Omics A Journal of Integrative Biology最新文献

{"title":"Integrated Computational Omics Approach to Identify Novel Natural Product Inhibitors Targeting KIF11 in Endometrial Carcinoma.","authors":"Shazma Sarwat, Koel Mukherjee","doi":"10.1177/15578100261446772","DOIUrl":"https://doi.org/10.1177/15578100261446772","url":null,"abstract":"<p><p>Endometrial carcinoma (EC) presents a growing global health challenge, characterized by significant molecular heterogeneity and the overexpression of the mitotic motor protein Kinesin Family Member 11 (KIF11). To address the critical need for targeted therapeutics, this study employed an integrated computational framework combining multiomics expression analysis with structural bioinformatics to identify novel natural product-based inhibitors. Validation using TCGA and CPTAC datasets confirmed significant upregulation of KIF11 in EC at both transcriptomic and proteomic levels. A pharmacophore-based virtual screening of approximately 400,000 natural compounds was conducted against the KIF11 active site (PDB ID: 2X7C), followed by ADMET profiling and molecular docking. While glycodeoxycholic acid (GDCA) exhibited the highest docking affinity (-9.5 kcal/mol), subsequent 100 ns molecular dynamics simulations revealed that glycocholic acid (GCA) possessed superior conformational stability. GCA demonstrated a stable RMSD profile (approximately 1.5 Å) and persistent hydrogen bonding with key residues LYS111 and GLU118, unlike the fluctuating profile observed in GDCA. This study identifies GCA as a robust lead candidate, underscoring the efficacy of integrating transcriptomic and proteomic data with structural biology to drive precision therapeutics for EC.</p>","PeriodicalId":19530,"journal":{"name":"Omics A Journal of Integrative Biology","volume":" ","pages":"15578100261446772"},"PeriodicalIF":1.6,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147818586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Casting the Caspase Activity and Apoptosis Inhibitor 1 Phosphoregulation Through Global Phosphoproteomes.","authors":"Pathiyil Sajini Sekhar, Amal Fahma, Athira Perunally Gopalakrishnan, Suhail Subair, Leona Dcunha, Althaf Mahin, Samseera Ummar, Prathik Basthikoppa Shivamurthy, Shuvechha Chakraborty, Rajesh Raju","doi":"10.1177/15578100261419491","DOIUrl":"10.1177/15578100261419491","url":null,"abstract":"<p><p>Caspase Activity and Apoptosis Inhibitor 1 (CAAP1) is a regulatory protein known to suppress apoptosis and support cell survival with implications in cancer progression, cell migration, and angiogenesis, yet its regulation at the post-transcriptional level remains poorly understood and is underexplored as a therapeutic target. This study aimed to investigate CAAP1 phosphorylation and its functional significance using global phosphoproteomic datasets. We systematically analyzed 885 human phosphoproteomic profiling and 172 differential expression datasets to identify Class 1 phosphorylation sites (PS) in CAAP1. Co-regulated protein phosphosites were examined to explore CAAP1's biological roles, and enrichment analysis was performed. The four PS, S203, S89, S312, and T90, were the predominantly detected sites. Our results reveal that the PS co-regulated with CAAP1 predominant sites were enriched in splicing-related processes, with strong associations with spliceosome-related proteins and apoptotic regulators. This phosphosite-centric study suggests that CAAP1 phosphoregulatory network is involved in splicing mechanisms, apoptosis regulation, and cancer progression. The study positions CAAP1 phosphorylation in processes frequently dysregulated in cancer and provides a foundation for future translational studies aimed at targeting CAAP1 phosphoregulation as a therapeutic strategy.</p>","PeriodicalId":19530,"journal":{"name":"Omics A Journal of Integrative Biology","volume":" ","pages":"224-234"},"PeriodicalIF":1.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146213687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuromedin U Signaling Map: Toward Neuropeptide Focused Therapeutic Targets in Cancer and Human Diseases.","authors":"Leona Dcunha, Bhavana Edakkad, Isha Fathima, Shobha Dagamajalu, Rajesh Raju, Rex Devasahayam Arokia Balaya, Saptami Kanekar","doi":"10.1177/15578100261422815","DOIUrl":"10.1177/15578100261422815","url":null,"abstract":"<p><p>Neuropeptides play pivotal roles in intercellular communication in the nervous system and peripheral tissues. However, the molecular events underlying their signaling lack a unified representation in the scientific literature. A case in point is Neuromedin U (NMU), a neuropeptide structurally conserved across diverse species with multifaceted roles in integrating metabolic, immune, and stress signaling. Dysregulation of NMU signaling has been correlated to neuronal functions and various metabolic disorders, and is associated with colorectal, breast, and pancreatic cancers. Despite growing interest in NMU as a disease-associated signaling neuropeptide, a comprehensive and standardized schematic representation of its signaling pathway is lacking. We report here a NMU signaling map by systematically curating the literature and classifying NMU signaling events according to known pathway standards. The NMU signaling map included seven activation/inhibition events, 16 enzyme catalysis events, 66 gene regulation events, 30 protein expression events, and 20 translocation events. This NMU signaling map offers a new molecular framework and possibilities for biomarker and drug discovery and development, owing to its relevance in neuronal functions, inflammatory, metabolic, and oncogenic pathways. By consolidating fragmented evidence into a standardized pathway representation, this study serves as a resource for future integrative analyses, hypothesis generation, and translational research toward NMU signaling and neuropeptide-focused therapeutics innovation in cancer and human diseases.