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Dysregulated Gene Expression in Lymphoblasts from Parkinson's Disease. 帕金森病淋巴细胞基因表达失调
IF 3.3
Proteomes Pub Date : 2022-06-01 DOI: 10.3390/proteomes10020020
Sarah Jane Annesley, Claire Yvonne Allan, Oana Sanislav, Andrew Evans, Paul Robert Fisher
{"title":"Dysregulated Gene Expression in Lymphoblasts from Parkinson's Disease.","authors":"Sarah Jane Annesley,&nbsp;Claire Yvonne Allan,&nbsp;Oana Sanislav,&nbsp;Andrew Evans,&nbsp;Paul Robert Fisher","doi":"10.3390/proteomes10020020","DOIUrl":"https://doi.org/10.3390/proteomes10020020","url":null,"abstract":"<p><p>Parkinson's disease is the second largest neurodegenerative disease worldwide and is caused by a combination of genetics and environment. It is characterized by the death of neurons in the substantia nigra of the brain but is not solely a disease of the brain, as it affects multiple tissues and organs. Studying Parkinson's disease in accessible tissues such as skin and blood has increased our understanding of the disease's pathogenesis. Here, we used lymphoblast cell lines generated from Parkinson's disease patient and healthy age- and sex-matched control groups and obtained their whole-cell transcriptomes and proteomes. Our analysis revealed, in both the transcriptomes and the proteomes of PD cells, a global downregulation of genes involved in protein synthesis, as well as the upregulation of immune processes and sphingolipid metabolism. In contrast, we discovered an uncoupling of mRNA and protein expression in processes associated with mitochondrial respiration in the form of a general downregulation in associated transcripts and an upregulation in proteins. Complex V was different to the other oxidative phosphorylation complexes in that the levels of its associated transcripts were also lower, but the levels of their encoded polypeptides were not elevated. This may suggest that further layers of regulation specific to Complex V are in play.</p>","PeriodicalId":20877,"journal":{"name":"Proteomes","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9230639/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40269177","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
A Comparison of Blood Plasma Small Extracellular Vesicle Enrichment Strategies for Proteomic Analysis. 血浆细胞外小泡富集策略在蛋白质组学分析中的比较。
IF 3.3
Proteomes Pub Date : 2022-06-01 DOI: 10.3390/proteomes10020019
Natalie P Turner, Pevindu Abeysinghe, Keith A Kwan Cheung, Kanchan Vaswani, Jayden Logan, Pawel Sadowski, Murray D Mitchell
{"title":"A Comparison of Blood Plasma Small Extracellular Vesicle Enrichment Strategies for Proteomic Analysis.","authors":"Natalie P Turner,&nbsp;Pevindu Abeysinghe,&nbsp;Keith A Kwan Cheung,&nbsp;Kanchan Vaswani,&nbsp;Jayden Logan,&nbsp;Pawel Sadowski,&nbsp;Murray D Mitchell","doi":"10.3390/proteomes10020019","DOIUrl":"https://doi.org/10.3390/proteomes10020019","url":null,"abstract":"<p><p>Proteomic analysis of small extracellular vesicles (sEVs) poses a significant challenge. A 'gold-standard' method for plasma sEV enrichment for downstream proteomic analysis is yet to be established. Methods were evaluated for their capacity to successfully isolate and enrich sEVs from plasma, minimise the presence of highly abundant plasma proteins, and result in the optimum representation of sEV proteins by liquid chromatography tandem mass spectrometry. Plasma from four cattle (Bos taurus) of similar physical attributes and genetics were used. Three methods of sEV enrichment were utilised: ultracentrifugation (UC), size-exclusion chromatography (SEC), and ultrafiltration (UF). These methods were combined to create four groups for methodological evaluation: UC + SEC, UC + SEC + UF, SEC + UC and SEC + UF. The UC + SEC method yielded the highest number of protein identifications (IDs). The SEC + UC method reduced plasma protein IDs compared to the other methods, but also resulted in the lowest number of protein IDs overall. The UC + SEC + UF method decreased sEV protein ID, particle number, mean and mode particle size, particle yield, and did not improve purity compared to the UC + SEC method. In this study, the UC + SEC method was the best method for sEV protein ID, purity, and overall particle yield. Our data suggest that the method and sequence of sEV enrichment strategy impacts protein ID, which may influence the outcome of biomarker discovery studies.</p>","PeriodicalId":20877,"journal":{"name":"Proteomes","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9229025/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40269176","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: 10
Pattern Analysis of Organellar Maps for Interpretation of Proteomic Data. 用于蛋白质组学数据解释的细胞器图谱模式分析
IF 4
Proteomes Pub Date : 2022-05-23 DOI: 10.3390/proteomes10020018
