High-Throughput最新文献_第4页

Mass Spectrometry-Based Methodologies for Targeted and Untargeted Identification of Protein Covalent Adducts (Adductomics): Current Status and Challenges. 基于质谱的蛋白质共价加合物的靶向和非靶向鉴定方法:现状和挑战。

High-Throughput Pub Date : 2019-04-23 DOI: 10.3390/ht8020009

João Nunes, Catarina Charneira, Judit Morello, João Rodrigues, Sofia A Pereira, Alexandra M M Antunes

{"title":"Mass Spectrometry-Based Methodologies for Targeted and Untargeted Identification of Protein Covalent Adducts (Adductomics): Current Status and Challenges.","authors":"João Nunes, Catarina Charneira, Judit Morello, João Rodrigues, Sofia A Pereira, Alexandra M M Antunes","doi":"10.3390/ht8020009","DOIUrl":"https://doi.org/10.3390/ht8020009","url":null,"abstract":"Protein covalent adducts formed upon exposure to reactive (mainly electrophilic) chemicals may lead to the development of a wide range of deleterious health outcomes. Therefore, the identification of protein covalent adducts constitutes a huge opportunity for a better understanding of events underlying diseases and for the development of biomarkers which may constitute effective tools for disease diagnosis/prognosis, for the application of personalized medicine approaches and for accurately assessing human exposure to chemical toxicants. The currently available mass spectrometry (MS)-based methodologies, are clearly the most suitable for the analysis of protein covalent modifications, providing accuracy, sensitivity, unbiased identification of the modified residue and conjugates along with quantitative information. However, despite the huge technological advances in MS instrumentation and bioinformatics tools, the identification of low abundant protein covalent adducts is still challenging. This review is aimed at summarizing the MS-based methodologies currently used for the identification of protein covalent adducts and the strategies developed to overcome the analytical challenges, involving not only sample pre-treatment procedures but also distinct MS and data analysis approaches.","PeriodicalId":53433,"journal":{"name":"High-Throughput","volume":"8 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3390/ht8020009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37179477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 18

Dark Proteome Database: Studies on Dark Proteins. 暗蛋白质组数据库:暗蛋白质的研究。

High-Throughput Pub Date : 2019-03-27 DOI: 10.3390/ht8020008

Nelson Perdigão, Agostinho Rosa

{"title":"Dark Proteome Database: Studies on Dark Proteins.","authors":"Nelson Perdigão, Agostinho Rosa","doi":"10.3390/ht8020008","DOIUrl":"https://doi.org/10.3390/ht8020008","url":null,"abstract":"The dark proteome, as we define it, is the part of the proteome where 3D structure has not been observed either by homology modeling or by experimental characterization in the protein universe. From the 550.116 proteins available in Swiss-Prot (as of July 2016), 43.2% of the eukarya universe and 49.2% of the virus universe are part of the dark proteome. In bacteria and archaea, the percentage of the dark proteome presence is significantly less, at 12.6% and 13.3% respectively. In this work, we present a necessary step to complete the dark proteome picture by introducing the map of the dark proteome in the human and in other model organisms of special importance to mankind. The most significant result is that around 40% to 50% of the proteome of these organisms are still in the dark, where the higher percentages belong to higher eukaryotes (mouse and human organisms). Due to the amount of darkness present in the human organism being more than 50%, deeper studies were made, including the identification of 'dark' genes that are responsible for the production of so-called dark proteins, as well as the identification of the 'dark' tissues where dark proteins are over represented, namely, the heart, cervical mucosa, and natural killer cells. This is a step forward in the direction of gaining a deeper knowledge of the human dark proteome.","PeriodicalId":53433,"journal":{"name":"High-Throughput","volume":"8 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3390/ht8020008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37110498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 12

Vertical Scanning Interferometry for Label-Free Detection of Peptide-Antibody Interactions. 垂直扫描干涉法无标记检测肽-抗体相互作用。

High-Throughput Pub Date : 2019-03-27 DOI: 10.3390/ht8020007

Andrea Palermo, Richard Thelen, Laura K Weber, Tobias Foertsch, Simone Rentschler, Verena Hackert, Julia Syurik, Alexander Nesterov-Mueller

