Bioinformatics and Biology Insights最新文献

{"title":"The TWW Growth Model and Its Application in the Analysis of Quantitative Polymerase Chain Reaction.","authors":"M Tabatabai, D Wilus, K P Singh, T L Wallace","doi":"10.1177/11779322241290126","DOIUrl":"10.1177/11779322241290126","url":null,"abstract":"<p><p>It is necessary to accurately capture the growth trajectory of fluorescence where the best fit, precision, and relative efficiency are essential. Having this in mind, a new family of growth functions called TWW (Tabatabai, Wilus, Wallace) was introduced. This model is capable of accurately analyzing quantitative polymerase chain reaction (qPCR). This new family provides a reproducible quantitation of gene copies and is less labor-intensive than current quantitative methods. A new cycle threshold based on TWW that does not need the assumption of equal reaction efficiency was introduced. The performance of TWW was compared with 3 classical models (Gompertz, logistic, and Richard) using qPCR data. TWW models the relationship between the cycle number and fluorescence intensity, outperforming some state-of-the-art models in performance measures. The 3-parameter TWW model had the best model fit in 68.57% of all cases, followed by the Richard model (28.57%) and the logistic (2.86%). Gompertz had the worst fit in 88.57% of all cases. It had the best precision in 85.71% of all cases followed by Richard (14.29%). For all cases, Gompertz had the worst precision. TWW had the best relative efficiency in 54.29% of all cases, while the logistic model was best in 17.14% of all cases. Richard and Gompertz tied for the best relative efficiency in 14.29% of all cases. The results indicate that TWW is a good competitor when considering model fit, precision, and efficiency. The 3-parameter TWW model has fewer parameters when compared to the Richard model in analyzing qPCR data, which makes it less challenging to reach convergence.</p>","PeriodicalId":9065,"journal":{"name":"Bioinformatics and Biology Insights","volume":"18 ","pages":"11779322241290126"},"PeriodicalIF":2.3,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11577475/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680788","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}

{"title":"Unlocking Benzosampangine's Potential: A Computational Approach to Investigating, Its Role as a PD-L1 Inhibitor in Tumor Immune Evasion via Molecular Docking, Dynamic Simulation, and ADMET Profiling.","authors":"Abderrahim Ait Ouchaoui, Salah Eddine El Hadad, Marouane Aherkou, Elkamili Fadoua, Mkamel Mouad, Youssef Ramli, Anass Kettani, Ilhame Bourais","doi":"10.1177/11779322241298591","DOIUrl":"10.1177/11779322241298591","url":null,"abstract":"<p><p>The interaction between programmed cell death protein 1 (PD-1) and its ligand PD-L1 plays a crucial role in tumor immune evasion, presenting a critical target for cancer immunotherapy. Despite being effective, current monoclonal antibodies present some drawbacks such as high costs, toxicity, and resistance development. Therefore, the development of small-molecule inhibitors is necessary, especially those derived from natural sources. In this study, benzosampangine is predicted as a promising PD-L1 inhibitor, with potential applications in cancer immunotherapy. Utilizing the high-resolution crystal structure of human PD-L1 (PDB ID: 5O45), we screened 511 natural compounds, identifying benzosampangine as a top candidate with exceptional inhibitory properties. Molecular docking predicted that benzosampangine exhibits a strong binding affinity for PD-L1 (-9.4 kcal/mol) compared with established controls such as CA-170 (-6.5 kcal/mol), BMS-202 (-8.6 kcal/mol), and pyrvinium (-8.9 kcal/mol). The compound's predicted binding efficacy is highlighted by robust interactions with key amino acids (ILE54, TYR56, GLN66, MET115, ILE116, SER117, ALA121, ASP122) within the active site, notably forming 3 Pi-sulfur interactions with MET115-an interaction absents in control inhibitors. In addition, ADMET profiling suggests that over the control molecules, benzosampangine has several key advantages, including favorable solubility, permeability, metabolic stability, and low toxicity, while adhering to Lipinski's rule of five. Molecular dynamic simulations predict the stability of the benzosampangine-PD-L1 complex, reinforcing its potential to sustain inhibition of the PD-1/PD-L1 pathway. MMGBSA analysis calculated a binding free energy (ΔGbind) of -39.39 kcal/mol for the benzosampangine-PD-L1 complex, with significant contributions from Coulombic, lipophilic, and Van der Waals interactions, validating the predicted docking results. This study investigates in silico benzosampangine, predicting its better molecular interactions and pharmacokinetic profile compared with several already known PD-L1 inhibitors.</p>","PeriodicalId":9065,"journal":{"name":"Bioinformatics and Biology Insights","volume":"18 ","pages":"11779322241298591"},"PeriodicalIF":2.3,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11574905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675160","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}

