Annotation Of Proteins Research Articles

ProFun-SOM: Protein Function Prediction for Specific Ontology Based on Multiple Sequence Alignment Reconstruction.

Protein function prediction is crucial for understanding species evolution, including viral mutations. Gene ontology (GO) is a standardized representation framework for describing protein functions with annotated terms. Each ontology is a specific functional category containing multiple child ontologies, and the relationships of parent and child ontologies create a directed acyclic graph. Protein functions are categorized using GO, which divides them into three main groups: cellular component ontology, molecular function ontology, and biological process ontology. Therefore, the GO annotation of protein is a hierarchical multilabel classification problem. This hierarchical relationship introduces complexities such as mixed ontology problem, leading to performance bottlenecks in existing computational methods due to label dependency and data sparsity. To overcome bottleneck issues brought by mixed ontology problem, we propose ProFun-SOM, an innovative multilabel classifier that utilizes multiple sequence alignments (MSAs) to accurately annotate gene ontologies. ProFun-SOM enhances the initial MSAs through a reconstruction process and integrates them into a deep learning architecture. It then predicts annotations within the cellular component, molecular function, biological process, and mixed ontologies. Our evaluation results on three datasets (CAFA3, SwissProt, and NetGO2) demonstrate that ProFun-SOM surpasses state-of-the-art methods. This study confirmed that utilizing MSAs of proteins can effectively overcome the two main bottlenecks issues, label dependency and data sparsity, thereby alleviating the root problem, mixed ontology. A freely accessible web server is available at http://bliulab.net/ ProFun-SOM/.

Sperm proteome and sperm parameters of captive Amazon squirrel monkeys (Saimiri collinsi Osgood, 1916) during the non-fatted and fatted condition

The aims of this work were (1) to characterize the proteome profile of Saimiri collinsi (Amazon squirrel monkey) sperm, and (2) to evaluate if there are meaningful differences in sperm quality and sperm protein landscape during the non-fatted and fatted conditions of the animals. Semen of adult males (n=4) was collected by electroejaculation and diluted in ACP-118® extender. Sperm concentration, motility, vigor, plasma membrane integrity and functionality, and sperm morphology were evaluated. Sperm proteome was characterized by mass spectrometry. The non-fatted and fatted conditions were defined according to the fattening index. There were increases in seminal volume, pH, and sperm motility of S. collinisi during the fatted in comparison with the non-fatted condition (p < 0.05). Animals in the fatted condition had greater body mass (909 ± 23.98 g) in comparison with the non-fatted condition (818.8 ± 5.97 g, p = 0.0001). There were 1161 proteins identified in the sperm of the monkeys. Thirty-seven proteins were upregulated (p < 0.05) in non-fatted condition (such as coiled-coil domain-containing protein 105, protein kinase C alpha type isoform X1, pyruvate dehydrogenase protein X component – mitochondrial and heat shock 70 kDa protein 1-like) and they were involved in cellular and metabolic processes, catalytic activity and binding. Twenty-eight sperm proteins proteins were upregulated (p < 0.05) in fatted condition (such as Cytochrome b-c1 complex subunit 2, mitochondrial; calcium-binding mitochondrial carrier protein SCaMC-1-like; heat shock 70 kDa protein 13, and izumo sperm-egg fusion protein 1), participating in cellular processes, metabolic processes, and localization, binding, catalytic activity, ATP-dependent activity, and transport activity. Functional annotations of sperm proteins upregulated in non-fatted condition were described as hydrogen ion transport, chaperone, cilium, flagellum, and cell projection. In in fatted conditions, such annotations were described as fertilization, spermatogenesis and transport, chaperone, and motor protein. The present study brings an unprecedent contribution to our understanding about the reproductive biology of adult Saimiri collinsi. It also provides support for conservation and development of assisted reproductive technologies for Neotropical primates.

In Silico Annotation of a Hypothetical Protein from Deinococcus Radiodurans

In Silico Annotation of a Hypothetical Protein from Deinococcus Radiodurans

In silico characterization, homology modelling and structure-based functional annotation of Labeo rohita TLR4 protein

In silico characterization, homology modelling and structure-based functional annotation of Labeo rohita TLR4 protein

Identification and Functional Annotation of Hypothetical Proteins of Pan-Drug-Resistant Providencia rettgeri Strain MRSN845308 Toward Designing Antimicrobial Drug Targets.