Jordan B Burton, Nicholas J Carruthers, Zhanjun Hou, Larry H Matherly, Paul M Stemmer
{"title":"Pattern Analysis of Organellar Maps for Interpretation of Proteomic Data.","authors":"Jordan B Burton, Nicholas J Carruthers, Zhanjun Hou, Larry H Matherly, Paul M Stemmer","doi":"10.3390/proteomes10020018","DOIUrl":"10.3390/proteomes10020018","url":null,"abstract":"<p><p>Localization of organelle proteins by isotope tagging (LOPIT) maps are a coordinate-directed representation of proteome data that can aid in biological interpretation. Analysis of organellar association for proteins as displayed using LOPIT is evaluated and interpreted for two types of proteomic data sets. First, test and control group protein abundances and fold change data obtained in a proximity labeling experiment are plotted on a LOPIT map to evaluate the likelihood of true protein interactions. Selection of true positives based on co-localization of proteins in the organellar space is shown to be consistent with carboxylase enrichment which serves as a positive control for biotinylation in streptavidin affinity selected proteome data sets. The mapping in organellar space facilitates discrimination between the test and control groups and aids in identification of proteins of interest. The same representation of proteins in organellar space is used in the analysis of extracellular vesicle proteomes for which protein abundance and fold change data are evaluated. Vesicular protein organellar localization patterns provide information about the subcellular origin of the proteins in the samples which are isolates from the extracellular milieu. The organellar localization patterns are indicative of the provenance of the vesicular proteome origin and allow discrimination between proteomes prepared using different enrichment methods. The patterns in LOPIT displays are easy to understand and compare which aids in the biological interpretation of proteome data.</p>","PeriodicalId":20877,"journal":{"name":"Proteomes","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2022-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9149908/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44122220","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
Wheat Proteomics for Abiotic Stress Tolerance and Root System Architecture: Current Status and Future Prospects 小麦抗非生物胁迫蛋白质组学与根系结构研究现状与展望
IF 3.3
Proteomes Pub Date : 2022-05-22 DOI: 10.3390/proteomes10020017
T. Halder, M. Choudhary, Hui Liu, Yinglong Chen, G. Yan, K. Siddique
{"title":"Wheat Proteomics for Abiotic Stress Tolerance and Root System Architecture: Current Status and Future Prospects","authors":"T. Halder, M. Choudhary, Hui Liu, Yinglong Chen, G. Yan, K. Siddique","doi":"10.3390/proteomes10020017","DOIUrl":"https://doi.org/10.3390/proteomes10020017","url":null,"abstract":"Wheat is an important staple cereal for global food security. However, climate change is hampering wheat production due to abiotic stresses, such as heat, salinity, and drought. Besides shoot architectural traits, improving root system architecture (RSA) traits have the potential to improve yields under normal and stressed environments. RSA growth and development and other stress responses involve the expression of proteins encoded by the trait controlling gene/genes. Hence, mining the key proteins associated with abiotic stress responses and RSA is important for improving sustainable yields in wheat. Proteomic studies in wheat started in the early 21st century using the two-dimensional (2-DE) gel technique and have extensively improved over time with advancements in mass spectrometry. The availability of the wheat reference genome has allowed the exploration of proteomics to identify differentially expressed or abundant proteins (DEPs or DAPs) for abiotic stress tolerance and RSA improvement. Proteomics contributed significantly to identifying key proteins imparting abiotic stress tolerance, primarily related to photosynthesis, protein synthesis, carbon metabolism, redox homeostasis, defense response, energy metabolism and signal transduction. However, the use of proteomics to improve RSA traits in wheat is in its infancy. Proteins related to cell wall biogenesis, carbohydrate metabolism, brassinosteroid biosynthesis, and transportation are involved in the growth and development of several RSA traits. This review covers advances in quantification techniques of proteomics, progress in identifying DEPs and/or DAPs for heat, salinity, and drought stresses, and RSA traits, and the limitations and future directions for harnessing proteomics in wheat improvement.","PeriodicalId":20877,"journal":{"name":"Proteomes","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2022-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47113422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 9