{"title":"Vertical Scanning Interferometry for Label-Free Detection of Peptide-Antibody Interactions.","authors":"Andrea Palermo, Richard Thelen, Laura K Weber, Tobias Foertsch, Simone Rentschler, Verena Hackert, Julia Syurik, Alexander Nesterov-Mueller","doi":"10.3390/ht8020007","DOIUrl":"https://doi.org/10.3390/ht8020007","url":null,"abstract":"Peptide microarrays are a fast-developing field enabling the mapping of linear epitopes in the immune response to vaccinations or diseases and high throughput studying of protein-protein interactions. In this respect, a rapid label-free measurement of protein layer topographies in the array format is of great interest but is also a great challenge due to the extremely low aspect ratios of the peptide spots. We have demonstrated the potential of vertical scanning interferometry (VSI) for a detailed morphological analysis of peptide arrays and binding antibodies. The VSI technique is shown to scan an array area of 5.1 square millimeters within 3⁻4 min at a resolution of 1.4 μm lateral and 0.1 nm vertical in the full automation mode. Topographies obtained by VSI do match the one obtained by AFM measurements, demonstrating the accuracy of the technique. A detailed topology of peptide-antibody layers on single spots was measured. Two different measurement regions are distinguished according to the antibody concentration. In the case of weakly diluted serum, the thickness of the antibody layer is independent of the serum dilution and corresponds to the physical thickness of the accumulated antibody layer. In strongly diluted serum, the thickness measured via VSI is linearly proportional to the serum dilution.","PeriodicalId":53433,"journal":{"name":"High-Throughput","volume":"8 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3390/ht8020007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37111336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Protein Adductomics: Methodologies for Untargeted Screening of Adducts to Serum Albumin and Hemoglobin in Human Blood Samples. 蛋白质加合物组学：人类血液样本中血清白蛋白和血红蛋白加合物的非靶向筛选方法。

High-Throughput Pub Date : 2019-03-08 DOI: 10.3390/ht8010006

Henrik Carlsson, Stephen M Rappaport, Margareta Törnqvist

引用次数: 40

A Pilot Study to Investigate the Balance between Proteases and α1-Antitrypsin in Bronchoalveolar Lavage Fluid of Lung Transplant Recipients. 肺移植受者支气管肺泡灌洗液中蛋白酶和α1-抗胰蛋白酶平衡的初步研究

High-Throughput Pub Date : 2019-02-13 DOI: 10.3390/ht8010005

Maddalena Cagnone, Davide Piloni, Ilaria Ferrarotti, Monica Di Venere, Simona Viglio, Sara Magni, Anna Bardoni, Roberta Salvini, Marco Fumagalli, Paolo Iadarola, Sabrina Martinello, Federica Meloni

{"title":"A Pilot Study to Investigate the Balance between Proteases and α1-Antitrypsin in Bronchoalveolar Lavage Fluid of Lung Transplant Recipients.","authors":"Maddalena Cagnone, Davide Piloni, Ilaria Ferrarotti, Monica Di Venere, Simona Viglio, Sara Magni, Anna Bardoni, Roberta Salvini, Marco Fumagalli, Paolo Iadarola, Sabrina Martinello, Federica Meloni","doi":"10.3390/ht8010005","DOIUrl":"https://doi.org/10.3390/ht8010005","url":null,"abstract":": The neutrophilic component in bronchiolitis obliterans syndrome (BOS, the main form of chronic lung rejection), plays a crucial role in the pathogenesis and maintenance of the disorder. Human Neutrophil Elastase (HNE), a serine protease responsible of elastin degradation whose action is counteracted by α1-antitrypsin (AAT), a serum inhibitor specific for this protease. This work aimed to investigate the relationship between HNE and AAT in bronchoalveolar lavage fluid (BALf) from stable lung transplant recipients and BOS patients to understand whether the imbalance between proteases and inhibitors is relevant to the development of BOS. To reach this goal a multidisciplinary procedure was applied which included: (i) the use of electrophoresis/western blotting coupled with liquid chromatography-mass spectrometric analysis; (ii) the functional evaluation of the residual antiprotease activity, and (iii) a neutrophil count.","PeriodicalId":53433,"journal":{"name":"High-Throughput","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3390/ht8010005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36980373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 6

