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1.
Brief Bioinform ; 24(5)2023 09 20.
Article in English | MEDLINE | ID: mdl-37466138

ABSTRACT

Accurately identifying phage-host relationships from their genome sequences is still challenging, especially for those phages and hosts with less homologous sequences. In this work, focusing on identifying the phage-host relationships at the species and genus level, we propose a contrastive learning based approach to learn whole-genome sequence embeddings that can take account of phage-host interactions (PHIs). Contrastive learning is used to make phages infecting the same hosts close to each other in the new representation space. Specifically, we rephrase whole-genome sequences with frequency chaos game representation (FCGR) and learn latent embeddings that 'encapsulate' phages and host relationships through contrastive learning. The contrastive learning method works well on the imbalanced dataset. Based on the learned embeddings, a proposed pipeline named CL4PHI can predict known hosts and unseen hosts in training. We compare our method with two recently proposed state-of-the-art learning-based methods on their benchmark datasets. The experiment results demonstrate that the proposed method using contrastive learning improves the prediction accuracy on known hosts and demonstrates a zero-shot prediction capability on unseen hosts. In terms of potential applications, the rapid pace of genome sequencing across different species has resulted in a vast amount of whole-genome sequencing data that require efficient computational methods for identifying phage-host interactions. The proposed approach is expected to address this need by efficiently processing whole-genome sequences of phages and prokaryotic hosts and capturing features related to phage-host relationships for genome sequence representation. This approach can be used to accelerate the discovery of phage-host interactions and aid in the development of phage-based therapies for infectious diseases.


Subject(s)
Bacteriophages , Bacteriophages/genetics , Genome, Viral , Whole Genome Sequencing , Chromosome Mapping
2.
Brief Bioinform ; 24(4)2023 07 20.
Article in English | MEDLINE | ID: mdl-37249547

ABSTRACT

Pathogen detection from biological and environmental samples is important for global disease control. Despite advances in pathogen detection using deep learning, current algorithms have limitations in processing long genomic sequences. Through the deep cross-fusion of cross, residual and deep neural networks, we developed DCiPatho for accurate pathogen detection based on the integrated frequency features of 3-to-7 k-mers. Compared with the existing state-of-the-art algorithms, DCiPatho can be used to accurately identify distinct pathogenic bacteria infecting humans, animals and plants. We evaluated DCiPatho on both learned and unlearned pathogen species using both genomics and metagenomics datasets. DCiPatho is an effective tool for the genomic-scale identification of pathogens by integrating the frequency of k-mers into deep cross-fusion networks. The source code is publicly available at https://github.com/LorMeBioAI/DCiPatho.


Subject(s)
Algorithms , Software , Humans , Neural Networks, Computer , Genome , Genomics
3.
Bioinformatics ; 40(6)2024 06 03.
Article in English | MEDLINE | ID: mdl-38851878

ABSTRACT

SUMMARY: Functional interpretation of biological entities such as differentially expressed genes is one of the fundamental analyses in bioinformatics. The task can be addressed by using biological pathway databases with enrichment analysis (EA). However, textual description of biological entities in public databases is less explored and integrated in existing tools and it has a potential to reveal new mechanisms. Here, we present a new R package biotextgraph for graphical summarization of omics' textual description data which enables assessment of functional similarities of the lists of biological entities. We illustrate application examples of annotating gene identifiers in addition to EA. The results suggest that the visualization based on words and inspection of biological entities with text can reveal a set of biologically meaningful terms that could not be obtained by using biological pathway databases alone. The results suggest the usefulness of the package in the routine analysis of omics-related data. The package also offers a web-based application for convenient querying. AVAILABILITY AND IMPLEMENTATION: The package, documentation, and web server are available at: https://github.com/noriakis/biotextgraph.


