Omics A Journal of Integrative Biology最新文献

{"title":"Integrative Genomic and Immune Profiling to Identify and Characterize High-Risk Subgroups in Acute Myeloid Leukemia: Development of a 20-Gene Predictive Signature and Its Clinical Implications.","authors":"Kubra Karagoz, M Guy Roukens, Lizzy Comijn, Asuman Celik, Lauren K Brady, Brandon W Higgs, Han Si","doi":"10.1177/15578100251370570","DOIUrl":"https://doi.org/10.1177/15578100251370570","url":null,"abstract":"<p><p>Acute myeloid leukemia (AML) is a heterogeneous malignancy with diverse genetic mutations and oncogenic pathways influencing treatment response. Despite therapeutic advances, relapse and resistance remain persistent issues. This study integrates genomic and transcriptomic profiling to identify biomarkers of high-risk AML, informing personalized medicine strategies. Nonnegative matrix factorization was applied to RNA sequencing data from the BeatAML cohort (<i>N</i> = 462) for patient subtyping, with survival analysis using the Kaplan-Meier method. Immune profiling via xCell and Gene Set Variation Analysis assessed the tumor microenvironment, with findings validated in the Cancer Genome Atlas AML cohort (<i>N</i> = 173). Using a random forest machine learning model, we developed a 20-gene signature identifying a high-risk subgroup comprising approximately 20% of patients with AML. The high-risk AML subtype was enriched for recurrent <i>FLT3</i>, <i>NPM1</i>, and <i>DNMT3A</i> mutations, activation of PI3K/AKT/mTOR, and complement pathways. Immune profiling revealed an immunosuppressive microenvironment with increased M2 macrophages and mesenchymal stem cells. The 20-gene signature predicted high-risk AML with high accuracy (area under the curve = 0.995, F1 = 0.89). AML cell lines representing high- and low-risk phenotypes identified using the 20-gene signature were tested for drug sensitivity, including the standard-of-care cytarabine, and two targeted therapies, the PI3K inhibitor LY294002 and the MAPK inhibitor selumetinib, selected based on enriched pathways in high-risk AML. High-risk AML cell lines exhibited reduced cytarabine sensitivity but greater responsiveness to PI3K and MAPK/ERK inhibitors, consistent with pathway enrichment results. These findings support molecular stratification and predictive signatures as tools to guide therapy in high-risk AML. Further clinical validation is warranted.</p>","PeriodicalId":19530,"journal":{"name":"Omics A Journal of Integrative Biology","volume":"29 9","pages":"458-472"},"PeriodicalIF":1.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963745","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":"Mast Cells Drive Ferroptosis in Gastric Tumors as Key Players in the Tumor Immune Microenvironment.","authors":"Fatma Sert, Ozlem Ulucan","doi":"10.1177/15578100251366980","DOIUrl":"10.1177/15578100251366980","url":null,"abstract":"<p><p>Ferroptosis, an iron-dependent form of oxidative cell death, plays a critical role in cancer progression and immune regulation. However, the functional connections of ferroptosis with specific immune cell types remain poorly defined, limiting the future possibilities to harness ferroptosis for cancer biology, diagnosis, and treatment. To address this knowledge gap, we conducted an integrated transcriptomic analysis to investigate ferroptosis-related immune dynamics in gastric cancer (GC). We utilized GC datasets from The Cancer Genome Atlas-stomach adenocarcinoma (<i>n</i> = 412) and the GSE66229 (<i>n</i> = 300) that were clustered into three GC immune subtypes based on single-sample Gene Set Enrichment Analysis scores of 29 immune gene sets. Bulk RNA-seq analysis revealed that the immune-inflamed subtype (HIS) of tumor samples in both GC datasets exhibited the highest ferroptosis enrichment and showed a positive correlation with activated mast cells and neutrophils. Given the regulatory role of mast cells in the tumor microenvironment (TME), particularly in recruiting neutrophils, we further examined their link to ferroptosis. In a fibroblast-mast cell coculture RNA-seq data (GSE223179), fibroblasts exhibited increased ferroptosis enrichment, supporting a mast cell-mediated