scholarly journals Identification of Novel Conopeptides and Distinct Gene Superfamilies in the Marine Cone Snail Conus quercinus

2021 ◽  
Vol 8 ◽  
Author(s):  
Han Zhang ◽  
Lei Wang ◽  
Xiang Yang ◽  
Zhiwei Lian ◽  
Yinbin Qiu ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Prokaryotic Expression ◽  
Disulfide Bonds ◽  
De Novo ◽  
Animal Experiments ◽  
Cone Snail ◽  
Active Peptides ◽  
Neuroscience Research ◽  
First Time ◽  
Mass Spectrometry Mass Spectrometry

Conopeptides from the marine cone snails are a mixture of cysteine-rich active peptides, representing a unique and fertile resource for neuroscience research and drug discovery. The ConoServer database includes 8,134 conopeptides from 122 Conus species, yet many more natural conopeptides remain to be discovered. Here, we identified 517 distinct conopeptide precursors in Conus quercinus using de novo deep transcriptome sequencing. Ten of these precursors were verified at the protein level using liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). The combined gene and protein analyses revealed two novel gene superfamilies (Que-MNCLQ and Que-MAMNV), and three other gene superfamilies (N, P, and I1) were reported for the first time in C. quercinus. From the Que-MAMNV superfamily, a novel conotoxin, Que-0.1, was obtained via cloning and prokaryotic expression. We also documented a new purification process that can be used to induce the expression of conopeptides containing multiple pairs of disulfide bonds. The animal experiments showed that Que-0.1 strongly inhibited neuroconduction; the effects of Que-1.0 were 6.25 times stronger than those of pethidine hydrochloride. In addition, a new cysteine framework (CC-C-C-C-C-C-CC-C-C-C-C-C) was found in C. quercinus. These discoveries accelerate our understanding of conopeptide diversity in the genus, Conus and supply promising materials for medical research.

scholarly journals Personalized deep learning of individual immunopeptidomes to identify neoantigens for cancer vaccines

2019 ◽  
Author(s):  
Ngoc Hieu Tran ◽  
Rui Qiao ◽  
Lei Xin ◽  
Xin Chen ◽  
Baozhen Shan ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Deep Learning ◽  
De Novo ◽  
Mass Spectrometry Data ◽  
Main Role ◽  
Accurate Identification ◽  
Identification Rate ◽  
Cell Responses ◽  
First Time ◽  
Deep Learning Model

AbstractTumor-specific neoantigens play the main role for developing personal vaccines in cancer immunotherapy. We propose, for the first time, a personalized de novo sequencing workflow to identify HLA-I and HLA-II neoantigens directly and solely from mass spectrometry data. Our workflow trains a personal deep learning model on the immunopeptidome of an individual patient and then uses it to predict mutated neoantigens of that patient. This personalized learning and mass spectrometry-based approach enables comprehensive and accurate identification of neoantigens. We applied the workflow to datasets of five melanoma patients and substantially improved the accuracy and identification rate of de novo HLA peptides by 14.3% and 38.9%, respectively. This subsequently led to the identification of 10,440 HLA-I and 1,585 HLA-II new peptides that were not presented in existing databases. Most importantly, our workflow successfully discovered 17 neoantigens of both HLA-I and HLA-II, including those with validated T cell responses and those novel neoantigens that had not been reported in previous studies.

scholarly journals A phylogeny-aware approach reveals unexpected venom components in divergent lineages of cone snails

2021 ◽  
Vol 288 (1954) ◽  
pp. 20211017
Author(s):  
Alexander Fedosov ◽  
Paul Zaharias ◽  
Nicolas Puillandre
Keyword(s):  
Biomedical Applications ◽  
De Novo ◽  
Toxin Gene ◽  
Cone Snail ◽  
Marine Gastropods ◽  
Venom Composition ◽  
Signal Region ◽  
Rare Gene ◽  
Cone Snails ◽  
First Time

