Omics A Journal of Integrative Biology最新文献

DeepGenomeScan of 15 Worldwide Bovine Populations Detects Spatially Varying Positive Selection Signals. 对全球 15 个牛种群的 DeepGenomeScan 检测到空间上不同的正向选择信号。

IF 2.2 3区生物学

Omics A Journal of Integrative Biology Pub Date : 2024-09-24 DOI: 10.1089/omi.2024.0154

Harshit Kumar, Xinghu Qin, Bharat Bhushan, Triveni Dutt, Manjit Panigrahi

{"title":"DeepGenomeScan of 15 Worldwide Bovine Populations Detects Spatially Varying Positive Selection Signals.","authors":"Harshit Kumar, Xinghu Qin, Bharat Bhushan, Triveni Dutt, Manjit Panigrahi","doi":"10.1089/omi.2024.0154","DOIUrl":"https://doi.org/10.1089/omi.2024.0154","url":null,"abstract":"Identifying genomic regions under selection is essential for understanding the genetic mechanisms driving species evolution and adaptation. Traditional methods often fall short in detecting complex, spatially varying selection signals. Recent advances in deep learning, however, present promising new approaches for uncovering subtle selection signals that traditional methods might miss. In this study, we utilized the deep learning framework DeepGenomeScan to detect spatially varying selection signatures across 15 bovine populations worldwide. Our analysis uncovered novel insights into selective sweep hotspots within the bovine genome, revealing key genes associated with physiological and adaptive traits that were previously undetected. We identified significant quantitative trait loci linked to milk protein and fat percentages. By comparing the selection signatures identified in this study with those reported in the Bovine Genome Variation Database, we discovered 38 novel genes under selection that were not identified through traditional methods. These genes are primarily associated with milk and meat yield and quality. Our findings enhance our understanding of spatially varying selection's impact on bovine genomic diversity, laying a foundation for future research in genetic improvement and conservation. This is the first deep learning-based study of selection signatures in cattle, offering new insights for evolutionary and livestock genomics research.","PeriodicalId":19530,"journal":{"name":"Omics A Journal of Integrative Biology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142308253","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}

引用次数: 0

Machine Learning-Aided Ultra-Low-Density Single Nucleotide Polymorphism Panel Helps to Identify the Tharparkar Cattle Breed: Lessons for Digital Transformation in Livestock Genomics. 机器学习辅助的超低密度单核苷酸多态性面板有助于识别塔帕卡尔牛品种：家畜基因组学数字化转型的启示。

IF 2.2 3区生物学

Omics A Journal of Integrative Biology Pub Date : 2024-09-20 DOI: 10.1089/omi.2024.0153

Harshit Kumar, Manjit Panigrahi, Dongwon Seo, Sunghyun Cho, Bharat Bhushan, Triveni Dutt

{"title":"Machine Learning-Aided Ultra-Low-Density Single Nucleotide Polymorphism Panel Helps to Identify the Tharparkar Cattle Breed: Lessons for Digital Transformation in Livestock Genomics.","authors":"Harshit Kumar, Manjit Panigrahi, Dongwon Seo, Sunghyun Cho, Bharat Bhushan, Triveni Dutt","doi":"10.1089/omi.2024.0153","DOIUrl":"https://doi.org/10.1089/omi.2024.0153","url":null,"abstract":"Cattle breed identification is crucial for livestock research and sustainable food systems, and advances in genomics and artificial intelligence present new opportunities to address these challenges. This study investigates the identification of the Tharparkar cattle breed using genomics tools combined with machine learning (ML) techniques. By leveraging data from the Bovine SNP 50K chip, we developed a breed-specific panel of single nucleotide polymorphisms (SNPs) for Tharparkar cattle and integrated data from seven other Indian cattle populations to enhance panel robustness. Genome-wide association studies (GWAS) and principal component analysis were employed to identify 500 SNPs, which were then refined using ML models-AdaBoost, bagging tree, gradient boosting machines, and random forest-to determine the minimal number of SNPs needed for accurate breed identification. Panels of 23 and 48 SNPs achieved accuracy rates of 95.2-98.4%. Importantly, the identified SNPs were associated with key productive and adaptive traits, thus attesting to the value and potentials of digital transformation in livestock genomics. The ML-aided ultra-low-density SNP panel approach reported here not only facilitates breed identification but also contributes to preserving genetic diversity and guiding future breeding programs.","PeriodicalId":19530,"journal":{"name":"Omics A Journal of Integrative Biology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142292697","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}