A Selective Review of Multi-Level Omics Data Integration Using Variable Selection. 使用变量选择的多级奥密克戎数据集成的选择性回顾。

High-Throughput Pub Date : 2019-01-18 DOI: 10.3390/ht8010004

Cen Wu, Fei Zhou, Jie Ren, Xiaoxi Li, Yu Jiang, Shuangge Ma

{"title":"A Selective Review of Multi-Level Omics Data Integration Using Variable Selection.","authors":"Cen Wu, Fei Zhou, Jie Ren, Xiaoxi Li, Yu Jiang, Shuangge Ma","doi":"10.3390/ht8010004","DOIUrl":"10.3390/ht8010004","url":null,"abstract":"High-throughput technologies have been used to generate a large amount of omics data. In the past, single-level analysis has been extensively conducted where the omics measurements at different levels, including mRNA, microRNA, CNV and DNA methylation, are analyzed separately. As the molecular complexity of disease etiology exists at all different levels, integrative analysis offers an effective way to borrow strength across multi-level omics data and can be more powerful than single level analysis. In this article, we focus on reviewing existing multi-omics integration studies by paying special attention to variable selection methods. We first summarize published reviews on integrating multi-level omics data. Next, after a brief overview on variable selection methods, we review existing supervised, semi-supervised and unsupervised integrative analyses within parallel and hierarchical integration studies, respectively. The strength and limitations of the methods are discussed in detail. No existing integration method can dominate the rest. The computation aspects are also investigated. The review concludes with possible limitations and future directions for multi-level omics data integration.","PeriodicalId":53433,"journal":{"name":"High-Throughput","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3390/ht8010004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36874921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 123

Acknowledgement to Reviewers of High-Throughput in 2018 对2018年高通量评审员的肯定

High-Throughput Pub Date : 2019-01-11 DOI: 10.3390/ht8010003

引用次数: 0

Low-Field, Benchtop NMR Spectroscopy as a Potential Tool for Point-of-Care Diagnostics of Metabolic Conditions: Validation, Protocols and Computational Models. 低场、台式核磁共振波谱作为代谢性疾病即时诊断的潜在工具:验证、协议和计算模型。

High-Throughput Pub Date : 2018-12-27 DOI: 10.3390/ht8010002

Benita C Percival, Martin Grootveld, Miles Gibson, Yasan Osman, Marco Molinari, Fereshteh Jafari, Tarsem Sahota, Mark Martin, Federico Casanova, Melissa L Mather, Mark Edgar, Jinit Masania, Philippe B Wilson

{"title":"Low-Field, Benchtop NMR Spectroscopy as a Potential Tool for Point-of-Care Diagnostics of Metabolic Conditions: Validation, Protocols and Computational Models.","authors":"Benita C Percival, Martin Grootveld, Miles Gibson, Yasan Osman, Marco Molinari, Fereshteh Jafari, Tarsem Sahota, Mark Martin, Federico Casanova, Melissa L Mather, Mark Edgar, Jinit Masania, Philippe B Wilson","doi":"10.3390/ht8010002","DOIUrl":"https://doi.org/10.3390/ht8010002","url":null,"abstract":"Novel sensing technologies for liquid biopsies offer promising prospects for the early detection of metabolic conditions through omics techniques. Indeed, high-field nuclear magnetic resonance (NMR) facilities are routinely used for metabolomics investigations on a range of biofluids in order to rapidly recognise unusual metabolic patterns in patients suffering from a range of diseases. However, these techniques are restricted by the prohibitively large size and cost of such facilities, suggesting a possible role for smaller, low-field NMR instruments in biofluid analysis. Herein we describe selected biomolecule validation on a low-field benchtop NMR spectrometer (60 MHz), and present an associated protocol for the analysis of biofluids on compact NMR instruments. We successfully detect common markers of diabetic control at low-to-medium concentrations through optimised experiments, including α-glucose (≤2.8 mmol/L) and acetone (25 µmol/L), and additionally in readily accessible biofluids, particularly human urine. We present a combined protocol for the analysis of these biofluids with low-field NMR spectrometers for metabolomics applications, and offer a perspective on the future of this technique appealing to 'point-of-care' applications.","PeriodicalId":53433,"journal":{"name":"High-Throughput","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3390/ht8010002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36809042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Identification and Interpretation of cis-Regulatory Noncoding Mutations in Cancer. 癌症中顺式调控非编码突变的鉴定和解释。