{"title":"Drug Repositioning for Scorpion Envenomation Treatment Through Dual Inhibition of Chlorotoxin and Leiurotoxin.","authors":"Gaouzi Zainab, Abbou Hanane, Zegrari Razana, Eljaoudi Rachid, Diawara Idrissa, Hakmi Mohammed, Mkamel Mouad","doi":"10.1177/11779322241294130","DOIUrl":"https://doi.org/10.1177/11779322241294130","url":null,"abstract":"<p><p>Scorpion envenomation, a grave public health concern, is primarily driven by the potent neurotoxins chlorotoxin and leiurotoxin present in Leiurus species venom. Developing effective treatments is crucial to mitigate its impact. Utilizing a drug-repositioning bioinformatics-based approach, potential inhibitors of these neurotoxins were identified from Food and Drug Administration (FDA)-approved drugs. Through virtual screening and subsequent molecular dynamics simulations, their ability to stabilize the peptides over time was evaluated. Among the compounds scrutinized, bolazine emerged as a promising candidate, demonstrating significant affinity for both neurotoxins, indicating potential dual inhibitory activity. Molecular dynamics simulations further corroborated the enhanced stability of bolazine complexes compared to neurotoxins alone. These findings suggest the feasibility of repurposing existing drugs to develop new therapeutic strategies to treat scorpion envenomation. Such interventions hold promise in alleviating the severe health repercussions of scorpion stings and meeting the urgent demand for effective remedies in affected communities.</p>","PeriodicalId":9065,"journal":{"name":"Bioinformatics and Biology Insights","volume":"18 ","pages":"11779322241294130"},"PeriodicalIF":2.3,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11544650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614604","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}

{"title":"Charting Peptide Shared Sequences Between 'Diabetes-Viruses' and Human Pancreatic Proteins, Their Structural and Autoimmune Implications.","authors":"Stephen A James, Istifanus A Joshua","doi":"10.1177/11779322241289936","DOIUrl":"10.1177/11779322241289936","url":null,"abstract":"<p><p>Diabetes mellitus (DM) is a metabolic syndrome characterized by hyperglycaemia, polydipsia, polyuria, and weight loss, among others. The pathophysiology for the disorders is complex and results in pancreatic abnormal function. Viruses have also been implicated in the metabolic syndrome. This study charted peptides to investigate and predict the autoimmune potential of shared sequences between 8 viral species proteins (which we termed 'diabetes-viruses') and the human pancreatic proteins. The structure and immunological relevance of shared sequences between viruses reported in DM onset and human pancreatic proteins were analysed. At nonapeptide mapping between human pancreatic protein and 'diabetic-viruses', reveal 1064 shared sequences distributed among 454 humans and 4288 viral protein sequences. The viral results showed herpesviruses, enterovirus (EV), human endogenous retrovirus, influenza A viruses, rotavirus, and rubivirus sequences are hosted by the human pancreatic protein. The most common shared nonapeptide was AAAAAAAAA, present in 30 human nonredundant sequences. Among the viral species, the shared sequence NSLEVLFQG occurred in 18 nonredundant EVs protein, while occurring merely in 1 human protein, whereas LGLDIEIAT occurred in 8 influenza A viruses overlapping to 1 human protein and KDELSEARE occurred in 2 rotaviruses. The prediction of the location of the shared sequences in the protein structures, showed most of the shared sequences are exposed and located either on the surface or cleft relative to the entire protein structure. Besides, the peptides in the viral protein shareome were predicted computationally for binding to MHC molecules. Here analyses showed that the entire 1064 shared sequences predicted 203 to be either HLA-A or B supertype-restricted epitopes. Fifty-one of the putative epitopes matched reported HLA ligands/T-cell epitopes majorly coming from EV B supertype representative allele restrictions. These data, shared sequences, and epitope charts provide important insight into the role of viruses on the onset of DM and its implications.</p>","PeriodicalId":9065,"journal":{"name":"Bioinformatics and Biology Insights","volume":"18 ","pages":"11779322241289936"},"PeriodicalIF":2.3,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11536397/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142580798","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}