Providencia rettgeri has increasingly been responsible for several infections, including urinary tract, post-burn wounds, neonatal sepsis, and others. The emergence of drug-resistant isolates of P rettgeri, accompanied by intrinsic and acquired antibiotic resistance, has exacerbated the challenge of treating such infections, necessitating the development of novel therapeutics. Hypothetical proteins (HPs) form a major portion of cellular proteins and can be targeted by these novel therapeutics. In this study, 410 HPs from a pan-drug-resistant (PDR) P rettgeri strain (MRSN845308) were functionally annotated and characterized by physicochemical properties, localization, virulence, essentiality, druggability, and functionality. Among 410 HPs, the VirulentPred 2.0 tool and VICMpred combinedly predicted 33 HPs as virulent, whereas 48 HPs were highly interacting proteins based on the STRING v12 database. BlastKOALA and eggNOG-mapper v2.1.12 predicted 13 HPs involved in several metabolic pathways like Riboflavin metabolism and Lipopolysaccharide biosynthesis. Overall, 83 HPs were selected as primary drug targets; however, only 80 remained after nonhomology searching and essentiality analysis. In addition, all were detected as novel drug targets according to DrugBank 5.1.12. Considering the potential of membrane and extracellular proteins, 29 HPs (extracellular, outer, and inner membrane) were selected based on the combined prediction from PSORTb v3.0.3, CELLO v.2.5, BUSCA, SOSUIGramN, and PSLpred. According to the prevalence of those HPs in different strains of P rettgeri sequences in National Center for Biotechnology Information Identical Protein Groups (NCBI-IPG), 5 HPs were selected as final drug targets. In addition, 5 other HPs annotated as transporter proteins were also added to the list. As no crystal structures of our targets are present, 3-dimensional structures of selected HPs were predicted by the AlphaFold Server powered by AlphaFold 3. Our findings might facilitate a better understanding of the mechanism of virulence and pathogenesis, and up-to-date annotations can make uncharacterized HPs easy to identify as targets for novel therapeutics.

Small but mighty: the rise of microprotein biology in neuroscience.

The mammalian central nervous system coordinates a network of signaling pathways and cellular interactions, which enable a myriad of complex cognitive and physiological functions. While traditional efforts to understand the molecular basis of brain function have focused on well-characterized proteins, recent advances in high-throughput translatome profiling have revealed a staggering number of proteins translated from non-canonical open reading frames (ncORFs) such as 5' and 3' untranslated regions of annotated proteins, out-of-frame internal ORFs, and previously annotated non-coding RNAs. Of note, microproteins < 100 amino acids (AA) that are translated from such ncORFs have often been neglected due to computational and biochemical challenges. Thousands of putative microproteins have been identified in cell lines and tissues including the brain, with some serving critical biological functions. In this perspective, we highlight the recent discovery of microproteins in the brain and describe several hypotheses that have emerged concerning microprotein function in the developing and mature nervous system.

Molecular mechanisms of the effect of standardized placental hydrolysate peptides on mitochondria functioning

Human placenta hydrolysates (HPH), the study of which was initiated by the scientific school of Vladimir P. Filatov, are currently being investigated using modern proteomic technologies. HPH is a promising tool for maintaining the function of mitochondria and regenerating tissues and organs with a high content of mitochondria (liver, heart muscle, skeletal muscles, etc.). The molecular mechanisms of action of HPH are practically not studied. Identification of mitochondrial support mitochondrial function-supporting peptides in HPH (Laennec, produced by Japan Bioproducts). Data on the chemical structure of the peptides were collected through a mass spectrometric experiment. Then, to establish the amino acid sequences of the peptides, de novo peptide sequencing algorithms based on the mathematical theory of topological and metric analysis of chemographs were applied. Bioinformatic analysis of the peptide composition of HPH was carried out using the integral protein annotation method. The biological functions of 41 peptides in the composition of HPH have been identified and described. Among the target proteins, the activity of which is regulated by the identified peptides and significantly affects the function of mitochondria, are caspases (CASP1, CASP3, CASP4) and other proteins regulating apoptosis (BCL2, CANPL1, PPARA), MAP kinases (MAPK1, MAPK3, MAPK4, MAPK8, MAPK9 , MAPK10, MAPK14), AKT1/GSK3B/MTOR cascade kinases, and a number of other target proteins (ADGRG6 receptor, inhibitor of NF-êB kinase IKKE, pyruvate dehydrogenase 2/3/4, SIRT1 sirtuin deacetylase, ULK1 kinase). HPH peptides have been identified that promote inhibition of mitochondrial pore formation, apoptosis, and excessive mitochondrial autophagy under conditions of oxidative/toxic stress, chronic inflammation, and/or hyperinsulinemia.