Marine gastropods of the genus Conus are renowned for their remarkable diversity and deadly venoms. While Conus venoms are increasingly well studied for their biomedical applications, we know surprisingly little about venom composition in other lineages of Conidae. We performed comprehensive venom transcriptomic profiling for Conasprella coriolisi and Pygmaeconus traillii , first time for both respective genera. We complemented reference-based transcriptome annotation by a de novo toxin prediction guided by phylogeny, which involved transcriptomic data on two additional ‘divergent’ cone snail lineages, Profundiconus , and Californiconus . We identified toxin clusters (SSCs) shared among all or some of the four analysed genera based on the identity of the signal region—a molecular tag present in toxins. In total, 116 and 98 putative toxins represent 29 and 28 toxin gene superfamilies in Conasprella and Pygmaeconus , respectively; about quarter of these only found by semi-manual annotation of the SSCs. Two rare gene superfamilies, originally identified from fish-hunting cone snails, were detected outside Conus rather unexpectedly, so we further investigated their distribution across Conidae radiation. We demonstrate that both these, in fact, are ubiquitous in Conidae, sometimes with extremely high expression. Our findings demonstrate how a phylogeny-aware approach circumvents methodological caveats of similarity-based transcriptome annotation.

Zeolites Fit For A Crown: Probing Host-Guest Interactions with Thermogravimetric Methods

2018 ◽  
Author(s):  
Asel Sartbaeva ◽  
Paul R. Raithby ◽  
Remi Castaing ◽  
Antony Nearchou
Keyword(s):  
Mass Spectrometry ◽  
Thermal Analysis ◽  
Differential Thermal Analysis ◽  
Petrochemical Industry ◽  
Rational Use ◽  
New Methodologies ◽  
First Time ◽  
Kinetics Of

Through a combination of thermogravimetry, mass spectrometry and differential thermal analysis, we demonstrate for the first time that all four zeolites show experimental differences in their host-guest interactions with 18C6. In addition, we have estimated the kinetics of 18C6 decomposition, which is a technique that has not been applied to zeolites previously. Using these findings as a toolkit, a more rational use of OSDAs can be utilised to prepare designer zeolites. Furthermore, the new methodologies presented herein can be applied to current zeolites, such as MFI-type zeolites used in the petrochemical industry.

Algorithm Development of de novo Peptide Sequencing Via Tandem Mass Spectrometry

2011 ◽  
Vol 37 (12) ◽  
pp. 1278-1288 ◽  
Author(s):  
Han-Chang SUN ◽  
Ji-Yang ZHANG ◽  
Hui LIU ◽  
Wei ZHANG ◽  
Chang-Ming XU ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Tandem Mass Spectrometry ◽  
De Novo ◽  
Peptide Sequencing ◽  
Tandem Mass ◽  
Algorithm Development

Untangling the Metabolic Reprogramming in Brain Cancer: Discovering Key Molecular Players Using Mass Spectrometry

2019 ◽  
Vol 19 (17) ◽  
pp. 1521-1534 ◽  
Author(s):  
Anatoly Sorokin ◽  
Vsevolod Shurkhay ◽  
Stanislav Pekov ◽  
Evgeny Zhvansky ◽  
Daniil Ivanov ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Brain Cancer ◽  
De Novo ◽  
Aerobic Glycolysis ◽  
Lipid Production ◽  
Dietary Fatty Acids ◽  
Metabolic Reprogramming ◽  
Detection Methods ◽  
Malignant Cells ◽  
Proliferating Cells

Cells metabolism alteration is the new hallmark of cancer, as well as an important method for carcinogenesis investigation. It is well known that the malignant cells switch to aerobic glycolysis pathway occurring also in healthy proliferating cells. Recently, it was shown that in malignant cells de novo synthesis of the intracellular fatty acid replaces dietary fatty acids which change the lipid composition of cancer cells noticeably. These alterations in energy metabolism and structural lipid production explain the high proliferation rate of malignant tissues. However, metabolic reprogramming affects not only lipid metabolism but many of the metabolic pathways in the cell. 2-hydroxyglutarate was considered as cancer cell biomarker and its presence is associated with oxidative stress influencing the mitochondria functions. Among the variety of metabolite detection methods, mass spectrometry stands out as the most effective method for simultaneous identification and quantification of the metabolites. As the metabolic reprogramming is tightly connected with epigenetics and signaling modifications, the evaluation of metabolite alterations in cells is a promising approach to investigate the carcinogenesis which is necessary for improving current diagnostic capabilities and therapeutic capabilities. In this paper, we overview recent studies on metabolic alteration and oncometabolites, especially concerning brain cancer and mass spectrometry approaches which are now in use for the investigation of the metabolic pathway.

