Lysine crotonylation (Kcr) is a recently discovered post‐translational modification that potentially regulates multiple biological processes. With an objective to expand the available crotonylation ...datasets, LC‐MS/MS is performed using mouse liver samples under normal physiological conditions to obtain in vivo crotonylome. A label‐free strategy is used and 10 034 Class I (localization probabilities > 0.75) crotonylated sites are identified in 2245 proteins. The KcrE, KcrD, and EKcr motifs are significantly enriched in the crotonylated peptides. The identified crotonylated proteins are mostly enzymes and primarily located in the cytoplasm and nucleus. Functional enrichment analysis based on Gene Ontology and Kyoto Encyclopedia of Genes and Genomes shows that the crotonylated proteins are closely related to the purine‐containing compound metabolic process, ribose phosphate metabolic process, carbon metabolism pathway, ribosome pathway, and a series of metabolism‐associated biological processes. To the best of the authors' knowledge, this research provides the first report on the mouse liver crotonylome. Furthermore, it offers additional evidence that crotonylation exists in non‐histone proteins, and is likely involved in various biological processes. The mass spectrometry proteomics data have been deposited in the ProteomeXchange Consortium with the dataset identifiers PXD019145.
The lysine succinylation (Ksucc) is involved in many core energy metabolism pathways and affects the metabolic process in mitochondria, making this modification highly valuable for studying diseases ...related to mitochondrial disorders. In this paper, we used liquid chromatography with tandem mass spectrometry (LC‐MS/MS) to perform the first global profiling of succinylation in human lungs under normal physiological conditions. Using an MS‐based platform, we identified 1485 Ksucc sites in 568 proteins. We then compared these sites with those previously identified in human succinylome studies to investigate specific succinylated proteins and identify their possible functions in the lung and to explore the substrate preferences of succinylation modifiers in different cell lines and at different subcellular localizations. Our work expands the succinylation database and supplementary materials on the human succinylome and will thus help in further study of the function of Ksucc and regulation under related physiological and pathological conditions.
Aging is a complex biological process accompanied by a time-dependent functional decline that affects most living organisms. Omics studies help to comprehensively understand the mechanism of aging ...and discover potential intervention methods. Old mice are frequently obese with a fatty liver. We applied mass spectrometry-based phosphoproteomics to obtain a global phosphorylation profile of the liver in mice aged 2 or 18 months. MaxQuant was used for quantitative analysis and PCA was used for unsupervised clustering. Through phosphoproteome analysis, a total of 5,685 phosphosites in 2,335 proteins were filtered for quantitative analysis. PCA analysis of both the phosphoproteome and transcriptome data could distinguish young and old mice. However, from kinase prediction, kinase-substrate interaction analysis, and KEGG functional enrichment analysis done with phosphoproteome data, we observed high phosphorylation of fatty acid biosynthesis, beta-oxidation, and potential secretory processes, together with low phosphorylation of the Egfr-Sos1-Araf/Braf-Map2k1-Mapk1 pathway and Ctnnb1 during aging. Proteins with differentially expressed phosphosites seemed more directly related to the aging-associated fatty liver phenotype than the differentially expressed transcripts. The phosphoproteome may reveal distinctive biological functions that are lost in the transcriptome. In summary, we constructed a phosphorylation-associated network in the mouse liver during normal aging, which may help to discover novel antiaging strategies.
Lysine crotonylation (Kcr) is an evolutionarily conserved protein post-translational modifications, which plays an important role in cellular physiology and pathology, such as chromatin remodeling, ...gene transcription regulation, telomere maintenance, inflammation, and cancer. Tandem mass spectrometry (LC-MS/MS) has been used to identify the global Kcr profiling of human, at the same time, many computing methods have been developed to predict Kcr sites without high experiment cost. Deep learning network solves the problem of manual feature design and selection in traditional machine learning (NLP), especially the algorithms in natural language processing which treated peptides as sentences, thus can extract more in-depth information and obtain higher accuracy. In this work, we establish a Kcr prediction model named ATCLSTM-Kcr which use self-attention mechanism combined with NLP method to highlight the important features and further capture the internal correlation of the features, to realize the feature enhancement and noise reduction modules of the model. Independent tests have proved that ATCLSTM-Kcr has better accuracy and robustness than similar prediction tools. Then, we design pipeline to generate MS-based benchmark dataset to avoid the false negatives caused by MS-detectability and improve the sensitivity of Kcr prediction. Finally, we develop a Human Lysine Crotonylation Database (HLCD) which using ATCLSTM-Kcr and the two representative deep learning models to score all lysine sites of human proteome, and annotate all Kcr sites identified by MS of current published literatures. HLCD provides an integrated platform for human Kcr sites prediction and screening through multiple prediction scores and conditions, and can be accessed on the website:www.urimarker.com/HLCD/.
Lysine crotonylation (Kcr) plays an important role in cellular physiology and pathology, such as chromatin remodeling, gene transcription regulation and cancer. To better elucidate the molecular mechanisms of crotonylation and reduce the high experimental cost, we establish a deep learning Kcr prediction model and solve the problem of false negatives caused by the detectability of mass spectrometry (MS). Finally, we develop a Human Lysine Crotonylation Database to score all lysine sites of human proteome, and annotate all Kcr sites identified by MS of current published literatures. Our work provides a convenient platform for human Kcr sites prediction and screening through multiple prediction scores and conditions.