Comprehensive bioinformatics-based annotation and functional characterization of bovine chymosin protein revealed novel biological insights

Chymosin, an aspartic protease present in the stomachs of young ruminants like cows (bovine), causes milk coagulation and cheese production through the breakdown of κ-casein peptide bonds at the Met105-Phe106 site. Bovine chymosin is first synthesized as a pre-prochymosin that is cleaved to produce the mature chymosin protein. Despite significant strides in research, our understanding of this crucial enzyme remains incomplete. The purpose of this work was to perform in silico evolutionary and functional analysis and to gain unique insights into the structure of this protein. For this, the sequence of Bos taurus chymosin from UniProt database was subjected to various bioinformatics analyses. We found that bovine chymosin is a low molecular weight and hydrophilic protein that has homologs in other Bovidae species. Two active sites of aspartic peptidases, along with a functional domain, were identified. Gene Ontology analysis further confirmed chymosin's involvement in proteolysis and aspartic endopeptidase activity. Potential disordered residues and post-translational modification sites were also uncovered. It was revealed that the secondary structure of bovine chymosin is comprised of beta strands (44.27%), coils (43.65%), and alpha helices (12.07%). A highly optimized 3D structure was also obtained. Moreover, crucial protein–protein interactions were unveiled. Altogether, these findings provide valuable insights that could guide future research on bovine chymosin and its biological roles.

Protein profiling of conjunctival impression cytology samples of aniridia subjects.

Congenital aniridia is a rare disease, which is in most cases related to PAX6 haploinsufficiency. Aniridia associated keratopathy (AAK) also belongs to ocular signs of congenital aniridia. In AAK, there is corneal epithelial thinning, corneal inflammation, vascularization and scarring. In advanced stage AAK, typically, conjunctival epithelial cells slowly replace the corneal epithelium. Based on previous results we hypothesize that alterations of the conjunctival cells in congenital aniridia may also support the corneal conjunctivalization process. The aim of this study was to identify deregulated proteins in conjunctival impression cytology samples of congenital aniridia subjects. Conjunctival impression cytology samples of eight patients with congenital aniridia [age 34.5 ± 9.9 (17-51) years, 50% female] and eight healthy subjects [age 34.1 ± 11.9 (15-54) years, 50% female] were collected and analysed using mass spectrometry. Proteomic profiles were analysed in terms of molecular functions, biological processes, cellular components and pathway enrichment using the protein annotation of the evolutionary relationship (PANTHER) classification system. In total, 3323 proteins could be verified and there were 127 deregulated proteins (p < 0.01) in congenital aniridia. From the 127 deregulated proteins (DEPs), 82 altered biological processes, 63 deregulated cellular components, 27 significantly altered molecular functions and 31 enriched signalling pathways were identified. Pathological alteration of the biological processes and molecular functions of retinol binding and retinoic acid biosynthesis, as well as lipid metabolism and apoptosis related pathways could be demonstrated. Protein profile of conjunctival impression cytology samples of aniridia subjects identifies alterations of retinol binding, retinoic acid biosynthesis, lipid metabolism and apoptosis related pathways. Whether these changes are directly related to PAX6 haploinsufficiency, must be investigated in further studies. These new findings offer the possibility to identify potential new drug targets.