</p>","PeriodicalId":19530,"journal":{"name":"Omics A Journal of Integrative Biology","volume":" ","pages":"211-223"},"PeriodicalIF":1.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146202352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering the Phospho-Signaling Network Associated with the Linker Region of Multidrug Resistance Protein 1.","authors":"Revathy Nandakumar, Althaf Mahin, Athira Perunelly Gopalakrishnan, Suhail Subair, Deepak Krishnan, Rajesh Raju","doi":"10.1177/15578100261422809","DOIUrl":"10.1177/15578100261422809","url":null,"abstract":"<p><p>The ATP-binding cassette subfamily C member 1 (ABCC1) is a key efflux pump that contributes to multidrug resistance in cancer by exporting chemotherapeutic agents and xenobiotics. Although ABCC1 is clinically important, the phosphorylation-dependent regulatory mechanisms governing its activity remain poorly understood, representing a major knowledge gap. To address this gap, we performed a large-scale integrative analysis of publicly available phosphoproteomic datasets curated from over 3800 PubMed-indexed studies. From 688 high-confidence datasets, we mapped Class I phosphosites on ABCC1 and focused on two predominant sites, S919 and S930, located within the cytoplasmic linker domain. Using phosphosite co-occurrence and co-regulation strategies, we identified phosphorylation events that consistently co-regulate with these key ABCC1 sites across diverse experimental conditions. Through multilevel statistical filtering (Fisher's exact test, <i>p</i> < 0.05), recurrence analysis, and experimental context diversity, we defined a high-confidence co-regulatory network comprising 1266 phosphosites across diverse proteins. Mechanistically, this network reveals coordinated phosphorylation of ABCC1 with its known interacting partners, including PTGES3, FASN, and STX4, as well as functionally associated drug transport proteins such as ABCC4, SLC16A1, and SLC20A2. Functional enrichment analysis further linked the ABCC1-centred phospho-network to carcinogenesis, cell-cycle regulation, and drug resistance pathways, highlighting its systems-level role in cancer biology. From a translational perspective, our findings identify phosphosites within the ABCC1 linker domain as actionable regulatory nodes that may be exploited to modulate transporter function, offering potential strategies to overcome chemoresistance.</p>","PeriodicalId":19530,"journal":{"name":"Omics A Journal of Integrative Biology","volume":" ","pages":"235-246"},"PeriodicalIF":1.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146202361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative Transcriptomic Profiling Identifies <i>TLR9</i> as a Key Biomarker of Diabetic Peripheral Neuropathy.","authors":"Alekhya Bandi, Krishna Varshitha Maradihalli, Samyuktha Sunkara, Srimari Srikanth, Venkatasubramanian Ulaganathan","doi":"10.1177/15578100261422824","DOIUrl":"10.1177/15578100261422824","url":null,"abstract":"<p><p>Diabetic peripheral neuropathy (DPN) is a prevalent complication of type 2 diabetes that is typically diagnosed after irreversible nerve damage, largely due to the lack of molecular biomarkers that distinguish neuropathy-specific changes from general diabetic pathology. From an integrative biology perspective, the network-level molecular mechanisms underlying DPN remain incompletely defined. In this study, transcriptomic profiles from peripheral blood mononuclear cells of healthy controls, patients with type 2 diabetes, and patients with DPN were analyzed using a systems-level, network-based bioinformatics framework. Comparative analysis identified genes specifically associated with DPN, distinct from broader diabetic alterations. Protein-protein interaction and network topology analyses prioritized key hub genes enriched in immune signaling, calcium transport, lipid metabolism, and inflammatory pathways implicated in neuronal dysfunction. Among these, Toll-like receptor 9 (<i>TLR9</i>) emerged as a prominent biomarker candidate, demonstrating high network centrality and strong diagnostic performance (area under the curve = 1.0). <i>TLR9</i> was significantly upregulated in DPN and functionally linked to mitogen-activated protein kinase and nuclear factor kappa-light-chain-enhancer of activated B-cell signaling pathways, consistent with immune-mediated mechanisms of neuropathic injury. Collectively, these findings define a DPN-specific molecular network and support <i>TLR9</i> as a biomarker candidate, providing a systems-level foundation for future experimental validation and translational research in diabetic neuropathy.