引用次数: 0

How Do You Start a Revolution for Systems Medicine in a Health Innovation Ecosystem? Think Orthogonally and Change Assumptions. 如何在健康创新生态系统中掀起一场系统医学革命？正向思考，改变假设。

IF 2.2 3区生物学

Omics A Journal of Integrative Biology Pub Date : 2024-09-18 DOI: 10.1089/omi.2024.0173

Vural Özdemir

{"title":"How Do You Start a Revolution for Systems Medicine in a Health Innovation Ecosystem? Think Orthogonally and Change Assumptions.","authors":"Vural Özdemir","doi":"10.1089/omi.2024.0173","DOIUrl":"https://doi.org/10.1089/omi.2024.0173","url":null,"abstract":"This paper defines a revolution as an orthogonal change in direction, a 90-degree perpendicular turn from the status quo ways of thinking, being and doing, so as to create a complete break, an abolitionist rupture with current and past ways of producing knowledge. David Bowie was a relatable example of a revolutionary and orthogonal innovator who completely and courageously broke with the past and the present and opened up new vistas in music and performing arts. The late anthropologist and public intellectual David Graeber also argued that a revolution fundamentally changes the assumptions in a given field of inquiry. Changing the entrenched assumptions that are long ossified, outdated or uncritically internalized by a knowledge community and profession can have multiplying revolutionary effects on downstream knowledge production. Thinking orthogonally to change the prevailing assumptions is indeed a revolutionary act. Orthogonal innovation as described in this paper is not a repackaging of an innovation in a different field. An orthogonal innovation is proposed as coalescence of ideas drawn from orthogonal domains, e.g., epistemologically speaking as in medicine and political theory, with an eye to pave the way for unprecedented social change and innovation. Grounding systems medicine in political determinants of planetary health, to link two fields of inquiry that have remained isolated and orthogonal since the 17th century, is nothing short of a revolution and orthogonal innovation in the making. For systems medicine to be a truly revolutionary field, it ought to acknowledge that there is no single-issue health nor single-issue politics.","PeriodicalId":19530,"journal":{"name":"Omics A Journal of Integrative Biology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142292696","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}

引用次数: 0

Unlocking the Door for Precision Medicine in Rare Conditions: Structural and Functional Consequences of Missense ACVR1 Variants. 打开罕见疾病精准医疗之门：错义 ACVR1 变异的结构和功能后果

IF 3.3 3区生物学

Omics A Journal of Integrative Biology Pub Date : 2024-09-17 DOI: 10.1089/omi.2024.0140

Garima Nagar,Shradheya R R Gupta,Vanshika Rustagi,Ravindran Kumar Pramod,Archana Singh,Monika Pahuja,Indrakant Kumar Singh

{"title":"Unlocking the Door for Precision Medicine in Rare Conditions: Structural and Functional Consequences of Missense ACVR1 Variants.","authors":"Garima Nagar,Shradheya R R Gupta,Vanshika Rustagi,Ravindran Kumar Pramod,Archana Singh,Monika Pahuja,Indrakant Kumar Singh","doi":"10.1089/omi.2024.0140","DOIUrl":"https://doi.org/10.1089/omi.2024.0140","url":null,"abstract":"Rare diseases and conditions have thus far received relatively less attention in the field of precision/personalized medicine than common chronic diseases. There is a dire need for orphan drug discovery and therapeutics in ways that are informed by the precision/personalized medicine scholarship. Moreover, people with rare conditions, when considered collectively across diseases worldwide, impact many communities. In this overarching context, Activin A Receptor Type 1 (ACVR1) is a transmembrane kinase from the transforming growth factor-β superfamily and plays a critical role in modulating the bone morphogenetic protein signaling. Missense variants of the ACVR1 gene result in modifications in structure and function and, by extension, abnormalities and have been predominantly linked with two rare conditions: fibrodysplasia ossificans progressiva and diffuse intrinsic pontine glioma. We report here an extensive bioinformatic analyses assessing the pool of 50,951 variants and forecast seven highly destabilizing mutations (R206H, G356D, R258S, G328W, G328E, R375P, and R202I) that can significantly alter the structure and function of the native protein. Protein-protein interaction and ConSurf analyses revealed the crucial interactions and localization of highly deleterious mutations in highly conserved domains that may impact the binding and functioning of the protein. cBioPortal, CanSAR Black, and existing literature affirmed the association of these destabilizing mutations with posterior fossa ependymoma, uterine corpus carcinoma, and pediatric brain cancer. The current findings suggest these deleterious nonsynonymous single nucleotide polymorphisms as potential candidates for future functional annotations and validations associated with rare conditions, further aiding the development of precision medicine in rare diseases.","PeriodicalId":19530,"journal":{"name":"Omics A Journal of Integrative Biology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142253358","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}

