Biology subjects

Liao, Q.

Publications and source records attributed to Liao, Q..

27 records · Page 2Linked to original sources

bioRxiv2021

Identification of cardiac afterload dynamics from data

The prospect of ex vivo functional evaluation of donor hearts is considered. Particularly, the dynamics of a synthetic cardiac afterload model are compared to those of normal physiology. A method for identification of continuous-time transfer functions from sampled data is developed and verified against results from the literature. The method relies on exact gradients and Hessians obtained through automatic differentiation. This also enables straightforward sensitivity analyses. Such analyses reveal that the 4-element Windkessel model is not practically identifiable from representative data while the 3-element model underfits the data. Pressure-volume (PV) loops are therefore suggested as an alternative for comparing afterload dynamics.

bioengineering↗

bioRxiv2020

The jasmine (Jasminum sambac) genome and flower fragrances

Jasminum sambac, a world-renowned plant appreciated for its exceptional flower fragrance, is of cultural and economic importance. However, the genetic basis of its fragrance is largely unknown. Here, we present the first de novo genome of J. sambac with 550.12 Mb (scaffold N50 = 40.1 Mb) assembled into 13 pseudochromosomes. Terpene synthase genes associated with flower fragrance are significantly amplified in the form of gene clusters through tandem duplications in the genome. Eleven homolog genes within the SABATH super-family were identified as related to phenylpropanoid/benzenoid compounds. Several key genes regulating jasmonate biosynthesis were duplicated causing increased copy numbers. Furthermore, multi-omics analyses identified various aromatic compounds and the key genes involved in fragrance biosynthesis pathways. Our genome of J. sambac offers a basic genetic resource for studying floral scent biosynthesis and provides an essential foundation for functional genomic research and variety improvements in Jasminum.

plant biology↗

bioRxiv2020

Morphologic Classification and Automatic Nugent Scoring of Bacterial Vaginosis by Deep Neural Networks

BackgroundBacterial vaginosis (BV) was the most common condition for womens health caused by the disruption of normal vaginal flora and an overgrowth of certain disease-causing bacteria, affecting 30-50% of women at some time in their lives. Gram stain followed by Nugent scoring (NS) based on bacterial morphotypes under the microscope was long considered golden standard for BV diagnosis. This conventional manual method was often considered labor intensive, time consuming, and variable results from person to person. MethodsWe developed four convolutional neural networks (CNN) models, and evaluated their ability to automatic identify vaginal bacteria and classify Nugent scores from microscope images. All the CNN models were first trained with 23280 microscopic images labeled with Nugent scores from top experts. A separate set of 5815 images were evaluated by the CNN models. The best CNN model was selected to generalize its application on an independent sets of 1082 images collecting from three teaching hospitals. Different hardwares were used to take images in hospitals. ResultsOur model could classify three Nugent Scores from images with high three classification accuracy of 89.3% (with 82.4% sensitivity and 96.6% specificity) on the 5815 test images, which was better diagnostic yield than the top-level technologists and obstetricians in China. The ability of generalization for our model was strong that it obtained 75.1%, which was 6.6% higher than the average of technologists. ConclusionThe CNN model over performed human healthcare practitioners on accuracy, efficiency and stability for BV diagnosis using microscopic image-based Nugent scores. The deep learning model may offer translational application in automating diagnosis of bacterial vaginosis with proper supporting hardware.

microbiology↗

bioRxiv2019

An optimized 16S rRNA sequencing protocol for vaginal microbiome to avoid biased abundance estimation