Subject(s)
Computational Biology , Software , Computational Biology/methods
4.
Bioinformatics ; 39(10)2023 10 03.
Article in English | MEDLINE | ID: mdl-37815839

ABSTRACT

MOTIVATION: In recent years, pre-training with the transformer architecture has gained significant attention. While this approach has led to notable performance improvements across a variety of downstream tasks, the underlying mechanisms by which pre-training models influence these tasks, particularly in the context of biological data, are not yet fully elucidated. RESULTS: In this study, focusing on the pre-training on nucleotide sequences, we decompose a pre-training model of Bidirectional Encoder Representations from Transformers (BERT) into its embedding and encoding modules to analyze what a pre-trained model learns from nucleotide sequences. Through a comparative study of non-standard pre-training at both the data and model levels, we find that a typical BERT model learns to capture overlapping-consistent k-mer embeddings for its token representation within its embedding module. Interestingly, using the k-mer embeddings pre-trained on random data can yield similar performance in downstream tasks, when compared with those using the k-mer embeddings pre-trained on real biological sequences. We further compare the learned k-mer embeddings with other established k-mer representations in downstream tasks of sequence-based functional prediction. Our experimental results demonstrate that the dense representation of k-mers learned from pre-training can be used as a viable alternative to one-hot encoding for representing nucleotide sequences. Furthermore, integrating the pre-trained k-mer embeddings with simpler models can achieve competitive performance in two typical downstream tasks. AVAILABILITY AND IMPLEMENTATION: The source code and associated data can be accessed at https://github.com/yaozhong/bert_investigation.


Subject(s)
Software , Base Sequence
5.
J Hum Genet ; 2024 Jul 31.
Article in English | MEDLINE | ID: mdl-39085457

ABSTRACT

Genomic sequences are traditionally represented as strings of characters: A (adenine), C (cytosine), G (guanine), and T (thymine). However, an alternative approach involves depicting sequence-related information through image representations, such as Chaos Game Representation (CGR) and read pileup images. With rapid advancements in deep learning (DL) methods within computer vision and natural language processing, there is growing interest in applying image-based DL methods to genomic sequence analysis. These methods involve encoding genomic information as images or integrating spatial information from images into the analytical process. In this review, we summarize three typical applications that use image processing with DL models for genome analysis. We examine the utilization and advantages of these image-based approaches.

6.
Exp Dermatol ; 33(9): e15173, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39246287

ABSTRACT

In this study, we aimed to examine the relationship between the serum cytokine levels of patients with pemphigus vulgaris (PV) and the Pemphigus Disease Area Index (PDAI), along with the presence of anti-desmoglein (Dsg) 1 antibody, anti-Dsg3 antibody and co-infection among patients with pemphigus vulgaris. This retrospective study included 62 PV patients and 59 healthy individuals who attended the Second Affiliated Hospital of Kunming Medical University from November 2014 to November 2022. The serum concentrations of cytokines and chemokines were assessed using the Luminex 200 System (a high-throughput cytokine detection method). Additionally, anti-Dsg1 and anti-Dsg3 antibodies were determined through enzyme-linked immunosorbent assay, while disease severity was evaluated using the PDAI scoring system. The PV group exhibited elevated levels of Th1 cytokines (such as interleukin (IL)-1RA, IL-1ß, IL-2, IL-12p70, GM-CSF, TNF-α, IL-18, IFN-γ), Th2 cytokines (IL-5, IL-10, IL-13) and Th17/Th22-related cytokines (IL-17A, IL-22) compared to the healthy control group (p < 0.05). Conversely, the levels of chemokines (macrophage inflammatory protein-1 alpha (MIP-1α), stromal cell-derived factor-1 alpha (SDF-1α), interferon-inducible protein-10 (IP-10), Regulated on Activation in Normal T-Cell Expressed And Secreted (RANTES), growth-regulated on-gene-alpha (GRO-α), MIP-1ß) and Th2 (IL-31) were lower in the PV group compared to the healthy control group (p < 0.05). No significant differences were observed in other cytokines and chemokines (p > 0.05). Additionally, IL-7, IFN-γ, IL-18 and GRO-α showed positive correlations with PDAI, IL-6 correlated positively with anti-Dsg3 antibody levels, and IL-12p70, IL-18, and IFN-γ correlated positively with anti-Dsg1 antibody levels. Furthermore, IL-15 exhibited a positive association with skin infections. PV patients have elevated levels of various cytokines and chemokines, and there are different degrees of elevation in cytokines and chemokines associated with the activation of various T cell subsets. PDAI and the Dsg1 antibody levels are mainly related to the Th1-related cytokines.