scholarly journals Induction of Promoter DNA Methylation Upon High-Pressure Spraying of Double-Stranded RNA in Plants

Agronomy ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 789
Author(s):  
Athanasios Dalakouras ◽  
Ioannis Ganopoulos
Keyword(s):  
High Pressure ◽  
De Novo ◽  
Epigenetic Changes ◽  
Double Stranded Rna ◽  
Rna Molecules ◽  
Promoter Sequences ◽  
Promoter Dna Methylation ◽  
Promoter Dna ◽  
First Time ◽  
De Novo Methylation

Exogenous application of RNA molecules is a potent method to trigger RNA interference (RNAi) in plants in a transgene-free manner. So far, all exogenous RNAi (exo-RNAi) applications have aimed to trigger mRNA degradation of a given target. However, the issue of concomitant epigenetic changes was never addressed. Here, we report for the first time that high-pressure spraying of dsRNAs can trigger de novo methylation of promoter sequences in plants.

scholarly journals General synthetic strategy for regioselective ultrafast formation of disulfide bonds in peptides and proteins

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Shay Laps ◽  
Fatima Atamleh ◽  
Guy Kamnesky ◽  
Hao Sun ◽  
Ashraf Brik
Keyword(s):  
Drug Discovery ◽  
Disulfide Bonds ◽  
Unsolved Problem ◽  
De Novo ◽  
Therapeutic Potential ◽  
Selective Activation ◽  
One Pot ◽  
Synthetic Strategy ◽  
The One ◽  
Game Changer

AbstractDespite six decades of efforts to synthesize peptides and proteins bearing multiple disulfide bonds, this synthetic challenge remains an unsolved problem in most targets (e.g., knotted mini proteins). Here we show a de novo general synthetic strategy for the ultrafast, high-yielding formation of two and three disulfide bonds in peptides and proteins. We develop an approach based on the combination of a small molecule, ultraviolet-light, and palladium for chemo- and regio-selective activation of cysteine, which enables the one-pot formation of multiple disulfide bonds in various peptides and proteins. We prepare bioactive targets of high therapeutic potential, including conotoxin, RANTES, EETI-II, and plectasin peptides and the linaclotide drug. We anticipate that this strategy will be a game-changer in preparing millions of inaccessible targets for drug discovery.

scholarly journals Analysis of Pembrolizumab in Human Plasma by LC-MS/HRMS. Method Validation and Comparison with Elisa

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 621
Author(s):  
Aurélien Millet ◽  
Nihel Khoudour ◽  
Jérôme Guitton ◽  
Dorothée Lebert ◽  
François Goldwasser ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Human Plasma ◽  
High Resolution Mass Spectrometry ◽  
Internal Standard ◽  
Therapeutic Drug ◽  
Limit Of Quantification ◽  
Immunoglobulin G4 ◽  
Positive Mode ◽  
Surrogate Peptide ◽  
First Time

Pembrolizumab is a humanized immunoglobulin G4-kappa anti-PD1 antibody used in the treatment of different solid tumors or haematological malignancies. A liquid chromatography coupled with a high resolution mass spectrometry (orbitrap technology) method was fully developed, optimized, and validated for quantitative analysis of pembrolizumab in human plasma. A mass spectrometry assay was used for the first time a full-length stable isotope-labelled pembrolizumab-like (Arginine 13C6-15N4 and Lysine 13C6-15N2) as an internal standard; the sample preparation was based on albumin depletion and trypsin digestion and, finally, one surrogate peptide was quantified in positive mode. The assay showed good linearity over the range of 1–100 μg/mL, a limit of quantification at 1 μg/mL, excellent accuracy from 4.4% to 5.1%, and also a between-day precision below 20% at the limit of quantification. In parallel, an in-house ELISA was developed with a linearity range from 2.5 to 50 µg/mL. Then, results were obtained from 70 plasma samples of cancer patients that were treated with pembrolizumab and quantified with both methods were compared using the Passing-Bablok regression analysis and Bland-Altman plotting. The LC-MS/HRMS method is easy to implement in the laboratory for use in the context of PK/PD studies, clinical trials, or therapeutic drug monitoring.

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