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1.
Trends Cancer ; 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-39048488

ABSTRACT

Metastatic hormone-naïve prostate cancer (mHNPC) is often the initial form of presentation for metastatic prostate cancer and encompasses a heterogeneous patient population with high inter-patient heterogeneity in prognosis and response to therapy. A more precise treatment of mHNPC, guided by evidence-based biomarkers, remains an unmet medical need. In addition, the limited number of representative laboratory models of mHNPC hampers the translation of basic research into clinical applications. We provide a comprehensive overview of the clinical and biological features that characterize mHNPC, highlight molecular data that could explain the unique prognostic characteristics of mHNPC, and identify key open questions.

2.
Life (Basel) ; 14(4)2024 Mar 25.
Article in English | MEDLINE | ID: mdl-38672708

ABSTRACT

The RNA world hypothesis suggests that early cellular ancestors relied solely on RNA molecules for both genetic information storage and cellular functions. RNA, composed of four nucleosides-adenosine, guanosine, cytidine, and uridine-forms the basis of this theory. These nucleosides consist of purine nucleobases, adenine and guanine, and pyrimidine nucleobases, cytosine and uracil, bonded to ribose sugar. Notably, carbonaceous chondrite meteorites have revealed the presence of these bases and sugar, hinting at the potential existence of nucleosides in space. This study aims to present the infrared spectra of four RNA nucleosides commonly found in terrestrial biochemistry, facilitating their detection in space, especially in astrobiological and astrochemical contexts. Laboratory measurements involved obtaining mid- and far-IR spectra at three temperatures (-180 °C, room temperature, and +180 °C), followed by calculating molar extinction coefficients (ε) and integrated molar absorptivities (ψ) for corresponding bands. These spectral data, along with ε and ψ values, serve to provide quantitative insights into the presence and relative abundance of nucleosides in space and aid in their detection.

3.
Vet Parasitol Reg Stud Reports ; 47: 100959, 2024 01.
Article in English | MEDLINE | ID: mdl-38199680

ABSTRACT

The genus Goniodes Nitzsch and Goniocotes Burmeister (Ischnocera: Goniogodidae) are distributed worldwide, and exclusively parasitizing avian hosts of the Galliformes. In Brazil, there are only four species recorded: Goniodes dissimilis Denny, Goniodes gigas (Taschenberg), Goniodes pavonis (L.), and Goniocotes gallinae (DeGeer). In the present study, we are reporting the co-parasitism of G. pavonis and G. rectangulatus Nitzsch [In Giebel] on specimens of the white Pavo cristatus, popularly known as 'white Indian peafowl' for the first time. Furthermore, a new Brazilian locality for G. pavonis species has been reported, as well as the first time that G. rectangulatus is reported to Brazil. Additionally, we provide the first molecular information for G. pavonis.


Subject(s)
Galliformes , Ischnocera , Animals , Brazil/epidemiology
4.
Oncologist ; 29(2): 106-116, 2024 Feb 02.
Article in English | MEDLINE | ID: mdl-37878787

ABSTRACT

Rare cancers and other rare nonmalignant tumors comprise 25% of all cancer diagnoses and account for 25% of all cancer deaths. They are difficult to study due to many factors, including infrequent occurrence, lack of a universal infrastructure for data and/or tissue collection, and a paucity of disease models to test potential treatments. For each individual rare cancer, the limited number of diagnosed cases makes it difficult to recruit sufficient patients for clinical studies, and rare cancer research studies are often siloed. As a result, progress has been slow for many of these cancers. While rare cancer research efforts have increased over time, the breadth of the research landscape is not known. A recent literature search revealed a sharp increase in rare tumor, and rare cancer publications began in the early 2000s. To identify rare cancer research efforts being conducted in the US and globally, we conducted an online search of rare tumor/rare cancer research programs and identified 76 programs. To gain a deeper understanding of these programs, we composed and conducted a survey to ask programs for details about their research efforts. Of the 42 programs contacted to complete the survey, 23 programs responded. Survey results show most programs are collecting clinical data, molecular data, and biospecimens, and many are conducting molecular analyses. This landscape analysis demonstrates that multiple rare cancer research efforts are ongoing, and the rare cancer community may benefit from collaboration among stakeholders to accelerate research and improve patient outcomes.