FunPredCATH: An ensemble method for predicting protein function using CATH

MotivationThe growth of unannotated proteins in UniProt increases at a very high rate every year due to more efficient sequencing methods. However, the experimental annotation of proteins is a lengthy and expensive process. Using computational techniques to narrow the search can speed up the process by providing highly specific Gene Ontology (GO) terms. MethodologyWe propose an ensemble approach that combines three generic base predictors that predict Gene Ontology (BP, CC and MF) terms from sequences across different species. We train our models on UniProtGOA annotation data and use the CATH domain resources to identify the protein families. We then calculate a score based on the prevalence of individual GO terms in the functional families that is then used as an indicator of confidence when assigning the GO term to an uncharacterised protein. MethodsIn the ensemble, we use a statistics-based method that scores the occurrence of GO terms in a CATH FunFam against a background set of proteins annotated by the same GO term. We also developed a set-based method that uses Set Intersection and Set Union to score the occurrence of GO terms within the same CATH FunFam. Finally, we also use FunFams-Plus, a predictor method developed by the Orengo Group at UCL to predict GO terms for uncharacterised proteins in the CAFA3 challenge. EvaluationWe evaluated the methods against the CAFA3 benchmark and DomFun. We used the Precision, Recall and Fmax metrics and the benchmark datasets that are used in CAFA3 to evaluate our models and compare them to the CAFA3 results. Our results show that FunPredCATH compares well with top CAFA methods in the different ontologies and benchmarks. ContributionsFunPredCATH compares well with other prediction methods on CAFA3, and the ensemble approach outperforms the base methods. We show that non-IEA models obtain higher Fmax scores than the IEA counterparts, while the models including IEA annotations have higher coverage at the expense of a lower Fmax score.

Functional Annotation of Uncharacterised Proteins Whose Expression Patterns Affect the Lifespan under Metformin Treatment in Fission Yeast

Functional Annotation of Uncharacterised Proteins Whose Expression Patterns Affect the Lifespan under Metformin Treatment in Fission Yeast

Phytocompounds from Phyllanthus acidus (L.) Skeels in the management of Monkeypox Virus infections

Monkeypox is a communicable disease similar to smallpox, primarily occurring in African countries. However, recently it has spread to countries outside Africa and may arise as the next threat after COVID-pandemic. The causative organism, i.e. Monkeypox Virus (MPV) spreads from one individual to another primarily through inhalation of respiratory droplets or through contact with skin lesions of infected individuals. No known drugs are available specifically for MPV. Due to its similarity with smallpox, treatment of monkeypox is being attempted through the administration of the smallpox vaccine. Therefore, we evaluated the efficacy of the plant Phyllanthus acidus against MPV since it is traditionally used in the treatment of chickenpox and smallpox. Through functional annotation, PASS prediction and Network pharmacology analysis, the effectiveness of these chosen P. acidus-derived phytocompounds against MPV was confirmed. Target prediction of the phytocompounds identified in GC-MS analysis of the plant extract showed them to be associated with 76 human proteins. The compounds also show good binding affinity with selected viral proteins: DNA polymerase (DNApol), Putative Virulence Factor (vPVF) and Cytokine Binding Protein. Prediction of Activity Spectra for Substances (PASS) and functional annotation of the target proteins further support their antiviral nature through interaction with these proteins. The compounds were found to modulate pathways related to symptoms of viral infection and this may help in maintaining homeostasis. Our study demonstrates antiviral activity as well as the therapeutic potential of the plant against MPV infection.Communicated by Ramaswamy H. Sarma

Investigating the role of hypothetical protein (AAB33144.1) in HIV-1 virus pathogenicity: A comparative study with FDA-Approved inhibitor compounds through In silico analysis and molecular docking

Aim and objectiveDue to the a lot of unexplored proteins in HIV-1, this research aimed to explore the functional roles of a hypothetical protein (AAB33144.1) that might play a key role in HIV-1 pathogenicity. MethodsThe homologous protein was identified along with building and validating the 3D structure by searching several bioinformatics tools. ResultsRetroviral aspartyl protease and retropepsin like functional domains and motifs, folding pattern (cupredoxins), and subcellular localization in cytoplasmic membrane were determined as biological activity. Besides, the functional annotation revealed that the chosen hypothetical protein possessed protease-like activity. To validate our generated protein 3D structure, molecular docking was performed with five compounds where nelfinavir showed (−8.2 kcal/mol) best binding affinity against HXB2 viral protease (PDB ID: 7SJX) and main protease (PDB ID: 4EYR) protein. ConclusionsThis study suggests that the annotated hypothetical protein related to protease action, which may be useful in viral genetics and drug discovery.

A Comparative Analysis of the Protein Cargo of Extracellular Vesicles from Helminth Parasites.

