Biology subjects

Zhao, C.

Publications and source records attributed to Zhao, C..

9 recordsLinked to original sources

bioRxiv2026

Impaired proteostasis is an early feature of the diabetic heart in humans and mice

Diabetes and obesity increase cardiac lipid levels leading to cardiomyopathy and heart failure. We hypothesized that intermittent fasting would reduce cardiac lipid levels. Surprisingly, intermittent fasting increased myocardial triglyceride content, but rescued mortality and attenuated cardiomyopathy in mice overexpressing cardiomyocyte acyl-CoA synthetase 1 (MHC-ACSL1). Lipid overload caused cardiomyocyte accumulation of polyubiquitinated protein aggregates containing desmin, a scaffolding intermediate filament protein, which intermittent fasting prevented. Furthermore, intermittent fasting reversed elevated myocardial C16:0 ceramide content, and knockdown of ceramide synthase CerS5 and CerS6 reduced palmitate-induced protein aggregation, highlighting a role for C16:0 ceramides in this pathology. Conversely, impairing aggrephagy with cardiomyocyte-specific p62 ablation induced heart failure in mice fed a high-fat diet, with paradoxically reduced cardiac lipid content. Crucially, non-failing diabetic human hearts also exhibited protein aggregate pathology. Taken together, these results demonstrate that impaired proteostasis characterizes cardiomyopathy from cardiac lipid overload and identify a promising new therapeutic target for this condition.

molecular biology↗

bioRxiv2018

Unilateral relapse of Behcet’s disease-associated uveitis does not appear to cause asymmetric tear protein profiles

Purpose: To explore whether unilateral relapse of Bechets disease uveitis (BDU) causes differences in the tear proteome between the diseased and the contralateral quiescent eye.\n\nExperimental design: To minimize interindividual variations, bilateral tear samples were collected from the same patient (n=15) with unilateral relapse of BDU. A data-independent acquisition (DIA) strategy was used to identify proteins that differed between active and quiescent eyes.\n\nResults: A total of 1,797 confident proteins were identified in the tear samples, of which 371 are also highly expressed in various tissues and organs. Sixty-two (3.5%) proteins differed in terms of expression between tears in active and quiescent eyes, similar to the number of differentially expressed proteins (74, 4.1%) identified in a randomized grouping strategy. Furthermore, the intrapair trend of the differentially expressed proteins was not consistent and none of the proteins showed the same trend in more than 9 pairs of eyes.\n\nConclusions and clinical relevance: Unilateral relapse of BDU does not appear to cause asymmetric changes in the tear proteome between active and contralateral quiescent eyes. Tear fluid is a valuable source for biomarker studies of systemic diseases.\n\nStatement of clinical relevanceTears are an easily, noninvasively accessible body fluid that is a valuable source of biomarkers for various diseases. Behcets disease uveitis (BDU) has high potential to cause blindness and represents the leading cause of morbidity in BD patients, especially in frequently relapsing cases. Here, we adopted a method combining a \"dry\" method for tear preservation and nano-LC-DIA-MS/MS system to explore whether unilateral relapse of BDU causes differences in the tear proteome between the diseased and the contralateral quiescent eye, with the aim of evaluating tear fluid as a source for biomarker studies of uveitis relapse.

molecular biology↗

bioRxiv2018

Different subtypes of EGFR exon19 mutation can affect prognosis of patients with non-small cell lung adenocarcinoma