High-Throughput Pub Date : 2018-12-20 DOI: 10.3390/ht8010001

Minal B Patel, Jun Wang

{"title":"The Identification and Interpretation of cis-Regulatory Noncoding Mutations in Cancer.","authors":"Minal B Patel, Jun Wang","doi":"10.3390/ht8010001","DOIUrl":"https://doi.org/10.3390/ht8010001","url":null,"abstract":"In the need to characterise the genomic landscape of cancers and to establish novel biomarkers and therapeutic targets, studies have largely focused on the identification of driver mutations within the protein-coding gene regions, where the most pathogenic alterations are known to occur. However, the noncoding genome is significantly larger than its protein-coding counterpart, and evidence reveals that regulatory sequences also harbour functional mutations that significantly affect the regulation of genes and pathways implicated in cancer. Due to the sheer number of noncoding mutations (NCMs) and the limited knowledge of regulatory element functionality in cancer genomes, differentiating pathogenic mutations from background passenger noise is particularly challenging technically and computationally. Here we review various up-to-date high-throughput sequencing data/studies and in silico methods that can be employed to interrogate the noncoding genome. We aim to provide an overview of available data resources as well as computational and molecular techniques that can help and guide the search for functional NCMs in cancer genomes.","PeriodicalId":53433,"journal":{"name":"High-Throughput","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3390/ht8010001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36796834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 7

Pharmacogenomic Profiling of ADME Gene Variants: Current Challenges and Validation Perspectives. ADME基因变体的药物基因组图谱：当前的挑战和验证前景。

High-Throughput Pub Date : 2018-12-18 DOI: 10.3390/ht7040040

Mariamena Arbitrio, Maria Teresa Di Martino, Francesca Scionti, Vito Barbieri, Licia Pensabene, Pierosandro Tagliaferri

{"title":"Pharmacogenomic Profiling of ADME Gene Variants: Current Challenges and Validation Perspectives.","authors":"Mariamena Arbitrio, Maria Teresa Di Martino, Francesca Scionti, Vito Barbieri, Licia Pensabene, Pierosandro Tagliaferri","doi":"10.3390/ht7040040","DOIUrl":"10.3390/ht7040040","url":null,"abstract":"In the past decades, many efforts have been made to individualize medical treatments, taking into account molecular profiles and the individual genetic background. The development of molecularly targeted drugs and immunotherapy have revolutionized medical treatments but the inter-patient variability in the anti-tumor drug pharmacokinetics (PK) and pharmacodynamics can be explained, at least in part, by genetic variations in genes encoding drug metabolizing enzymes and transporters (ADME) or in genes encoding drug receptors. Here, we focus on high-throughput technologies applied for PK screening for the identification of predictive biomarkers of efficacy or toxicity in cancer treatment, whose application in clinical practice could promote personalized treatments tailored on individual's genetic make-up. Pharmacogenomic tools have been implemented and the clinical utility of pharmacogenetic screening could increase safety in patients for the identification of drug metabolism-related biomarkers for a personalized medicine. Although pharmacogenomic studies were performed in adult cohorts, pharmacogenetic pediatric research has yielded promising results. Additionally, we discuss the current challenges and theoretical bases for the implementation of pharmacogenetic tests for translation in the clinical practice taking into account that pharmacogenomics platforms are discovery oriented and must open the way for the setting of robust tests suitable for daily practice.","PeriodicalId":53433,"journal":{"name":"High-Throughput","volume":"7 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3390/ht7040040","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36787989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 27