influence. Single-cell RNA-seq data confirmed stronger interactions between mast cells and fibroblasts in GC compared to normal tissues. Specifically, they revealed a positive correlation between mast cell activity and ferroptosis enrichment in tumor-associated fibroblasts. In conclusion, these findings suggest that mast cells may promote ferroptosis in the TME through paracrine signaling, possibly via annexin and cyclophilin A. By uncovering this novel pathophysiological axis, our study reveals a previously unrecognized role of mast cells in regulating ferroptosis within the TME. The findings call for translational and experimental medical research and have potential implications for innovation toward GC diagnostics and therapeutics.</p>","PeriodicalId":19530,"journal":{"name":"Omics A Journal of Integrative Biology","volume":" ","pages":"429-441"},"PeriodicalIF":1.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144883385","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":"Toward Natural Products-Based Drug Development for Erectile Dysfunction: A Molecular Candidate from Plant <i>Tribulus terrestris</i> Identified by an Integrated <i>In Silico</i> Study.","authors":"Riya Vishwakarma, Abel John Koshy, Haritha Kalath, Krishnapriya Ramakrishnan, Anish John, Sowmya Soman, Rajesh Raju, Niyas Rehman, Amjesh Revikumar","doi":"10.1177/15578100251370567","DOIUrl":"https://doi.org/10.1177/15578100251370567","url":null,"abstract":"<p><p>Conventional pharmacological interventions for erectile dysfunction (ED) primarily rely on the phosphodiesterase-5 (PDE5) inhibitors such as sildenafil, tadalafil, vardenafil, and avanafil that have side effects despite their therapeutic effects. PDE5 is the primary cyclic guanosine monophosphate-degrading enzyme located in the smooth muscles of the corpus cavernosum in the penile tissue that helps in relieving erection. Natural products and phytochemicals are viable sources of molecular leads for drug discovery and development and, thus, offer prospects for innovation in ED treatment. This <i>in silico</i> study reports the screening of phytochemicals from the plant <i>Tribulus terrestris</i> with an eye to identify molecular candidates that inhibit PDE5. Natural products-based compounds that selectively target PDE5 are poised to be useful in clinical management of ED, and potentially with lesser side effects. The following top three phytochemicals identified from <i>T. terrestris</i> showed higher negative binding affinities for the PDE5 enzyme: diosgenin,dehydro (-11.1 kcal/mol), ruscogenin (-11.1 kcal/mol), and hecogenin (-10.3 kcal/mol) compared with the control drug sildenafil (-8.8 kcal/mol). Hydrogen bonds and Van der Waals interactions were the predominant forces influencing the interactions formed in the protein-ligand complexes. The ΔG_bind binding free energies for these top three phytochemicals, diosgenin,dehydro, ruscogenin, and hecogenin, were -19.99 ± 5.99 kcal/mol, -9.05 ± 5.16 kcal/mol, and -14.11 ± 5.33 kcal/mol, respectively. Importantly, diosgenin,dehydro, a saponin obtained from <i>T. terrestris</i>, was identified as a particularly promising candidate for PDE5 inhibition by virtue of its higher negative binding affinity and, therefore, displaying a potential in drug discovery and development for ED. In addition, <i>in silico</i> pharmacokinetic analysis and toxicity assessments support the prospects of these <i>T. terrestris</i>-derived phytochemicals for future <i>in vitro</i> and <i>in vivo</i> research for innovation in ED therapeutics.</p>","PeriodicalId":19530,"journal":{"name":"Omics A Journal of Integrative Biology","volume":"29 9","pages":"442-457"},"PeriodicalIF":1.