We applied three 16S rRNA sequencing protocols on vaginal microbiome samples, to evaluate whether they produce unbiased estimation of vaginal microbiome composition. We modified the 27F primer (hereafter denoted as 27F). Using vaginal samples from 28 healthy women and 10 women with bacterial vaginosis, we sequenced three 16S rRNA sequencing protocols, i.e., 27F-338R, 27F-338R and 341F-806R protocols, naming after their PCR primer sets, to test whether the sequencing results are consistent with the clinical diagnostics, morphology and qPCR results. First, the 27F primer would not align with Gardnerlla vaginalis very well, leading to poor amplification of such species. By modifying the primer sequences, the modified 27F primer (27F) was able to amplify Gardnerlla vaginalis very well. Second, the DNA sequence of characteristic species Lactobacillus crispatus is identical with Lactobacillus garrinarum, leading to biased estimation of abundance of Lactobacillus crispatus when using V3-V4 as PCR target region; in contrast, such bias did not occur when using V1-V2 as a target region. Third, optimized 27F-338R avoided above-mentioned biases and restored the well-established community state types (CSTs) clustering. ImportanceVaginal microbiome has profound effects on the health of women and their newborns. Our study found that two well-established 16S rDNA sequencing protocols led to systementical biased estimation of characteristic species of vaginal microbiome. Subsequent analysis proved that the PCR primer fetching efficacy and target region identity were major contributor for such bias. With carefully selected target region and optimized PCR primer set, we were able to eliminate such biases and provide accurate estimation of vaginal microbiome, which showed high consistency with clinical diagnostics. We modified the 27F primer (27F). Using the optimized PCR primer set of 27F and 338R to target the V1-V2 hyper-variable region, our 16S rRNA sequencing correctly evaluate the composition of vaginal microbiome.

microbiology↗

bioRxiv2019

Stability of Aβ-fibril fragments in the presence of fatty acids

We consider the effect of lauric acid on the stability of various fibril-like assemblies of A{beta} peptides. For this purpose, we have performed molecular dynamics simulations of these assemblies either in complex with lauric acid or without presence of the ligand. While we do not observe a stabilizing effect on A{beta}40-fibrils we find that addition of lauric acid strengthen the stability of fibrils built from the more toxic triple-stranded S-shaped A{beta}42-peptides. Or results may help to understand how specifics of the brain-environment modulate amyloid formation and propagation.

biophysics↗

bioRxiv2018

Population based hospitalization burden of laboratory-confirmed hand, foot and mouth disease caused by multiple enterovirus serotypes in southern China

BackgroundHand, foot and mouth disease (HFMD) is spread widely across Asia, and the hospitalization burden is as yet not well understood. Here, we estimated serotype-specific and age-specific hospitalization rates of HFMD in Southern China.\n\nMethodsWe enrolled pediatric patients admitted to 3/3 county-level hospitals and 3/23 township level hospitals in Anhua county, Hunan (CN) with HFMD, and collected samples to identify enterovirus serotypes by RT-PCRs between October 2013 and September 2016. The information of other eligible but un-enrolled patients were retrospectively collected from the same six hospitals. Monthly number of hospitalizations for all causes was collected from each of 23 township level hospitals to extrapolate hospitalizations associated with HFMD among these.\n\nResultsDuring the three years, an estimated 3,236 pediatric patients were hospitalized with lab-confirmed HFMD, and among these only one patient was severe. The mean hospitalization rates were 660 (95% CI: 638-684) per 100,000 person-years for lab-confirmed HFMD, with higher rates among CV-A16 and CV-A6 associated HFMD (213 vs 209 per 100,000 person-years), and lower among EV-A71, CV-A10 and other enteroviruses associated HFMD (134, 39 and 66 per 100,000 person-years, p<0.001). Children aged 12-23 months had the highest hospitalization rates (3,594/100,000 person-years), followed by those aged 24-35 months (1,828/100,000 person-years) and 6-11 months (1,572/100,000 person-years). Compared with other serotypes, CV-A6-associated hospitalizations were evident at younger ages.\n\nConclusionsOur study indicates a substantial hospitalization burden associated with non-severe HFMD in a rural county in southern China. Future mitigation policies should take into account the disease burden identified, and optimize interventions for HFMD.

epidemiology↗

bioRxiv2017

NRT1.1-dependent NH4+ toxicity in Arabidopsis is associated with disturbed balance between NH4+ uptake and assimilation