{"title":"Approaches for Benchmarking Single-Cell Gene Regulatory Network Methods.","authors":"Karamveer, Yasin Uzun","doi":"10.1177/11779322241287120","DOIUrl":"10.1177/11779322241287120","url":null,"abstract":"<p><p>Gene regulatory networks are powerful tools for modeling genetic interactions that control the expression of genes driving cell differentiation, and single-cell sequencing offers a unique opportunity to build these networks with high-resolution genomic data. There are many proposed computational methods to build these networks using single-cell data, and different approaches are used to benchmark these methods. However, a comprehensive discussion specifically focusing on benchmarking approaches is missing. In this article, we lay the GRN terminology, present an overview of common gold-standard studies and data sets, and define the performance metrics for benchmarking network construction methodologies. We also point out the advantages and limitations of different benchmarking approaches, suggest alternative ground truth data sets that can be used for benchmarking, and specify additional considerations in this context.</p>","PeriodicalId":9065,"journal":{"name":"Bioinformatics and Biology Insights","volume":"18 ","pages":"11779322241287120"},"PeriodicalIF":2.3,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11536393/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581244","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}

{"title":"<i>Conyza bonariensis (L.)</i> Impact on Carbohydrate Metabolism and Oxidative Stress in a Type 2 Diabetic Rat Model.","authors":"Imtiaz Mustafa, Shahzad Irfan, Ghulam Hussain, Muhammad Umar Ijaz, Muhammad Irfan Ullah, Jaweria Nisar, Tahir Maqbool, Haseeb Anwar","doi":"10.1177/11779322241292239","DOIUrl":"10.1177/11779322241292239","url":null,"abstract":"<p><p>This study was conducted to assess the possible antidiabetic potential of <i>Conyza bonariensis</i> by employing <i>in vitro</i> as well as <i>in vivo</i> assessments. The dried plant material was extracted in methanol, ethanol, and water. The in vitro results showed that the ethanolic extract (EthCb) was found to have higher antioxidant and antidiabetic potential as compared with the aqueous (AqCb) and methanolic extracts (MthCb) so it was further evaluated in the in vivo trial using a diabetic rat model. Diabetes was induced in male Wistar rats by administering 5% sucrose in drinking water and a cafeteria diet for 8 weeks, followed by nicotinamide and streptozotocin administration. Subsequently, the diabetic rats were divided into 4 groups (n = 8 each): Positive control (no treatment), standard control (Metformin @ 10 mg/kg bw), treatment 1 (<i>C. bonariensis</i> ethanolic extract @ 200 mg/kg bw), and treatment 2 (<i>C. bonariensis</i> ethanolic extract @ 400 mg/kg bw). In addition, there was a negative control group of 8 rats without diabetes induction or treatment. After 21 days of treatment, blood samples were collected from all rats. The serum was evaluated through different means for glucose level, lipid profile, oxidative stress, carbohydrate metabolic enzymes and thyroid hormones. ANOVA was used to evaluate the data statistically. Total oxidant status (TOS) and the serum glucose levels of the streptozotocin-treated rats were reduced significantly (<i>P</i> ⩽ .05) in <i>Conyza bonariensis</i> treated group. Whereas total antioxidant capacity (TAC) along with enzymes like paraoxonase and arylesterase were increased in <i>Conyza bonariensis</i> treated group. The antihyperlipidemic activity was also observed in <i>Conyza bonariensis</i> treated group Interestingly the subnormal levels of T3 and T4 which were observed in the PC group were also normalized in both treatment groups. This study demonstrated the antidiabetic as well as antioxidant activity of different extracts of <i>Conyza bonariensis</i>.</p>","PeriodicalId":9065,"journal":{"name":"Bioinformatics and Biology Insights","volume":"18 ","pages":"11779322241292239"},"PeriodicalIF":2.3,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11528660/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566603","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}