Subject(s)
Chemokines , Cytokines , Desmoglein 1 , Pemphigus , Humans , Pemphigus/blood , Pemphigus/immunology , Retrospective Studies , Male , Female , Cytokines/blood , Middle Aged , Adult , Desmoglein 1/immunology , Chemokines/blood , Desmoglein 3/immunology , Severity of Illness Index , Aged , Autoantibodies/blood , Case-Control Studies , Clinical Relevance
7.
BMC Cancer ; 24(1): 129, 2024 Jan 24.
Article in English | MEDLINE | ID: mdl-38267901

ABSTRACT

BACKGROUND: Esophageal cancer (EC) is a deadly disease with limited therapeutic options. Although circulating tumor DNA (ctDNA) could be a promising tool in this regard, the availiable evidence is limited. We performed a systematic review and meta-analysis to summarize the clinical applicability of the next-generation sequencing (NGS) and droplet digital polymerase chain reaction (ddPCR) technology on the ctDNA detection of the EC and listed the current challenges. METHODS: We systematically searched MEDLINE (via PubMed), Embase (via OVID), ISI Web of Science database and Cochrane Library from January, 2000 to April, 2023. Progression-free survival (PFS) and overall survival (OS) were set as primary outcome endpoints. Pathologic response was evaluated by tumor regression grade (TRG), according to the eighth edition of the American Joint Committee on Cancer (AJCC). Major pathologic regression (MPR) was defined as TRG 1 and 2. The MPR was set as secondary endpoint. Hazard rate (HR) and associated 95% CI were used as the effect indicators the association between ctDNA and prognosis of EC. MPR rates were also calculated. Fixed-effect model (Inverse Variance) or random-effect model (Mantel-Haenszel method) was performed depending on the statistically heterogeneity. RESULTS: Twenty-two studies, containing 1144 patients with EC, were included in this meta-analysis. The results showed that OS (HR = 3.87; 95% CI, 2.86-5.23) and PFS (HR = 4.28; 95% CI, 3.34-5.48) were shorter in ctDNA-positive patients. In the neoadjuvant therapy, the sensitivity analysis showed the clarified HR of ctDNA-positive was 1.13(95% CI, 1.01-1.28). We also found that TP53, NOTCH1, CCND1 and CNKN2A are the most frequent mutation genes. CONCLUSIONS: Positive ctDNA is associated with poor prognosis, which demonstrated clinical value of ctDNA. Longitudinal ctDNA monitoring showed potential prognostic value in the neoadjuvant therapy. In an era of precision medicine, ctDNA could be a promising tool to individualize treatment planning and to improve outcomes in EC. PROSPERO REGISTRATION NUMBER: CRD42023412465.


Subject(s)
Circulating Tumor DNA , Esophageal Neoplasms , Humans , Circulating Tumor DNA/genetics , Esophageal Neoplasms/genetics , Esophageal Neoplasms/therapy , Databases, Factual , Gene Library , Genes, cdc
8.
Bioinformatics ; 38(18): 4264-4270, 2022 09 15.
Article in English | MEDLINE | ID: mdl-35920769

ABSTRACT

MOTIVATION: Bacteriophages/phages are the viruses that infect and replicate within bacteria and archaea, and rich in human body. To investigate the relationship between phages and microbial communities, the identification of phages from metagenome sequences is the first step. Currently, there are two main methods for identifying phages: database-based (alignment-based) methods and alignment-free methods. Database-based methods typically use a large number of sequences as references; alignment-free methods usually learn the features of the sequences with machine learning and deep learning models. RESULTS: We propose INHERIT which uses a deep representation learning model to integrate both database-based and alignment-free methods, combining the strengths of both. Pre-training is used as an alternative way of acquiring knowledge representations from existing databases, while the BERT-style deep learning framework retains the advantage of alignment-free methods. We compare INHERIT with four existing methods on a third-party benchmark dataset. Our experiments show that INHERIT achieves a better performance with the F1-score of 0.9932. In addition, we find that pre-training two species separately helps the non-alignment deep learning model make more accurate predictions. AVAILABILITY AND IMPLEMENTATION: The codes of INHERIT are now available in: https://github.com/Celestial-Bai/INHERIT. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Subject(s)
Bacteriophages , Humans , Bacteriophages/genetics , Software , Metagenome , Machine Learning , Bacteria
9.
Eur Radiol ; 33(12): 9347-9356, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37436509