Subject(s)
Neoplasms , Humans , Tissue Banks
5.
Methods Mol Biol ; 2732: 145-154, 2024.
Article in English | MEDLINE | ID: mdl-38060123

ABSTRACT

Retrieval and visualization of biological data are essential for understanding complex systems. With the increasing volume of data generated from high-throughput sequencing technologies, effective and optimized data visualization tools have become indispensable. This is particularly relevant in the COVID-19 postpandemic period, where understanding the diversity and interactions of microbial communities (i.e., viral and bacterial) constitutes an important asset to develop and plan suitable interventions.In this chapter, we show the usage and the potentials of ExTaxsI (Exploring Taxonomy Information) tool to retrieve viral biodiversity data stored in National Center for Biotechnology Information (NCBI) databases and create the related visualization. In addition, by integrating different functions and modules, the tool generates relevant types of visualization plots to facilitate the exploration of microbial biodiversity communities useful to deep dive into ecological and taxonomic relationships among different species and identify potential significant targets.Using the Monkeypox virus as a case study, this work points out significant perspectives on biological data visualization, which can be used to gain insights into the ecology, evolution, and pathogenesis of viruses. Accordingly, we show the potentiality of ExTaxsI to organize and describe the available/downloaded data in an easy, simple, and interpretable way allowing the user to interact dynamically with the visualization plots through specific filters, zoom, and explore functions.


Subject(s)
Mpox (monkeypox) , Viruses , Humans , Biodiversity , Databases, Factual , Bacteria , Viruses/genetics
6.
Vet Parasitol Reg Stud Reports, v. 47, 100959, jan. 2024.
Article in English | Sec. Est. Saúde SP, SESSP-IBPROD, Sec. Est. Saúde SP | ID: bud-5228

ABSTRACT

The genus Goniodes Nitzsch and Goniocotes Burmeister (Ischnocera: Goniogodidae) are distributed worldwide, and exclusively parasitizing avian hosts of the Galliformes. In Brazil, there are only four species recorded: Goniodes dissimilis Denny, Goniodes gigas (Taschenberg), Goniodes pavonis (L.), and Goniocotes gallinae (DeGeer). In the present study, we are reporting the co-parasitism of G. pavonis and G. rectangulatus Nitzsch [In Giebel] on specimens of the white Pavo cristatus, popularly known as ‘white Indian peafowl’ for the first time. Furthermore, a new Brazilian locality for G. pavonis species has been reported, as well as the first time that G. rectangulatus is reported to Brazil. Additionally, we provide the first molecular information for G. pavonis.

7.
Cancers (Basel) ; 15(18)2023 Sep 19.
Article in English | MEDLINE | ID: mdl-37760597

ABSTRACT

Glioma grading plays a pivotal role in guiding treatment decisions, predicting patient outcomes, facilitating clinical trial participation and research, and tailoring treatment strategies. Current glioma grading in the clinic is based on tissue acquired at the time of resection, with tumor aggressiveness assessed from tumor morphology and molecular features. The increased emphasis on molecular characteristics as a guide for management and prognosis estimation underscores is driven by the need for accurate and standardized grading systems that integrate molecular and clinical information in the grading process and carry the expectation of the exposure of molecular markers that go beyond prognosis to increase understanding of tumor biology as a means of identifying druggable targets. In this study, we introduce a novel application (GradWise) that combines rank-based weighted hybrid filter (i.e., mRMR) and embedded (i.e., LASSO) feature selection methods to enhance the performance of feature selection and machine learning models for glioma grading using both clinical and molecular predictors. We utilized publicly available TCGA from the UCI ML Repository and CGGA datasets to identify the most effective scheme that allows for the selection of the minimum number of features with their names. Two popular feature selection methods with a rank-based weighting procedure were employed to conduct comprehensive experiments with the five supervised models. The computational results demonstrate that our proposed method achieves an accuracy rate of 87.007% with 13 features and an accuracy rate of 80.412% with five features on the TCGA and CGGA datasets, respectively. We also obtained four shared biomarkers for the glioma grading that emerged in both datasets and can be employed with transferable value to other datasets and data-based outcome analyses. These findings are a significant step toward highlighting the effectiveness of our approach by offering pioneering results with novel markers with prospects for understanding and targeting the biologic mechanisms of glioma progression to improve patient outcomes.