</p>","PeriodicalId":19530,"journal":{"name":"Omics A Journal of Integrative Biology","volume":" ","pages":"203-210"},"PeriodicalIF":1.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146202383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metagenomics in Obstructive Lung Diseases: Insights into Microbial Dysbiosis, Host-Microbe Interactions, and the Gut-Lung Axis.","authors":"Sanjukta Dasgupta","doi":"10.1177/15578100261419483","DOIUrl":"10.1177/15578100261419483","url":null,"abstract":"<p><p>Obstructive lung diseases (OLDs), including asthma and chronic obstructive pulmonary disease (COPD), arise from complex interactions among microbial ecosystems, host immunity, metabolic regulation, and environmental exposures. Metagenomic approaches have substantially advanced understanding of these interactions by enabling comprehensive profiling of respiratory and gut-associated microbiomes and their functional potential. Evidence indicates that asthma is frequently associated with early-life microbial perturbations, reduced community diversity, enrichment of <i>Streptococcus</i>, <i>Moraxella</i>, and allergen-associated fungi, and gut dysbiosis that influences immune maturation and tolerance. In contrast, COPD is characterized by adult-onset dysbiosis with Proteobacteria dominance, depletion of commensal anaerobes such as <i>Prevotella</i> and <i>Veillonella</i>, and functional signatures linked to chronic inflammation, xenobiotic metabolism, and exacerbation risk. Across both diseases, alterations in gut microbial composition and metabolite profiles, including short-chain fatty acids, highlight the gut-lung axis as a key regulatory interface shaping airway immune responses. Despite these advances, critical knowledge gaps remain, including limited longitudinal data, incomplete multi-kingdom analyses, and insufficient mechanistic and translational validation of disease-associated microbiome signatures. This review integrates current metagenomic evidence to delineate disease-specific and shared microbial patterns, examines host-microbe interaction pathways within molecular and clinical contexts, and critically evaluates the implications and limitations of microbiome-based interventions. By framing microbiome research within a systems biology and public health perspective, this article underscores the importance of context-dependent interpretation and identifies priorities for future longitudinal, mechanistic, and translational studies in OLDs.</p>","PeriodicalId":19530,"journal":{"name":"Omics A Journal of Integrative Biology","volume":" ","pages":"191-202"},"PeriodicalIF":1.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147575036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic Sequencing from Sanger to Next-Generation Sequencing: Historical Context, Comparative Advances, and Prospects for Next-Generation Phenomics.","authors":"Akash Ranga, Anvita Gupta Malhotra, Jitendra Singh, Khushhali M Pandey","doi":"10.1177/15578100261433762","DOIUrl":"https://doi.org/10.1177/15578100261433762","url":null,"abstract":"<p><p>DNA sequencing has revolutionized biological and biomedical research, offering profound insights into genome organization, function, and variability. From the pioneering Sanger capillary electrophoresis method to the advent of next-generation sequencing, the field has evolved toward unprecedented speed, scalability, and cost decreases over the years. These advancements have enabled diverse applications across genomics, transcriptomics, metagenomics, epigenomics, and precision medicine, powering global initiatives such as the Human Genome Project, the Human Microbiome Project, and the 1000 Genomes Project. Bioinformatics has also advanced in data processing, variant detection, and functional annotation, helping transform raw sequencing data into biologically meaningful insights and knowledge. Although highly advanced, sequencing technologies still encounter challenges, including accuracy trade-offs and the need for efficient management of rapidly increasing volumes of data. Leveraging the genomic revolution, this review explores the shifts toward next-generation phenomics (NGP), an archetype that uses artificial intelligence that integrates multi-omics data with digital phenotyping, the Internet of Things, and real-time analytics. The goal of NGP is to integrate genotypic and phenotypic data to support predictive modeling of health, disease, and environmental interactions. By tracing history, advances in sequencing technologies, and future perspectives on NGP, this article offers a comprehensive overview for researchers and clinicians, highlighting how the integration of omics and digital data will drive the generation of personalized and systems-level biology.