引用次数: 0

Systems Biology and Machine Learning Identify Genetic Overlaps Between Lung Cancer and Gastroesophageal Reflux Disease. 系统生物学和机器学习识别肺癌和胃食管反流病的基因重叠。

IF 3.3 3区生物学

Omics A Journal of Integrative Biology Pub Date : 2024-09-13 DOI: 10.1089/omi.2024.0150

Sanjukta Dasgupta

{"title":"Systems Biology and Machine Learning Identify Genetic Overlaps Between Lung Cancer and Gastroesophageal Reflux Disease.","authors":"Sanjukta Dasgupta","doi":"10.1089/omi.2024.0150","DOIUrl":"https://doi.org/10.1089/omi.2024.0150","url":null,"abstract":"One Health and planetary health place emphasis on the common molecular mechanisms that connect several complex human diseases as well as human and planetary ecosystem health. For example, not only lung cancer (LC) and gastroesophageal reflux disease (GERD) pose a significant burden on planetary health, but also the coexistence of GERD in patients with LC is often associated with a poor prognosis. This study reports on the genetic overlaps between these two conditions using systems biology-driven bioinformatics and machine learning-based algorithms. A total of nine hub genes including IGHV1-3, COL3A1, ITGA11, COL1A1, MS4A1, SPP1, MMP9, MMP7, and LOC102723407 were found to be significantly altered in both LC and GERD as compared with controls and with pathway analyses suggesting a significant association with the matrix remodeling pathway. The expression of these genes was validated in two additional datasets. Random forest and K-nearest neighbor, two machine learning-based algorithms, achieved accuracies of 89% and 85% for distinguishing LC and GERD, respectively, from controls using these hub genes. Additionally, potential drug targets were identified, with molecular docking confirming the binding affinity of doxycycline to matrix metalloproteinase 7 (binding affinity: -6.8 kcal/mol). The present study is the first of its kind that combines in silico and machine learning algorithms to identify the gene signatures that relate to both LC and GERD and promising drug candidates that warrant further research in relation to therapeutic innovation in LC and GERD. Finally, this study also suggests upstream regulators, including microRNAs and transcription factors, that can inform future mechanistic research on LC and GERD.","PeriodicalId":19530,"journal":{"name":"Omics A Journal of Integrative Biology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142253357","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}

引用次数: 0

Does Microbiome Contribute to Longevity? Compositional and Functional Differences in Gut Microbiota in Chinese Long-Living (>90 Years) and Elderly (65-74 Years) Adults. 微生物群是否有助于长寿？中国长寿者（大于 90 岁）和老年人（65-74 岁）肠道微生物群的组成和功能差异。

IF 2.2 3区生物学

Omics A Journal of Integrative Biology Pub Date : 2024-09-01 Epub Date: 2024-08-16 DOI: 10.1089/omi.2024.0120

Jie Liu, Wen-Jing Wang, Ge-Fang Xu, Yue-Xia Wang, Ying Lin, Xin Zheng, Shui-Hong Yao, Kun-Hua Zheng