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963733","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":"Collagen Type 1 Alpha 1 Chain as a Potential Therapeutic Target Shared Among Subtypes of Head and Neck Squamous Cell Carcinoma: Quantum Chemical Modeling of Bleomycin for Anticancer Drug Repurposing.","authors":"Ashok Kumar, Jency Roshni, Mahema Sivakumar, Janakiraman Velayudam, Sheikh F Ahmad, Sabry M Attia, Shiek S S J Ahmed","doi":"10.1177/15578100251359275","DOIUrl":"10.1177/15578100251359275","url":null,"abstract":"<p><p>Head and neck squamous cell carcinoma (HNSCC) displays significant molecular heterogeneity, which hinders effective and safe treatments and clinical outcomes. This predicament also points to the need for an individually tailored personalized/precision medicine approach in HNSCC that includes the oral, hypopharyngeal, nasopharyngeal, and laryngeal subtypes. This study, with the overarching aim of personalized/precision medicine, attempted to identify (1) a molecular target shared by the HNSCC subtypes and (2) screen for potential anticancer drugs for repurposing that may work across the HNSCC subtypes. The National Center for Biotechnology Information-Gene Expression Omnibus database was used to select the datasets (GSE127165, GSE2379, GSE37991, and GSE12452) for the analyses of differentially expressed genes in HNSCC subtypes. Our transcriptome analyses of the HNSCC subtypes revealed 305 upregulated genes. Subsequently, protein network construction with 305 genes showed three closely interconnected high-risk HNSCC prognostic clusters. Importantly, COL1A1 was identified as the pivotal target regulating the pathogenic cluster protein implicated in cancer pathways. Molecular docking with 1040 anticancer drugs identified bleomycin as a potential candidate, exhibiting a binding affinity of -12.425 kcal/mol and a favorable binding free energy of -92.05 kcal/mol. The dynamic simulations confirmed the stability of the system, with stable interactions over 200 ns. Quantum calculations provided insights into bleomycin's chemical and electronic properties, revealing crucial interactions with COL1A1. In conclusion, our study proposes COL1A1 as a promising potential therapeutic target among HNSCC subtypes, with bleomycin demonstrating notable repurposing potential for HNSCC.</p>","PeriodicalId":19530,"journal":{"name":"Omics A Journal of Integrative Biology","volume":" ","pages":"404-414"},"PeriodicalIF":1.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144637688","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":"A Gel-Free Genome Annotation Provides Insights into the Proteome of the Oomycete <i>Phytophthora meadii</i>, a Disease-Causing Pathogen in Economically Important Crops.","authors":"Bhagya Nekrakalaya, Chinmaya Narayana Kotimoole, Mohammad Arefian, Thottethodi Subrahmanya Keshava Prasad, Gangaraj Karyath Palliyath, Prathibha Veerappa Hanumanthappa, Thava Prakasa Pandian Ramasubramania, Nirmal Kumar Bangalore Jayaseelan, Chaithra Muddumadiah, Paulraj Santhappan, Rajesh Muliyar Krishna","doi":"10.1177/15578100251359566","DOIUrl":"10.1177/15578100251359566","url":null,"abstract":"<p><p><i>Phytophthora meadii</i> is a polyphagous oomycete causing fatal diseases in economically important cash crops such as rubber, arecanut, cardamom, and other crops and plants of economic significance. Although information on the proteogenomic and proteomic analysis is available for several <i>Phytophthora</i> species, no information on the proteome repertoire of <i>P. meadii</i> is available. In the present study, a gel-free protein annotation was performed using liquid chromatography with tandem mass spectrometry analysis of the <i>P. meadii</i> hyphae, followed by bioinformatics analysis. The results were compared with a global <i>Phytophthora</i> proteome database-based search and an in-house <i>P. meadii</i> genome database, along with RefSeq proteome databases of other selected species of <i>Phytophthora</i>. A total of 7725 and 3979 proteins were exclusively matched with global and in-house databases, respectively. Basic Local Alignment Search Tool analysis showed 209 unique peptide sequences belonging to 85 proteins of <i>P. meadii</i>. Gene Ontology-based functional analysis of the <i>P. meadii</i> mycelial proteome categorized the proteins based on their role in cellular components, molecular functions, and biological processes. Kyoto Encyclopedia of Genes and Genomes pathway and protein-protein network analysis further revealed the role of these proteins in growth and development functions. In addition, proteins potentially involved in virulence, infections in the host system, and several signaling mechanisms were deduced. The current study is the first report on the <i>P. meadii</i> mycelial proteins under optimum growth conditions. These omics data also have socioeconomic implications since <i>Phytophthora</i> causes disease in a wide range of economically noteworthy crops and forest ecosystems.