</p>","PeriodicalId":19530,"journal":{"name":"Omics A Journal of Integrative Biology","volume":" ","pages":"15578100261433762"},"PeriodicalIF":1.6,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147499455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How Can We Improve Subtyping of Colon Adenocarcinoma for Precision Oncology? Multi-Omics Consensus Clustering Reveals Immunologically Active and Therapeutically Distinct Molecular Groups.","authors":"Güllü Elif Özdemir, Kazim Yalcin Arga","doi":"10.1177/15578100261419489","DOIUrl":"10.1177/15578100261419489","url":null,"abstract":"<p><p>Colon adenocarcinoma (COAD) is a heterogeneous malignancy whose molecular complexity limits effective therapy. Existing transcriptome-based classifications capture only part of this diversity. To refine COAD stratification, we integrated genomic, epigenomic, and transcriptomic data from 297 The Cancer Genome Atlas patients. Ten complementary clustering algorithms were combined through a consensus ensemble framework to ensure robust and unbiased subtype discovery. The resulting molecular subtypes were characterized by genomic alterations, signaling pathways, tumor microenvironment features, and predicted therapeutic responses. As a result, four reproducible molecular subtypes (CS1-CS4) were identified. CS1 displayed enrichment of extracellular matrix organization and epithelial-mesenchymal transition signatures, suggesting invasive potential. CS2 exhibited transcriptional similarity to PD-1 responders, indicating potential benefit from immune checkpoint blockade. CS3 represented a mutation-driven subtype with frequent <i>APC</i>, <i>TP53</i>, and <i>KRAS</i> alterations and extensive copy number gains. CS4 showed the highest immune infiltration, elevated tumor mutational burden, and enhanced sensitivity to 5-fluorouracil and cetuximab. Validation across four independent cohorts confirmed the reproducibility of these subtypes. This integrative multi-omics framework refines the molecular taxonomy of COAD, revealing immunologically active and therapeutically distinct subgroups. The classification not only bridges genomic, epigenomic, and transcriptomic regulation but also provides a practical roadmap for precision oncology by linking molecular features to potential treatment strategies.</p>","PeriodicalId":19530,"journal":{"name":"Omics A Journal of Integrative Biology","volume":" ","pages":"158-176"},"PeriodicalIF":1.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146119183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptomic Correlation Identifies Cell Model Representatives for <i>MYCN</i>-Amplified Pediatric Neuroblastoma, Downstream Impact of Model Choice on Functional Interpretation, and Potential Drug Repositioning Candidates.","authors":"Simran Venkatraman, Pisut Pongchaikul, Brinda Balasubramanian, Usanarat Anurathapan, Jarek Meller, Rutaiwan Tohtong, Suradej Hongeng, Somchai Chutipongtanate","doi":"10.1177/15578100261419486","DOIUrl":"10.1177/15578100261419486","url":null,"abstract":"<p><p>Neuroblastoma (NB) is the most common extracranial solid malignancy of children, and <i>MYCN</i> amplification defines a high-risk subtype with poor outcomes. Although widely used in preclinical drug discovery, NB cell lines are often selected based on availability rather than the molecular characteristics of patient-derived tumors, leading to a critical translational gap between experimental outcomes and clinical relevance. To address this, we developed a rank-based transcriptomic correlation framework to assess the concordance between patient-derived tumors (<i>n</i> = 642; combined from the SEQC/MAQC-III and TARGET cohorts) and publicly available NB cell lines (<i>n</i> = 39). This system-level analysis enabled the identification of cell model representatives (CMRs) that closely recapitulate the gene expression landscapes of clinical tumors. COG-N-557, SMS-KAN, and NB-SD emerged as the top CMRs for <i>MYCN</i>-amplified tumors, whereas COG-N-549, FELIX, and SK-N-SH were identified for <i>MYCN</i>-nonamplified tumors. Pathway enrichment analyses indicated that <i>MYCN</i>-amplified CMRs retain key transcriptional programs involved in neuronal development and tumor proliferation, supporting their biological relevance. Leveraging these models, we integrated pharmacogenomic connectivity mapping and drug-gene network analyses to uncover kinase inhibitors and epigenetic modulators as promising therapeutic candidates capable of targeting <i>MYCN</i>-driven transcriptional programs, despite <i>MYCN</i> being an undruggable oncogene. In conclusion, this study addresses a fundamental systems biology and translational research gap by establishing a data-driven framework for selecting NB cell lines that accurately reflect patient-derived tumor biology with direct implications for prioritizing therapeutically relevant drug candidates. Future studies should prioritize the top CMRs as <i>in vitro</i> models to enhance translational relevance and accelerate precision drug discovery in high-risk pediatric NB.</p>","PeriodicalId":19530,"journal":{"name":"Omics A Journal of Integrative Biology","volume":" ","pages":"134-145"},"PeriodicalIF":1.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146125218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Omics in the Context of Environmental Health.","authors":"K Shuvo Bakar","doi":"10.1177/15578100261419495","DOIUrl":"https://doi.org/10.1177/15578100261419495","url":null,"abstract":"","PeriodicalId":19530,"journal":{"name":"Omics A Journal of Integrative Biology","volume":"30 3","pages":"131-133"},"PeriodicalIF":1.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147468902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}