Computational Biology and Chemistry最新文献

{"title":"Development and validation of AI-driven multi-omics language models for cancer genomics: A comprehensive review","authors":"Medha Jha,&nbsp;Yasha Hasija","doi":"10.1016/j.compbiolchem.2025.108662","DOIUrl":"10.1016/j.compbiolchem.2025.108662","url":null,"abstract":"<div><div>The pervasive challenges in cancer management, ranging from accurate early diagnosis to effective personalised therapies and precise patient stratification, represent significant clinical unmet needs. Artificial intelligence (AI) is transforming cancer research by offering unprecedented capabilities in analysing complex genomic datasets. AI has completely transformed omics research by simplifying the integration of multi-omics data, offering more profound insights into cancer heterogeneity, and enhancing predictive models for patient treatment responses. In the past decade, numerous studies have highlighted how AI has revolutionised omics research. AI models are instrumental in enhancing oncology by addressing these unmet needs through improved clinical trial matching, refined risk assessment, and precise treatment selection. They contribute to more personalised and effective cancer care by classifying cancer types and subtypes, identifying biomarkers, predicting drug responses, stratifying patients, and analysing tumour evolution and heterogeneity. This comprehensive review specifically focuses on the development and validation of AI-powered multi-omics language models for cancer genomics. We posit that the integration of diverse omics data types provides synergistic insights beyond single-omics approaches, which are critical for unravelling cancer heterogeneity and addressing the complex challenges within cancer genomics. The review highlights recent advances, current difficulties, and potential paths forward for these integrated AI approaches. We also detail the main elements of these models, such as their architectures, training plans, evaluation techniques, and data preprocessing. All things considered, multi-omics language models powered by AI hold immense promise for deriving biological insights from intricate cancer genomic data and converting them into actionable information for clinical settings.</div></div>","PeriodicalId":10616,"journal":{"name":"Computational Biology and Chemistry","volume":"120 ","pages":"Article 108662"},"PeriodicalIF":3.1,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144916593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sesquiterpene metabolites from Pogostemon cablin leaf essential oil as acetylcholinesterase inhibitors: An integrated computational and phytochemical study","authors":"Prajisha Jayaprakash,&nbsp;Sujata Bhattacharyya,&nbsp;Handrika Saikia,&nbsp;Twahira Begum,&nbsp;Mohan Lal","doi":"10.1016/j.compbiolchem.2025.108652","DOIUrl":"10.1016/j.compbiolchem.2025.108652","url":null,"abstract":"<div><div>Neurological disorders are the major factor of dementia worldwide, presenting significant and escalating challenges to global healthcare systems. Alzheimer's disease (AD) is a leading cause of dementia, creating substantial challenges for international healthcare. Medicinal and aromatic plants offer diverse pharmaceutical properties owing to their richness in chemical constituents. This study aimed to evaluate the <em>in vitro</em> anti-acetylcholinesterase activity of essential oil from <em>Pogostemon cablin</em> (patchouli), which demonstrated inhibitory potential, indicating its possible role in AD management. Preliminary phytochemical screening, followed by Gas Chromatography-Mass Spectrometry (GC-MS) analysis, led to the identification of seventeen compounds, collectively accounting for 97.70 % of the total area, with patchouli alcohol (26.21 %) emerging as the predominant constituent. <em>In-vitro</em> anti-acetylcholinesterase activity tests revealed that sesquiterpene-rich patchouli essential oil had a lower (IC₅₀ 24.15 µg/mL) than the standard galantamine (IC₅₀ 25.66 µg/mL), highlighting the higher inhibition potential of patchouli essential oil on acetylcholinesterase. <em>In-silico</em> studies revealed that patchouli alcohol exhibited the highest binding affinity with a docking score of −8.5 kcal/mol, while 1H-Cycloprop[<em>e</em>]azulene, 1a,2,3,4,6,7,7a,7b-octahydro-1,1,4,7-tetramethyl showed the lowest docking score of −6.8 kcal/mol, highlighting the differential binding interactions of the compounds with the acetylcholinesterase enzyme. All key compounds demonstrated acceptable ADME properties, including compliance with Lipinski's rule of five, favorable topological polar surface area (TPSA), high gastrointestinal (GI) absorption, blood-brain barrier (BBB) permeability, and suitable bioavailability scores. Molecular dynamics simulations (600 ns) confirmed stable AChE-ligand interactions (six complexes), with RMSD values of ∼2.5–3.5 Å, SASA around 2050–2200 Ų, and Rg between 21.8 and 23.4 Å, indicating compact and stable protein-ligand complexes, indicating its potential as an AD therapeutic agent.