Applications of Proteomics in Ovarian Cancer: Dawn of a New Era 蛋白质组学在卵巢癌中的应用:一个新时代的黎明
IF 3.3
Proteomes Pub Date : 2022-05-09 DOI: 10.3390/proteomes10020016
Aruni Ghose, Srikar Gullapalli, Naila Chohan, A. Bolina, M. Moschetta, E. Rassy, S. Boussios
{"title":"Applications of Proteomics in Ovarian Cancer: Dawn of a New Era","authors":"Aruni Ghose, Srikar Gullapalli, Naila Chohan, A. Bolina, M. Moschetta, E. Rassy, S. Boussios","doi":"10.3390/proteomes10020016","DOIUrl":"https://doi.org/10.3390/proteomes10020016","url":null,"abstract":"The ability to identify ovarian cancer (OC) at its earliest stages remains a challenge. The patients present an advanced stage at diagnosis. This heterogeneous disease has distinguishable etiology and molecular biology. Next-generation sequencing changed clinical diagnostic testing, allowing assessment of multiple genes, simultaneously, in a faster and cheaper manner than sequential single gene analysis. Technologies of proteomics, such as mass spectrometry (MS) and protein array analysis, have advanced the dissection of the underlying molecular signaling events and the proteomic characterization of OC. Proteomics analysis of OC, as well as their adaptive responses to therapy, can uncover new therapeutic choices, which can reduce the emergence of drug resistance and potentially improve patient outcomes. There is an urgent need to better understand how the genomic and epigenomic heterogeneity intrinsic to OC is reflected at the protein level, and how this information could potentially lead to prolonged survival.","PeriodicalId":20877,"journal":{"name":"Proteomes","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2022-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45972906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 51
Proteomes of Uropathogenic Escherichia coli Growing in Human Urine and in J82 Urinary Bladder Cells 尿路致病性大肠杆菌在人尿和J82膀胱细胞中的蛋白质组学研究
IF 3.3
Proteomes Pub Date : 2022-05-05 DOI: 10.3390/proteomes10020015
S. Andersen, A. Nawrocki, A. E. Johansen, Ana Herrero-Fresno, Vanesa García Menéndez, J. Møller-Jensen, J. E. Olsen
{"title":"Proteomes of Uropathogenic Escherichia coli Growing in Human Urine and in J82 Urinary Bladder Cells","authors":"S. Andersen, A. Nawrocki, A. E. Johansen, Ana Herrero-Fresno, Vanesa García Menéndez, J. Møller-Jensen, J. E. Olsen","doi":"10.3390/proteomes10020015","DOIUrl":"https://doi.org/10.3390/proteomes10020015","url":null,"abstract":"Uropathogenic Escherichia coli (UPEC) are the most common cause of urinary tract infection (UTI). UPEC normally reside in the intestine, and during establishment of UTI, they undergo metabolic adaptations, first to urine and then upon tissue invasion to the bladder cell interior. To understand these adaptations, we used quantitative proteomic profiling to characterize protein expression of the UPEC strain UTI89 growing in human urine and when inside J82 bladder cells. In order to facilitate detection of UPEC proteins over the excess amount of eukaryotic proteins in bladder cells, we developed a method where proteins from UTI89 grown in MOPS and urine was spiked-in to enhance detection of bacterial proteins. More than 2000 E. coli proteins were detected. During growth in urine, proteins associated with iron acquisition and several amino acid uptake and biosynthesis systems, most prominently arginine metabolism, were significantly upregulated. During growth in J82 cells, proteins related to iron uptake and arginine metabolisms were likewise upregulated together with proteins involved in sulfur compound turnover. Ribosomal proteins were downregulated relative to growth in MOPS in this environment. There was no direct correlation between upregulated proteins and proteins reported to be essential for infections, showing that upregulation during growth does not signify that the proteins are essential for growth under a condition.","PeriodicalId":20877,"journal":{"name":"Proteomes","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2022-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46687601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 3
Transcriptional and Epigenetic Factors Associated with Early Thrombosis of Femoral Artery Involved in Arteriovenous Fistula 动静脉瘘早期股动脉血栓形成的转录和表观遗传学因素
IF 3.3
Proteomes Pub Date : 2022-04-30 DOI: 10.3390/proteomes10020014
Vikrant Rai, D. Agrawal