ABSTRACT

OBJECTIVE: Based on ultrasound (US) images, this study aimed to detect and quantify calcifications of thyroid nodules, which are regarded as one of the most important features in US diagnosis of thyroid cancer, and to further investigate the value of US calcifications in predicting the risk of lymph node metastasis (LNM) in papillary thyroid cancer (PTC). METHODS: Based on the DeepLabv3+ networks, 2992 thyroid nodules in US images were used to train a model to detect thyroid nodules, of which 998 were used to train a model to detect and quantify calcifications. A total of 225 and 146 thyroid nodules obtained from two centers, respectively, were used to test the performance of these models. A logistic regression method was used to construct the predictive models for LNM in PTCs. RESULTS: Calcifications detected by the network model and experienced radiologists had an agreement degree of above 90%. The novel quantitative parameters of US calcification defined in this study showed a significant difference between PTC patients with and without cervical LNM (p < 0.05). The calcification parameters were beneficial to predicting the LNM risk in PTC patients. The LNM prediction model using these calcification parameters combined with patient age and other US nodular features showed a higher specificity and accuracy than the calcification parameters alone. CONCLUSIONS: Our models not only detect the calcifications automatically, but also have value in predicting cervical LNM risk of PTC patients, thereby making it possible to investigate the relationship between calcifications and highly invasive PTC in detail. CLINICAL RELEVANCE STATEMENT: Due to the high association of US microcalcifications with thyroid cancers, our model will contribute to the differential diagnosis of thyroid nodules in daily practice. KEY POINTS: • We developed an ML-based network model for automatically detecting and quantifying calcifications within thyroid nodules in US images. • Three novel parameters for quantifying US calcifications were defined and verified. • These US calcification parameters showed value in predicting the risk of cervical LNM in PTC patients.


Subject(s)
Calcinosis , Carcinoma, Papillary , Carcinoma , Deep Learning , Thyroid Neoplasms , Thyroid Nodule , Humans , Thyroid Nodule/diagnostic imaging , Thyroid Nodule/pathology , Thyroid Cancer, Papillary/pathology , Lymphatic Metastasis/pathology , Carcinoma/pathology , Carcinoma, Papillary/diagnostic imaging , Carcinoma, Papillary/pathology , Thyroid Neoplasms/pathology , Lymph Nodes/pathology , Calcinosis/complications , Calcinosis/diagnostic imaging , Calcinosis/pathology , Risk Factors , Retrospective Studies
10.
Gastroenterology ; 160(6): 2089-2102.e12, 2021 05.
Article in English | MEDLINE | ID: mdl-33577875

ABSTRACT

BACKGROUND & AIMS: Fecal microbiota transplantation (FMT) is an effective therapy for recurrent Clostridioides difficile infection (rCDI). However, the overall mechanisms underlying FMT success await comprehensive elucidation, and the safety of FMT has recently become a serious concern because of the occurrence of drug-resistant bacteremia transmitted by FMT. We investigated whether functional restoration of the bacteriomes and viromes by FMT could be an indicator of successful FMT. METHODS: The human intestinal bacteriomes and viromes from 9 patients with rCDI who had undergone successful FMT and their donors were analyzed. Prophage-based and CRISPR spacer-based host bacteria-phage associations in samples from recipients before and after FMT and in donor samples were examined. The gene functions of intestinal microorganisms affected by FMT were evaluated. RESULTS: Metagenomic sequencing of both the viromes and bacteriomes revealed that FMT does change the characteristics of intestinal bacteriomes and viromes in recipients after FMT compared with those before FMT. In particular, many Proteobacteria, the fecal abundance of which was high before FMT, were eliminated, and the proportion of Microviridae increased in recipients. Most temperate phages also behaved in parallel with the host bacteria that were altered by FMT. Furthermore, the identification of bacterial and viral gene functions before and after FMT revealed that some distinctive pathways, including fluorobenzoate degradation and secondary bile acid biosynthesis, were significantly represented. CONCLUSIONS: The coordinated action of phages and their host bacteria restored the recipients' intestinal flora. These findings show that the restoration of intestinal microflora functions reflects the success of FMT.