</div></div>","PeriodicalId":10616,"journal":{"name":"Computational Biology and Chemistry","volume":"120 ","pages":"Article 108652"},"PeriodicalIF":3.1,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144916595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adenine bolsters the monomeric conformations of the intrinsically disordered A53T mutant of α-Synuclein protein","authors":"Payal Singh,&nbsp;Almas Akhtar,&nbsp;Nikita Admane,&nbsp;Abhinav Grover","doi":"10.1016/j.compbiolchem.2025.108661","DOIUrl":"10.1016/j.compbiolchem.2025.108661","url":null,"abstract":"<div><div>Parkinson's disease (PD) is significantly characterized by the accumulation of α-synuclein (α-Syn) amyloid aggregates, especially in the form of Lewy bodies. Our study explores the effect of one of the four nucleobases, adenine, on the amyloid transformation of the A53T mutant of α-Syn (A53T Syn), which is linked to the early-onset PD characterized by increased protofibril production and fast aggregation. Systematic analysis using biophysical techniques in conjunction with computational methods demonstrated that adenine stabilizes the monomeric conformations of A53T Syn by interacting with the NAC domain of the protein through non-covalent interactions. Adenine specifically prevents the amyloid transformation of the intrinsically disordered A53T Syn protein and has no effect on the fibrillation of the wild type α-Syn protein. Replica exchange molecular dynamics (REMD) simulations established that adenine decreases the tendency of A53T Syn to form amyloid aggregates by reducing intramolecular hydrogen bonds and abrogating malicious structural transitions into β-sheet rich conformations. This decrease in β-sheet rich conformations is also corroborated by nearly 85 % decrease in Thioflavin T binding at the saturation phase of amyloid transformation kinetics. Adenine stabilizes the monomeric conformations of A53T Syn, preventing the formation of cross-β amyloids. Through several morphological investigations employing TEM, AFM, and particle size distribution analysis by DLS, we validated the amyloid-modulatory effects of adenine. Our findings collectively demonstrate that adenine shows a selective efficacy against A53T Syn and poses as a good therapeutic candidate for early-onset PD. Further investigations on adenine using cellular and animal models can support early intervention strategies and possible treatments.</div></div>","PeriodicalId":10616,"journal":{"name":"Computational Biology and Chemistry","volume":"120 ","pages":"Article 108661"},"PeriodicalIF":3.1,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144913969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FoodABSANet: Developing an adaptive graph convolutional neural network for aspect-based sentiment analysis of food reviews with a weighted polarity score","authors":"Akkireddi Vara Prasad,&nbsp;K. Vedavathi","doi":"10.1016/j.compbiolchem.2025.108635","DOIUrl":"10.1016/j.compbiolchem.2025.108635","url":null,"abstract":"<div><div>-Aspect-Based Sentiment Analysis (ABSA) is considered a unique variant, which intends to identify the opinions regarding delicate topics. However, it is a neglected topic of study, ABSA attempts to find out the sentiment polarity on particular characteristics within statements, enabling more precise mining of consumers' emotional polarities regarding various aspects. The conversion of the conventional rating-aided recommendation approach into an effective aspect-aided procedure is made easier by this evaluation. The ABSA in hotel ratings serves as an essential. ABSA analyses an extensive choice of comments that expand a far trouble-free good, poor opinions that delve into particular factors addressed in the analysis. However, ABSA struggles to maintain numerous aspects that influence one another. In the past few years, deep learning techniques have been employed to analyze text emotion with outstanding outcomes.</div></div>","PeriodicalId":10616,"journal":{"name":"Computational Biology and Chemistry","volume":"120 ","pages":"Article 108635"},"PeriodicalIF":3.1,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145004245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"OCR: OmniNet-Fusion: A hybrid attention-based CNN-RNN model for multi-omics integration in precision cancer drug response prediction","authors":"Syed Mohammed Azmal,&nbsp;Sajja Tulasi Krishna","doi":"10.1016/j.compbiolchem.2025.108658","DOIUrl":"10.1016/j.compbiolchem.2025.108658","url":null,"abstract":"<div><div>The growing complexity of cancer therapeutics challenges the use of state-of-the-art computational models for drug response prediction. Design and implementation of the OmniNet-Fusion (OCR), a