8.
Ecol Evol ; 13(7): e10356, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37484930

ABSTRACT

Conserving species and their genetic variation are a global priority to safeguard evolutionary potential in a rapidly changing world. Species are fundamental units in research and nature management, but taxonomic work is increasingly undermined. Increasing knowledge on the species genetic diversity would aid in prioritizing conservation efforts. Sphagnum is a diverse, well-known bryophyte genus, which makes the genus suited to study speciation and cryptic variation. The species share specific characteristics and can be difficult to separate in the field. By combining molecular data with thorough morphological examination, new species have recently been discovered. Still, there are taxonomic uncertainties, even for species assessed on the IUCN Red List of threatened species. Here, we use molecular data to examine three rare species within the subgenus Acutifolia described based on morphological characters. All species have narrow distributions and limited dispersability. First, we confirm the genetic origin of S. skyense. Second, we show that S. venustum is a haploid species genetically distinct from morphologically similar species. Lastly, S. nitidulum was found to have a distinct haplotype, but cannot be genetically separated from other red Acutifolia species. We also found high genetic variation within red Acutifolia specimens, indicating the need of further morphological examination and possibly taxonomic revision. Until then, our results have shown that genetic data can aid in prioritizing targets of conservation efforts when taxonomy is unresolved. All three taxa should be further searched for by field biologists to increase knowledge about their distribution ranges.

9.
Zool Stud ; 62: e23, 2023.
Article in English | MEDLINE | ID: mdl-37408703

ABSTRACT

A new species of the genus Pycnogonum was discovered in the mesophotic zone of Munseom Islet, Jejudo Island, Korea. Pycnogonum (Nulloviger) bifurcatum sp. nov. is the first case of sea spiders in Korean fauna not only included in the subgenus Nulloviger but also collected in the mesophotic zone of Munseom Islet. The new species is morphologically close to Pycnogonum (Pycnogonum) asiaticum and P. (N.) carinatum, sharing the granular integument, the dorsomedian tubercles on the trunk, and the post-ocular tubercle. The new species can be easily distinguished from the congeners by combination of the following characteristics: the prominent dorsomedian tubercles on the trunk, the lateral processes 1-3 touching each other, and the small auxiliary claws. A key is provided to distinguish 12 species of the subgenus Nulloviger morphologically, and molecular data of the new species are provided for species identification and further studies.

10.
Zookeys ; 1161: 169-202, 2023.
Article in English | MEDLINE | ID: mdl-37234742

ABSTRACT

Uncertainties regarding the taxonomic status and biogeographical distribution of some species of the genus Emerita from the western Atlantic led to thorough examination of the subtle morphological differences between two coexistent species (E.brasiliensis Schmitt, 1935 and E.portoricensis Schmitt, 1935) along the Brazilian coast and compare them using two genetic markers. The molecular phylogenetic analysis based on sequences of the 16S rRNA and COI genes showed that individuals identified as E.portoricensis were clustered into two clades: one containing representatives from the Brazilian coast and another containing specimens distributed in Central America. Our molecular-based phylogeny, combined with a detailed morphological analysis, revealed the Brazilian population as a new species, which is described here as Emeritaalmeidai Mantelatto & Balbino, sp. nov. The number of species in the genus Emerita is now raised to 12, with five of them occurring in the western Atlantic, five in the Indo-Pacific, and two in the eastern Pacific.

11.
ACS Synth Biol ; 12(6): 1716-1726, 2023 06 16.
Article in English | MEDLINE | ID: mdl-37192389

ABSTRACT

Novel enzymatic methods are poised to become the dominant processes for de novo synthesis of DNA, promising functional, economic, and environmental advantages over the longstanding approach of phosphoramidite synthesis. Before this can occur, however, enzymatic synthesis methods must be parallelized to enable production of multiple DNA sequences simultaneously. As a means to this parallelization, we report a polymerase-nucleotide conjugate that is cleaved using electrochemical oxidation on a microelectrode array. The developed conjugate maintains polymerase activity toward surface-bound substrates with single-base control and detaches from the surface at mild oxidative voltages, leaving an extendable oligonucleotide behind. Our approach readies the way for enzymatic DNA synthesis on the scale necessary for DNA-intensive applications such as DNA data storage or gene synthesis.