Subject(s)
Enterocolitis, Pseudomembranous/therapy , Fecal Microbiota Transplantation , Gastrointestinal Microbiome , Gastrointestinal Tract/microbiology , Virome , Adult , Aged , Bacteriophages , Clostridioides difficile , Enterocolitis, Pseudomembranous/microbiology , Feces/microbiology , Female , Gastrointestinal Microbiome/genetics , Gastrointestinal Tract/virology , Humans , Male , Metagenomics , Microviridae , Middle Aged , Proteobacteria , Virome/genetics
11.
Bioinformatics ; 37(22): 4291-4295, 2021 11 18.
Article in English | MEDLINE | ID: mdl-34009289

ABSTRACT

MOTIVATION: Digital pathology supports analysis of histopathological images using deep learning methods at a large-scale. However, applications of deep learning in this area have been limited by the complexities of configuration of the computational environment and of hyperparameter optimization, which hinder deployment and reduce reproducibility. RESULTS: Here, we propose HEAL, a deep learning-based automated framework for easy, flexible and multi-faceted histopathological image analysis. We demonstrate its utility and functionality by performing two case studies on lung cancer and one on colon cancer. Leveraging the capability of Docker, HEAL represents an ideal end-to-end tool to conduct complex histopathological analysis and enables deep learning in a broad range of applications for cancer image analysis. AVAILABILITY AND IMPLEMENTATION: The docker image of HEAL is available at https://hub.docker.com/r/docurdt/heal and related documentation and datasets are available at http://heal.erc.monash.edu.au. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Subject(s)
Colonic Neoplasms , Deep Learning , Humans , Software , Reproducibility of Results
12.
PLoS Comput Biol ; 17(10): e1009186, 2021 10.
Article in English | MEDLINE | ID: mdl-34634042

ABSTRACT

Read-depths (RDs) are frequently used in identifying structural variants (SVs) from sequencing data. For existing RD-based SV callers, it is difficult for them to determine breakpoints in single-nucleotide resolution due to the noisiness of RD data and the bin-based calculation. In this paper, we propose to use the deep segmentation model UNet to learn base-wise RD patterns surrounding breakpoints of known SVs. We integrate model predictions with an RD-based SV caller to enhance breakpoints in single-nucleotide resolution. We show that UNet can be trained with a small amount of data and can be applied both in-sample and cross-sample. An enhancement pipeline named RDBKE significantly increases the number of SVs with more precise breakpoints on simulated and real data. The source code of RDBKE is freely available at https://github.com/yaozhong/deepIntraSV.


Subject(s)
Deep Learning , Genomic Structural Variation/genetics , Models, Genetic , Whole Genome Sequencing/methods , Genome, Human/genetics , Genomics , Humans
13.
Eur Radiol ; 32(3): 2120-2129, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34657970

ABSTRACT

OBJECTIVES: From the viewpoint of ultrasound (US) physicians, an ideal thyroid US computer-assisted diagnostic (CAD) system for thyroid cancer should perform well in suspicious thyroid nodules with atypical risk features and be able to output explainable results. This study aims to develop an explainable US CAD model for suspicious thyroid nodules. METHODS: A total of 2992 solid or almost-solid thyroid nodules were analyzed retrospectively. All nodules had pathological results (1070 malignancies and 1992 benignities) confirmed by ultrasound-guided fine-needle aspiration cytology and histopathology after thyroidectomy. A deep learning model (ResNet50) and a multiple risk features learning ensemble model (XGBoost) were used to train the US images of 2794 thyroid nodules. Then, an integrated AI model was generated by combining both models. The diagnostic accuracies of the three AI models (ResNet50, XGBoost, and the integrated model) were predicted in a testing set including 198 thyroid nodules and compared to the diagnostic efficacy of five ultrasonographers. RESULTS: The accuracy of the integrated model was 76.77%, while the mean accuracy of the ultrasonographers was 68.38%. Of the risk features, microcalcifications showed the highest contribution to the diagnosis of malignant nodules. CONCLUSIONS: The integrated AI model in our study can improve the diagnostic accuracy of suspicious thyroid nodules and output the known risk features simultaneously, thus aiding in training young ultrasonographers by linking the explainable results to their clinical experience and advancing the acceptance of AI diagnosis for thyroid cancer in clinical practice. KEY POINTS: • We developed an artificial intelligence (AI) diagnosis model based on both deep learning and multiple risk feature ensemble learning methods. • The AI diagnosis model showed higher diagnostic accuracy for suspicious thyroid nodules than ultrasonographers. • The AI diagnosis model showed partial explainability by outputting the known risk features, thus aiding young ultrasonic doctors in increasing the diagnostic level for thyroid cancer.