</p>","PeriodicalId":19530,"journal":{"name":"Omics A Journal of Integrative Biology","volume":" ","pages":"384-393"},"PeriodicalIF":1.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144668065","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":"The Genome Sequence of the Rugose Spiraling Whitefly (<i>Aleurodicus rugioperculatus</i> Martin): Insights on Biology of an Invasive Agricultural Insect Pest and Implications for Pest Control.","authors":"Rajesh Muliyar Krishna, Sujithra Maruthakasi, Josephrajkumar Arulappan, Latha Kasargodu Raghava, Sabana Abdulla Abdulla, Roli Budhwar, Praveen Kumar Oraon, Alpana Das, Thottethodi Subrahmanya Keshava Prasad","doi":"10.1177/15578100251359300","DOIUrl":"10.1177/15578100251359300","url":null,"abstract":"<p><p>The Rugose Spiraling Whitefly (RSW) (<i>Aleurodicus rugioperculatus</i> Martin), a pest native to Central America, infests coconut palms and has been introduced to other regions of the world including North America (e.g., Florida) and Southeast Asia. In India, RSW was first reported in 2016, and rapidly expanded to multiple states nationwide. Currently, RSW has growing global relevance as an agricultural insect pest. In addition to coconut, the RSW exhibits a broad host range, causing damage to various palms, fruit crops such as guava, vegetables, and ornamental shrubs. In this study, we present a high-quality draft genome assembly for this insect pest, generated using Pacific Bioscience long-read HiFi sequencing. The assembled genome spans 1.10 Gb, with a contig N50 value of 10.23 Mb. Approximately 521 Mb of sequences, accounting for 47.30% of the genome, were identified as repeat elements. The assembly includes 35,884 predicted coding sequences and exhibits high completeness, with 98.4% of Benchmarking Universal Single-Copy Orthologs genes recovered for the core insect gene set. The sequencing of the RSW genome offers valuable insights into the biology of one of the most significant and pervasive agricultural pests. The expansion of gene families associated with insecticide resistance may indicate this pest's ability to metabolize selective insecticides. These data have the potential to greatly enhance strategies for managing the RSW insect population size and limiting its invasive capacity for pest control. Additionally, the genome provides a foundation for comparative studies of whitefly genomes, and possibly informing the future design and development of novel insecticides.</p>","PeriodicalId":19530,"journal":{"name":"Omics A Journal of Integrative Biology","volume":" ","pages":"394-403"},"PeriodicalIF":1.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144643098","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":"Clinical and Genetic Predictors of Sickle Cell Nephropathy: A Global Systematic Review.","authors":"Kambe Banda, Arthemon Nguweneza, Khuthala Mnika, Victoria Nembaware, George Chagaluka, Ambroise Wonkam","doi":"10.1177/15578100251359276","DOIUrl":"10.1177/15578100251359276","url":null,"abstract":"<p><p>Sickle cell disease (SCD) affects nearly 300,000 newborns annually worldwide, with 80% born in Africa. Sickle cell nephropathy (SCN) affects 5-18% of patients with SCD and contributes significantly to morbidity and mortality. Identifying SCN-associated factors would promote effective clinical management. We conducted a global systematic review in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines (Prospective Register of Systematic Reviews, registration number: CRD42020185763) to explore clinical and genetic correlates of SCN. We sought after cohort, case-control, and cross-sectional studies published up to December 31, 2024 that reported on clinical and/or genetic predictors of SCN in different populations globally. A total of 70 hospital-based study articles were finally included, with a leading percentage (45.7%) of the included