{"title":"Does Microbiome Contribute to Longevity? Compositional and Functional Differences in Gut Microbiota in Chinese Long-Living (>90 Years) and Elderly (65-74 Years) Adults.","authors":"Jie Liu, Wen-Jing Wang, Ge-Fang Xu, Yue-Xia Wang, Ying Lin, Xin Zheng, Shui-Hong Yao, Kun-Hua Zheng","doi":"10.1089/omi.2024.0120","DOIUrl":"10.1089/omi.2024.0120","url":null,"abstract":"The study of longevity and its determinants has been revitalized with the rise of microbiome scholarship. The gut microbiota have been established to play essential protective, metabolic, and physiological roles in human health and disease. The gut dysbiosis has been identified as an important factor contributing to the development of multiple diseases. Accordingly, it is reasonable to hypothesize that the gut microbiota of long-living individuals have healthy antiaging-associated gut microbes, which, by extension, might provide specific molecular targets for antiaging treatments and interventions. In the present study, we compared the gut microbiota of Chinese individuals in two different age groups, long-living adults (aged over 90 years) and elderly adults (aged 65-74 years) who were free of major diseases. We found significantly lower relative abundances of bacteria in the genera Sutterella and Megamonas in the long-living individuals. Furthermore, we established that while biological processes such as autophagy (GO:0006914) and telomere maintenance through semiconservative replication (GO:0032201) were enhanced in the long-living group, response to lipopolysaccharide (GO:0032496), nicotinamide adenine dinucleotide oxidation (GO:0006116), and S-adenosyl methionine metabolism (GO:0046500) were weakened. Moreover, the two groups were found to differ with respect to amino acid metabolism. We suggest that these compositional and functional differences in the gut microbiota may potentially be associated with mechanisms that contribute to determining longevity or aging.","PeriodicalId":19530,"journal":{"name":"Omics A Journal of Integrative Biology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141988424","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}

引用次数: 0

Rosalind Franklin Society Proudly Announces the 2023 Award Recipient for OMICS: A Journal of Integrative Biology. 罗莎琳德-富兰克林学会自豪地宣布《OMICS: A Journal of Integrative Biology》2023 年度获奖者。

IF 2.2 3区生物学

Omics A Journal of Integrative Biology Pub Date : 2024-09-01 DOI: 10.1089/omi.2024.78325.rfs2023

Theodora Katsila

引用次数: 0

Expanding Beyond Genetic Subtypes in B-Cell Acute Lymphoblastic Leukemia: A Pathway-Based Stratification of Patients for Precision Oncology. 超越 B 细胞急性淋巴细胞白血病的基因亚型：基于路径的精准肿瘤学患者分层。

IF 2.2 3区生物学

Omics A Journal of Integrative Biology Pub Date : 2024-09-01 Epub Date: 2024-08-19 DOI: 10.1089/omi.2024.0145

Ozlem Ulucan

{"title":"Expanding Beyond Genetic Subtypes in B-Cell Acute Lymphoblastic Leukemia: A Pathway-Based Stratification of Patients for Precision Oncology.","authors":"Ozlem Ulucan","doi":"10.1089/omi.2024.0145","DOIUrl":"10.1089/omi.2024.0145","url":null,"abstract":"Precision oncology promises individually tailored drugs and clinical care for patients with cancer: That is, \"the right drug, for the right patient, at the right dose, and at the right time.\" Although stratification of the risk for treatment resistance and toxicity is key to precision oncology, there are multiple ways in which such stratification can be achieved, for example, genetic, functional pathway based, among others. Moving toward precision oncology is sorely needed in the case of acute lymphoblastic leukemia (ALL) wherein adult patients display survival rates ranging from 30% to 70%. The present study reports on the pathway activity signature of adult B-ALL, with an eye to precision oncology. Transcriptome profiles from three different expression datasets, comprising 346 patients who were adolescents or adults with B-ALL, were harnessed to determine the activity of signaling pathways commonly disrupted in B-ALL. Pathway activity analyses revealed that Ph-like ALL closely resembles Ph-positive ALL. Although this was the case at the average pathway activity level, the pathway activity patterns in B-ALL differ from genetic subtypes. Importantly, clustering analysis revealed that five distinct clusters exist in B-ALL patients based on pathway activity, with each cluster displaying a unique pattern of pathway activation. Identifying pathway-based subtypes thus appears to be crucial, considering the inherent heterogeneity among patients with the same genetic subtype. In conclusion, a pathway-based stratification of the B-ALL could potentially allow for simultaneously targeting highly active pathways within each ALL subtype, and thus might open up new avenues of innovation for personalized/precision medicine in this cancer that continues to have poor prognosis in adult patients compared with the children.","PeriodicalId":19530,"journal":{"name":"Omics A Journal of Integrative Biology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142000479","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}

引用次数: 0

Will Precision Medicine Meet Digital Health? A Systematic Review of Pharmacogenomics Clinical Decision Support Systems Used in Clinical Practice. 精准医学能否满足数字健康？临床实践中使用的药物基因组学临床决策支持系统的系统回顾。

IF 2.2 3区生物学

Omics A Journal of Integrative Biology Pub Date : 2024-09-01 Epub Date: 2024-08-13 DOI: 10.1089/omi.2024.0131