Subject(s)
Thyroid Neoplasms , Thyroid Nodule , Artificial Intelligence , Humans , Retrospective Studies , Sensitivity and Specificity , Thyroid Neoplasms/diagnostic imaging , Thyroid Nodule/diagnostic imaging , Ultrasonography
14.
BMC Bioinformatics ; 21(Suppl 3): 136, 2020 Apr 23.
Article in English | MEDLINE | ID: mdl-32321433

ABSTRACT

BACKGROUND: Nanopore sequencing is a rapidly developing third-generation sequencing technology, which can generate long nucleotide reads of molecules within a portable device in real-time. Through detecting the change of ion currency signals during a DNA/RNA fragment's pass through a nanopore, genotypes are determined. Currently, the accuracy of nanopore basecalling has a higher error rate than the basecalling of short-read sequencing. Through utilizing deep neural networks, the-state-of-the art nanopore basecallers achieve basecalling accuracy in a range from 85% to 95%. RESULT: In this work, we proposed a novel basecalling approach from a perspective of instance segmentation. Different from previous approaches of doing typical sequence labeling, we formulated the basecalling problem as a multi-label segmentation task. Meanwhile, we proposed a refined U-net model which we call UR-net that can model sequential dependencies for a one-dimensional segmentation task. The experiment results show that the proposed basecaller URnano achieves competitive results on the in-species data, compared to the recently proposed CTC-featured basecallers. CONCLUSION: Our results show that formulating the basecalling problem as a one-dimensional segmentation task is a promising approach, which does basecalling and segmentation jointly.


Subject(s)
Nanopore Sequencing/methods , DNA/genetics , Neural Networks, Computer , RNA/genetics
15.
Sensors (Basel) ; 20(8)2020 Apr 17.
Article in English | MEDLINE | ID: mdl-32316556

ABSTRACT

To solve the real-time complex mission-planning problem for Multiple heterogeneous Unmanned Aerial Vehicles (UAVs) in the dynamic environments, this paper addresses a new approach by effectively adapting the Consensus-Based Bundle Algorithms (CBBA) under the constraints of task timing, limited UAV resources, diverse types of tasks, dynamic addition of tasks, and real-time requirements. We introduce the dynamic task generation mechanism, which satisfied the task timing constraints. The tasks that require the cooperation of multiple UAVs are simplified into multiple sub-tasks to perform by a single UAV independently. We also introduce the asynchronous task allocation mechanism. This mechanism reduces the computational complexity of the algorithm and the communication time between UAVs. The partial task redistribution mechanism has been adopted for achieving the dynamic task allocation. The real-time performance of the algorithm is assured on the premise of optimal results. The feasibility and real-time performance of the algorithm are validated by conducting dynamic simulation experiments.