studies performed in the United States, whereas 24.3% were from Sub-Saharan Africa. Most had a cross-sectional design (68.6%) involving children and adults. Genetic studies (17/70) identified associations with α-thalassemia, <i>APOL1</i>, and <i>HMOX1</i> genes. The only genome-wide association study identified six suggestive variants in <i>CRYL1</i>, <i>VWF</i>, <i>ADAMTS7</i>, <i>LRP1B</i>, <i>linc02288</i>, and <i>FPGT-TNNI3K/TNNI3K</i> among adult patients. In conclusion, this systematic review (1) unpacks and highlights the role of clinical, genetic, and biochemical factors in the pathogenesis and progression of SCN and (2) reveals the consistent association of SCN with the 3.7 Kb deletion in <i>HBA</i> and variants in <i>APOL1</i> and <i>HMOX1</i> genes. This systematic review underscores the paucity of data from Africa, emphasizing the need for large-scale prospective studies on African SCN cohorts. Our findings also provide a foundation for the early identification of individuals at risk for SCN and the avenues for clinical and public health management strategies. To the best of our knowledge, this is the first systematic review summarizing risk factors for kidney dysfunction in SCD populations worldwide, which includes, specifically, a meta-analysis for <i>APOL1</i> association with albuminuria.</p>","PeriodicalId":19530,"journal":{"name":"Omics A Journal of Integrative Biology","volume":" ","pages":"353-373"},"PeriodicalIF":1.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144732503","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":"Unraveling the Microbiome-Asthma Axis: Metagenomic Insights from Airway and Gut Microbial Communities.","authors":"Sanjukta Dasgupta","doi":"10.1177/15578100251358958","DOIUrl":"10.1177/15578100251358958","url":null,"abstract":"<p><p>Asthma is a heterogeneous respiratory disease with complex pathogenesis involving immune dysregulation, environmental triggers, and increasingly recognized to have contributions from the human microbiome. Emerging evidence from longitudinal birth cohorts and multi-omics studies reveals that early-life microbial colonization patterns in both the gastrointestinal and respiratory tracts play a crucial role in shaping immune trajectories and influencing asthma susceptibility. This expert review highlights the findings from pivotal studies that associate dysbiosis in the gut and airway microbiota with asthma development and its diverse phenotypic manifestations. Reduced abundance of immunomodulatory genera such as <i>Bifidobacterium</i>, <i>Faecalibacterium</i>, and <i>Lachnospira</i> in the gut has been consistently associated with increased asthma risk. In the airways, increased colonization by potentially pathogenic taxa, including <i>Moraxella</i>, <i>Haemophilus</i>, and <i>Streptococcus</i>, correlates with viral respiratory infections and persistent wheezing. Microbiome diversity patterns also differ between asthma phenotypes: eosinophilic asthma typically features a community profile closer to healthy individuals, while neutrophilic asthma is marked by enrichment of pro-inflammatory bacterial species. Moreover, protective genera such as <i>Dolosigranulum</i> and <i>Corynebacterium</i> in the upper airways are associated with lower risk of asthma and reduced respiratory infections. Elucidating these microbiome-mediated mechanisms holds promise for the development of targeted microbiota-based strategies for asthma prevention and phenotype-specific therapeutic interventions. The present review unpacks these localized microbial patterns and their mechanistic implications for asthma development, severity, and endotypic variation. Finally, unraveling the microbiome-asthma axis from airway and gut microbial communities also has implications for new ways of thinking personalized medicine in the future.</p>","PeriodicalId":19530,"journal":{"name":"Omics A Journal of Integrative Biology","volume":" ","pages":"374-383"},"PeriodicalIF":1.