{"title":"detectCilia: An R Package for Automated Detection and Length Measurement of Primary Cilia.","authors":"Kai Budde-Sagert, Simone Krueger, Clemens Sehlke, Heiko Lemcke, Anika Jonitz-Heincke, Robert David, Rainer Bader, Adelinde M Uhrmacher","doi":"10.1177/11779322241280431","DOIUrl":"10.1177/11779322241280431","url":null,"abstract":"<p><strong>Background and objective: </strong>The primary cilium is a small protrusion found on most mammalian cells. It acts as a cellular antenna, being involved in various cell signaling pathways. The length of the primary cilium affects its function. To study the impact of physical or chemical stimuli on cilia, their lengths must be determined easily and reproducibly.</p><p><strong>Methods: </strong>We have developed and evaluated an open-source R package called detectCilia to detect and measure primary cilia automatically. As a case study to demonstrate the capability of our tool, we compared the influence of 4 different cell culture media compositions on the lengths of primary cilia in human chondrocytes. These media compositions include (1) insulin-transferrin-selenium (ITS); (2) ITS and dexamethasone (Dexa); (3) ITS, Dexa, insulin-like growth factor 1 (IGF-1), and transforming growth factor beta 1 (TGF-β1); and (4) fetal bovine serum (FBS).</p><p><strong>Results: </strong>The assessment of detectCilia included a comparison with 2 similar tools: ACDC (Automated Cilia Detection in Cells) and CiliaQ. Several differences and advantages of our package make it a valuable addition to these tools. In the case study, we have observed variations in the ciliary lengths associated with using different media compositions.</p><p><strong>Conclusions: </strong>We conclude that detectCilia can automatically and reproducibly detect and measure primary cilia in confocal microscopy images with low false-positive rates without requiring extensive user interaction.</p>","PeriodicalId":9065,"journal":{"name":"Bioinformatics and Biology Insights","volume":"18 ","pages":"11779322241280431"},"PeriodicalIF":2.3,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11490958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457715","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}

{"title":"Intrinsically Disordered Compositional Bias in Proteins: Sequence Traits, Region Clustering, and Generation of Hypothetical Functional Associations.","authors":"Paul M Harrison","doi":"10.1177/11779322241287485","DOIUrl":"https://doi.org/10.1177/11779322241287485","url":null,"abstract":"<p><p>Compositionally biased regions (CBRs), ie, tracts that are dominated by a subset of residue types, are common features of eukaryotic proteins. These are often found bounded within or almost coterminous with intrinsically disordered or 'natively unfolded' parts. Here, it is investigated how the function of such intrinsically disordered compositionally biased regions (ID-CBRs) is directly linked to their compositional traits, focusing on the well-characterized yeast (<i>Saccharomyces cerevisiae</i>) proteome as a test case. The ID-CBRs that are clustered together using compositional distance are discovered to have clear functional linkages at various levels of diversity. The specific case of the Sup35p and Rnq1p proteins that underlie causally linked prion phenomena ([PSI+] and [RNQ+]) is highlighted. Their prion-forming ID-CBRs are typically clustered very close together indicating some compositional engendering for [RNQ+] seeding of [PSI+] prions. Delving further, ID-CBRs with distinct types of residue patterning such as 'blocking' or relative segregation of residues into homopeptides are found to have significant functional trends. Specific examples of such ID-CBR functional linkages that are discussed are: Q/N-rich ID-CBRs linked to transcriptional coactivation, S-rich to transcription-factor binding, R-rich to DNA-binding, S/E-rich to protein localization, and D-rich linked to chromatin remodelling. These data may be useful in informing experimental hypotheses for proteins containing such regions.</p>","PeriodicalId":9065,"journal":{"name":"Bioinformatics and Biology Insights","volume":"18 ","pages":"11779322241287485"},"PeriodicalIF":2.3,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11481073/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457716","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}

