data heterogeneity and batch effect among multiple individuals in a unified Bayesian hierarchical model framework. Results from extensive simulations and application of BAMM-SC to in-house scRNA-seq datasets using blood, lung and skin cells from humans or mice demonstrated that BAMM-SC outperformed existing clustering methods with improved clustering accuracy and reduced impact from batch effects. BAMM-SC has been implemented in a user-friendly R package with a detailed tutorial available on www.pitt.edu/~Cwec47/singlecell.html.

bioinformatics↗

bioRxiv2018

Fast-backward replay of sequentially memorized items in humans

Storing temporal sequences of events (i.e., sequence memory) is fundamental to many cognitive functions. However, how the sequence order information is maintained and represented in working memory and its behavioral significance, particularly in human subjects, remains unknown. Here, we recorded electroencephalography (EEG) in combination with a temporal response function (TRF) method to dissociate item-specific neuronal reactivations. We demonstrate that serially remembered items are successively reactivated during memory retention. The sequential replay displays two interesting properties compared to the actual sequence. First, the item-by-item reactivation is compressed within a 200-400 ms window, suggesting that external events are associated within a plasticity-relevant window to facilitate memory consolidation. Second, the replay is in a temporally reversed order and is strongly related to the recency effect in behavior. This fast-backward replay, previously revealed in rat hippocampus and demonstrated here in human cortical activities, might constitute a general neural mechanism for sequence memory and learning.

neuroscience↗

bioRxiv2018

Mother centrioles are dispensable for deuterosome formation and function during basal body amplification

Mammalian epithelial cells use a pair of mother centrioles (MCs) and numerous deuterosomes as platforms for efficient basal body assembly during multiciliogenesis. How deuterosomes form and function, however, remain controversial. They are proposed to either arise spontaneously followed by maturation into larger ones with increased procentriole-producing capacity or be assembled solely on the young MC, nucleate procentrioles under the MCs guidance, and released as procentriole-occupied \"halos\". Here we show that both MCs are dispensable for deuterosome formation in multiciliate cells. In both mouse tracheal epithelial and ependymal cells (mTECs and mEPCs), discrete deuterosomes in the cytoplasm were initially procentriole-free and then grew into halos. More importantly, eliminating the young MC or both MCs in proliferating precursor cells through shRNA-mediated depletion of Plk4, a kinase essential to procentriole assembly, did not abolish deuterosome formation when these cells were induced to differentiate into mEPCs. The average deuterosome numbers per cell only reduced by 21% as compared to control mEPCs. Therefore, MC is not essential to the assembly of both deuterosomes and deuterosome-mediated procentrioles.

cell biology↗

bioRxiv2018

Population assignment from cancer genome profiling data

For a variety of human malignancies, incidence, treatment efficacy and overall prognosis show considerable variation between different populations and ethnic groups. Disentangling the effects related to particular population backgrounds can help in both understanding cancer biology and in tailoring therapeutic interventions. Because self-reported or inferred patient data can be incomplete or misleading due to migration and genomic admixture, a data-driven ancestry estimation should be preferred. While algorithms to analyze ancestry structure from healthy individuals have been developed, an easy-to-use tool to assign population groups based on genotyping data from SNP profiles is still missing and benchmarking for the validity of population assignment strategy for aberrant cancer genomes was not tested.\n\nWe benchmarked the consistency and accuracy of cross-platform population assignment. We also demonstrated its high accuracy to process unaltered as well as cancer genomes. Despite widespread and extensive somatic mutations of cancer profiling data, population assignment consistency between germline and highly mutated samples from cancer patients reached of 97% and 92% for assignment into 5 and 26 populations re-spectively. Comparison of our benchmarked results with self-reported meta-data estimated a matching rate between 88% to 92%. Despite a relatively high matching rate, the ethnicity labels indicated in meta-data are vague compared to the standardized output from our tool.\n\nWe have developed a bioinformatics tool to assign the populations from genome profiling data and validated its performance in healthy as well as aberrant cancer genomes. It is ready-to-use for genotyping data from nine commercial SNP array platforms or sequencing data. This tool is effective to scrutinize the population structure in cancer genomes and provides better measure to integrate genotyping data from various platforms instead of self-reported information. It will facilitate research on interplay between ethnicity related genetic background and molecular patterns in cancer entities and disentangling possible hereditary contributions.\n\nThe docker image of the tool is provided in DockerHub as \"baudisgroup/snp2pop\".

bioinformatics↗

bioRxiv2018

Structural determinants of the interactions between Influenza A Virus Matrix protein M1 and lipid membranes

Influenza A virus is a pathogen responsible for severe seasonal epidemics threatening human and animal populations every year. One of the ten proteins encoded by the viral genome, the matrix protein M1, is abundantly produced in infected cells and plays a structural role in determining the morphology of the virus. During assembly of new viral particles, M1 is recruited to the host cell membrane where it associates with lipids and other viral proteins. The structure of M1 is only partially known. In particular, structural details of M1 interactions with the cellular plasma membrane as well as M1-protein interactions and multimerization have not been clarified, yet.\n\nIn this work, we employed a set of complementary experimental and theoretical tools to tackle these issues. Using raster image correlation, surface plasmon resonance and circular dichroism spectroscopies, we quantified membrane association and oligomerization of full-length M1 and of different genetically engineered M1 constructs (i.e., N- and C-terminally truncated constructs and a mutant of the polybasic region, residues 95-105). Furthermore, we report novel information on structural changes in M1 occurring upon binding to membranes. Our experimental results are corroborated by an all-atom model of the full-length M1 protein bound to a negatively charged lipid bilayer.