multi-omics deep excavating learning framework for precision medicine. The model uses Convolutional Neural Networks (CNNs) for spatial feature learning and Recurrent Neural Networks (RNNs) for temporal pattern capturing and contains an attention mechanism for focusing on key features among omics layers. Lasso regression and mutual information filter are used for feature selection, and principal component analysis (PCA) enables reduction of the dimension for computing the log p-values. The model was developed based on the CTRPv2 dataset19 which is publicly available. The predictive performance was evaluated based on the experimental results, which were 94.2 % of accuracy, +92.8 % of precision, 91.5 % of recall, and 0.96 of AUC-ROC, indicating superiority over some state-of-the-art baseline methods. Although the OCR model greatly enhances the prediction accuracy and biological interpretability, it also has several issues such as that it requires much more training time because of complex architecture, heavy memory load due to the multi-omics data fusion, and minimal validation in real-time clinical scenarios. Notwithstanding such limitations, OmniNet-Fusion makes a significant contribution towards personalized oncology by providing a scalable and interpretable framework for precision prediction of drug response, while promoting the development of AI-enabled precision medicine.</div></div>","PeriodicalId":10616,"journal":{"name":"Computational Biology and Chemistry","volume":"120 ","pages":"Article 108658"},"PeriodicalIF":3.1,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144925461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ligand-mediated structural modulation and membrane stabilization of LPA1 receptor: Insights from molecular dynamics simulations","authors":"Yahui Zhang,&nbsp;Mengxia Zhao,&nbsp;Yiru Wang,&nbsp;Yanyan Zhu,&nbsp;Yujie Chen,&nbsp;Li Chen,&nbsp;Huiyu Li","doi":"10.1016/j.compbiolchem.2025.108655","DOIUrl":"10.1016/j.compbiolchem.2025.108655","url":null,"abstract":"<div><div>Lysophosphatidic acid (LPA) is an important bioactive signaling molecule that activates six distinct G protein-coupled receptors (GPCRs), among which the LPA1 subtype possesses high therapeutic target potential due to its critical roles in malignant tumors, pulmonary fibrosis, inflammation, and neuropathic pain. Recent studies have shown that the small molecule ONO-0740556 can effectively disrupt the overall structure of LPA1 in solution; however, its effects in a native membrane environment remain unclear. According to the Traditional Chinese Medicine Systems Pharmacology Database (TCMS), Dan Shen(Salvia miltiorrhiza) exhibits anti-inflammatory and anti-pulmonary fibrosis properties, and its natural compound cryptoxanthin may serve as a novel LPA1 inhibitor. Here, we employed microsecond-scale all-atom molecular dynamics simulations to systematically compare the structural modulation of LPA1 by ONO-0740556 and cryptoxanthin in a membrane environment. The results indicate that both ligands enlarge the entrance of the LPA1 ligand-binding channel, weaken the interactions between transmembrane helix 7 (TM7) and other structural communities, and reduce hydrophobic interactions between LPA1 and the membrane, thereby inducing membrane structural perturbations. Notably, cryptoxanthin exerts a more pronounced effect in widening the binding channel and selectively attenuating TM7–community interactions. These findings provide atomic-level insights into how small molecules modulate LPA1 structure in its physiologically relevant membrane environment. Such mechanistic understanding not only offers a theoretical basis for the rational design of LPA1-targeted therapeutics but also supports the discovery of natural product–derived inhibitors as viable drug candidates. Moreover, our results highlight potential allosteric sites and dynamic features of LPA1 that could be exploited to develop highly selective modulators, paving the way for more precise therapeutic interventions against LPA1-related diseases.</div></div>","PeriodicalId":10616,"journal":{"name":"Computational Biology and Chemistry","volume":"120 ","pages":"Article 108655"},"PeriodicalIF":3.1,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144922917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Esculetin attenuates doxorubicin-induced cardiac toxicity: Evidence from gene expression, enzyme activity, and molecular docking analyses","authors":"Yeliz Demir ,&nbsp;Hamid Ceylan ,&nbsp;Esra Nur Yeşilkent ,&nbsp;Duygu Kizir ,&nbsp;Melike Karaman ,&nbsp;Cüneyt Türkeş ,&nbsp;Şükrü Beydemir","doi":"10.1016/j.compbiolchem.2025.108654","DOIUrl":"10.1016/j.compbiolchem.2025.108654","url":null,"abstract":"<div><div>Doxorubicin (DOX) is a potent chemotherapeutic agent whose dose-dependent cardiotoxicity is associated with oxidative stress, inflammation, and enzymatic