A high concentration of a sole ammonium (NH4+) source in growth media is often toxic to plants. The nitrate transporter NRT1.1 is involved in plant NH4+ toxicity; however, its mechanism remains undefined. In this study, wild-type Arabidopsis (Col-0) and NRT1.1 mutants (chl1-1 and chl1-5) were grown hydroponically in NH4NO3 and (NH4)2SO4 media to evaluate NRT1.1 function in NH4+ stress responses. All plants grew normally in mixed N sources, but Col-0 displayed more chlorosis, and lower biomass and photosynthesis than the NRT1.1 mutants in the (NH4)2SO4 condition. Grafting experiments between Col-0 and chl1-5 further confirmed that NH4+ toxicity is NRT1.1-dependent. In (NH4)2SO4 medium, NRT1.1 facilitated the higher expression of NH4+ transporters, increasing NH4+ uptake. Additionally, glutamine synthetase (GS) and glutamate synthetase (GOGAT) in roots of Col-0 plants decreased and soluble sugar accumulated significantly, whereas pyruvate kinase (PK)-mediated glycolysis was not affected, all of which contributed to NH4+ accumulation. In contrast, the NRT1.1 mutants reduced NH4+ accumulation and enhanced NH4+ assimilation through glutamate dehydrogenase (GDH) and glutamate-oxaloacetate transamination (GOT) activity. In addition, the upregulation of genes involved in senescence in Col-0 plants treated with (NH4)2SO4 suggests that ethylene could be involved in NH4+ toxicity responses. Our results indicate that NH4+ toxicity is dependent on NRT1.1 in Arabidopsis, characterized by enhanced NH4+ accumulation and by perturbed NH4+ metabolism, which stimulated ethylene-induced plant senescence.\n\nHighlight: Nitrate transporter NRT1.1 enhances NH4+ accumulation, disturbs the NH4+ metabolism, and aggravates NH4+ toxicity in Arabidopsis when grown under sole NH4+ condition.

plant biology↗

bioRxiv2017

Mitochondrial Methylation Two-Peak Profile Absent in Parkinson's Disease Patient

Whole-mitochondrial genome methylation profiles were obtained for mitochondrial DNA (mtDNA) from blood samples of one sporadic Parkinsons Disease (PD) patient and one healthy control donor, via Whole-Genome Next-Generation Bisulfite Sequencing. Methylation frequency was determined at 836 CpG sites out of the 1146 CpG sites in mtDNA (73% of the total). The control mtDNA methylation profile exhibited a two-peak frequency distribution, with most CpG sites showing either no methylation, or a methylation above 7%. Instead, the sporadic PD mtDNA methylation profile exhibited a generic bell-shaped frequency distribution. The data is suggestive of the bell-shaped methylation profile arising via a degradation towards randomness of the healthy sample two-peak methylation pattern. Overall, this finding provides a possible explanation for the repeated observation of PD-phenotypic characteristics in cybrid cell lines where solely the mtDNA originates from a PD patient. We discuss the finding in terms of the sporadic PD Hematopoietic Origin Theory (HOT).

cell biology↗

bioRxiv2017

DNA 5-Hydroxymethylcytosines from Cell-free Circulating DNA as Diagnostic Biomarkers for Human Cancers

DNA modifications such as 5-methylcytosines (5mC) and 5-hydroxymethylcytosines (5hmC) are epigenetic marks known to affect global gene expression in mammals(1, 2). Given their prevalence in the human genome, close correlation with gene expression, and high chemical stability, these DNA epigenetic marks could serve as ideal biomarkers for cancer diagnosis. Taking advantage of a highly sensitive and selective chemical labeling technology(3), we report here genome-wide 5hmC profiling in circulating cell-free DNA (cfDNA) and in genomic DNA of paired tumor/adjacent tissues collected from a cohort of 90 healthy individuals and 260 patients recently diagnosed with colorectal, gastric, pancreatic, liver, or thyroid cancer. 5hmC was mainly distributed in transcriptionally active regions coincident with open chromatin and permissive histone modifications. Robust cancer-associated 5hmC signatures in cfDNA were identified with specificity for different cancers. 5hmC-based biomarkers of circulating cfDNA demonstrated highly accurate predictive value for patients with colorectal and gastric cancers versus healthy controls, superior to conventional biomarkers, and comparable to 5hmC biomarkers from tissue biopsies. This new strategy could lead to the development of effective blood-based, minimally-invasive cancer diagnosis and prognosis approaches.

cancer biology↗