16.
Clin Exp Hypertens ; 41(6): 589-598, 2019.
Article in English | MEDLINE | ID: mdl-30806090

ABSTRACT

Objective: To investigate the effects of angiotensin-converting enzyme 2 (ACE2) activation on pulmonary arterial cell apoptosis during pulmonary vascular remodeling associated with pulmonary arterial hypertension (PAH) and to elucidate potential mechanisms related to Hippo signaling. Methods: PAH model was developed by injecting monocrotaline combined with left pneumonectomy using Sprague-Dawley rat. Then, resorcinolnaphthalein (Res; ACE2 activator), MLN-4760 (ACE2 inhibitor), A-779 (Mas inhibitor), and 4-((5,10-dimethyl-6-oxo-6,10-dihydro-5H-pyrimido[5,4-b]thieno[3,2-e][1,4]diazepin-2-yl)amino) benzenesulfonamide (XMU-MP-1; MST1/2 inhibitor) were administered via continuous subcutaneous or intraperitoneal injection for 3 weeks. Animals were randomly divided into six groups: control, PAH, PAH+Res, PAH+Res+MLN-4760, PAH+Res+A-779, and PAH+Res+XMU-MP-1. On 21 day, hemodynamics and pathologic lesions were evaluated. Apoptosis and apoptosis-associated proteins were detected by TUNEL and western blotting. ACE2 activity and Hippo pathway components including large tumor suppressor 1 (LATS1), Yes-associated protein (Yap), and phosphorylated Yap (p-Yap) were investigated by fluorogenic peptide assays and western blotting. Results: In the PAH models, the mean pulmonary arterial pressure, right ventricular hypertrophy index, pulmonary vascular remodeling, anti-apoptotic protein Bcl-2 and Yap were all increased but the pulmonary arterial cell apoptosis, pro-apoptotic proteins caspase-3 and Bax were lower. ACE2 activation significantly ameliorated pulmonary arterial remodeling, this action was related to increased apoptosis and up-regulation of LATS1 and p-Yap. These protective effects were mitigated by the co-administration of A779 or MLN-4760. Moreover, inhibiting the Hippo/LATS1/Yap pathway with XMU-MP-1 blocked apoptosis in pulmonary vascular cells induced by ACE2 activation during the prevention of PAH. Conclusions: Our findings suggest that ACE2 activation attenuates pulmonary vascular remodeling by inducing pulmonary arterial cell apoptosis via Hippo/Yap signaling during the development of PAH.


Subject(s)
Hypertension, Pulmonary/physiopathology , Peptidyl-Dipeptidase A/metabolism , Protein Serine-Threonine Kinases/metabolism , Pulmonary Artery/physiopathology , Vascular Remodeling/physiology , Angiotensin-Converting Enzyme 2 , Animals , Apoptosis , Disease Models, Animal , Hippo Signaling Pathway , Hypertension, Pulmonary/metabolism , Male , Phosphorylation , Rats , Rats, Sprague-Dawley , Signal Transduction/drug effects
17.
Molecules ; 23(4)2018 Mar 22.
Article in English | MEDLINE | ID: mdl-29565816

ABSTRACT

The effect of solvent polarity on the quality of self-assembled n-octadecanethiol (C18SH) on Cu surfaces was systematically analyzed using first-principles calculations. The results indicate that the adsorption energy for C18SH on a Cu surface is -3.37 eV, which is higher than the adsorption energies of the solvent molecules. The higher adsorption energy of dissociated C18SH makes the monolayer self-assembly easier on a Cu (111) surface through competitive adsorption. Furthermore, the adsorption energy per unit area for C18SH decreases from -3.24 eV·Å-2 to -3.37 eV·Å-2 in solvents with an increased dielectric constant of 1 to 78.54. Detailed energy analysis reveals that the electrostatic energy gradually increases, while the kinetic energy decreases with increasing dielectric constant. The increased electrostatic energies are mainly attributable to the disappearance of electrostatic interactions on the sulfur end of C18SH. The decreased kinetic energy is mainly due to the generated push force in the polar solvent, which limits the mobility of C18SH. A molecular dynamics simulation also confirms that the -CH3 site has a great interaction with CH3(CH2)4CH3 molecules and a weak interaction with CH3CH2OH molecules. The different types of interactions help to explain why the surface coverage of C18SH on Cu in a high-polarity ethanol solution is significantly larger than that in a low-polarity n-hexane solution at the stabilized stage.