dysfunction. This study evaluates the cardioprotective potential of esculetin, a natural coumarin derivative, against DOX-induced cardiac injury in rats. Forty-eight male Sprague-Dawley rats were divided into six groups, including control, DOX, esculetin (50 and 100 mg/kg), and combination treatments. DOX markedly altered the expression of oxidative stress-related genes (<em>Ache, Ar, Sord</em> upregulated; <em>Pon1, Gst</em> downregulated) and impaired enzyme activities, accompanied by increased malondialdehyde and depleted glutathione levels. Esculetin administration, particularly at 100 mg/kg, reversed these molecular and biochemical disturbances, restoring antioxidant defense and normalizing gene expression. Molecular docking revealed strong binding interactions of esculetin with the active sites of key enzymes including AR, SORD, AChE, GST, and PON1, supporting its regulatory role. These findings suggest that esculetin exerts multi-targeted protective effects and may serve as a promising candidate for mitigating chemotherapy-induced cardiotoxicity. Further research is warranted to explore its integration into clinical cardioprotective strategies.</div></div>","PeriodicalId":10616,"journal":{"name":"Computational Biology and Chemistry","volume":"120 ","pages":"Article 108654"},"PeriodicalIF":3.1,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144907694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery and validation of novel drug combinations for pulmonary fibrosis via Traditional Chinese Medicine insights and computer screening","authors":"Haiting Yan ,&nbsp;Ping Yuan ,&nbsp;Beibei He ,&nbsp;Hua Ye","doi":"10.1016/j.compbiolchem.2025.108660","DOIUrl":"10.1016/j.compbiolchem.2025.108660","url":null,"abstract":"<div><h3>Background</h3><div>Pulmonary fibrosis is a chronic interstitial lung disease that poses a serious threat to human health. The multi-target actions and favorable safety profile of Traditional Chinese Medicine (TCM) offer new therapeutic possibilities.</div></div><div><h3>Methods</h3><div>We implemented an integrated strategy combining clinical expertise, computer-aided drug design (CADD), and TCM GuiJing theory for novel formula discovery. The interactions between TCM and disease targets were verified by molecular docking and molecular dynamics (MD) simulations. Furthermore, the efficacy of the newly discovered formulas was demonstrated by their correlation with ameliorated changes in the intestinal flora.</div></div><div><h3>Results</h3><div>The core medicines used by famous doctors was Huangqi, and 69 groups of Huangqi-containing herb pairs were obtained. Using lung, heart, and spleen meridians as screening conditions, and by integrating the study of disease targets and compounds, the Huangqi-Gancao, Huangqi-Yinyanghuo, Huangqi-Ziwan, Huangqi-Tinglizi, and Huangqi-Mahuang pairs were identified as components of the potential new formula. All 95 molecular docking complexes exhibited favorable binding energies (ΔG ≤ −5.0 kcal/mol), and molecular dynamics stability was further determined. Moreover, these herbs may also be anti-pulmonary fibrosis by modulating the composition of gut microbiota, increasing Akkermansia abundance, and improving nicotinate and nicotinamide metabolism.</div></div><div><h3>Conclusion</h3><div>We establish an integrated TCM-GuiJing-CADD framework for the precision discovery of anti-fibrotic drug combinations. This strategy synthesizes clinical experience, CADD, and the GuiJing theory, providing a theoretical support for the precise application of TCM in treating complex diseases.</div></div>","PeriodicalId":10616,"journal":{"name":"Computational Biology and Chemistry","volume":"120 ","pages":"Article 108660"},"PeriodicalIF":3.1,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144932602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular dynamics study of M-Trifluoromethyl diphenyl diselenide binding to the μ-opioid receptor: A computational perspective on morphine-induced tolerance","authors":"Madiha Sardar ,&nbsp;Nadeem Ahmad ,&nbsp;Muhammad Huzaifa ,&nbsp;Mamoona Mushtaq ,&nbsp;Mohammad Nur-e-Alam ,&nbsp;Pinghua Sun ,&nbsp;Zaheer Ul-Haq","doi":"10.1016/j.compbiolchem.2025.108659","DOIUrl":"10.1016/j.compbiolchem.2025.108659","url":null,"abstract":"<div><div>Chronic pain is a maladaptive state where pain signals persist beyond the expected resolution of injury or illness. Morphine and related compounds, acting as µ-opioid receptor (µOR) agonists, are effective analgesics for managing this condition. However, chronic morphine administration can disrupt µOR trafficking and activate β-arrestin-mediated pathways, leading to opioid tolerance. The role of µOR in mood disorders is less well-defined. The organoselenium compound <em>m</em>-trifluoromethyl diphenyl diselenide (TFDD) has shown promising antinociceptive and antidepressant-like effects in experimental models and attenuated morphine withdrawal symptoms in mice.