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144608970","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":"Targeting Cyclin-Dependent Kinase 12 (CDK12) for Cancer Therapy: Structure-Based Discovery of Two Novel CDK12 Inhibitors <i>In Silico</i> Using Integrated Bioinformatics.","authors":"Zehra, Lina I Alnajjar, Nawaf Alshammari, Romana Ishrat, Md Imtaiyaz Hassan","doi":"10.1089/omi.2025.0060","DOIUrl":"10.1089/omi.2025.0060","url":null,"abstract":"<p><p>Cyclin-dependent kinase 12 (CDK12) is thought to play an important role in cancer biology pathogenesis and development. Novel, selective, safe, and effective CDK12 inhibitors are actively sought after in drug discovery and clinical development. We report here the structure-based discovery of two novel CDK12 inhibitors using integrated molecular docking, simulation, and molecular mechanics Poisson-Boltzmann surface area methods. We performed a virtual high-throughput screening of potential inhibitors sourced from the ZINC database, which contains ∼90,000 molecules. Various filters were applied to separate bioactive molecules using Lipinski's rule of five, Absorption, Distribution, Metabolism, Excretion, and Toxicity properties, Ghose filters, and Pan-assay interference compound filters. Furthermore, the elucidated compounds were subjected to molecular docking to evaluate their binding toward the target. Interaction analysis of the selected compounds showed favorable interactions with the active site pocket residues of CDK12 for ZINC 02096057 and ZINC 02094702. These two compounds modulate both the active and adenosine triphosphate (ATP)-binding sites of the target CDK12, inhibiting its biological activity. Moreover, flavopiridol, a known inhibitor of CDK12, was used to cross-check with the selected ligands to validate our findings. Molecular dynamics simulation was performed at 500 ns to evaluate the dynamics of each atom in the system. Finally, we suggest that ZINC 02096057 and ZINC 02094702 offer prospects as novel inhibitors of CDK12, which warrant further <i>in vitro</i> and <i>in vivo</i> studies. Cancer therapeutics specifically, and drug discovery more generally, stand to benefit from novel molecular leads for CDK12 inhibition.</p>","PeriodicalId":19530,"journal":{"name":"Omics A Journal of Integrative Biology","volume":" ","pages":"341-351"},"PeriodicalIF":2.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144285957","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":"Alterations in Gut Microbiota-Brain Axis in Major Depressive Disorder as Identified by Machine Learning.","authors":"Atacan Deniz Oncu, Arzucan Ozgur, Kutlu O Ulgen","doi":"10.1089/omi.2025.0084","DOIUrl":"10.1089/omi.2025.0084","url":null,"abstract":"<p><p>Major depressive disorder (MDD) is a complex mental health condition whose causes may extend beyond purely biological explanations and are increasingly understood within wider ecological and social frameworks. Emerging research on the human gut-brain axis with the help of statistical and artificial intelligence tools aims to elucidate the links between the gut microbiota, diet, environment, and MDD. In this study, we analyzed data from the American Gut Project (AGP), including 361 control and 23 MDD samples, to find potential biomarkers associated with MDD. While alpha and beta diversity analyses revealed no significant differences except for age, multiple differential abundance tools and machine learning (ML) models (Random Forest and XGBoost), whose results were analyzed using Shapley Additive Explanations values, consistently detected a decrease in <i>Bifidobacterium adolescentis</i> and increases in <i>Odoribacter</i>, <i>Ruminococcus</i>, and <i>Adlercreutzia</i> among MDD samples. These four organisms influence inflammation, neurotransmitter balance, gut permeability, and other pathways associated with depression and thus can be recognized as potential biomarkers for MDD. This study highlights the promise of ML to decode the gut-brain axis as a first step in biomarker discovery, thus providing new possibilities for a personalized treatment approach and an improvement in diagnostic tools for MDD.</p>","PeriodicalId":19530,"journal":{"name":"Omics A Journal of Integrative Biology","volume":" ","pages":"309-319"},"PeriodicalIF":2.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144476212","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}