Anastasia Farmaki, Evangelos Manolopoulos, Pantelis Natsiavas

{"title":"Will Precision Medicine Meet Digital Health? A Systematic Review of Pharmacogenomics Clinical Decision Support Systems Used in Clinical Practice.","authors":"Anastasia Farmaki, Evangelos Manolopoulos, Pantelis Natsiavas","doi":"10.1089/omi.2024.0131","DOIUrl":"10.1089/omi.2024.0131","url":null,"abstract":"Digital health, an emerging scientific domain, attracts increasing attention as artificial intelligence and relevant software proliferate. Pharmacogenomics (PGx) is a core component of precision/personalized medicine driven by the overarching motto \"the right drug, for the right patient, at the right dose, and the right time.\" PGx takes into consideration patients' genomic variations influencing drug efficacy and side effects. Despite its potentials for individually tailored therapeutics and improved clinical outcomes, adoption of PGx in clinical practice remains slow. We suggest that e-health tools such as clinical decision support systems (CDSSs) can help accelerate the PGx, precision/personalized medicine, and digital health emergence in everyday clinical practice worldwide. Herein, we present a systematic review that examines and maps the PGx-CDSSs used in clinical practice, including their salient features in both technical and clinical dimensions. Using Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines and research of the literature, 29 relevant journal articles were included in total, and 19 PGx-CDSSs were identified. In addition, we observed 10 technical components developed mostly as part of research initiatives, 7 of which could potentially facilitate future PGx-CDSSs implementation worldwide. Most of these initiatives are deployed in the United States, indicating a noticeable lack of, and the veritable need for, similar efforts globally, including Europe.","PeriodicalId":19530,"journal":{"name":"Omics A Journal of Integrative Biology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971589","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}

引用次数: 0

Enriching Anticancer Drug Pipeline with Potential Inhibitors of Cyclin-Dependent Kinase-8 Identified from Natural Products. 从天然产品中发现潜在的 Cyclin-Dependent Kinase-8 抑制剂，丰富抗癌药物产品线。

IF 2.2 3区生物学

Omics A Journal of Integrative Biology Pub Date : 2024-09-01 Epub Date: 2024-08-16 DOI: 10.1089/omi.2024.0128

Zehra, Afzal Hussain, Mohamed F AlAjmi, Romana Ishrat, Md Imtaiyaz Hassan

{"title":"Enriching Anticancer Drug Pipeline with Potential Inhibitors of Cyclin-Dependent Kinase-8 Identified from Natural Products.","authors":"Zehra, Afzal Hussain, Mohamed F AlAjmi, Romana Ishrat, Md Imtaiyaz Hassan","doi":"10.1089/omi.2024.0128","DOIUrl":"10.1089/omi.2024.0128","url":null,"abstract":"Cyclin-dependent kinase 8 (CDK8) is highly expressed in various cancers and common complex human diseases, and an important therapeutic target for drug discovery and development. The CDK8 inhibitors are actively sought after, especially among natural products. We performed a virtual screening using the ZINC library comprising approximately 90,000 natural compounds. We applied Lipinski's rule of five, absorption, distribution, metabolism, excretion, and toxicity properties, and pan-assay interference compounds filter to eliminate promiscuous binders. Subsequently, the filtered compounds underwent molecular docking to predict their binding affinity and interactions with the CDK8 protein. Interaction analysis were carried out to elucidate the interaction mechanism of the screened hits with binding pockets of the CDK8. The ZINC02152165, ZINC04236005, and ZINC02134595 were selected with appreciable specificity and affinity with CDK8. An all-atom molecular dynamic (MD) simulation followed by essential dynamics was performed for 200 ns. Taken together, the results suggest that ZINC02152165, ZINC04236005, and ZINC02134595 can be harnessed as potential leads in therapeutic development. Moreover, the binding of the molecules brings change in protein conformation in a way that blocks the ATP-binding site of the protein, obstructing its kinase activity. These new findings from natural products offer insights into the molecular mechanisms underlying CDK8 inhibition. CDK8 was previously associated with behavioral and neurological diseases such as autism spectrum disorder, and cancers, for example, colorectal, prostate, breast, and acute myeloid leukemia. Hence, we call for further research and experimental validation, and with an eye to inform future clinical drug discovery and development in these therapeutic fields.","PeriodicalId":19530,"journal":{"name":"Omics A Journal of Integrative Biology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141988425","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}

引用次数: 0