{"title":"Transcriptional and Epigenetic Factors Associated with Early Thrombosis of Femoral Artery Involved in Arteriovenous Fistula","authors":"Vikrant Rai, D. Agrawal","doi":"10.3390/proteomes10020014","DOIUrl":"https://doi.org/10.3390/proteomes10020014","url":null,"abstract":"Arteriovenous fistulas (AVFs), created for hemodialysis in end-stage renal disease patients, mature through the outward remodeling of the outflow vein. However, early thrombosis and chronic inflammation are detrimental to the process of AVF maturation and precipitate AVF maturation failure. For the successful remodeling of the outflow vein, blood flow through the fistula is essential, but early arterial thrombosis attenuates this blood flow, and the vessels become thrombosed and stenosed, leading to AVF failure. The altered expression of various proteins involved in maintaining vessel patency or thrombosis is regulated by genes of which the expression is regulated by transcription factors and microRNAs. In this study, using thrombosed and stenosed arteries following AVF creation, we delineated transcription factors and microRNAs associated with differentially expressed genes in bulk RNA sequencing data using upstream and causal network analysis. We observed changes in many transcription factors and microRNAs that are involved in angiogenesis; vascular smooth muscle cell proliferation, migration, and phenotypic changes; endothelial cell function; hypoxia; oxidative stress; vessel remodeling; immune responses; and inflammation. These factors and microRNAs play a critical role in the underlying molecular mechanisms in AVF maturation. We also observed epigenetic factors involved in gene regulation associated with these molecular mechanisms. The results of this study indicate the importance of investigating the transcriptional and epigenetic regulation of AVF maturation and maturation failure and targeting factors precipitating early thrombosis and stenosis.","PeriodicalId":20877,"journal":{"name":"Proteomes","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2022-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43126381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 4
Insights on Proteomics-Driven Body Fluid-Based Biomarkers of Cervical Cancer 癌症蛋白质组学驱动的体液生物标志物研究进展
IF 3.3
Proteomes Pub Date : 2022-04-29 DOI: 10.3390/proteomes10020013
A. Mukherjee, Chinmay Pednekar, Siddhant Sujit Kolke, Megha Kattimani, Subhiksha Duraisamy, A. Burli, Sudeep Gupta, Sanjeeva Srivastava
{"title":"Insights on Proteomics-Driven Body Fluid-Based Biomarkers of Cervical Cancer","authors":"A. Mukherjee, Chinmay Pednekar, Siddhant Sujit Kolke, Megha Kattimani, Subhiksha Duraisamy, A. Burli, Sudeep Gupta, Sanjeeva Srivastava","doi":"10.3390/proteomes10020013","DOIUrl":"https://doi.org/10.3390/proteomes10020013","url":null,"abstract":"Cervical cancer is one of the top malignancies in women around the globe, which still holds its place despite being preventable at early stages. Gynecological conditions, even maladies like cervical cancer, still experience scrutiny from society owing to prevalent taboo and invasive screening methods, especially in developing economies. Additionally, current diagnoses lack specificity and sensitivity, which prolong diagnosis until it is too late. Advances in omics-based technologies aid in discovering differential multi-omics profiles between healthy individuals and cancer patients, which could be utilized for the discovery of body fluid-based biomarkers. Body fluids are a promising potential alternative for early disease detection and counteracting the problems of invasiveness while also serving as a pool of potential biomarkers. In this review, we will provide details of the body fluids-based biomarkers that have been reported in cervical cancer. Here, we have presented our perspective on proteomics for global biomarker discovery by addressing several pertinent problems, including the challenges that are confronted in cervical cancer. Further, we also used bioinformatic methods to undertake a meta-analysis of significantly up-regulated biomolecular profiles in CVF from cervical cancer patients. Our analysis deciphered alterations in the biological pathways in CVF such as immune response, glycolytic processes, regulation of cell death, regulation of structural size, protein polymerization disease, and other pathways that can cumulatively contribute to cervical cancer malignancy. We believe, more extensive research on such biomarkers, will speed up the road to early identification and prevention of cervical cancer in the near future.","PeriodicalId":20877,"journal":{"name":"Proteomes","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2022-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41970898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Multi-Omics Integrative Approach of Extracellular Vesicles: A Future Challenging Milestone 细胞外囊泡的多组学综合方法:未来具有挑战性的里程碑
IF 3.3
Proteomes Pub Date : 2022-04-22 DOI: 10.3390/proteomes10020012
E. Shaba, L. Vantaggiato, L. Governini, A. Haxhiu, G. Sebastiani, Daniela Fignani, G. Grieco, L. Bergantini, L. Bini, C. Landi