Subject(s)
DNA Nucleotidylexotransferase , Nucleotides , DNA Nucleotidylexotransferase/genetics , DNA , Oligonucleotides , Base Sequence
12.
Folia Parasitol (Praha) ; 702023 Apr 12.
Article in English | MEDLINE | ID: mdl-37114799

ABSTRACT

Proteocephalid tapeworms of frogs of the family Ranidae ('true' frogs) are reviewed with emphasis on their species diversity, host specificity and geographical distribution. New molecular data (nuclear lsrDNA and mitochondrial COI sequences) are presented for tapeworms of four species of ranid frogs in North America, including the poorly known Ophiotaenia saphena Osler, 1931 of Rana clamitans Latreille and R. catesbeiana (Shaw), which is redescribed using new material from Arkansas, USA. Tapeworms of R. sphenocephala (Cope) and R. pipiens Schreber, the latter previously identified as O. saphena, represent another, putative new species, but are not formally described due to insufficient available material. Proteocephalus papuensis Bursey, Goldberg et Kraus, 2008 from Sylvirana supragrisea (Menzies) is transferred to Ophiotaenia La Rue, 1911 as a new combination. After a critical review of the literature, only nine nominal species of Ophiotaenia are recognised as valid, which is in contrast to the large number of ranid frogs (> 440 spp.). The reasons for this striking disparity are briefly discussed, and a key based on morphology is presented for the identification of all species of Ophiotaenia from the Ranidae. Molecular data are available for only two taxa from North America that form a monophyletic group. The relationships among tapeworms of ranid frogs occurring in other zoogeographical regions are not yet known. The taxonomic status of Batrachotaenia Rudin, 1917, which was erected to accommodate proteocephalids from amphibians, is also discussed. To facilitate future studies, a tabulated summary of all 32 species of proteocephalids belonging to three genera reported from amphibians (frogs and salamanders) is presented, with information on their hosts, distribution, and taxonomically important characters, including key measurements.


Subject(s)
Cestoda , Cestode Infections , Animals , Cestode Infections/epidemiology , Cestode Infections/veterinary , Ranidae , North America
13.
Radiat Oncol ; 18(1): 51, 2023 Mar 11.
Article in English | MEDLINE | ID: mdl-36906590

ABSTRACT

Despite intensive basic scientific, translational, and clinical efforts in the last decades, glioblastoma remains a devastating disease with a highly dismal prognosis. Apart from the implementation of temozolomide into the clinical routine, novel treatment approaches have largely failed, emphasizing the need for systematic examination of glioblastoma therapy resistance in order to identify major drivers and thus, potential vulnerabilities for therapeutic intervention. Recently, we provided proof-of-concept for the systematic identification of combined modality radiochemotherapy treatment vulnerabilities via integration of clonogenic survival data upon radio(chemo)therapy with low-density transcriptomic profiling data in a panel of established human glioblastoma cell lines. Here, we expand this approach to multiple molecular levels, including genomic copy number, spectral karyotyping, DNA methylation, and transcriptome data. Correlation of transcriptome data with inherent therapy resistance on the single gene level yielded several candidates that were so far underappreciated in this context and for which clinically approved drugs are readily available, such as the androgen receptor (AR). Gene set enrichment analyses confirmed these results, and identified additional gene sets, including reactive oxygen species detoxification, mammalian target of rapamycin complex 1 (MTORC1) signaling, and ferroptosis/autophagy-related regulatory circuits to be associated with inherent therapy resistance in glioblastoma cells. To identify pharmacologically accessible genes within those gene sets, leading edge analyses were performed yielding candidates with functions in thioredoxin/peroxiredoxin metabolism, glutathione synthesis, chaperoning of proteins, prolyl hydroxylation, proteasome function, and DNA synthesis/repair. Our study thus confirms previously nominated targets for mechanism-based multi-modal glioblastoma therapy, provides proof-of-concept for this workflow of multi-level data integration, and identifies novel candidates for which pharmacological inhibitors are readily available and whose targeting in combination with radio(chemo)therapy deserves further examination. In addition, our study also reveals that the presented workflow requires mRNA expression data, rather than genomic copy number or DNA methylation data, since no stringent correlation between these data levels could be observed. Finally, the data sets generated in the present study, including functional and multi-level molecular data of commonly used glioblastoma cell lines, represent a valuable toolbox for other researchers in the field of glioblastoma therapy resistance.