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•Establish a lysine crotonylation prediction model which using the attention mechanism to achieve feature enhancement and noise reduction.•Design a pipeline to generate MS-based benchmark datasets to avoid potential false negatives caused by the MS-detectability of peptides.•Develop a database platform for prediction and screening all crotonylated sites of human proteome through multiple scores and annotations.
Neurological damage caused by coronavirus disease 2019 (COVID-19) has attracted increasing attention. Recently, through autopsies of patients with COVID-19, the direct identification of severe acute ...respiratory syndrome coronavirus 2 (SARS-CoV-2) in their central nervous system (CNS) has been reported, indicating that SARS-CoV-2 might directly attack the CNS. The need to prevent COVID-19-induced severe injuries and potential sequelae is urgent, requiring the elucidation of large-scale molecular mechanisms in vivo.
In this study, we performed liquid chromatography-mass spectrometry-based proteomic and phosphoproteomic analyses of the cortex, hippocampus, thalamus, lungs, and kidneys of SARS-CoV-2-infected K18-hACE2 female mice. We then performed comprehensive bioinformatic analyses, including differential analyses, functional enrichment, and kinase prediction, to identify key molecules involved in COVID-19.
We found that the cortex had higher viral loads than did the lungs, and the kidneys did not have SARS-COV-2. After SARS-CoV-2 infection, RIG-I-associated virus recognition, antigen processing and presentation, and complement and coagulation cascades were activated to different degrees in all five organs, especially the lungs. The infected cortex exhibited disorders of multiple organelles and biological processes, including dysregulated spliceosome, ribosome, peroxisome, proteasome, endosome, and mitochondrial oxidative respiratory chain. The hippocampus and thalamus had fewer disorders than did the cortex; however, hyperphosphorylation of Mapt/Tau, which may contribute to neurodegenerative diseases, such as Alzheimer's disease, was found in all three brain regions. Moreover, SARS-CoV-2-induced elevation of human angiotensin-converting enzyme 2 (hACE2) was observed in the lungs and kidneys, but not in the three brain regions. Although the virus was not detected, the kidneys expressed high levels of hACE2 and exhibited obvious functional dysregulation after infection. This indicates that SARS-CoV-2 can cause tissue infections or damage via complicated routes. Thus, the treatment of COVID-19 requires a multipronged approach.
This study provides observations and in vivo datasets for COVID-19-associated proteomic and phosphoproteomic alterations in multiple organs, especially cerebral tissues, of K18-hACE2 mice. In mature drug databases, the differentially expressed proteins and predicted kinases in this study can be used as baits to identify candidate therapeutic drugs for COVID-19. This study can serve as a solid resource for the scientific community. The data in this manuscript will serve as a starting point for future research on COVID-19-associated encephalopathy.
This study was supported by grants from the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, the National Natural Science Foundation of China, and the Natural Science Foundation of Beijing.
To analyze the short-term outcomes of redo coronary artery bypass grafting (CABG) using on-pump and off-pump CABG techniques.
From January 2003 to August 2013, non-randomized 80 patients were treated ...with redo CABG in the Department of Cardiac Surgery, Peking University Third Hospital. Among these patients, 40 underwent on-pump CABG technique (redo-ONCAB group) and 40 underwent off-pump CABG technique (redo-OPCAB group). Furthermore, transmyocardial laser revascularization was performed in high-risk patients who were not suitable to conventional grafting. Clinical data of the two groups were recorded and analyzed including operation time, coronary grafts, incomplete revascularization, postoperative ventilation, perioperative stroke, and low output syndrome, etc.
There were no significantly differences in age, gender distribution, incidences of hypertension, stroke, and other clinical characteristics between redo-OPCAB group and redo-ONCAB group (all P>0.05), except for incidences of renal dysfunction and pulmonary disease (all P<0.05). The number of grafting vessels in the redo-ONCAB and redo-OPCAB groups was 2.1 ± 0.74 and 1.4 ±0.52 respectively. There was significant difference between the two groups (P=0.0243). Compared with the redo-ONCAB group, there was shorter operation time (P=0.0045), postoperative ventilation (P=0.0211) and intensive care unit stay (P=0.0400), as well as fewer use of platelet (P=0.0338) and blood transfusion (P=0.0034) in the redo-OPCAB group. The incidence of incomplete revascularization (P=0.0253) and the use of transmyocardial laser revascularization (P=0.0052) were higher in the redo-OPCAB group than those in the redo-ONCAB group (all P<0.05). However, no significant differences were showed for the incidence of the use of intra aortic balloon pump and continuous renal replacement therapy, perioperative stroke, low output syndrome, and in-hospital mortality between the two groups (all P>0.05).
Redo CABG is the safety and efficacy surgical procedure, and redo-OPCAB technique with better outcomes is commended especially in high-risk patients.
Codon bias refers to the nonrandom usage of synonymous codons for encoding amino acids in organisms. As it is related to the carrier molecular of genetic information (DNA) and functional molecular ...(protein) of life, this phenomenon implicates important biological sense. In this review, we summarize the basic theories and analysis methods about codon bias; and present the softwares and websites which are usually used for codon usage analysis. The related fields about codon bias and the research progress are also introduced.
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