{"title":"Multi-Omics Integrative Approach of Extracellular Vesicles: A Future Challenging Milestone","authors":"E. Shaba, L. Vantaggiato, L. Governini, A. Haxhiu, G. Sebastiani, Daniela Fignani, G. Grieco, L. Bergantini, L. Bini, C. Landi","doi":"10.3390/proteomes10020012","DOIUrl":"https://doi.org/10.3390/proteomes10020012","url":null,"abstract":"In the era of multi-omic sciences, dogma on singular cause-effect in physio-pathological processes is overcome and system biology approaches have been providing new perspectives to see through. In this context, extracellular vesicles (EVs) are offering a new level of complexity, given their role in cellular communication and their activity as mediators of specific signals to target cells or tissues. Indeed, their heterogeneity in terms of content, function, origin and potentiality contribute to the cross-interaction of almost every molecular process occurring in a complex system. Such features make EVs proper biological systems being, therefore, optimal targets of omic sciences. Currently, most studies focus on dissecting EVs content in order to either characterize it or to explore its role in various pathogenic processes at transcriptomic, proteomic, metabolomic, lipidomic and genomic levels. Despite valuable results being provided by individual omic studies, the categorization of EVs biological data might represent a limit to be overcome. For this reason, a multi-omic integrative approach might contribute to explore EVs function, their tissue-specific origin and their potentiality. This review summarizes the state-of-the-art of EVs omic studies, addressing recent research on the integration of EVs multi-level biological data and challenging developments in EVs origin.","PeriodicalId":20877,"journal":{"name":"Proteomes","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2022-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45778232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 9
Quantitative Proteogenomic Characterization of Inflamed Murine Colon Tissue Using an Integrated Discovery, Verification, and Validation Proteogenomic Workflow. 使用集成的发现,验证和验证蛋白质基因组工作流程的炎症小鼠结肠组织的定量蛋白质基因组学表征
IF 4
Proteomes Pub Date : 2022-04-14 DOI: 10.3390/proteomes10020011
Andrew T Rajczewski, Qiyuan Han, Subina Mehta, Praveen Kumar, Pratik D Jagtap, Charles G Knutson, James G Fox, Natalia Y Tretyakova, Timothy J Griffin
{"title":"Quantitative Proteogenomic Characterization of Inflamed Murine Colon Tissue Using an Integrated Discovery, Verification, and Validation Proteogenomic Workflow.","authors":"Andrew T Rajczewski, Qiyuan Han, Subina Mehta, Praveen Kumar, Pratik D Jagtap, Charles G Knutson, James G Fox, Natalia Y Tretyakova, Timothy J Griffin","doi":"10.3390/proteomes10020011","DOIUrl":"10.3390/proteomes10020011","url":null,"abstract":"<p><p>Chronic inflammation of the colon causes genomic and/or transcriptomic events, which can lead to expression of non-canonical protein sequences contributing to oncogenesis. To better understand these mechanisms, <i>Rag2</i><sup>-/-</sup><i>Il10</i><sup>-/-</sup> mice were infected with <i>Helicobacter hepaticus</i> to induce chronic inflammation of the cecum and the colon. Transcriptomic data from harvested proximal colon samples were used to generate a customized FASTA database containing non-canonical protein sequences. Using a proteogenomic approach, mass spectrometry data for proximal colon proteins were searched against this custom FASTA database using the Galaxy for Proteomics (Galaxy-P) platform. In addition to the increased abundance in inflammatory response proteins, we also discovered several non-canonical peptide sequences derived from unique proteoforms. We confirmed the veracity of these novel sequences using an automated bioinformatics verification workflow with targeted MS-based assays for peptide validation. Our bioinformatics discovery workflow identified 235 putative non-canonical peptide sequences, of which 58 were verified with high confidence and 39 were validated in targeted proteomics assays. This study provides insights into challenges faced when identifying non-canonical peptides using a proteogenomics approach and demonstrates an integrated workflow addressing these challenges. Our bioinformatic discovery and verification workflow is publicly available and accessible via the Galaxy platform and should be valuable in non-canonical peptide identification using proteogenomics.</p>","PeriodicalId":20877,"journal":{"name":"Proteomes","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2022-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9036229/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48322736","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
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