{"title":"Commitment Complex Splicing Factors in Cancers of the Gastrointestinal Tract-An In Silico Study.","authors":"Yun Zhang, Alexandria Carrasquillo Simko, Uzondu Okoro, Deja Jamese Sibert, Jin Hyung Moon, Bin Liu, Angabin Matin","doi":"10.1177/11779322241287115","DOIUrl":"https://doi.org/10.1177/11779322241287115","url":null,"abstract":"<p><p>The initial step in pre-mRNA splicing involves formation of a spliceosome commitment complex (CC) or E-complex by factors that serve to bind and mark the exon-intron boundaries that will undergo splicing. The CC component U1 snRNP assembles at the 5'-splice site (ss), whereas SF1, U2AF2, and U2AF1 define the 3'-ss of the intron. A PRP40 protein bridges U1 snRNP with factors at the 3'-ss. To determine how defects in CC components impact cancers, we analyzed human gastrointestinal (GI) cancer patient tissue and clinical data from cBioPortal. cBioPortal datasets were analyzed for CC factor alterations and patient outcomes in GI cancers (bowel, stomach, esophagus, pancreas, and liver). In addition, co-expression datasets were used to determine the splicing targets of the CC. Our analysis found that frequency of genetic changes was low (1%-13%), but when combined with changes in expression levels, there was an overall surprisingly high incidence of CC component (>30%) alterations in GI cancers. Colon cancer patients carrying <i>BRAF</i> driver gene mutations had high incidences of CC alterations (19%-61%), whereas patients with <i>APC</i>, <i>KRAS</i>, or <i>TP53</i> gene mutations had low (<5%) incidences of CC alterations. Most significantly, patients with mutations in CC genes exhibited a consistent trend of favorable survival rates, indicating that mutations that impair or lower CC component expression favor patient survival. Conversely, patients with high CC expression had worse survival. Pathway analysis indicates that the CC regulates specific metabolic and tumor suppressor pathways. Metabolic pathways involved in cell survival, nutrition, biosynthesis, autophagy, cellular movement (invasion), or immune surveillance pathways correlated with CC factor upregulation, whereas tumor suppressor pathways, which regulate cell proliferation and apoptosis, were inversely correlated with CC factor upregulation. This study demonstrates the versatility of in silico analysis to determine molecular function of large macromolecular complexes such as the spliceosome CC. Furthermore, our analysis indicates that therapeutic lowering of CC levels in colon cancer patients may enhance patient survival.</p>","PeriodicalId":9065,"journal":{"name":"Bioinformatics and Biology Insights","volume":"18 ","pages":"11779322241287115"},"PeriodicalIF":2.3,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11483837/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457714","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}

{"title":"Structure, Inhibitors, and Biological Function in Nervous System and Cancer of Ubiquitin-Specific Protease 46.","authors":"Khanh Huyen Thi Pham, Manh Hung Tran, Le Ba Nam, Phu Tran Vinh Pham, Tan Khanh Nguyen","doi":"10.1177/11779322241285982","DOIUrl":"https://doi.org/10.1177/11779322241285982","url":null,"abstract":"<p><p>Deubiquitinating enzymes (DUBs) prevent ubiquitination by eliminating ubiquitin from their substrates. Deubiquitinating enzymes have important roles in a number of cell biology subfields that are highly relevant to diseases like neurodegeneration, cancer, autoimmune disorders, and long-term inflammation. Deubiquitinating enzymes feature a well-defined active site and, for the most part, catalytic cysteine, which makes them appealing targets for small-molecule drug development. Ubiquitin-specific protease 46 (USP46) is a member of the ubiquitin-specific protease family, the largest subfamily of DUBs. Over the past 10 years, some studies have steadily demonstrated the significance of USP46 in several biological processes, although it was identified later and early research progress was modest. Specifically, in the last few years, the carcinogenic properties of USP46 have become more apparent. In the current review, we provide a comprehensive overview of the current knowledge about USP46 including its characteristics, structure, inhibitors, function in diseases, especially in the nervous system, and the correlation of USP46 with cancers.</p>","PeriodicalId":9065,"journal":{"name":"Bioinformatics and Biology Insights","volume":"18 ","pages":"11779322241285982"},"PeriodicalIF":2.3,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11475357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457717","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}