Subject(s)
Brain Neoplasms , Glioblastoma , Humans , Glioblastoma/drug therapy , Temozolomide/therapeutic use , Signal Transduction , Prognosis , Cell Line, Tumor , Brain Neoplasms/drug therapy
14.
Pathol Res Pract ; 242: 154311, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36657221

ABSTRACT

SARS-CoV-2 pandemic is the current threat of the world with enormous number of deceases. As most of the countries have constraints on resources, particularly for intensive care and oxygen, severity prediction with high accuracy is crucial. This prediction will help the medical society in the selection of patients with the need for these constrained resources. Literature shows that using clinical data in this study is the common trend and molecular data is rarely utilized in this prediction. As molecular data carry more disease related information, in this study, three different types of RNA molecules ( lncRNA, miRNA and mRNA) of SARS-COV-2 patients are used to predict the severity stage and treatment stage of those patients. Using seven different machine learning algorithms along with several feature selection techniques shows that in both phenotypes, feature importance selected features provides the best accuracy along with random forest classifier. Further to this, it shows that in the severity stage prediction miRNA and lncRNA give the best performance, and lncRNA data gives the best in treatment stage prediction. As most of the studies related to molecular data uses mRNA data, this is an interesting finding.


Subject(s)
COVID-19 , MicroRNAs , RNA, Long Noncoding , Humans , SARS-CoV-2/genetics , RNA, Long Noncoding/genetics , Algorithms , MicroRNAs/genetics , RNA, Messenger/genetics
15.
Int J Mol Sci ; 23(22)2022 Nov 16.
Article in English | MEDLINE | ID: mdl-36430631

ABSTRACT

Determining the aggressiveness of gliomas, termed grading, is a critical step toward treatment optimization to increase the survival rate and decrease treatment toxicity for patients. Streamlined grading using molecular information has the potential to facilitate decision making in the clinic and aid in treatment planning. In recent years, molecular markers have increasingly gained importance in the classification of tumors. In this study, we propose a novel hierarchical voting-based methodology for improving the performance results of the feature selection stage and machine learning models for glioma grading with clinical and molecular predictors. To identify the best scheme for the given soft-voting-based ensemble learning model selections, we utilized publicly available TCGA and CGGA datasets and employed four dimensionality reduction methods to carry out a voting-based ensemble feature selection and five supervised models, with a total of sixteen combination sets. We also compared our proposed feature selection method with the LASSO feature selection method in isolation. The computational results indicate that the proposed method achieves 87.606% and 79.668% accuracy rates on TCGA and CGGA datasets, respectively, outperforming the LASSO feature selection method.


Subject(s)
Algorithms , Glioma , Humans , Glioma/genetics , Machine Learning
16.
Parasitology ; 149(14): 1811-1814, 2022 12.
Article in English | MEDLINE | ID: mdl-36226653

ABSTRACT

Fish (Elasmobranchia and Actinopterygii) inhabit the majority of aquatic habitats globally. They are crucial for human nutrition but they may be negatively affected by parasitic protists and metazoan parasites. Fish parasites are also an extraordinary group of animals because of their ecological and evolutionary importance and unique adaptations to parasitism. They also play a key role in ecosystem functioning. In the present special issue, 13 review and research articles on major groups of fish parasites are provided to document the current advancement in our understanding of different aspects of their biology, ecology and associations with their fish hosts. The existing gaps in our knowledge of these peculiar animals are mapped and future trends in their research outlined.


Subject(s)
Fish Diseases , Parasites , Animals , Humans , Ecosystem , Host-Parasite Interactions , Fishes/parasitology , Biological Evolution , Fish Diseases/parasitology
17.
Zookeys ; 1097: 103-116, 2022.
Article in English | MEDLINE | ID: mdl-35837581

ABSTRACT

Ivelayini sp. nov., is described from Guangdong, China based on morphological characters and molecular data. Adults, including genitalia and wing venation, and pupa are illustrated and compared to those of similar species. A key to Chinese Ivela species is provided. Assignment of the new species to Ivela Swinhoe is based primarily on a molecular phylogenetic analysis and is corroborated by morphology. Life histories of I.yini and Dendrophlepssemihyalina Hampson are discussed.