biophysics↗

bioRxiv2018

Co-culture of soil biofilm isolates enables the discovery of novel antibiotics

Bacterial natural products (NPs) are considered to be a promising source of drug discovery. However, the biosynthesis gene clusters (BGCs) of NP are not often expressed, making it difficult to identify them. Recently, the study of biofilm community showed bacteria may gain competitive advantages by the secretion of antibiotics, implying a possible way to screen antibiotic by evaluating the social behavior of bacteria. In this study, we have described an efficient workflow for novel antibiotic discovery by employing the bacterial social interaction strategy with biofilm cultivation, co-culture, transcriptomic and genomic methods. We showed that a biofilm dominant species, i.e. Pseudomonas sp. G7, which was isolated from cultivated soil biofilm community, was highly competitive in four-species biofilm communities, as the synergistic combinations preferred to exclude this strain while the antagonistic combinations did not. Through the analysis of transcriptomic changes in four-species co-culture and the complete genome of Pseudomonas sp. G7, we finally discovered two novel non-ribosomal polypeptide synthetic (NRPS) BGCs, whose products were predicted to have seven and six amino acid components, respectively. Furthermore, we provide evidence showing that only when Pseudomonas sp. G7 was co-cultivated with at least two or three other bacterial species can these BGC genes be induced, suggesting that the co-culture of the soil biofilm isolates is critical to the discovery of novel antibiotics. As a conclusion, we set a model of applying microbial interaction to the discovery of new antibiotics.

microbiology↗

bioRxiv2018

segment_liftover: a Python tool to convert segments between genome assemblies

The process of assembling a species reference genome may be performed in a number of iterations, with subsequent genome assemblies differing in the coordinates of mapped elements. The conversion of genome coordinates between different assemblies is required for many integrative and comparative studies. While currently a number of bioinformatics tools are available to accomplish this task, most of them are tailored towards the conversion of single genome coordinates. When converting the boundary positions of segments spanning larger genome regions, segments may be mapped into smaller subsegments if the original segments continuity is disrupted in the target assembly. Such a conversion may lead to a relevant degree of data loss in some circumstances such as copy number variation (CNV) analysis, where the quantitative representation of a genomic region takes precedence over base-specific accuracy. segment_liftover aims at continuity-preserving remapping of genome segments between assemblies and provides features such as approximate locus conversion, automated batch processing and comprehensive logging to facilitate processing of datasets containing large numbers of structural genome variation data.

bioinformatics↗

bioRxiv2017

Relevance of host cell surface glycan structure for cell specificity of influenza A virus

Influenza A viruses (IAV) initiate infection via binding of the viral hemagglutinin (HA) to sialylated glycan receptors on host cells. HAs receptor specificity towards sialic acid (SA) is well studied and clearly critical for virus infection, but the contribution of the highly complex cellular plasma membrane to the cellular specificity remains elusive. In addition, some studies indicated that other host cell factors such as the epidermal growth factor receptor might contribute to the initial virus-cell contact and further downstream signaling1.\n\nHere we use two complementary methods, glycan arrays and single-virus force spectroscopy (SVFS) to compare influenza virus receptor specificity with actual host cell binding. Unexpectedly, our study reveals that HAs receptor binding preference does not necessarily reflect virus-cell specificity. We propose SVFS as a tool to elucidate the cell binding preference of IAV thereby including the complex environment of sialylated receptors within the plasma membrane of living cells.

microbiology↗

bioRxiv2017

Signal Peptide Hydrophobicity Modulates Interaction With The Twin-Arginine Translocase

The general secretory pathway (Sec) and twin-arginine translocase (Tat) operate in parallel to export proteins across the cytoplasmic membrane of prokaryotes and the thylakoid membrane of plant chloroplasts. Substrates are targeted to their respective machineries by N-terminal signal peptides that share a common tripartite organization, however Tat signal peptides harbor a conserved and almost invariant arginine pair that are critical for efficient targeting to the Tat machinery. Tat signal peptides interact with a membrane-bound receptor complex comprised of TatB and TatC components, with TatC containing the twin-arginine recognition site. Here we isolated suppressors in the signal peptide of the Tat substrate, SufI, that restored Tat transport in the presence of inactivating substitutions in the TatC twin-arginine binding site. These suppressors increased signal peptide hydrophobicity, and co-purification experiments indicated that they restored binding to the variant TatBC complex. The hydrophobic suppressors could also act in cis to suppress substitutions at the signal peptide twin-arginine motif that normally prevent targeting to the Tat pathway. Highly hydrophobic variants of the SufI signal peptide containing four leucine substitutions retained the ability to interact with the Tat system. The hydrophobic signal peptides of two Sec substrates, DsbA and OmpA, containing twin lysine residues, were shown to mediate export by the Tat pathway and to co-purify with TatBC. These findings indicate that there is unprecedented overlap between Sec and Tat signal peptides and that neither the signal peptide twin-arginine motif nor the TatC twin-arginine recognition site are essential mechanistic features for operation of the Tat pathway.\n\nImportanceProtein export is an essential process in all prokaryotes, The Sec and Tat export pathways operate in parallel, with the Sec machinery transporting unstructured precursors and the Tat pathway transporting folded proteins. Proteins are targeted to the Tat pathway by N-terminal signal peptides that contain an almost invariant twin-arginine motif. Here we make the surprising discovery that the twin-arginines are not essential for recognition of substrates by the Tat machinery, and that this requirement can be bypassed by increasing the signal peptide hydrophobicity. We further show that signal peptides of bona fide Sec substrates can also mediate transport by the Tat pathway. Our findings suggest that key features of the Tat targeting mechanism have evolved to prevent mis-targeting of substrates to the Sec pathway rather than being a critical requirement for function of the Tat pathway.

microbiology↗