¹ However, the molecular mechanisms governing TFDD's interaction with the µOR at the atomic level remain unexplored through theoretical methodologies. To bridge this knowledge gap, the current research sought to characterize the pharmacological profile of TFDD using an integrated computational approach that included quantum chemical calculations, molecular dynamics simulations, and thermodynamic analysis. The simulations revealed the formation of persistent halogen bonds between TFDD's trichlorobenzene moiety and specific residues within the µOR binding pocket, namely Gln124^2.60 and Glu299^5.58 with bond distances of 2.83 and 3.73 Å respectively. These interactions, spanning transmembrane helices 2 through 5 (TM2-TM5), contribute to the stabilization of TFDD within the receptor's binding site. Notably, key microswitch residues, such as Asp147^3.32, Met151^3.36, and Trp293^6.48, which are critical for maintaining the µOR active conformation and modulating β-arrestin signaling, were observed to interact with TFDD. These conformational dynamics subsequently influence the G protein-biased activation of the µOR. To examine the conformational space of the µOR bound to TFDD and the morphinan agonist BU72, principal component analysis was used to determine the leading modes of motion. Subsequently, free energy landscapes were constructed to identify energetically favorable conformational states and the transitions between them, providing insights into the thermodynamic behavior of the µOR-ligand bound complexes. Furthermore, dynamic cross-correlation matrix analysis was performed to evaluate differences in the correlated motions of µOR residues upon binding of BU72 and TFDD. Alchemical free energy calculations, utilizing thermodynamic integration across various λ states, were employed to quantitatively estimate the binding affinities of both ligands TFDD and BU72. The calculated total binding free energy values were −42.54 ± 1.92 kJ/mol for TFDD and −39.76 ± 0.74 kJ/mol for BU72. This computational study elucidates the molecular basis of TFDD's interaction with µOR, integrating experimental data with atomic-level modeling. This enhances our understanding of TFDD's potential to reduce morphine tolerance, improve pain relief, and ","PeriodicalId":10616,"journal":{"name":"Computational Biology and Chemistry","volume":"120 ","pages":"Article 108659"},"PeriodicalIF":3.1,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144913970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered protein lipidation in cancer: A hidden link to sensory neuronal dysfunction","authors":"Iman H Ibrahim ,&nbsp;Ahmed Abdellatif ,&nbsp;Heba A. Eassa","doi":"10.1016/j.compbiolchem.2025.108656","DOIUrl":"10.1016/j.compbiolchem.2025.108656","url":null,"abstract":"<div><div>Protein lipidation/delipidation affects protein functions, interactions, and membrane trafficking. Dysregulation of this process might lead to tissue disorganization, abnormal proliferation, migration, and poor prognosis in cancer. While dysregulation of lipidation/delipidation in neurons has been associated with several neurodegenerative diseases, its potential link to neuronal dysfunction in cancer patients remains unexplored. The aim of the study is to explore the association of altered protein lipidation with neurological problems in cancer patients via bioinformatic analysis. Gene list related to protein lipidation was retrieved and the effect of gene set alteration on overall survival on cancer patients was inquired using public dataset of cancer. Differentially expressed genes were analyzed for susceptibility to protein lipidation, distribution on chromosomes, Gene Ontology, and pathway enrichment analysis. Further enrichment and transcription factor targets analyses were performed. Differentially expressed genes (DEGs) in cancer patients with altered protein lipidation/delipidation were found to be associated with enrichment of neuronal regeneration/degeneration pathways, olfactory receptor signaling, and sensory perception pathways. Specifically, targets of Translational elongation factor EF-1 (TEF1) and signal transducer and activator of transcription 1 (STAT1) were enriched in the DEGs of patients with altered protein lipidation. Both TEF1 and STAT1 require lipidation for proper functioning. Therefore, altered lipidation in cancer patients could be associated with the disturbance of their downstream targets. These targets are significantly correlated to multiple pathways and processes related to neurological, sensory, and motor functions.</div></div>","PeriodicalId":10616,"journal":{"name":"Computational Biology and Chemistry","volume":"120 ","pages":"Article 108656"},"PeriodicalIF":3.1,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144916625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}