Subject(s)
Copper/chemistry , Solvents/chemistry , Sulfhydryl Compounds/chemistry , Molecular Dynamics Simulation , Surface Properties
18.
BMC Genomics ; 18(Suppl 1): 1044, 2017 01 25.
Article in English | MEDLINE | ID: mdl-28198674

ABSTRACT

BACKGROUND: The recent success of deep learning techniques in machine learning and artificial intelligence has stimulated a great deal of interest among bioinformaticians, who now wish to bring the power of deep learning to bare on a host of bioinformatical problems. Deep learning is ideally suited for biological problems that require automatic or hierarchical feature representation for biological data when prior knowledge is limited. In this work, we address the sequence-specific bias correction problem for RNA-seq data redusing Recurrent Neural Networks (RNNs) to model nucleotide sequences without pre-determining sequence structures. The sequence-specific bias of a read is then calculated based on the sequence probabilities estimated by RNNs, and used in the estimation of gene abundance. RESULT: We explore the application of two popular RNN recurrent units for this task and demonstrate that RNN-based approaches provide a flexible way to model nucleotide sequences without knowledge of predetermined sequence structures. Our experiments show that training a RNN-based nucleotide sequence model is efficient and RNN-based bias correction methods compare well with the-state-of-the-art sequence-specific bias correction method on the commonly used MAQC-III data set. CONCLUSTIONS: RNNs provides an alternative and flexible way to calculate sequence-specific bias without explicitly pre-determining sequence structures.


Subject(s)
Computational Biology/methods , Computational Biology/standards , Neural Networks, Computer , Sequence Analysis, RNA/methods , Sequence Analysis, RNA/standards , Algorithms , Bias , Gene Expression Profiling , Humans , Models, Statistical
19.
Nanotechnology ; 28(14): 145302, 2017 Apr 07.
Article in English | MEDLINE | ID: mdl-28281466

ABSTRACT

Tremendous progress has been made in synthesizing various types of one-dimensional (1D) nanostructures (NSs), such as nanotubes and nanowires, but some technical challenges still remain in the deterministic assembly of the solution-processed 1D NSs for device integration. In this work we investigate a scalable yet inexpensive nanomaterial assembly method, namely filtration-guided assembly (FGA), to place nanomaterials into desired locations as either an individual entity or ensembles, and form functional devices. FGA not only addresses the assembly challenges but also encompasses the notion of green nanomanufacturing, maximally utilizing nanomaterials and eliminating a waste stream of nanomaterials into the environment. FGA utilizes selective filtration of 1D NSs through the open windows on the nanoporous filter membrane whose surface is patterned by a polymer mask for guiding the 1D NS deposition. The modified soft-lithographic technique called blanket transfer (BT) is employed to create the various photoresist patterns of sub-10-micron resolution on the nanoporous filter membrane like mixed cellulose acetate. We use single-walled carbon nanotubes (SWCNTs) as a model 1D NS and demonstrate the fabrication of an array pattern of homogeneous 1D NS network films over an area of 20 cm2 within 10 min. The FGA-patterned SWCNT network films are transferred onto the substrate using the adhesive-based transfer technique, and show the highly uniform film thickness and resistance measurements across the entire substrate. Finally, the electrical performance of the back-gated transistors made from the FGA and transfer method of 95% pure SWCNTs is demonstrated.

20.
Nano Lett ; 15(6): 4234-9, 2015 Jun 10.
Article in English | MEDLINE | ID: mdl-25993273

ABSTRACT

The photo-Dember effect arises from the asymmetric diffusivity of photoexcited electrons and holes, which creates a transient spatial charge distribution and hence the buildup of a voltage. Conventionally, a strong photo-Dember effect is only observed in semiconductors with a large asymmetry between the electron and hole mobilities, such as in GaAs or InAs, and is considered negligible in graphene due to its electron-hole symmetry. Here, we report the observation of a strong lateral photo-Dember effect induced by nonequilibrium hot carrier dynamics when exciting a graphene-metal interface with a femtosecond laser. Scanning photocurrent measurements reveal the extraction of photoexcited hot carriers is driven by the transient photo-Dember field, and the polarity of the photocurrent is determined by the device's mobility asymmetry. Furthermore, ultrafast pump-probe measurements indicate the magnitude of photocurrent is related to the hot carrier cooling rate. Our simulations also suggest that the lateral photo-Dember effect originates from graphene's 2D nature combined with its unique electrical and optical properties. Taken together, these results not only reveal a new ultrafast photocurrent generation mechanism in graphene but also suggest new types of terahertz sources based on 2D nanomaterials.

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