Helminth parasites cause debilitating-sometimes fatal-diseases in humans and animals. Despite their impact on global health, mechanisms underlying host-parasite interactions are still poorly understood. One such mechanism involves the exchange of extracellular vesicles (EVs), which are membrane-enclosed subcellular nanoparticles. To date, EV secretion has been studied in helminth parasites, including EV protein content. However, information is highly heterogeneous, since it was generated in multiple species, using varied protocols for EV isolation and data analysis. Here, we compared the protein cargo of helminth EVs to identify common markers for each taxon. For this, we integrated published proteomic data and performed a comparative analysis through an orthology approach. Overall, only three proteins were common in the EVs of the seven analyzed species. Additionally, varied repertoires of proteins with moonlighting activity, vaccine antigens, canonical and non-canonical proteins related to EV biogenesis, taxon-specific proteins of unknown function and RNA-binding proteins were observed in platyhelminth and nematode EVs. Despite the lack of consensus on EV isolation protocols and protein annotation, several proteins were shown to be consistently detected in EV preparations from organisms at different taxa levels, providing a starting point for a selective biochemical characterization.

The Plant Parasitic Nematodes Database: A Comprehensive Genomic Data Platform for Plant Parasitic Nematode Research

Plant parasitic nematodes are important phytopathogens that greatly affect the growth of agricultural and forestry plants. Scientists have conducted several studies to prevent and treat the diseases they cause. With the advent of the genomics era, the genome sequencing of plant parasitic nematodes has been considerably accelerated, and a large amount of data has been generated. This study developed the Plant Parasitic Nematodes Database (PPND), a platform to combine these data. The PPND contains genomic, transcriptomic, protein, and functional annotation data, allowing users to conduct BLAST searches and genome browser analyses and download bioinformatics data for in-depth research. PPND will be continuously updated, and new data will be integrated. PPND is anticipated to become a comprehensive genomics data platform for plant parasitic nematode research.

PoSSuM v.3: A Major Expansion of the PoSSuM Database for Finding Similar Binding Sites of Proteins.

Information on structures of protein-ligand complexes, including comparisons of known and putative protein-ligand-binding pockets, is valuable for protein annotation and drug discovery and development. To facilitate biomedical and pharmaceutical research, we developed PoSSuM (https://possum.cbrc.pj.aist.go.jp/PoSSuM/), a database for identifying similar binding pockets in proteins. The current PoSSuM database includes 191 million similar pairs among almost 10 million identified pockets. PoSSuM drug search (PoSSuMds) is a resource for investigating ligand and receptor diversity among a set of pockets that can bind to an approved drug compound. The enhanced PoSSuMds covers pockets associated with both approved drugs and drug candidates in clinical trials from the latest release of ChEMBL. Additionally, we developed two new databases: PoSSuMAg for investigating antibody-antigen interactions and PoSSuMAF to simplify exploring putative pockets in AlphaFold human protein models.

Scaling of Protein Function across the Tree of Life.

Scaling laws are a powerful way to compare genomes because they put all organisms onto a single curve and reveal nontrivial generalities as genomes change in size. The abundance of functional categories across genomes has previously been found to show power law scaling with respect to the total number of functional categories, suggesting that universal constraints shape genomic category abundance. Here, we look across the tree of life to understand how genome evolution may be related to functional scaling. We revisit previous observations of functional genome scaling with an expanded taxonomy by analyzing 3,726 bacterial, 220 archaeal, and 79 unicellular eukaryotic genomes. We find that for some functional classes, scaling is best described by multiple exponents, revealing previously unobserved shifts in scaling as genome-encoded protein annotations increase or decrease. Furthermore, we find that scaling varies between phyletic groups at both the domain and phyla levels and is less universal than previously thought. This variability in functional scaling is not related to taxonomic phylogeny resolved at the phyla level, suggesting that differences in cell plan or physiology outweigh broad patterns of taxonomic evolution. Since genomes are maintained and replicated by the functional proteins encoded by them, these results point to functional degeneracy between taxonomic groups and unique evolutionary trajectories toward these. We also find that individual phyla frequently span scaling exponents of functional classes, revealing that individual clades can move across scaling exponents. Together, our results reveal unique shifts in functions across the tree of life and highlight that as genomes grow or shrink, proteins of various functions may be added or lost.