AimsIn this study, we determined whether different subtypes of epidermal growth factor receptor (EGFR) exon19 mutation are associated with the therapeutic effect of EGFR-tyrosine kinase inhibitors (TKIs) on advanced non-small cell lung adenocarcinoma.\n\nMethodsA total of 122 patients with stage III or IV non-small cell lung adenocarcinoma were retrospectively reviewed. Clinical characteristics of these patients, including progression-free survival (PFS) outcome for EGFR-TKI treatment, were analyzed.\n\nResultsAccording to the mutation pattern, we classified the in-frame deletions detected on EGFR Exon19 into three different types: codon deletion (CD), with a deletion of one or more original codons; codon substitution and skipping (CSS), with a deletion of one or two nucleotides but the residues could be translated into a new amino acid without changing following amino acid sequence; CD or CSS plus single nucleotide variant (SNV) (CD/CSS+SNV), exclude CD or CSS, theres another SNV nearby the deletion region. The clinical characteristics of three groups were analyzed and as a result, no significant difference was found. By comparing the average number of missing bases and amino acids of the three mutation subtypes, it could be discovered that the number of missing bases and amino acids of the three mutation subtypes is diverse, and group CSS> group CD> group CD/CSS+SNV. Finally, survival analysis was performed between three groups of patients. The median PFS of group CD, group CSS and group CD/CSS+SNV was 11 months, 9 months and 14 months respectively. There was a distinct difference in the PFS between group CSS and group CD/CSS+SNV (P=0.035<0.05), and the PFS of group CD/CSS+SNV was longer.\n\nConclusionsDifferent mutation subtypes of EGFR exon19 can predict the therapeutic effect of EGFR-TKIs on advanced non-small cell lung adenocarcinoma.

cancer biology↗

bioRxiv2018

Sunbeam: a pipeline for next-generation metagenomic sequencing experiments

BackgroundAnalysis of mixed microbial communities using metagenomic sequencing experiments requires multiple preprocessing and analytical steps to interpret the microbial and genetic composition of samples. Analytical steps include quality control, adapter trimming, host decontamination, metagenomic classification, read assembly, and alignment to reference genomes. ResultsWe present a modular and user-extensible pipeline called Sunbeam that performs these steps in a consistent and reproducible fashion. It can be installed in a single step, does not require administrative access to the host computer system, and can work with most cluster computing frameworks. We also introduce Komplexity, a software tool to eliminate potentially problematic, low-complexity nucleotide sequences from metagenomic data. Unique components of the Sunbeam pipeline include direct analysis of data from NCBI SRA and an easy-to-use extension framework that enables users to add custom processing or analysis steps directly to the workflow. The pipeline and its extension framework are well documented, in routine use, and regularly updated. ConclusionsSunbeam provides a foundation to build more in-depth analyses and to enable comparisons in metagenomic sequencing experiments by removing problematic low complexity reads and standardizing post-processing and analytical steps. Sunbeam is written in Python using the Snakemake workflow management software and is freely available at github.com/sunbeam-labs/sunbeam under the GPLv3.

bioinformatics↗

bioRxiv2017

Proteomic Architecture of Human Coronary and Aortic Atherosclerosis

The inability to detect premature atherosclerosis significantly hinders implementation of personalized therapy to prevent coronary heart disease. A comprehensive understanding of arterial protein networks and how they change in early atherosclerosis could identify new biomarkers for disease detection and improved therapeutic targets. Here we describe the human arterial proteome and the proteomic features strongly associated with early atherosclerosis based on mass-spectrometry analysis of coronary artery and aortic specimens from 100 autopsied young adults (200 arterial specimens). Convex analysis of mixtures, differential dependent network modeling and bioinformatic analyses defined the composition, network re-wiring and likely regulatory features of the protein networks associated with early atherosclerosis. Among other things the results reveal major differences in mitochondrial protein mass between the coronary artery and distal aorta in both normal and atherosclerotic samples - highlighting the importance of anatomic specificity and dynamic network structures in in the study of arterial proteomics. The publicly available data resource and the description of the analysis pipeline establish a new foundation for understanding the proteomic architecture of atherosclerosis and provide a template for similar investigations of other chronic diseases characterized by multi-cellular tissue phenotypes.\n\nHighlightsO_LILC MS/MS analysis performed on 200 human aortic or coronary artery samples\nC_LIO_LINumerous proteins, networks, and regulatory pathways associated with early atherosclerosis\nC_LIO_LIMitochondrial proteins mass and selected metabolic regulatory pathways vary dramatically by disease status and anatomic location\nC_LIO_LIPublically available data resource and analytic pipeline are provided or described in detail\nC_LI