18.
BMC Genomics ; 23(1): 156, 2022 Feb 22.
Article in English | MEDLINE | ID: mdl-35193494

ABSTRACT

BACKGROUND: Patient-derived xenografts (PDX) mice models play an important role in preclinical trials and personalized medicine. Sharing data on the models is highly valuable for numerous reasons - ethical, economical, research cross validation etc. The EurOPDX Consortium was established 8 years ago to share such information and avoid duplicating efforts in developing new PDX mice models and unify approaches to support preclinical research. EurOPDX Data Portal is the unified data sharing platform adopted by the Consortium. MAIN BODY: In this paper we describe the main features of the EurOPDX Data Portal ( https://dataportal.europdx.eu/ ), its architecture and possible utilization by researchers who look for PDX mice models for their research. The Portal offers a catalogue of European models accessible on a cooperative basis. The models are searchable by metadata, and a detailed view provides molecular profiles (gene expression, mutation, copy number alteration) and treatment studies. The Portal displays the data in multiple tools (PDX Finder, cBioPortal, and GenomeCruzer in future), which are populated from a common database displaying strictly mutually consistent views. (SHORT) CONCLUSION: EurOPDX Data Portal is an entry point to the EurOPDX Research Infrastructure offering PDX mice models for collaborative research, (meta)data describing their features and deep molecular data analysis according to users' interests.


Subject(s)
Neoplasms , Animals , Heterografts , Humans , Information Dissemination , Mice , Neoplasms/genetics , Precision Medicine , Xenograft Model Antitumor Assays
19.
Biol Lett ; 18(2): 20210603, 2022 02.
Article in English | MEDLINE | ID: mdl-35135314

ABSTRACT

The use of molecular data for living groups is vital for interpreting fossils, especially when morphology-only analyses retrieve problematic phylogenies for living forms. These topological discrepancies impact on the inferred phylogenetic position of many fossil taxa. In Crocodylia, morphology-based phylogenetic inferences differ fundamentally in placing Gavialis basal to all other living forms, whereas molecular data consistently unite it with crocodylids. The Cenomanian Portugalosuchus azenhae was recently described as the oldest crown crocodilian, with affinities to Gavialis, based on morphology-only analyses, thus representing a potentially important new molecular clock calibration. Here, we performed analyses incorporating DNA data into these morphological datasets, using scaffold and supermatrix (total evidence) approaches, in order to evaluate the position of basal crocodylians, including Portugalosuchus. Our analyses incorporating DNA data robustly recovered Portugalosuchus outside Crocodylia (as well as thoracosaurs, planocraniids and Borealosuchus spp.), questioning the status of Portugalosuchus as crown crocodilian and any future use as a node calibration in molecular clock studies. Finally, we discuss the impact of ambiguous fossil calibration and how, with the increasing size of phylogenomic datasets, the molecular scaffold might be an efficient (though imperfect) approximation of more rigorous but demanding supermatrix analyses.


Subject(s)
Alligators and Crocodiles , Alligators and Crocodiles/genetics , Animals , Calibration , Fossils , Phylogeny
20.
Angew Chem Int Ed Engl ; 61(13): e202116718, 2022 03 21.
Article in English | MEDLINE | ID: mdl-35104375

ABSTRACT

Rewriting data stored on synthetic macromolecules is an interesting feature, even though it is considered as being quite challenging within the area of digital macromolecules. In this context, we initially studied a strategy for modifying the position tag of sequence-encoded macromolecules in a reversible manner. The efficiency of this method, which relies on the orthogonal cleavage of a thioester moiety via aminolysis, was demonstrated by modifying parts of an exemplary sentence. Simultaneously, a novel algorithm was developed to ease the read-out of macromolecular information by means of MS/MS techniques. This program, Oligoreader, can identify potential information-containing macromolecules from a series of MS1 spectra, analyze the corresponding MS2 spectra, and finally decode the data. Consequently, the algorithm simplifies the entire read-out process by avoiding any interference from the operator, which increases the potential for blind sequencing of uniform macromolecules.


Subject(s)
Information Storage and Retrieval , Tandem Mass Spectrometry , Algorithms , Macromolecular Substances , Tandem Mass Spectrometry/methods
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