Identification and Preliminary Clinical Validation of Key Extracellular Proteins as the Potential Biomarkers in Hashimoto's Thyroiditis by Comprehensive Analysis.

Hashimoto's thyroiditis (HT) is an autoimmune disruption manifested by immune cell infiltration in thyroid tissue and the production of antibodies against thyroid-specific antigens, such as the thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TGAb). TPOAb and TGAb are commonly used in clinical tests; however, handy indicators of the diagnosis and progression of HT are still scarce. Extracellular proteins are glycosylated and are likely to enter body fluids and become readily available and detectable biomarkers. Our research aimed to discover extracellular biomarkers and potential treatment targets associated with HT through integrated bioinformatics analysis and clinical sample validations. A total of 19 extracellular protein-differentially expressed genes (EP-DEGs) were screened by the GSE138198 dataset from the Gene Expression Omnibus (GEO) database and protein annotation databases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to analyze the function and pathway of EP-DEGs. STRING, Cytoscape, MCODE, and Cytohubba were used to construct a protein-protein interaction (PPI) network and screen key EP-DEGs. Six key EP-DEGs (CCL5, GZMK, CXCL9, CXCL10, CXCL11, and CXCL13) were further validated in the GSE29315 dataset and the diagnostic curves were evaluated, which all showed high diagnostic accuracy (AUC > 0.95) for HT. Immune profiling revealed the correlation of the six key EP-DEGs and the pivotal immune cells in HT, such as CD8+ T cells, dendritic cells, and Th2 cells. Further, we also confirmed the key EP-DEGs in clinical thyroid samples. Our study may provide bioinformatics and clinical evidence for revealing the pathogenesis of HT and improving the potential diagnosis biomarkers and therapeutic strategies for HT.

Comparative proteomic analysis of vancomycin-sensitive and vancomycin-intermediate resistant Staphylococcus aureus.

The extensive use of vancomycin has led to the development of Staphylococcus aureus strains with varying degrees of resistance to vancomycin. The present study aimed to explore the molecular causes of vancomycin resistance by conducting a proteomics analysis of subcellular fractions isolated from vancomycin-intermediate resistant S. aureus (VISA) and vancomycin-sensitive S. aureus (VSSA) strains. We conducted proteomics analysis of subcellular fractions isolated from 2 isogenic S. aureus strains: strain 11 (VSSA) and strain 11Y (VISA). We used an integrated quantitative proteomics approach assisted by bioinformatics analysis, and comprehensively investigated the proteome profile. Intensive bioinformatics analysis, including protein annotation, functional classification, functional enrichment, and functional enrichment-based cluster analysis, was used to annotate quantifiable targets. We identified 128 upregulated proteins and 21 downregulated proteins in strain 11Y as compared to strain 11. The largest group of differentially expressed proteins was composed of enzymatic proteins associated with metabolic and catalytic activity, which accounted for 32.1% and 50% of the total proteins, respectively. Some proteins were indispensable parts of the regulatory networks of S. aureus that were altered with vancomycin treatment, and these proteins were related to cell wall metabolism, cell adhesion, proteolysis, and pressure response. Our proteomics study revealed regulatory proteins associated with vancomycin resistance in S. aureus. Some of these proteins were involved in the regulation of cell metabolism and function, which provides potential targets for the development of strategies to manage vancomycin resistance in S. aureus.

CGG toolkit: Software components for computational genomics

Public-domain availability for bioinformatics software resources is a key requirement that ensures long-term permanence and methodological reproducibility for research and development across the life sciences. These issues are particularly critical for widely used, efficient, and well-proven methods, especially those developed in research settings that often face funding discontinuities. We re-launch a range of established software components for computational genomics, as legacy version 1.0.1, suitable for sequence matching, masking, searching, clustering and visualization for protein family discovery, annotation and functional characterization on a genome scale. These applications are made available online as open source and include MagicMatch, GeneCAST, support scripts for CoGenT-like sequence collections, GeneRAGE and DifFuse, supported by centrally administered bioinformatics infrastructure funding. The toolkit may also be conceived as a flexible genome comparison software pipeline that supports research in this domain. We illustrate basic use by examples and pictorial representations of the registered tools, which are further described with appropriate documentation files in the corresponding GitHub release.