molecular biology↗

bioRxiv2017

CAM: A Quality Control Pipeline For MNase-Seq Data

Nucleosome organization affects the accessibility of cis-elements to trans-acting factors. Micrococcal nuclease digestion followed by high-throughput sequencing (MNase-seq) is the most popular technology used to profile nucleosome organization on a genome-wide scale. Evaluating the data quality of MNase-seq data remains challenging, especially in mammalian. There is a strong need for a convenient and comprehensive approach to obtain dedicated quality control (QC) for MNase-seq data analysis. Here we developed CAM, which is a comprehensive QC pipeline for MNase-seq data. The CAM pipeline provides multiple informative QC measurements and nucleosome organization profiles on different potentially functional regions for given MNase-seq data. CAM also includes 268 historical MNase-seq datasets from human and mouse as a reference atlas for unbiased assessment. CAM is freely available at: http://www.tongji.edu.cn/~zhanglab/CAM

bioinformatics↗

bioRxiv2017

Dr.seq2: A Quality Control And Analysis Pipeline For Parallel Single Cell Transcriptome And Epigenome Data

An increasing number of single cell transcriptome and epigenome technologies, including single cell ATAC-seq (scATAC-seq), have been recently developed as powerful tools to analyze the features of many individual cells simultaneously. However, the methods and software were designed for one certain data type and only for single cell transcriptome data. A systematic approach for epigenome data and multiple types of transcriptome data is needed to control data quality and to perform cell-to-cell heterogeneity analysis on these ultra-high-dimensional transcriptome and epigenome datasets. Here we developed Dr.seq2, a Quality Control (QC) and analysis pipeline for multiple types of single cell transcriptome and epigenome data, including scATAC-seq and Drop-ChIP data. Application of this pipeline provides four groups of QC measurements and different analyses, including cell heterogeneity analysis. Dr.seq2 produced reliable results on published single cell transcriptome and epigenome datasets. Overall, Dr.seq2 is a systematic and comprehensive QC and analysis pipeline designed for parallel single cell transcriptome and epigenome data. Dr.seq2 is freely available at: http://www.tongji.edu.cn/~zhanglab/drseq2/ and https://github.com/ChengchenZhao/DrSeq2.

bioinformatics↗

bioRxiv2017

A Dry Method For Preserving Tear Samples

Tears covering the ocular surface is an important bio-fluid containing thousands of molecules, including proteins, lipids, metabolites, nucleic acids, and electrolytes. Tears are valuable resources for biomarker research of ocular and even systemic diseases. For application in biomarker studies, tear samples should ideally be stored using a simple, low-cost, and efficient method along with the patients medical records. For this purpose, we developed a novel Schirmers strip-based dry method that allows for storage of tear samples in vacuum bags at room temperature. Using this method, tear protein patterns can also be preserved. Liquid chromatography-mass spectrometry/mass spectrometry analysis of proteins recovered from the dry method and traditional wet method showed no significant difference. Some tissue/organ enriched proteins were identified in tear, thus tear might be a good window for monitoring the change of these tissues or organs. This dry method facilitates sample transportation and enables the storage of tear samples on a large scale, increasing the availability of samples for studying disease biomarkers in tears.

biochemistry↗

bioRxiv2017

Emergent community agglomeration from data set geometry

In the statistical learning language, samples are snapshots of random vectors drawn from some unknown distribution. Such vectors usually reside in a high-dimensional Euclidean space, and thus, the \"curse of dimensionality\" often undermines the power of learning methods, including community detection and clustering algorithms, that rely on Euclidean geometry. This paper presents the idea of effective dissimilarity transformation (EDT) on empirical dissimilarity hyperspheres and studies its effects using synthetic and gene expression data sets. Iterating the EDT turns a static data distribution into a dynamical process purely driven by the empirical data set geometry and adaptively ameliorates the curse of dimensionality, partly through changing the topology of a Euclidean feature space [R]n into a compact hypersphere Sn. The EDT often improves the performance of hierarchical clustering via the automatic grouping information emerging from global interactions of data points. The EDT is not restricted to hierarchical clustering, and other learning methods based on pairwise dissimilarity should also benefit from the many desirable properties of EDT.\n\nPACS numbers: 89.20.Ff, 87.85.mg

bioinformatics↗